History of macrolide use in pediatrics.

PubMed

Klein, J O

1997-04-01

Erythromycin, the prototypical macrolide, has been widely used since the 1950s in the management of pediatric infections. Erythromycin is the drug of choice for infants and children with Legionnaire's disease, pertussis, diphtheria, lower respiratory tract infections caused by Mycoplasma pneumoniae, Chlamydia pneumoniae and Chlamydia trachomatis and enteritis caused by Campylobacter jejuni. It is also indicated for treatment of syphilis; for streptococcal, staphylococcal and pneumococcal infections; genital infections caused by Ureaplasma urealyticum; and for the prevention of rheumatic fever and endocarditis in patients who are allergic to beta-lactam antibiotics. The new macrolides azithromycin and clarithromycin are also active against Borrelia burgdorferi, Helicobacter pylori, Mycobacterium avium-intracellulare complex, Cryptosporidium spp. and Toxoplasma gondii. Erythromycin is associated with a low risk of serious side effects, although gastric distress occurs in a significant proportion of patients. Drug interactions with theophylline, carbamazepine, warfarin, cyclosporine, terfenadine and digoxin limit erythromycin use. The newer macrolides azithromycin and clarithromycin are more stable, better absorbed and better tolerated than erythromycin. Azithromycin is more active than erythromycin against Haemophilus influenzae. Excellent tissue and intracellular penetration may contribute to their clinical efficacy. In children both azithromycin and clarithromycin are indicated for acute otitis media caused by Streptococcus pneumoniae, H. influenzae and Moraxella catarrhalis and for pharyngitis/tonsillitis caused by Streptococcus pyogenes. (As of December, 1996, azithromycin for oral suspension was approved for community-acquired pneumonia in children caused by C. pneumoniae, H. influenzae, M. pneumoniae and S. pneumoniae.) Claritromycin is also indicated for acute maxillary sinusitis, uncomplicated skin and skin structure infections, pneumonia and disseminated mycobacterial infections. Azithromycin and clarithromycin are associated with a lower incidence of gastrointestinal side effects, a low rate of drug discontinuation caused by side effects and a low potential for interaction with other drugs.

Chromatographic methods for determination of macrolide antibiotic residues in tissues and milk of food-producing animals.

PubMed

Moats, W A

1985-01-01

Tylosin, an antibiotic developed specifically for agricultural use, and erythromycin are the main macrolide antibiotics used in animal production. Two-dimensional thin layer chromatography has been used for detection of tylosin in poultry meat, eggs, and milk and for erythromycin in poultry meat. Detection limits reported are, for tylosin, 0.1 ppm in poultry meat, 0.05 ppm in egg, and 0.01 ppm in milk, and for erythromycin, 0.25 ppm in poultry meat. Liquid chromatography (LC) has also been used for determination of tylosin in milk, blood, and tissues of animals. Samples (milk, blood serum, or tissue homogenates in water or pH 2.2 buffer) were deproteinized with acetonitrile, tylosin was partitioned into methylene chloride, and the extracts were concentrated and dissolved in acetonitrile. Chromatography was done on a reverse phase end-capped C18 column using 0.002-0.005 M ammonium dihydrogen phosphate-acetonitrile-methanol (10 + 60 + 30-5 + 80 + 15). Solvent composition was varied with the type of sample analyzed. The method will detect 0.1 ppm tylosin in tissues and less in milk and blood serum. The LC method was more sensitive than microbiological assays for detection of tylosin in tissues of treated swine; recoveries of tylosin by the LC method were frequently several-fold higher.

Analysis of macrolide antibiotics in water by magnetic solid-phase extraction and liquid chromatography-tandem mass spectrometry.

PubMed

Pérez, Rosa Ana; Albero, Beatriz; Férriz, Macarena; Tadeo, José Luis

2017-11-30

Macrolides are one of the most commonly used families of antibiotics employed in human and veterinary treatment. These compounds are considered emerging contaminants with potential ecological and human health risks that could be present in surface water. This paper describes the development and application of a simple and efficient extraction procedure for the determination of tilmicosin; erythromycin, tylosin and erythromycin-H 2 O from water samples. Sample extraction was carried out using magnetic solid-phase extraction using oleate functionalized magnetic nanoparticles followed by LC-MS/MS analysis. The effects of several parameters on the extraction efficiency of MLs from water were evaluated. The recovery results obtained were >84% for most of the compounds, except for erytromycin. The LOD and LOQ values ranged from 11.5 to 26ngL -1 and from 34 to 77ngL -1 , respectively. The selected method was applied to monitor these contaminants in water samples from different sources. Tilmicosin and tylosin were not detected in any of the samples, but erythromycin and erythromycin-H 2 O were found in 50% of the surface water samples at levels from

Seasonal variation, flux estimation, and source analysis of dissolved emerging organic contaminants in the Yangtze Estuary, China.

PubMed

Zhao, Heng; Cao, Zhen; Liu, Xue; Zhan, Yi; Zhang, Jing; Xiao, Xi; Yang, Yi; Zhou, Junliang; Xu, Jiang

2017-12-15

The occurrence and seasonal variation of 24 dissolved emerging organic contaminants in the Yangtze Estuary were studied, including 12 non-antibiotic pharmaceuticals, seven sulfonamides, two macrolides and three chloramphenicols. Sulfadiazine, erythromycin, thiamphenicol and paracetamol were the primary contaminants in sulfonamides, macrolides, chloramphenicols and non-antibiotic pharmaceutical groups, respectively. Compared to the concentrations at Datong, chloramphenicols at Xuliujing were significantly higher in autumn and winter, while macrolides were lower in spring. Based on the flux estimation, approximately 37.1 tons of sulfonamides, 17.4 tons of macrolides, 79.2 tons of chloramphenicols and 14.1 tons of non-antibiotic pharmaceuticals were discharged into the Yangtze Estuary from June 2013 to May 2014. However, the total flux from the Huangpu River only represented 5% of the total. The pharmaceutical sources were speculated on by analyzing the seasonal variations in pharmaceutical concentrations and fluxes at various sites. Both environmental and social factors might affect the fluxes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synergism between macrolide antibiotics and the azole fungicide ketoconazole in growth inhibition testing of the green alga Pseudokirchneriella subcapitata.

PubMed

Yamagishi, Takahiro; Horie, Yoshifumi; Tatarazako, Norihisa

2017-05-01

Macrolide antibiotics and azole fungicides are detected widely in the aquatic environment as a result of their increased use in humans and animal livestock disease and their incomplete removal by wastewater treatment plants. In most cases, ecotoxicological tests are performed by using individual chemical substances, but because of the coexistence of a number of chemicals in the environment, organisms are exposed to many chemicals simultaneously. Therefore, it is important to evaluate effects of chemical interactions, adding to potential hazards of individual chemical. Here, we investigated the synergetic effects of combined chemicals (the azole fungicide ketoconazole and either of two macrolide antibiotics, erythromycin and clarithromycin) in growth inhibition testing using Pseudokirchneriella subcapitata according to OECD Test guideline 201. Combination index plots, isobolograms, and curve-shift analyses revealed that the combination of macrolide antibiotic and ketoconazole at various ratios resulted in strong synergism that enhanced growth inhibition of P. subcapitata, suggesting the necessity of investigating potential hazard of combined chemicals for regulatory purposes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Biotransformation of macrolide antibiotics using enriched activated sludge culture: Kinetics, transformation routes and ecotoxicological evaluation.

PubMed

Terzic, Senka; Udikovic-Kolic, Nikolina; Jurina, Tamara; Krizman-Matasic, Ivona; Senta, Ivan; Mihaljevic, Ivan; Loncar, Jovica; Smital, Tvrtko; Ahel, Marijan

2018-05-05

The biotransformation of three prominent macrolide antibiotics (azithromycin, clarithromycin and erythromycin) by an activated sludge culture, which was adapted to high concentrations of azithromycin (10 mg/L) was investigated. The study included determination of removal kinetics of the parent compounds, identification of their major biotransformation products (TPs) and assessment of ecotoxicological effects of biotransformation. The chemical analyses were performed by ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry, which enabled a tentative identification of TPs formed during the experiments. The ecotoxicological evaluation included two end-points, residual antibiotic activity and toxicity to freshwater algae. The enriched activated sludge culture was capable of degrading all studied macrolide compounds with high removal efficiencies (>99%) of the parent compounds at elevated concentrations (10 mg/L). The elimination of all three macrolide antibiotics was associated with the formation of different TPs, including several novel compounds previously unreported in the literature. Some of the TPs were rather abundant and contributed significantly to the overall mass balance at the end of the biodegradation experiments. Biodegradation of all investigated macrolides was associated with a pronounced reduction of the residual antibiotic activity and algal toxicity, indicating a rather positive ecotoxicological outcome of the biotransformation processes achieved by the enriched sludge culture. Copyright © 2018 Elsevier B.V. All rights reserved.

High frequency of the 23S rRNA A2058G mutation of Treponema pallidum in Shanghai is associated with a current strategy for the treatment of syphilis.

PubMed

Lu, Haikong; Li, Kang; Gong, Weimin; Yan, Limeng; Gu, Xin; Chai, Ze; Guan, Zhifang; Zhou, Pingyu

2015-02-01

The preferred drugs for the treatment of syphilis, benzathine and procaine penicillin, have not been available in Shanghai for many years, and currently, the incidence of syphilis is increasing. Alternative antibiotics for patients with syphilis during the benzathine and procaine penicillin shortage include macrolides. The failure of macrolide treatment in syphilis patients has been reported in Shanghai, but the reason for this treatment failure remains unclear. We used polymerase chain reaction technology to detect a 23S rRNA A2058G mutation in Treponema pallidum in 109 specimens from syphilis patients. The use of azithromycin/erythromycin in the syphilis patients and the physicians' prescription habits were also assessed based on two questionnaires regarding the use of macrolides. A total of 104 specimens (95.4%) were positive for the A2058G mutation in both copies of the 23S rRNA gene, indicating macrolide resistance. A questionnaire provided to 122 dermatologists showed that during the penicillin shortage, they prescribed erythromycin and azithromycin for 8.24±13.95% and 3.21±6.37% of their patients, respectively, and in the case of penicillin allergy, erythromycin and azithromycin were prescribed 15.24±22.89% and 7.23±16.60% of the time, respectively. A second questionnaire provided to the syphilis patients showed that 150 (33.7%), 106 (23.8%) and 34 (7.6%) individuals had used azithromycin, erythromycin or both, respectively, although the majority did not use the drugs for syphilis treatment. Our findings suggest that macrolide resistance in Treponema pallidum is widespread in Shanghai. More than half of the syphilis patients had a history of macrolide use for other treatment purposes, which may have led to the high prevalence of macrolide resistance. Physicians in China are advised to not use azithromycin for early syphilis.

Electronic structure of antibiotic erythromycin

NASA Astrophysics Data System (ADS)

Novak, Igor; Kovač, Branka

2015-03-01

The electronic structure of erythromycin A (ERYMA) molecule has been studied by UV photoelectron spectroscopy and assigned (in the low ionization energy region only) by empirical arguments. The two orbitals with highest energy (lowest ionization energy) are localized on the nitrogen of the desosamine sugar functional group and on the ester group of macrolide (lactone) ring. We discuss how these orbital energies can help to rationalize the known mode of binding of ERYMA to their biological receptors.

Measurement of the Dissociation-Equilibrium Constants for Low Affinity Antibiotic Binding Interaction with Bacterial Ribosomes by the T2 (CPMG) and Line-Broadening Methods

NASA Astrophysics Data System (ADS)

Verdier, L.; Gharbi-Benarous, J.; Bertho, G.; Mauvais, P.; Girault, J.-P.

1999-10-01

In this study the dissociation constants of the low antibiotic-ribosomes interaction were determined by the T2 (CPMG), the Carr-Purcell-Meiboom-Gill spin-echo decay rate and the line-broadening methods. Three MLSB antibiotics were studied, a macrolide roxithromycin, a ketolide HMR 3647 and a lincosamide clindamycin for their weak interaction with three bacterial ribosomes, E. coli, Staphylococcus aureus sensitive and resistant to erythromycin. Nous avons mesuré la constante de dissociation, Kd correspondant à l'interaction faible antibiotique-ribosome bactérien pour des antibiotiques de différentes classes, un macrolide (roxithromycine), un kétolide (HMR 3647) et une lincosamide (clindamycine) avec des ribosomes de différentes souches bactériennes (E. coli, Staphylococcus aureus sensible ou résistant à l'erythromycin) par deux méthodes : l'une basée sur la variation des largeurs de raies et l'autre sur les temps de relaxation transversaux T2 en utilisant une séquence CPMG.

Liposomes as carriers of macrolides: preferential association of erythromycin A and azithromycin with liposomes of phosphatidylglycerol containing unsaturated fatty acid(s).

PubMed

Stuhne-Sekalec, L; Stanacev, N Z; Djokic, S

1991-01-01

To assess the most favourable phospholipid composition of a liposomal carrier for antibiotics, small multilamellar liposomes were prepared from phosphatidylcholine, phosphatidylethanolamine and phosphatidylglycerol of varying fatty acid composition in the presence of erythromycin A and azithromycin. Crude liposomes were subjected to Sepharose CL-4B column chromatography, and liposomes containing antibiotics were well separated from free antibiotics. These experiments established that the greatest association of antibiotics was achieved with liposomes prepared from phosphatidylglycerol rather than phosphatidylcholine or phosphatidylethanolamine. Furthermore, the composition of fatty acids in phosphatidylglycerol liposomes influenced the amount of antibiotics associated with liposomes; the highest amount was obtained with dioleoylphosphatidylglycerol followed by phosphatidylglycerol of fatty acid composition similar to that of egg yolk lecithin. It was established that purified liposomes, prepared from [3H]phosphatidylglycerol containing unsaturated fatty acid(s) bind about 25 per cent of originally present antibiotic. Both antibiotics, erythromycin A and azithromycin, were similar in respect to the amount of their association with liposomes. Determination of the size of phosphatidylglycerol/antibiotic liposomes established that the mean diameter of liposomes containing antibiotics was 200-350 nm, very close to that of liposomes without them.

Serotypes, antibiotic susceptibilities, and multi-locus sequence type profiles of Streptococcus agalactiae isolates circulating in Beijing, China.

PubMed

Wang, Ping; Tong, Jing-jing; Ma, Xiu-hua; Song, Feng-li; Fan, Ling; Guo, Cui-mei; Shi, Wei; Yu, Sang-jie; Yao, Kai-hu; Yang, Yong-hong

2015-01-01

To investigate the serotypes, antibiotic susceptibilities, and multi-locus sequence type (MLST) profiles of Streptococcus agalactiae (S. agalactiae) in Beijing to provide references for the prevention and treatment of S. agalactiae infections. All isolates were identified using the CAMP test and the latex-agglutination assay and serotyped using a Strep-B-Latex kit, after which they were assessed for antibiotic susceptibility, macrolide-resistance genes, and MLST profiles. In total, 56 S. agalactiae isolates were identified in 863 pregnant women (6.5%). Serotypes Ia, Ib, II, III, and V were identified, among which types III (32.1%), Ia (17.9%), Ib (16.1%), and V (14.3%) were the predominant serotypes. All isolates were susceptible to penicillin and ceftriaxone. The nonsusceptiblity rates measured for erythromycin, clarithromycin, azithromycin, telithromycin, clindamycin, tetracycline, and levofloxacin were 85.7%, 92.9%, 98.2%, 30.4%, 73.2%, 91%, and 39.3%, respectively. We identified 14 sequence types (STs) for the 56 isolates, among which ST19 (30.4%) was predominant. The rate of fluoroquinolone resistance was higher in serotype III than in the other serotypes. Among the 44 erythromycin-resistant isolates, 32 (72.7%) carried ermB. S. agalactiae isolates of the serotypes Ia, Ib, III, and V are common in Beijing. Among the S. agalactiae isolates, the macrolide and clindamycin resistance rates are extremely high. Most of the erythromycin-resistant isolates carry ermB.

Comprehensive determination of macrolide antibiotics, their synthesis intermediates and transformation products in wastewater effluents and ambient waters by liquid chromatography-tandem mass spectrometry.

PubMed

Senta, Ivan; Krizman-Matasic, Ivona; Terzic, Senka; Ahel, Marijan

2017-08-04

Macrolide antibiotics are a prominent group of emerging contaminants frequently found in wastewater effluents and wastewater-impacted aquatic environments. In this work, a novel analytical method for simultaneous determination of parent macrolide antibiotics (azithromycin, erythromycin, clarithromycin and roxithromycin), along with their synthesis intermediates, byproducts, metabolites and transformation products in wastewater and surface water was developed and validated. Samples were enriched using solid-phase extraction on Oasis HLB cartridges and analyzed by reversed-phase liquid chromatography coupled to electrospray ionization tandem mass spectrometry. The target macrolide compounds were separated on an ACE C18 PFP column and detected using multiple reaction monitoring in positive ionization polarity. The optimized method, which included an additional extract clean-up on strong anion-exchange cartridges (SAX), resulted in high recoveries and accuracies, low matrix effects and improved chromatographic separation of the target compounds, even in highly complex matrices, such as raw wastewater. The developed method was applied to the analysis of macrolide compounds in wastewater and river water samples from Croatia. In addition to parent antibiotics, several previously unreported macrolide transformation products and/or synthesis intermediates were detected in municipal wastewater, some of them reaching μg/L levels. Moreover, extremely high concentrations of macrolides up to mg/L level were found in pharmaceutical industry effluents, indicating possible importance of this source to the total loads into ambient waters. The results revealed a significant contribution of synthesis intermediates and transformation products to the overall mass balance of macrolides in the aquatic environment. Copyright © 2017. Published by Elsevier B.V.

Effect of subtherapeutic vs. therapeutic administration of macrolides on antimicrobial resistance in Mannheimia haemolytica and enterococci isolated from beef cattle

PubMed Central

Zaheer, Rahat; Cook, Shaun R.; Klima, Cassidy L.; Stanford, Kim; Alexander, Trevor; Topp, Edward; Read, Ron R.; McAllister, Tim A.

2013-01-01

Macrolides are the first-line treatment against bovine respiratory disease (BRD), and are also used to treat infections in humans. The macrolide, tylosin phosphate, is often included in the diet of cattle as a preventative for liver abscesses in many regions of the world outside of Europe. This study investigated the effects of administering macrolides to beef cattle either systemically through a single subcutaneous injection (therapeutic) or continuously in-feed (subtherapeutic), on the prevalence and antimicrobial resistance of Mannheimia haemolytica and Enterococcus spp. isolated from the nasopharynx and faeces, respectively. Nasopharyngeal and faecal samples were collected weekly over 28 days from untreated beef steers and from steers injected once with tilmicosin or tulathromycin or continuously fed tylosin phosphate at dosages recommended by manufacturers. Tilmicosin and tulathromycin were effective in lowering (P < 0.05) the prevalence of M. haemolytica, whereas subtherapeutic tylosin had no effect. M. haemolytica isolated from control- and macrolide-treated animals were susceptible to macrolides as well as to other antibiotics. Major bacteria co-isolated with M. haemolytica from the nasopharynx included Pasteurella multocida, Staphylococcus spp., Acinetobacter spp., Escherichia coli and Bacillus spp. With the exception of M. haemolytica and P. multocida, erythromycin resistance was frequently found in other isolated species. Both methods of macrolide administration increased (P < 0.05) the proportion of erythromycin resistant enterococci within the population, which was comprised almost exclusively of Enterococcus hirae. Injectable macrolides impacted both respiratory and enteric microbes, whereas orally administered macrolides only influenced enteric bacteria. PMID:23750157

Serotypes, Antibiotic Susceptibilities, and Multi-Locus Sequence Type Profiles of Streptococcus agalactiae Isolates Circulating in Beijing, China

PubMed Central

Ma, Xiu-hua; Song, Feng-li; Fan, Ling; Guo, Cui-mei; Shi, Wei; Yu, Sang-jie; Yao, Kai-hu; Yang, Yong-hong

2015-01-01

Background To investigate the serotypes, antibiotic susceptibilities, and multi-locus sequence type (MLST) profiles of Streptococcus agalactiae (S. agalactiae) in Beijing to provide references for the prevention and treatment of S. agalactiae infections. Methods All isolates were identified using the CAMP test and the latex-agglutination assay and serotyped using a Strep-B-Latex kit, after which they were assessed for antibiotic susceptibility, macrolide-resistance genes, and MLST profiles. Results In total, 56 S. agalactiae isolates were identified in 863 pregnant women (6.5%). Serotypes Ia, Ib, II, III, and V were identified, among which types III (32.1%), Ia (17.9%), Ib (16.1%), and V (14.3%) were the predominant serotypes. All isolates were susceptible to penicillin and ceftriaxone. The nonsusceptiblity rates measured for erythromycin, clarithromycin, azithromycin, telithromycin, clindamycin, tetracycline, and levofloxacin were 85.7%, 92.9%, 98.2%, 30.4%, 73.2%, 91%, and 39.3%, respectively. We identified 14 sequence types (STs) for the 56 isolates, among which ST19 (30.4%) was predominant. The rate of fluoroquinolone resistance was higher in serotype III than in the other serotypes. Among the 44 erythromycin-resistant isolates, 32 (72.7%) carried ermB. Conclusion S. agalactiae isolates of the serotypes Ia, Ib, III, and V are common in Beijing. Among the S. agalactiae isolates, the macrolide and clindamycin resistance rates are extremely high. Most of the erythromycin-resistant isolates carry ermB. PMID:25781346

Ribosomal Mutations Conferring Macrolide Resistance in Legionella pneumophila

PubMed Central

Ginevra, Christophe; Jacotin, Nathalie; Forey, Françoise; Chastang, Joëlle; Kay, Elisabeth; Etienne, Jerome; Lina, Gérard; Doublet, Patricia; Jarraud, Sophie

2017-01-01

ABSTRACT Monitoring the emergence of antibiotic resistance is a recent issue in the treatment of Legionnaires' disease. Macrolides are recommended as first-line therapy, but resistance mechanisms have not been studied in Legionella species. Our aim was to determine the molecular basis of macrolide resistance in L. pneumophila. Twelve independent lineages from a common susceptible L. pneumophila ancestral strain were propagated under conditions of erythromycin or azithromycin pressure to produce high-level macrolide resistance. Whole-genome sequencing was performed on 12 selected clones, and we investigated mutations common to all lineages. We reconstructed the dynamics of mutation for each lineage and demonstrated their involvement in decreased susceptibility to macrolides. The resistant mutants were produced in a limited number of passages to obtain a 4,096-fold increase in erythromycin MICs. Mutations affected highly conserved 5-amino-acid regions of L4 and L22 ribosomal proteins and of domain V of 23S rRNA (G2057, A2058, A2059, and C2611 nucleotides). The early mechanisms mainly affected L4 and L22 proteins and induced a 32-fold increase in the MICs of the selector drug. Additional mutations related to 23S rRNA mostly occurred later and were responsible for a major increase of macrolide MICs, depending on the mutated nucleotide, the substitution, and the number of mutated genes among the three rrl copies. The major mechanisms of the decreased susceptibility to macrolides in L. pneumophila and their dynamics were determined. The results showed that macrolide resistance could be easily selected in L. pneumophila and warrant further investigations in both clinical and environmental settings. PMID:28069647

Insights into resistance mechanism of the macrolide biosensor protein MphR(A) binding to macrolide antibiotic erythromycin by molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Feng, Tingting; Zhang, Yanjun; Ding, Jing-Na; Fan, Song; Han, Ju-Guang

2015-12-01

Macrolide biosensor protein MphR(A) has been known as a key regulatory protein in metabolite sensing and genetic expression regulating. MphR(A) protein binds to macrolide antibiotic erythromycin (Ery) and releases the gene operon, thus activates expression of the mphA gene and initiates Ery resistance. The two mutant amino acid residues (V66L and V126L) might potentially disrupt Ery binding to MphR(A). In these studies, the binding of macrolide antibiotic Ery to wild type (Wt) MphR(A) and double mutant (V66L/V126L) MphR(A) are explored by molecular dynamics simulations. Compared to the Apo-MphR(A) protein and Wt-MphR(A)-Ery complex, many interesting effects owing to the double mutant (V66L/V126L) are discovered. In the case of Ery, Helix I which plays an important role in transcription shows itself a right-hand α helix in Wt-MphR(A)-Ery, whereas the activated helix is broken down in double mutant-V66L/V126L-MphR(A)-Ery. The calculated results exhibit that the double mutant V66L/V126L reduces the binding affinity of the V66L/V126L-MphR(A) to Ery, resulting in the block of Ery resistance. The binding free energy decomposition analysis reveals that the decrease of the binding affinity for the variant V66L/V126L-MphR(A)-Ery is mainly attributed to the gas phase electrostatic energies. The residue Leu66, Thr154, and Arg122 enhance the binding affinity of V66L/V126L-MphR(A) to Ery. The residues Tyr103 and His147 contributes mainly to binding energies in the Wt-MphR(A)-Ery complex, whereas the two residues have no contribution to the binding free energy inV66L/V126L-MphR(A)-Ery complex. Our study gives useful insights into the nature of amino acids mutation effect, the mechanism of blocking drug resistance at the atomic level and the characteristics in binding affinity for Ery to double mutant (V66L/V126L) MphR(A), which will contribute to the design of more effective macrolide antibiotics.

Detection of macrolide resistance genes in culture-negative specimens from Bangladeshi children with invasive pneumococcal diseases.

PubMed

Hasanuzzaman, Md; Malaker, Roly; Islam, Maksuda; Baqui, Abdullah H; Darmstadt, Gary L; Whitney, Cynthia G; Saha, Samir K

2017-03-01

In recent years, an increasing prevalence of macrolide resistance among pneumococci in Bangladesh has been observed. However, the scenario remains incomplete, as few isolates (<1%) are available from pneumonia cases and most pneumococcal meningitis cases (>80%) are culture-negative. This study optimised a triplex PCR method to detect macrolide resistance genes (MRGs) (mefA and ermB) and cpsA from culture-negative pneumococcal cases to predict the prevalence and level of macrolide resistance. The presence of MRGs among pneumococcal strains (n=153) with a wide range of erythromycin MICs (<0.5 to ≥256mg/L) was determined by PCR. Triplex PCR was validated by simultaneous detection of MRG(s) and cpsA in culture-negative clinical specimens and corresponding isolates. The known impact of the presence of specific MRG(s) on MICs of strains was used to predict the MICs of non-culturable strains based on the presence/absence of MRG(s) in the specimens. None of the erythromycin-susceptible isolates possessed any of the MRGs, and all non-susceptible strains had ≥1 MRG. MICs were 2-16mg/L and ≥256mg/L for 93% of strains with mefA and ermB, respectively, whereas 100% of isolates with both genes had MICs≥256mg/L. PCR for body fluids showed 100% concordance with corresponding isolates when tested for MRG(s) in parallel. Erythromycin MICs can be predicted for non-culturable strains with 93-100% precision based on detection of ermB and/or mefA. This method will be useful for establishing comprehensive surveillance for macrolide resistance among pneumococci, specifically in the population with prior antibiotic use. Copyright © 2017. Published by Elsevier Ltd.

Drug-Sensing by the Ribosome Induces Translational Arrest via Active Site Perturbation

PubMed Central

Arenz, Stefan; Meydan, Sezen; Starosta, Agata L.; Berninghausen, Otto; Beckmann, Roland; Vázquez-Laslop, Nora; Wilson, Daniel N.

2014-01-01

SUMMARY During protein synthesis, nascent polypeptide chains within the ribosomal tunnel can act in cis to induce ribosome stalling and regulate expression of downstream genes. The Staphylococcus aureus ErmCL leader peptide induces stalling in the presence of clinically important macrolide antibiotics, such as erythromycin, leading to the induction of the downstream macrolide resistance methyltransferase ErmC. Here, we present a cryo-electron microscopy (EM) structure of the erythromycin-dependent ErmCL-stalled ribosome at 3.9 Å resolution. The structure reveals how the ErmCL nascent chain directly senses the presence of the tunnel-bound drug and thereby induces allosteric conformational rearrangements at the peptidyltransferase center (PTC) of the ribosome. ErmCL-induced perturbations of the PTC prevent stable binding and accommodation of the aminoacyl-tRNA at the A-site leading to inhibition of peptide bond formation and translation arrest. PMID:25306253

Photodegradation of antibiotics under simulated solar radiation: implications for their environmental fate.

PubMed

Batchu, Sudha Rani; Panditi, Venkata R; O'Shea, Kevin E; Gardinali, Piero R

2014-02-01

Roxithromycin, erythromycin, ciprofloxacin and sulfamethoxazole are frequently detected antibiotics in environmental waters. Direct and indirect photolysis of these problematic antibiotics were investigated in pure and natural waters (fresh and salt water) under irradiation of different light sources. Fundamental photolysis parameters such as molar absorption coefficient, quantum yield and first order rate constants are reported and discussed. The antibiotics are degraded fastest under ultraviolet 254 nm, followed by 350 nm and simulated solar radiation. The composition of the matrix (pH, dissolved organic content, chloride ion concentration) played a significant role in the observed photodegradation. Under simulated solar radiation, ciprofloxacin and sulfamethoxazole degrade relatively quickly with half-lives of 0.5 and 1.5h, respectively. However, roxithromycin and erythromycin, macrolides are persistent (half-life: 2.4-10 days) under solar simulation. The transformation products (15) of the targeted antibiotics produced under irradiation experiments were identified using high resolution mass spectrometry and degradation pathways were proposed. © 2013.

Ribosomal Mutations Conferring Macrolide Resistance in Legionella pneumophila.

PubMed

Descours, Ghislaine; Ginevra, Christophe; Jacotin, Nathalie; Forey, Françoise; Chastang, Joëlle; Kay, Elisabeth; Etienne, Jerome; Lina, Gérard; Doublet, Patricia; Jarraud, Sophie

2017-03-01

Monitoring the emergence of antibiotic resistance is a recent issue in the treatment of Legionnaires' disease. Macrolides are recommended as first-line therapy, but resistance mechanisms have not been studied in Legionella species. Our aim was to determine the molecular basis of macrolide resistance in L. pneumophila Twelve independent lineages from a common susceptible L. pneumophila ancestral strain were propagated under conditions of erythromycin or azithromycin pressure to produce high-level macrolide resistance. Whole-genome sequencing was performed on 12 selected clones, and we investigated mutations common to all lineages. We reconstructed the dynamics of mutation for each lineage and demonstrated their involvement in decreased susceptibility to macrolides. The resistant mutants were produced in a limited number of passages to obtain a 4,096-fold increase in erythromycin MICs. Mutations affected highly conserved 5-amino-acid regions of L4 and L22 ribosomal proteins and of domain V of 23S rRNA (G2057, A2058, A2059, and C2611 nucleotides). The early mechanisms mainly affected L4 and L22 proteins and induced a 32-fold increase in the MICs of the selector drug. Additional mutations related to 23S rRNA mostly occurred later and were responsible for a major increase of macrolide MICs, depending on the mutated nucleotide, the substitution, and the number of mutated genes among the three rrl copies. The major mechanisms of the decreased susceptibility to macrolides in L. pneumophila and their dynamics were determined. The results showed that macrolide resistance could be easily selected in L. pneumophila and warrant further investigations in both clinical and environmental settings. Copyright © 2017 American Society for Microbiology.

Molecular basis for erythromycin-dependent ribosome-stalling during translation of the ErmBL leader peptide

PubMed Central

Arenz, Stefan; Ramu, Haripriya; Gupta, Pulkit; Berninghausen, Otto; Beckmann, Roland; Vázquez-Laslop, Nora; Mankin, Alexander S.; Wilson, Daniel N.

2014-01-01

In bacteria, ribosome-stalling during translation of ErmBL leader peptide occurs in the presence of the antibiotic erythromycin and leads to induction of expression of the downstream macrolide resistance methyltransferase ErmB. The lack of structures of drug-dependent stalled ribosome complexes (SRCs) has limited our mechanistic understanding of this regulatory process. Here, we present a cryo-electron microscopy (EM) structure of the erythromycin-dependent ErmBL-SRC. The structure reveals that the antibiotic does not interact directly with ErmBL, but rather redirects the path of the peptide within the tunnel. Furthermore, we identify a key peptide-ribosome interaction that defines an important relay pathway from the ribosomal tunnel to the peptidyltransferase center (PTC). The PTC of the ErmBL-SRC appears to adopt an uninduced state that prevents accommodation of Lys-tRNA at the A-site, thus providing structural bases for understanding how the drug and the nascent peptide cooperate to inhibit peptide-bond formation and induce translation arrest. PMID:24662426

Induction of Efflux-Mediated Macrolide Resistance in Streptococcus pneumoniae ▿

PubMed Central

Chancey, Scott T.; Zhou, Xiaoliu; Zähner, Dorothea; Stephens, David S.

2011-01-01

The antimicrobial efflux system encoded by the operon mef(E)-mel on the mobile genetic element MEGA in Streptococcus pneumoniae and other Gram-positive bacteria is inducible by macrolide antibiotics and antimicrobial peptides. Induction may affect the clinical response to the use of macrolides. We developed mef(E) reporter constructs and a disk diffusion induction and resistance assay to determine the kinetics and basis of mef(E)-mel induction. Induction occurred rapidly, with a >15-fold increase in transcription within 1 h of exposure to subinhibitory concentrations of erythromycin. A spectrum of environmental conditions, including competence and nonmacrolide antibiotics with distinct cellular targets, did not induce mef(E). Using 16 different structurally defined macrolides, induction was correlated with the amino sugar attached to C-5 of the macrolide lactone ring, not with the size (e.g., 14-, 15- or 16-member) of the ring or with the presence of the neutral sugar cladinose at C-3. Macrolides with a monosaccharide attached to C-5, known to block exit of the nascent peptide from the ribosome after the incorporation of up to eight amino acids, induced mef(E) expression. Macrolides with a C-5 disaccharide, which extends the macrolide into the ribosomal exit tunnel, disrupting peptidyl transferase activity, did not induce it. The induction of mef(E) did not require macrolide efflux, but the affinity of macrolides for the ribosome determined the availability for efflux and pneumococcal susceptibility. The induction of mef(E)-mel expression by inducing macrolides appears to be based on specific interactions of the macrolide C-5 saccharide with the ribosome that alleviate transcriptional attenuation of mef(E)-mel. PMID:21537010

Toward the rational design of macrolide antibiotics to combat resistance

DOE PAGES

Pavlova, Anna; Parks, Jerry M.; Oyelere, Adegboyega K.; ...

2017-04-17

Here, macrolides, one of the most prescribed classes of antibiotics, bind in the bacterial ribosome's polypeptide exit tunnel and inhibit translation. However, mutations and other ribosomal modifications, especially to the base A2058 of the 23S rRNA, have led to a growing resistance problem. Here, we have used molecular dynamics simulations to study the macrolides erythromycin and azithromycin in wild-type, A2058G-mutated, and singly or doubly A2058-methylated Escherichia coli ribosomes. We find that the ribosomal modifications result in less favorable interactions between the base 2058 and the desosamine sugar of the macrolides, as well as greater displacement of the macrolides from theirmore » crystal structure position, illuminating the causes of resistance. We have also examined four azithromycin derivatives containing aromatic indole-analog moieties, which were previously designed based on simulations of the stalling peptide SecM in the ribosome. Surprisingly, we found that the studied moieties could adopt very different geometries when interacting with a key base in the tunnel, A751, possibly explaining their distinct activities. Based on our simulations, we propose modifications to the indole-analog moieties that should increase their interactions with A751 and, consequently, enhance the potency of future azithromycin derivatives.« less

Toward the rational design of macrolide antibiotics to combat resistance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pavlova, Anna; Parks, Jerry M.; Oyelere, Adegboyega K.

Here, macrolides, one of the most prescribed classes of antibiotics, bind in the bacterial ribosome's polypeptide exit tunnel and inhibit translation. However, mutations and other ribosomal modifications, especially to the base A2058 of the 23S rRNA, have led to a growing resistance problem. Here, we have used molecular dynamics simulations to study the macrolides erythromycin and azithromycin in wild-type, A2058G-mutated, and singly or doubly A2058-methylated Escherichia coli ribosomes. We find that the ribosomal modifications result in less favorable interactions between the base 2058 and the desosamine sugar of the macrolides, as well as greater displacement of the macrolides from theirmore » crystal structure position, illuminating the causes of resistance. We have also examined four azithromycin derivatives containing aromatic indole-analog moieties, which were previously designed based on simulations of the stalling peptide SecM in the ribosome. Surprisingly, we found that the studied moieties could adopt very different geometries when interacting with a key base in the tunnel, A751, possibly explaining their distinct activities. Based on our simulations, we propose modifications to the indole-analog moieties that should increase their interactions with A751 and, consequently, enhance the potency of future azithromycin derivatives.« less

Legionella: macrolides or quinolones?

PubMed

Pedro-Botet, L; Yu, V L

2006-05-01

Following the first outbreaks of legionnaire's disease, erythromycin emerged as the treatment of choice without the foundation of rigorous clinical trials. The number of therapeutic failures with erythromycin, as well as the side-effects and drug interactions, led to the consideration of other drugs such as the new macrolides and quinolones for the treatment of legionnaire's disease in the 1990s. In this article, 19 studies in in-vitro intracellular models and seven animal studies that compared macrolides to quinolones were reviewed. Quinolones were found to have greater activity in intracellular models and improved efficacy in animal models compared with macrolides. No randomised trials comparing the clinical efficacy of the new macrolides and new quinolones have ever been performed. Three observational studies totalling 458 patients with legionnaire's disease have compared the clinical efficacy of macrolides (not including azithromycin) and quinolones (mainly levofloxacin). The results suggested that quinolones may produce a superior clinical response compared with the macrolides (erythromycin and clarithromycin) with regard to defervescence, complications, and length of hospital stay. Little data exist for direct comparison of quinolones and azithromycin.

Occurrence of antibiotics and their impacts to primary productivity in fishponds around Tai Lake, China.

PubMed

Song, Chao; Zhang, Cong; Fan, Limin; Qiu, Liping; Wu, Wei; Meng, Shunlong; Hu, Gengdong; Kamira, Barry; Chen, Jiazhang

2016-10-01

Antibiotics are widely used to improve the health and yields of farmed animals, including fish, but their use is accompanied by undesirable ecological effects. Relatively little is known about the water-body burden of antibiotics and their influence on primary productivity in aquaculture ecosystem. In this study, antibiotics usage within 24 fishponds, covering 4 areas, sampled 5 times, and having 5 fish species, was investigated surrounding Tai Lake in China. The study analyzed 15 antibiotics (including 5 sulfonamides, 2 quinolones, 3 β-lactams, 3 tetracyclines, 1 amphenicol, and 1 macrolide), and all of them were detected in water samples, with a detection frequency of 2-60%. Sulfonamides were the most prevalent, and concentrations of sulfamethoxazole, sulfamonomethoxine, and florfenicol being over 2000 ng L(-1) in some samples, while the other antibiotics levels ranged from ND (no detection) to 551.18 ng L(-1). Significant differences were observed in antibiotic burden among different regions for total antibiotics, sulfonamides, quinolones, and amphenicols; among time points for quinolones, β-lactams, and tetracyclines; and among species for quinolones and macrolides. Furthermore, basing on the risk quotient (RQ) method, the assessment revealed that florfenicol was of highest risk to algae with RQ values exceeding 0.1, while macrolide erythromycin posed the second highest risk. The partial correlation coefficient between total antibiotics and chlorophyll (a) was -0.035 that clearly indicated total antibiotics were detrimental to green algae growth, while the nutrient input and other physical - chemical factors were much more beneficial. Overall, holistic far-reaching measures of antibiotics control are recommended to preserve aquaculture ecosystem health. Copyright © 2016 Elsevier Ltd. All rights reserved.

Results from the Survey of Antibiotic Resistance (SOAR) 2012–14 in Thailand, India, South Korea and Singapore

PubMed Central

Torumkuney, D.; Chaiwarith, R.; Reechaipichitkul, W.; Malatham, K.; Chareonphaibul, V.; Rodrigues, C.; Chitins, D. S.; Dias, M.; Anandan, S.; Kanakapura, S.; Park, Y. J.; Lee, K.; Lee, H.; Kim, J. Y.; Lee, Y.; Lee, H. K.; Kim, J. H.; Tan, T. Y.; Heng, Y. X.; Mukherjee, P.; Morrissey, I.

2016-01-01

Objectives To provide susceptibility data for community-acquired respiratory tract isolates of Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae and Moraxella catarrhalis collected in 2012–14 from four Asian countries. Methods MICs were determined using Etest® for all antibiotics except erythromycin, which was evaluated by disc diffusion. Susceptibility was assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. For macrolide/clindamycin interpretation, breakpoints were adjusted for incubation in CO2 where available. Results Susceptibility of S. pneumoniae was generally lower in South Korea than in other countries. Penicillin susceptibility assessed using CLSI oral or EUCAST breakpoints ranged from 21.2% in South Korea to 63.8% in Singapore. In contrast, susceptibility using CLSI intravenous breakpoints was much higher, at 79% in South Korea and ∼95% or higher elsewhere. Macrolide susceptibility was ∼20% in South Korea and ∼50%–60% elsewhere. Among S. pyogenes isolates (India only), erythromycin susceptibility (∼20%) was lowest of the antibiotics tested. In H. influenzae antibiotic susceptibility was high except for ampicillin, where susceptibility ranged from 16.7% in South Korea to 91.1% in India. South Korea also had a high percentage (18.1%) of β-lactamase-negative ampicillin-resistant isolates. Amoxicillin/clavulanic acid susceptibility for each pathogen (PK/PD high dose) was between 93% and 100% in all countries except for H. influenzae in South Korea (62.5%). Conclusions Use of EUCAST versus CLSI breakpoints had profound differences for cefaclor, cefuroxime and ofloxacin, with EUCAST showing lower susceptibility. There was considerable variability in susceptibility among countries in the same region. Thus, continued surveillance is necessary to track future changes in antibiotic resistance. PMID:27048580

Genetic and phenotypic characterization of resistance to macrolides in Streptococcus pyogenes from Argentina.

PubMed

Martínez, Silvia; Amoroso, Ana M; Famiglietti, Angela; de Mier, Carmen; Vay, Carlos; Gutkind, Gabriel O

2004-01-01

Five hundred and seventy-eight strains of group A streptococci (GAS) isolated mostly from paediatric pharyngeal swabs were tested to evaluate their susceptibility to erythromycin. Resistant strains were then tested for their MICs to erythromycin and clindamycin, their phenotype of resistance to macrolides-lincosamides-streptogramin (MLS(B)) and for the presence of macrolide resistance genes. The rate of resistance to erythromycin was 8.2%. Constitutive, inducible and M phenotypes of resistance were detected in 2.1, 2.1 and 95.8% of resistant strains, respectively. All M phenotypes harboured the mefA gene, whereas constitutive and inducible phenotypes had ermB and ermTR genes, respectively.

Chronic toxicity of diphenhydramine hydrochloride and erythromycin thiocyanate to Daphnia, Daphnia magna, in a continuous exposure test system

USGS Publications Warehouse

Meinertz, Jeffery R.; Schreier, Theresa M.; Bernardy, Jeffry A.; Franz, Jeanne L.

2011-01-01

Diphenhydramine hydrochloride (DH; Benadryl(TM), an over-the-counter antihistamine) and erythromycin thiocyanate (ET; a commonly used macrolide antibiotic) are pharmaceutical compounds whose chronic toxicity to Daphnia magna had not been characterized. Continuous exposure to DH concentrations about 5 times greater than the maximum reported environmental concentration of 0.023 μg/L for 21 days or to ET concentrations about 40 times the maximum reported environmental concentration of 6 μg/L for 21 days did not significantly impact D. magna survival and production. In this study the no observable effect concentration for DH was 0.12 μg/L and for ET was 248 μg/L.

A quantitative method for residues of macrolide antibiotics in porcine kidney by liquid chromatography/tandem mass spectrometry.

PubMed

Dickson, Leslie C; O'Byrne, Collin; Chan, Wayne

2012-01-01

An LC/MS/MS-based multiresidue quantitative method was developed for the macrolides erythromycin A, neospiramycin I, oleandomycin, spiramycin I, tilmicosin, and tylosin A in porcine kidney tissues. The Canadian Food Inspection Agency (CFIA) had as part of its analytical scope an LC/UV method for quantification of residues of two macrolide antibiotics, tilmicosin and tylosin A, in the kidney, liver, and muscle of cattle, swine, and poultry. The method could not reliably detect concentrations below 10 microg/kg. To increase the scope of the CFIA's analytical capabilities, a sensitive multiresidue quantitative method for macrolide residues in food animal tissues was required. Porcine kidney samples were extracted with acetonitrile and alkaline buffer and cleaned-up using silica-based C18 SPE cartridges. Sample extracts were analyzed using LC/MS/MS with positive electrospray ionization. Fitness for purpose was verified in a single-laboratory validation study using a second analyst. The working analytical range was 5 to 50 microg/kg. LOD and LOQ were 0.5 to 0.6 microg/kg and 1.5 to 3.0 microg/kg, respectively. Limits of identification were 0.5 to 2.0 microg/kg. Relative intermediate precisions were 8 to 17%. Average absolute recoveries were 68 to 76%.

Susceptibility of Legionella spp. to mycinamicin I and II and other macrolide antibiotics: effects of media composition and origin of organisms.

PubMed Central

Edelstein, P H; Pasiecznik, K A; Yasui, V K; Meyer, R D

1982-01-01

Thirty-three strains of Legionella spp., 29 of which were L. pneumophila, were tested for their susceptibilities to erythromycin (EM), rosaramicin, tylosin, mycinamicin I (Sch-27897), and mycinamicin II (Sch-27896). Testing was performed using an agar dilution method with two different types of media: buffered charcoal yeast extract medium supplemented with 0.1% alpha-ketoglutarate (BCYE alpha) and filter-sterilized yeast extract medium with 0.1% alpha-ketoglutarate (BYE alpha). The minimal inhibitory concentrations (MICs) of the drugs tested relative to the MICs of erythromycin were: rosaramicin, MIC approximately equal to 0.2 EM MIC; tylosin, MIC approximately equal to 2 EM MIC; mycinamicin I, MIC approximately equal to 0.5 EM MIC; and mycinamicin II, MIC approximately equal to EM MIC. Both types of media caused equivalent partial inactivation of the macrolides which was apparently due entirely to pH effect. MICs on BCYE alpha were one to five times more than those observed on BYE alpha; this may be due to poorer growth on BYE alpha. PMID:7125633

Coagulase-negative staphylococci (CoNS) isolated from ready-to-eat food of animal origin--phenotypic and genotypic antibiotic resistance.

PubMed

Chajęcka-Wierzchowska, Wioleta; Zadernowska, Anna; Nalepa, Beata; Sierpińska, Magda; Łaniewska-Trokenheim, Łucja

2015-04-01

The aim of this work was to study the pheno- and genotypical antimicrobial resistance profile of coagulase negative staphylococci (CoNS) isolated from 146 ready-to-eat food of animal origin (cheeses, cured meats, sausages, smoked fishes). 58 strains were isolated, they were classified as Staphylococcus xylosus (n = 29), Staphylococcus epidermidis (n = 16); Staphylococcus lentus (n = 7); Staphylococcus saprophyticus (n = 4); Staphylococcus hyicus (n = 1) and Staphylococcus simulans (n = 1) by phenotypic and genotypic methods. Isolates were tested for resistance to erythromycin, clindamycin, gentamicin, cefoxitin, norfloxacin, ciprofloxacin, tetracycline, tigecycline, rifampicin, nitrofurantoin, linezolid, trimetoprim, sulphamethoxazole/trimethoprim, chloramphenicol, quinupristin/dalfopristin by the disk diffusion method. PCR was used for the detection of antibiotic resistance genes encoding: methicillin resistance--mecA; macrolide resistance--erm(A), erm(B), erm(C), mrs(A/B); efflux proteins tet(K) and tet(L) and ribosomal protection proteins tet(M). For all the tet(M)-positive isolates the presence of conjugative transposons of the Tn916-Tn1545 family was determined. Most of the isolates were resistant to cefoxitin (41.3%) followed by clindamycin (36.2%), tigecycline (24.1%), rifampicin (17.2%) and erythromycin (13.8%). 32.2% staphylococcal isolates were multidrug resistant (MDR). All methicillin resistant staphylococci harboured mecA gene. Isolates, phenotypic resistant to tetracycline, harboured at least one tetracycline resistance determinant on which tet(M) was most frequent. All of the isolates positive for tet(M) genes were positive for the Tn916-Tn1545 -like integrase family gene. In the erythromycin-resistant isolates, the macrolide resistance genes erm(C) or msr(A/B) were present. Although coagulase-negative staphylococci are not classical food poisoning bacteria, its presence in food could be of public health significance due to the possible spread of antibiotic resistance. Copyright © 2014 Elsevier Ltd. All rights reserved.

Molecular epidemiology and distribution of serotypes, genotypes, and antibiotic resistance genes of Streptococcus agalactiae clinical isolates from Guelma, Algeria and Marseille, France.

PubMed

Bergal, A; Loucif, L; Benouareth, D E; Bentorki, A A; Abat, C; Rolain, J-M

2015-12-01

This study describes, for the first time, the genetic and phenotypic diversity among 93 Streptococcus agalactiae (group B Streptococcus, GBS) isolates collected from Guelma, Algeria and Marseille, France. All strains were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The molecular support of antibiotic resistance and serotyping were investigated by polymerase chain reaction (PCR). The phylogenetic lineage of each GBS isolate was determined by multilocus sequence typing (MLST) and grouped into clonal complexes (CCs) using eBURST. The isolates represented 37 sequence types (STs), 16 of which were novel, grouped into five CCs, and belonging to seven serotypes. Serotype V was the most prevalent serotype in our collection (44.1%). GBS isolates of each serotype were distributed among multiple CCs, including cps III/CC19, cps V/CC1, cps Ia/CC23, cps II/CC10, and cps III/CC17. All isolates presented susceptibility to penicillin, whereas resistance to erythromycin was detected in 40% and tetracycline in 82.2% of isolates. Of the 37 erythromycin-resistant isolates, 75.7% showed the macrolide-lincosamide-streptogramin B (MLSB)-resistant phenotype and 24.3% exhibited the macrolide (M)-resistant phenotype. Constitutive MLSB resistance (46%) mediated by the ermB gene was significantly associated with the Guelma isolates, whereas the M resistance phenotype (24.3%) mediated by the mefA/E gene dominated among the Marseille isolates and belonged to ST-23. Tetracycline resistance was predominantly due to tetM, which was detected alone (95.1%) or associated with tetO (3.7%). These results provide epidemiological data in these regions that establish a basis for monitoring increased resistance to erythromycin and also provide insight into correlations among clones, serotypes, and resistance genes.

Occurrence, removal, and risk assessment of antibiotics in 12 wastewater treatment plants from Dalian, China.

PubMed

Zhang, Xin; Zhao, Hongxia; Du, Juan; Qu, Yixuan; Shen, Chen; Tan, Feng; Chen, Jingwen; Quan, Xie

2017-07-01

In this study, the occurrence and removal efficiencies of 31 antibiotics, including 11 sulfonamides (SAs), five fluoroquinolones (FQs), four macrolides (MLs), four tetracyclines (TCs), three chloramphenicols (CAPs), and four other antibiotics (Others), were investigated in 12 municipal wastewater treatment plants (WWTPs) in Dalian, China. A total of 29 antibiotics were detected in wastewater samples with the concentration ranging from 63.6 to 5404.6 ng/L. FQs and SAs were the most abundant antibiotic classes in most wastewater samples, accounting for 42.2 and 23.9% of total antibiotic concentrations, respectively, followed by TCs (16.0%) and MLs (14.8%). Sulfamethoxazole, erythromycin, clarithromycin, azithromycin, ofloxacin, and norfloxacin were the most frequently detected antibiotics; of these, the concentration of ofloxacin was the highest in most of influent (average concentration = 609.8 ng/L) and effluent (average concentration = 253.4 ng/L) samples. The removal efficiencies varied among WWTPs in the range of -189.9% (clarithromycin) to 100% (enoxacin, doxycycline, etc), and more than 50% of antibiotics could not be efficiently removed with the removal efficiency less than 65%. An environmental risk assessment was also performed in the WWTP effluents by calculating the risk quotient (RQ), and high RQ values (>1) indicated erythromycin and clarithromycin might cause the ecological risk on organisms in surrounding water near discharge point of WWTPs in this area, which warrants further attention.

Antibiotic susceptibility pattern and erythromycin resistance mechanisms in beta-hemolytic group G Streptococcus dysgalactiae subspecies equisimilis isolates from central Taiwan.

PubMed

Lo, Hsueh-Hsia; Nien, Hao-Hsiang; Cheng, Ya-Yu; Su, Fang-Yi

2015-12-01

Information concerning antibiotics susceptibilities of beta-hemolytic group G Streptococcus dysgalactiae subspecies equisimilis (SDSE) clinical isolates in central Taiwan was limited. Totally, 246 SDSE isolates were collected from mainly five regional hospitals, from February 2007 to August 2011. Disk diffusion method, broth microdilution method, and clindamycin induction test (D test) were respectively performed according to the guidelines of the Clinical and Laboratory Standards Institute. Polymerase chain reaction was used to detect the corresponding erythromycin resistance genes. All isolates were susceptible to penicillin, cefotaxime, and vancomycin. The rate of erythromycin resistance was 24.0% (59/246), whereas that of clindamycin resistance was 12.2% (30/246). The resistance rates of isolates from different hospitals varied from 15.0% to 45.5% for erythromycin and from 7.1% to 36.4% for clindamycin. For erythromycin-resistant SDSE isolates, three different phenotypes with resistance to macrolides (M), lincosamides (L), and type B streptogramins (SB) were observed: M (49.2%), constitutive MLSB (cMLSB, 35.6%), and inducible MLSB (iMLSB, 15.3%). All M phenotypic isolates carried mefA. The most prevalent genotypes among cMLSB and iMLSB phenotypic isolates were ermB, followed by ermTR. One isolate with cMLSB phenotype carried both ermB and ermTR, whereas one isolate with iMLSB phenotype carried both ermB and ermC. This is the first trial investigating the antimicrobial susceptibility pattern and erythromycin resistance mechanisms of beta-hemolytic group G SDSE isolates in central Taiwan. The resistance rates for both erythromycin and clindamycin varied significantly among hospitals located in this area and should be monitored continuously in the future. Copyright © 2014. Published by Elsevier B.V.

Lack of evidence for erm(B) infiltration into erythromycin-resistant Campylobacter spp. from commercial turkey production in the southeastern United States

USDA-ARS?s Scientific Manuscript database

In Campylobacter spp., resistance to erythromycin and other macrolides has typically implicated ribosomal mutations, especially substitutions in the 23S rRNA gene. In 2014, the macrolide resistance gene erm(B) was reported for the first time in Campylobacter, and shown to be harbored in a multidrug ...

Effect of erythromycin exposure on the growth, antioxidant system and photosynthesis of Microcystis flos-aquae.

PubMed

Wan, Jinjin; Guo, Peiyong; Peng, Xiaofang; Wen, Keqi

2015-01-01

Erythromycin, a macrolide antibiotic, is commonly used in human life. This compound and its derivatives have been detected in various aquatic compartments and may pose a serious threat to aquatic organisms. This study investigated the effects of erythromycin on the growth, antioxidant system and photosynthesis of Microcystis flos-aquae. The results showed that at 0.001-0.1 μg L(-1), erythromycin could stimulate the growth of M. flos-aquae and increase its photosynthetic activity; however, it did not significantly increase the activities of superoxide dismutase (SOD) and catalase (CAT) or the levels of malondialdehyde (MDA) and reactive oxygen species (ROS). In contrast, the growth of M. flos-aquae was significantly inhibited (p<0.01) at high levels of erythromycin, reaching an inhibition rate of 81.6% at 40 μg L(-1) erythromycin. At the same time, the activities of SOD and CAT along with MDA content also increased significantly (p<0.01), indicating that the high concentrations of erythromycin caused a severe oxidative stress on algae. However, the balance between oxidants and antioxidant enzymes were disrupted because ROS content simultaneously increased. In addition, the fluorescence parameters of M. flos-aquae decreased significantly with both exposure time and increasing concentration of erythromycin, indicating that photosynthesis was inhibited. Copyright © 2014 Elsevier B.V. All rights reserved.

Characterization of resistance to selected antibiotics and Panton-Valentine leukocidin-positive Staphylococcus aureus in a healthy student population at a Malaysian University

PubMed Central

Suhaili, Zarizal; Rafee, Putri ’Amira; Mat Azis, Norhidayah; Yeo, Chew Chieng; Nordin, Syafinaz Amin; Abdul Rahim, Abdul Rachman; Al-Obaidi, Mazen M. Jamil; Mohd Desa, Mohd Nasir

2018-01-01

Abstract Introduction This study aims to assess the antimicrobial susceptibility profiles of Staphylococcus aureus strains isolated from university students and to determine the prevalence of constitutive and inducible clindamycin resistance, the latter being able to cause therapeutic failure due to false in vitro clindamycin susceptibility. Methods S. aureus strains were isolated from the nasal swabs of 200 health sciences students of a Malaysian university. Twelve classes of antibiotics were used to evaluate the antimicrobial susceptibility profiles with the macrolide-lincosamide-streptogramin B (MLSB) phenotype for inducible clindamycin resistance determined by the double-diffusion test (D-test). Carriage of resistance and virulence genes was performed by PCR on S. aureus isolates that were methicillin resistant, erythromycin resistant and/or positive for the leukocidin gene, pvl (n=15). Results Forty-nine isolates were viable and identified as S. aureus with four of the isolates characterized as methicillin-resistant S. aureus (MRSA; 2.0%). All isolates were susceptible to the antibiotics tested except for penicillin (resistance rate of 49%), erythromycin (16%), oxacillin (8%), cefoxitin (8%) and clindamycin (4%). Of the eight erythromycin-resistant isolates, iMLSB was identified in five isolates (three of which were also MRSA). The majority of the erythromycin-resistant isolates harbored the msrA gene (four iMLSB) with the remaining iMLSB isolate harboring the ermC gene. Conclusion The presence of MRSA isolates which are also iMLSB in healthy individuals suggests that nasal carriage may play a role as a potential reservoir for the transmission of these pathogens. PMID:29564245

Characterization of resistance to selected antibiotics and Panton-Valentine leukocidin-positive Staphylococcus aureus in a healthy student population at a Malaysian University.

PubMed

Suhaili, Zarizal; Rafee, Putri 'Amira; Mat Azis, Norhidayah; Yeo, Chew Chieng; Nordin, Syafinaz Amin; Abdul Rahim, Abdul Rachman; Al-Obaidi, Mazen M Jamil; Mohd Desa, Mohd Nasir

2018-03-01

This study aims to assess the antimicrobial susceptibility profiles of Staphylococcus aureus strains isolated from university students and to determine the prevalence of constitutive and inducible clindamycin resistance, the latter being able to cause therapeutic failure due to false in vitro clindamycin susceptibility. S. aureus strains were isolated from the nasal swabs of 200 health sciences students of a Malaysian university. Twelve classes of antibiotics were used to evaluate the antimicrobial susceptibility profiles with the macrolide-lincosamide-streptogramin B (MLS B ) phenotype for inducible clindamycin resistance determined by the double-diffusion test (D-test). Carriage of resistance and virulence genes was performed by PCR on S. aureus isolates that were methicillin resistant, erythromycin resistant and/or positive for the leukocidin gene, pvl (n=15). Forty-nine isolates were viable and identified as S. aureus with four of the isolates characterized as methicillin-resistant S. aureus (MRSA; 2.0%). All isolates were susceptible to the antibiotics tested except for penicillin (resistance rate of 49%), erythromycin (16%), oxacillin (8%), cefoxitin (8%) and clindamycin (4%). Of the eight erythromycin-resistant isolates, iMLS B was identified in five isolates (three of which were also MRSA). The majority of the erythromycin-resistant isolates harbored the msrA gene (four iMLS B ) with the remaining iMLS B isolate harboring the ermC gene. The presence of MRSA isolates which are also iMLS B in healthy individuals suggests that nasal carriage may play a role as a potential reservoir for the transmission of these pathogens.

Results from the Survey of Antibiotic Resistance (SOAR) 2012-14 in Thailand, India, South Korea and Singapore.

PubMed

Torumkuney, D; Chaiwarith, R; Reechaipichitkul, W; Malatham, K; Chareonphaibul, V; Rodrigues, C; Chitins, D S; Dias, M; Anandan, S; Kanakapura, S; Park, Y J; Lee, K; Lee, H; Kim, J Y; Lee, Y; Lee, H K; Kim, J H; Tan, T Y; Heng, Y X; Mukherjee, P; Morrissey, I

2016-05-01

To provide susceptibility data for community-acquired respiratory tract isolates of Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae and Moraxella catarrhalis collected in 2012-14 from four Asian countries. MICs were determined using Etest(®) for all antibiotics except erythromycin, which was evaluated by disc diffusion. Susceptibility was assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. For macrolide/clindamycin interpretation, breakpoints were adjusted for incubation in CO2 where available. Susceptibility of S. pneumoniae was generally lower in South Korea than in other countries. Penicillin susceptibility assessed using CLSI oral or EUCAST breakpoints ranged from 21.2% in South Korea to 63.8% in Singapore. In contrast, susceptibility using CLSI intravenous breakpoints was much higher, at 79% in South Korea and ∼95% or higher elsewhere. Macrolide susceptibility was ∼20% in South Korea and ∼50%-60% elsewhere. Among S. pyogenes isolates (India only), erythromycin susceptibility (∼20%) was lowest of the antibiotics tested. In H. influenzae antibiotic susceptibility was high except for ampicillin, where susceptibility ranged from 16.7% in South Korea to 91.1% in India. South Korea also had a high percentage (18.1%) of β-lactamase-negative ampicillin-resistant isolates. Amoxicillin/clavulanic acid susceptibility for each pathogen (PK/PD high dose) was between 93% and 100% in all countries except for H. influenzae in South Korea (62.5%). Use of EUCAST versus CLSI breakpoints had profound differences for cefaclor, cefuroxime and ofloxacin, with EUCAST showing lower susceptibility. There was considerable variability in susceptibility among countries in the same region. Thus, continued surveillance is necessary to track future changes in antibiotic resistance. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Results from the Survey of Antibiotic Resistance (SOAR) 2011–14 in the Democratic Republic of Congo, Ivory Coast, Republic of Senegal and Kenya

PubMed Central

Kacou-Ndouba, A.; Revathi, G.; Mwathi, P.; Seck, A.; Diop, A.; Kabedi-Bajani, M. J.; Mwiti, W.; Anguibi-Pokou, M. J.; Morrissey, I.; Torumkuney, D.

2016-01-01

Objectives To assess antibiotic susceptibility of community-acquired respiratory tract isolates from Ivory Coast, Kenya, Democratic Republic of Congo (DRC) and Senegal in 2011–14. Methods Bacterial isolates were collected and MICs determined using Etest® for all antibiotics except erythromycin, for which testing was by disc diffusion. Susceptibility was assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. For macrolide interpretation, CLSI breakpoints were adjusted for incubation in CO2. Results Susceptibility to penicillin (using CLSI oral or EUCAST breakpoints) was low among isolates of Streptococcus pneumoniae from the DRC and Kenya (17.4% and 19%, respectively) but higher among isolates from the Ivory Coast (70%) and Senegal (85.7%). Penicillin susceptibility using CLSI iv breakpoints was higher in all countries, but still only 69.6% in the DRC. Macrolide susceptibility (based on CLSI erythromycin disc diffusion breakpoints) was also low in Kenya (∼65%) but 87%–100% elsewhere. Haemophilus influenzae were only collected in the DRC and Senegal, with β-lactamase prevalence of 39% and 4%, respectively. Furthermore, β-lactamase-negative ampicillin-resistant (BLNAR) isolates were found in DRC (four isolates, 17%), but only two isolates were found in Senegal (by EUCAST definition). Amoxicillin/clavulanic acid in vitro susceptibility was 73.9% in the DRC and 100% in Senegal based on CLSI breakpoints, but this reduced to 65.2% in the DRC when BLNAR rates were considered. Clarithromycin susceptibility was >95% in both countries. Conclusions There was considerable variability in antibiotic susceptibility among the African countries participating in the surveillance programme. Thus, continued surveillance is necessary to track future changes in antibiotic resistance. Use of EUCAST versus CLSI breakpoints showed profound differences for cefaclor and ofloxacin against S. pneumoniae, with EUCAST showing lower susceptibility. PMID:27048579

Antibiotic therapy in preterm premature rupture of the membranes.

PubMed

Yudin, Mark H; van Schalkwyk, Julie; Eyk, Nancy Van

2009-09-01

To review the evidence and provide recommendations on the use of antibiotics in preterm premature rupture of the membranes (PPROM). Outcomes evaluated include the effect of antibiotic treatment on maternal infection, chorioamnionitis, and neonatal morbidity and mortality. Published literature was retrieved through searches of Medline, EMBASE, CINAHL, and The Cochrane Library, using appropriate controlled vocabulary and key words (PPROM, infection, and antibiotics). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and new material incorporated in the guideline to July 2008. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care. Guideline implementation should assist the practitioner in developing an approach to the use of antibiotics in women with PPROM. Patients will benefit from appropriate management of this condition. This guideline has been reviewed and approved by the Infectious Diseases Committee and the Maternal Fetal Medicine Committee of the SOGC, and approved by the Executive and Council of the SOGC. The Society of Obstetricians and Gynaecologists of Canada. 1. Following PPROM at < or = 32 weeks' gestation, antibiotics should be administered to women who are not in labour in order to prolong pregnancy and to decrease maternal and neonatal morbidity. (I-A) 2. The use of antibiotics should be gestational-age dependent. The evidence for benefit is greater at earlier gestational ages (< 32 weeks). (I-A) 3. For women with PPROM at > 32 weeks' gestation, administration of antibiotics to prolong pregnancy is recommended if fetal lung maturity can not be proven and/or delivery is not planned. (I-A) 4. Antibiotic regimens may consist of an initial parenteral phase followed by an oral phase, or may consist of only an oral phase. (I-A) 5. Antibiotics of choice are penicillins or macrolide antibiotics (erythromycin) in parenteral and/or oral forms. (I-A) In patients allergic to penicillin, macrolide antibiotics should be used alone. (III-B) 6. The following two regimens may be used (the two regimens were used in the largest PPROM randomized controlled trials that showed a decrease in both maternal and neonatal morbidity): (1) ampicillin 2 g IV every 6 hours and erythromycin 250 mg IV every 6 hours for 48 hours followed by amoxicillin 250 mg orally every 8 hours and erythromycin 333 mg orally every 8 hours for 5 days (I-A); (2) erythromycin 250 mg orally every 6 hours for 10 days (I-A) 7. Amoxicillin/clavulanic acid should not be used because of an increased risk of necrotizing enterocolitis in neonates exposed to this antibiotic. Amoxicillin without clavulanic acid is safe. (I-A) 8. Women presenting with PPROM should be screened for urinary tract infections, sexually transmitted infections, and group B streptococcus carriage, and treated with appropriate antibiotics if positive. (II-2B).

Separation analysis of macrolide antibiotics with good performance on a positively charged C18HCE column.

PubMed

Wei, Jie; Shen, Aijin; Yan, Jingyu; Jin, Gaowa; Yang, Bingcheng; Guo, Zhimou; Zhang, Feifang; Liang, Xinmiao

2016-03-01

The separation of basic macrolide antibiotics suffers from peak tailing and poor efficiency on traditional silica-based reversed-phase liquid chromatography columns. In this work, a C18HCE column with positively charged surface was applied to the separation of macrolides. Compared with an Acquity BEH C18 column, the C18HCE column exhibited superior performance in the aspect of peak shape and separation efficiency. The screening of mobile phase additives including formic acid, acetic acid and ammonium formate indicated that formic acid was preferable for providing symmetrical peak shapes. Moreover, the influence of formic acid content was investigated. Analysis speed and mass spectrometry compatibility were also taken into account when optimizing the separation conditions for liquid chromatography coupled with tandem mass spectrometry. The developed method was successfully utilized for the determination of macrolide residues in a honey sample. Azithromycin was chosen as the internal standard for the quantitation of spiramycin and tilmicosin, while roxithromycin was used for erythromycin, tylosin, clarithromycin, josamycin and acetylisovaleryltylosin. Good correlation coefficients (r(2) > 0.9938) for all macrolides were obtained. The intra-day and inter-day recoveries were 73.7-134.7% and 80.7-119.7% with relative standard deviations of 2.5-8.0% and 3.9-16.1%, respectively. Outstanding sensitivity with limits of quantitation (S/N ≥ 10) of 0.02-1 μg/kg and limits of detection (S/N ≥ 3) of 0.01-0.5 μg/kg were achieved. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Group a streptococcus antibiotic resistance in southern Brazil: a 17-year surveillance study.

PubMed

Torres, Rosângela Stadnick Lauth de Almeida; Torres, Renato Pedro de Almeida; Smeesters, Pierre Robert; Palmeiro, Jussara Kasuko; de Messias-Reason, Iara José; Dalla-Costa, Libera M

2011-06-01

Scarce data are available about the antimicrobial resistance of Group A Streptococcus in South America. This study evaluated the antimicrobial susceptibility profile of 1,112 isolates of Group A Streptococcus during the period from 1993 to 2009 in Curitiba city, Brazil. Macrolide-resistant isolates were characterized by emm typing and pulsed-field gel electrophoresis. All isolates were susceptible to penicillin, vancomycin, and tigecycline. On the contrary, 18.6% of the isolates were resistant to tetracycline, presenting a minimum inhibitory concentration (MIC)(50)/MIC(90) of 32/64 mg/L. Erythromycin resistance rose from 1.9% before 2000 to 4% after 2000 and was associated with a marked increased of MIC levels. Simultaneously, both the phenotype and genotype of macrolide resistance were modified as the M phenotypes (mef(A) genotype) were replaced by the cMLS(B) phenotypes (erm(B) genotype). This polyclonal spreading of cMLS(B) macrolide resistance has not been previously observed in South America and should stimulate further epidemiological surveillance in this part of the world.

Mechanisms of action of systemic antibiotics used in periodontal treatment and mechanisms of bacterial resistance to these drugs

PubMed Central

SOARES, Geisla Mary Silva; FIGUEIREDO, Luciene Cristina; FAVERI, Marcelo; CORTELLI, Sheila Cavalca; DUARTE, Poliana Mendes; FERES, Magda

2012-01-01

Antibiotics are important adjuncts in the treatment of infectious diseases, including periodontitis. The most severe criticisms to the indiscriminate use of these drugs are their side effects and, especially, the development of bacterial resistance. The knowledge of the biological mechanisms involved with the antibiotic usage would help the medical and dental communities to overcome these two problems. Therefore, the aim of this manuscript was to review the mechanisms of action of the antibiotics most commonly used in the periodontal treatment (i.e. penicillin, tetracycline, macrolide and metronidazole) and the main mechanisms of bacterial resistance to these drugs. Antimicrobial resistance can be classified into three groups: intrinsic, mutational and acquired. Penicillin, tetracycline and erythromycin are broad-spectrum drugs, effective against gram-positive and gram-negative microorganisms. Bacterial resistance to penicillin may occur due to diminished permeability of the bacterial cell to the antibiotic; alteration of the penicillin-binding proteins, or production of β-lactamases. However, a very small proportion of the subgingival microbiota is resistant to penicillins. Bacteria become resistant to tetracyclines or macrolides by limiting their access to the cell, by altering the ribosome in order to prevent effective binding of the drug, or by producing tetracycline/macrolide-inactivating enzymes. Periodontal pathogens may become resistant to these drugs. Finally, metronidazole can be considered a prodrug in the sense that it requires metabolic activation by strict anaerobe microorganisms. Acquired resistance to this drug has rarely been reported. Due to these low rates of resistance and to its high activity against the gram-negative anaerobic bacterial species, metronidazole is a promising drug for treating periodontal infections. PMID:22858695

Antipneumococcal activities of two novel macrolides, GW 773546 and GW 708408, compared with those of erythromycin, azithromycin, clarithromycin, clindamycin, and telithromycin.

PubMed

Matic, Vlatka; Kosowska, Klaudia; Bozdogan, Bulent; Kelly, Linda M; Smith, Kathy; Ednie, Lois M; Lin, Gengrong; Credito, Kim L; Clark, Catherine L; McGhee, Pamela; Pankuch, Glenn A; Jacobs, Michael R; Appelbaum, Peter C

2004-11-01

The MICs of GW 773546, GW 708408, and telithromycin for 164 macrolide-susceptible and 161 macrolide-resistant pneumococci were low. The MICs of GW 773546, GW 708408, and telithromycin for macrolide-resistant strains were similar, irrespective of the resistance genotypes of the strains. Clindamycin was active against all macrolide-resistant strains except those with erm(B) and one strain with a 23S rRNA mutation. GW 773546, GW 708408, and telithromycin at two times their MICs were bactericidal after 24 h for 7 to 8 of 12 strains. Serial passages of 12 strains in the presence of sub-MICs yielded 54 mutants, 29 of which had changes in the L4 or L22 protein or the 23S rRNA sequence. Among the macrolide-susceptible strains, resistant mutants developed most rapidly after passage in the presence of clindamycin, GW 773546, erythromycin, azithromycin, and clarithromycin and slowest after passage in the presence of GW 708408 and telithromycin. Selection of strains for which MICs were >/=0.5 microg/ml from susceptible parents occurred only with erythromycin, azithromycin, clarithromycin, and clindamycin; 36 resistant clones from susceptible parent strains had changes in the sequences of the L4 or L22 protein or 23S rRNA. No mef(E) strains yielded resistant clones after passage in the presence of erythromycin and azithromycin. Selection with GW 773546, GW 708408, telithromycin, and clindamycin in two mef(E) strains did not raise the erythromycin, azithromycin, and clarithromycin MICs more than twofold. There were no change in the ribosomal protein (L4 or L22) or 23S rRNA sequences for 15 of 18 mutants selected for macrolide resistance; 3 mutants had changes in the L22-protein sequence. GW 773546, GW 708408, and telithromycin selected clones for which MICs were 0.03 to >2.0 microg/ml. Single-step studies showed mutation frequencies <5.0 x 10(-10) to 3.5 x 10(-7) for GW 773546, GW 708408, and telithromycin for macrolide-susceptible strains and 1.1 x 10(-7) to >4.3 x 10(-3) for resistant strains. The postantibiotic effects of GW 773546, GW 708408, and telithromycin were 2.4 to 9.8 h.

Antipneumococcal Activities of Two Novel Macrolides, GW 773546 and GW 708408, Compared with Those of Erythromycin, Azithromycin, Clarithromycin, Clindamycin, and Telithromycin

PubMed Central

Matic, Vlatka; Kosowska, Klaudia; Bozdogan, Bulent; Kelly, Linda M.; Smith, Kathy; Ednie, Lois M.; Lin, Gengrong; Credito, Kim L.; Clark, Catherine L.; McGhee, Pamela; Pankuch, Glenn A.; Jacobs, Michael R.; Appelbaum, Peter C.

2004-01-01

The MICs of GW 773546, GW 708408, and telithromycin for 164 macrolide-susceptible and 161 macrolide-resistant pneumococci were low. The MICs of GW 773546, GW 708408, and telithromycin for macrolide-resistant strains were similar, irrespective of the resistance genotypes of the strains. Clindamycin was active against all macrolide-resistant strains except those with erm(B) and one strain with a 23S rRNA mutation. GW 773546, GW 708408, and telithromycin at two times their MICs were bactericidal after 24 h for 7 to 8 of 12 strains. Serial passages of 12 strains in the presence of sub-MICs yielded 54 mutants, 29 of which had changes in the L4 or L22 protein or the 23S rRNA sequence. Among the macrolide-susceptible strains, resistant mutants developed most rapidly after passage in the presence of clindamycin, GW 773546, erythromycin, azithromycin, and clarithromycin and slowest after passage in the presence of GW 708408 and telithromycin. Selection of strains for which MICs were ≥0.5 μg/ml from susceptible parents occurred only with erythromycin, azithromycin, clarithromycin, and clindamycin; 36 resistant clones from susceptible parent strains had changes in the sequences of the L4 or L22 protein or 23S rRNA. No mef(E) strains yielded resistant clones after passage in the presence of erythromycin and azithromycin. Selection with GW 773546, GW 708408, telithromycin, and clindamycin in two mef(E) strains did not raise the erythromycin, azithromycin, and clarithromycin MICs more than twofold. There were no change in the ribosomal protein (L4 or L22) or 23S rRNA sequences for 15 of 18 mutants selected for macrolide resistance; 3 mutants had changes in the L22-protein sequence. GW 773546, GW 708408, and telithromycin selected clones for which MICs were 0.03 to >2.0 μg/ml. Single-step studies showed mutation frequencies <5.0 × 10−10 to 3.5 × 10−7 for GW 773546, GW 708408, and telithromycin for macrolide-susceptible strains and 1.1 × 10−7 to >4.3 × 10−3 for resistant strains. The postantibiotic effects of GW 773546, GW 708408, and telithromycin were 2.4 to 9.8 h. PMID:15504828

High prevalence of Streptococcus agalactiae from vaginas of women in Taiwan and its mechanisms of macrolide and quinolone resistance.

PubMed

Lee, Wen-Tsung; Lai, Mei-Chin

2015-10-01

Streptococcus agalactiae (GBS), is the most common pathogen causing infections among perinatal women and neonatal babies. Nonetheless, there are few studies on the occurrence of GBS among the pregnant women and the mechanisms of GBS resistance to quinolones and macrolides in Taiwan. GBS were isolated from vaginas of the pregnant and non-pregnant symptomatic women in Taiwan. The prevalence, antimicrobial susceptibility, and mechanisms of resistance against erythromycin and quinolone of total 188 isolates were studied. The isolation rate of GBS from pregnant women was significantly higher at 21.8% compare with the non-pregnant women of 13.2%. Antibiotic susceptibility test of the 188 GBS isolates revealed a high non-susceptible rate for erythromycin (50.0%) while the rate for levofloxacin was only 4.8%. Among 94 erythromycin non-susceptible GBS isolates, ermB gene was detected 83.1% (59/71) for those GBS that were non-susceptible to both clindamycin and tetracycline, which was significantly higher than GBS that are susceptible to clindamycin but resistant to tetracycline at 43.8% (7/16). No ermA or mef gene was detected in any isolate. Mutations were detected in the parC and gyrA genes in 14 out of 18 levofloxacin non-susceptible isolates. The predominant mutation type was the combination of Ser79Tyr in parC and Ser81Leu mutations in gyrA. GBS is the most common isolated pathogens in vaginal infections in Taiwan, resistance to tetracycline and erythromycin is higher than the rate observed for other regions of the world, while the resistance rate for levofloxacin was relatively lower in Taiwan. Copyright © 2014. Published by Elsevier B.V.

Occurrence, species distribution, antimicrobial resistance and clonality of methicillin- and erythromycin-resistant staphylococci in the nasal cavity of domestic animals.

PubMed

Bagcigil, Funda A; Moodley, Arshnee; Baptiste, Keith E; Jensen, Vibeke F; Guardabassi, Luca

2007-04-15

beta-Lactams and macrolides are important antibiotics for treatment of staphylococcal infections in both humans and animals. The aim of the study was to investigate the occurrence, species distribution and clonality of methicillin- and erythromycin-resistant staphylococci in the nasal cavity of dogs, horses, pigs, and cattle in Denmark. Nasal swabs were collected from a total of 400 animals, including 100 individuals of each species. Methicillin- and erythromycin-resistant staphylococci were isolated on selective media, identified by 16S rDNA sequencing, and typed by pulsed field gel electrophoresis (PFGE). Methicillin-resistant coagulase-negative staphylococci (MRCoNS) harbouring mecA were isolated from horses (50%) and dogs (13%), but not from food animals. The species identified were S. haemolyticus (n=21), S. vitulinus (n=19), S. sciuri (n=13), S. epidermidis (n=8), and S. warneri (n=2). mecA-mediated methicillin resistance in S. vitulinus was described for the first time. Methicillin-resistant S. aureus was not detected. PFGE analysis revealed the presence of specific MRCoNS clones in samples originating from the same veterinary hospital or equine farm. Erythromycin-resistant S. aureus (ERSA) was detected in 38% of pigs and all isolates harboured a constitutively expressed erm(C) gene. The vast majority (37/38) of pigs carrying ERSA originated from a farm characterized by frequent use of macrolides. Most ERSA isolates (28/38) displayed indistinguishable or closely related PFGE patterns, indicating clonal distribution within the farm. Based on the analysis of data on antimicrobial consumption, the occurrence of MRCoNS in companion animals and that of ERSA in pigs reflected national and local patterns of antimicrobial usage.

Uptake of antibiotics by human polymorphonuclear leukocyte cytoplasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hand, W.L.; King-Thompson, N.L.

Enucleated human polymorphonuclear leukocytes (PMN cytoplasts), which have no nuclei and only a few granules, retain many of the functions of intact neutrophils. To better define the mechanisms and intracellular sites of antimicrobial agent accumulation in human neutrophils, we studied the antibiotic uptake process in PMN cytoplasts. Entry of eight radiolabeled antibiotics into PMN cytoplasts was determined by means of a velocity gradient centrifugation technique. Uptakes of these antibiotics by cytoplasts were compared with our findings in intact PMN. Penicillin entered both intact PMN and cytoplasts poorly. Metronidazole achieved a concentration in cytoplasts (and PMN) equal to or somewhat lessmore » than the extracellular concentration. Chloramphenicol, a lipid-soluble drug, and trimethoprim were concentrated three- to fourfold by cytoplasts. An unusual finding was that trimethroprim, unlike other tested antibiotics, was accumulated by cytoplasts more readily at 25 degrees C than at 37 degrees C. After an initial rapid association with cytoplasts, cell-associated imipenem declined progressively with time. Clindamycin and two macrolide antibiotics (roxithromycin, erythromycin) were concentrated 7- to 14-fold by cytoplasts. This indicates that cytoplasmic granules are not essential for accumulation of these drugs. Adenosine inhibited cytoplast uptake of clindamycin, which enters intact phagocytic cells by the membrane nucleoside transport system. Roxithromycin uptake by cytoplasts was inhibited by phagocytosis, which may reduce the number of cell membrane sites available for the transport of macrolides. These studies have added to our understanding of uptake mechanisms for antibiotics which are highly concentrated in phagocytes.« less

Occurrence and fate of most prescribed antibiotics in different water environments of Tehran, Iran.

PubMed

Mirzaei, Roya; Yunesian, Masud; Nasseri, Simin; Gholami, Mitra; Jalilzadeh, Esfandiyar; Shoeibi, Shahram; Mesdaghinia, Alireza

2018-04-01

The presence of most prescribed antibiotic compounds from four therapeutic classes (β-lactam, cephalosporins, macrolides, fluoroquinolones) were studied at two full-scale WWTPs, two rivers, thirteen groundwater resources, and five water treatment plants in Tehran. Analytical methodology was based on high performance liquid chromatography/tandem mass spectrometry after solid-phase extraction. Samples were collected at 33 sample locations on three sampling periods over four months from June to August 2016. None of the target antibiotics were detected in groundwater resources and water treatment plants, while seven out of nine target antibiotics were analyzed in two studied river waters as well as the influent and effluent of wastewater treatment plants at concentrations ranging from

Structural basis for the interaction of antibiotics with peptidyl transferase center in eubacteria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schlunzen, Frank; Zarivach, Raz; Harms, Jörg

2009-10-07

Ribosomes, the site of protein synthesis, are a major target for natural and synthetic antibiotics. Detailed knowledge of antibiotic binding sites is central to understanding the mechanisms of drug action. Conversely, drugs are excellent tools for studying the ribosome function. To elucidate the structural basis of ribosome-antibiotic interactions, we determined the high-resolution X-ray structures of the 50S ribosomal subunit of the eubacterium Deinococcus radiodurans, complexed with the clinically relevant antibiotics chloramphenicol, clindamycin and the three macrolides erythromycin, clarithromycin and roxithromycin. We found that antibiotic binding sites are composed exclusively of segments of 23S ribosomal RNA at the peptidyl transferase cavitymore » and do not involve any interaction of the drugs with ribosomal proteins. Here we report the details of antibiotic interactions with the components of their binding sites. Our results also show the importance of putative Mg{sup +2} ions for the binding of some drugs. This structural analysis should facilitate rational drug design.« less

Occurrence of antibiotics in wastewater treatment facilities in Wisconsin, USA

USGS Publications Warehouse

Karthikeyan, K.G.; Meyer, M.T.

2006-01-01

Samples from several wastewater treatment facilities in Wisconsin were screened for the presence of 21 antibiotic compounds. These facilities spanned a range of community size served (average daily flow from 0.0212 to 23.6 million gallons/day), secondary treatment processes, geographic locations across the state, and they discharged the treated effluents to both surface and ground waters (for ground water after a soil passage). A total of six antibiotic compounds were detected (1-5 compounds per site), including two sulfonamides (sulfamethazine, sulfamethoxazole), one tetracycline (tetracycline), fluoroquinolone (ciprofloxacin), macrolide (erythromycin-H2O) and trimethoprim. The frequency of detection of antibiotics was in the following order: tetracycline and trimethoprim (80%) > sulfamethoxazole (70%) > erythromycin-H2O (45%) > ciprofloxacin (40%) > sulfamethazine (10%). However, the soluble concentrations were in the parts-per-billion (ppb) range (??? 1.3 ??g/L), and importantly were unaffected by the size of the wastewater treatment facility. The concentrations detected were within an order of magnitude of those reported for similar systems in Europe and Canada: they were within a factor of two in comparison to those reported for Canada but generally lower relative to those measured in wastewater systems in Europe. Only sulfamethoxazole and tetracycline were detected in groundwater monitoring wells adjacent to the treatment systems. Future intensive wastewater monitoring programs in Wisconsin may be limited to the six antibiotic compounds detected in this study. ?? 2005 Elsevier B.V. All rights reserved.

Occurrence of antibiotics in wastewater treatment facilities in Wisconsin, USA.

PubMed

Karthikeyan, K G; Meyer, Michael T

2006-05-15

Samples from several wastewater treatment facilities in Wisconsin were screened for the presence of 21 antibiotic compounds. These facilities spanned a range of community size served (average daily flow from 0.0212 to 23.6 million gallons/day), secondary treatment processes, geographic locations across the state, and they discharged the treated effluents to both surface and ground waters (for ground water after a soil passage). A total of six antibiotic compounds were detected (1-5 compounds per site), including two sulfonamides (sulfamethazine, sulfamethoxazole), one tetracycline (tetracycline), fluoroquinolone (ciprofloxacin), macrolide (erythromycin-H(2)O) and trimethoprim. The frequency of detection of antibiotics was in the following order: tetracycline and trimethoprim (80%)>sulfamethoxazole (70%)>erythromycin-H(2)O (45%)>ciprofloxacin (40%)>sulfamethazine (10%). However, the soluble concentrations were in the parts-per-billion (ppb) range (

Improved detection of multiple environmental antibiotics through an optimized sample extraction strategy in liquid chromatography-mass spectrometry analysis.

PubMed

Yi, Xinzhu; Bayen, Stéphane; Kelly, Barry C; Li, Xu; Zhou, Zhi

2015-12-01

A solid-phase extraction/liquid chromatography/electrospray ionization/multi-stage mass spectrometry (SPE-LC-ESI-MS/MS) method was optimized in this study for sensitive and simultaneous detection of multiple antibiotics in urban surface waters and soils. Among the seven classes of tested antibiotics, extraction efficiencies of macrolides, lincosamide, chloramphenicol, and polyether antibiotics were significantly improved under optimized sample extraction pH. Instead of only using acidic extraction in many existing studies, the results indicated that antibiotics with low pK a values (<7) were extracted more efficiently under acidic conditions and antibiotics with high pK a values (>7) were extracted more efficiently under neutral conditions. The effects of pH were more obvious on polar compounds than those on non-polar compounds. Optimization of extraction pH resulted in significantly improved sample recovery and better detection limits. Compared with reported values in the literature, the average reduction of minimal detection limits obtained in this study was 87.6% in surface waters (0.06-2.28 ng/L) and 67.1% in soils (0.01-18.16 ng/g dry wt). This method was subsequently applied to detect antibiotics in environmental samples in a heavily populated urban city, and macrolides, sulfonamides, and lincomycin were frequently detected. Antibiotics with highest detected concentrations were sulfamethazine (82.5 ng/L) in surface waters and erythromycin (6.6 ng/g dry wt) in soils. The optimized sample extraction strategy can be used to improve the detection of a variety of antibiotics in environmental surface waters and soils.

Macrolide antibiotics for bronchiectasis.

PubMed

Kelly, Carol; Chalmers, James D; Crossingham, Iain; Relph, Nicola; Felix, Lambert M; Evans, David J; Milan, Stephen J; Spencer, Sally

2018-03-15

Bronchiectasis is a chronic respiratory disease characterised by abnormal and irreversible dilatation and distortion of the smaller airways. Bacterial colonisation of the damaged airways leads to chronic cough and sputum production, often with breathlessness and further structural damage to the airways. Long-term macrolide antibiotic therapy may suppress bacterial infection and reduce inflammation, leading to fewer exacerbations, fewer symptoms, improved lung function, and improved quality of life. Further evidence is required on the efficacy of macrolides in terms of specific bacterial eradication and the extent of antibiotic resistance. To determine the impact of macrolide antibiotics in the treatment of adults and children with bronchiectasis. We identified trials from the Cochrane Airways Trials Register, which contains studies identified through multiple electronic searches and handsearches of other sources. We also searched trial registries and reference lists of primary studies. We conducted all searches on 18 January 2018. We included randomised controlled trials (RCTs) of at least four weeks' duration that compared macrolide antibiotics with placebo or no intervention for the long-term management of stable bronchiectasis in adults or children with a diagnosis of bronchiectasis by bronchography, plain film chest radiograph, or high-resolution computed tomography. We excluded studies in which participants had received continuous or high-dose antibiotics immediately before enrolment or before a diagnosis of cystic fibrosis, sarcoidosis, or allergic bronchopulmonary aspergillosis. Our primary outcomes were exacerbation, hospitalisation, and serious adverse events. Two review authors independently screened the titles and abstracts of 103 records. We independently screened the full text of 40 study reports and included 15 trials from 30 reports. Two review authors independently extracted outcome data and assessed risk of bias for each study. We analysed dichotomous data as odds ratios (ORs) and continuous data as mean differences (MDs) or standardised mean differences (SMDs). We used standard methodological procedures as expected by Cochrane. We included 14 parallel-group RCTs and one cross-over RCT with interventions lasting from 8 weeks to 24 months. Of 11 adult studies with 690 participants, six used azithromycin, four roxithromycin, and one erythromycin. Four studies with 190 children used either azithromycin, clarithromycin, erythromycin, or roxithromycin.We included nine adult studies in our comparison between macrolides and placebo and two in our comparison with no intervention. We included one study with children in our comparison between macrolides and placebo and one in our comparison with no intervention.In adults, macrolides reduced exacerbation frequency to a greater extent than placebo (OR 0.34, 95% confidence interval (CI) 0.22 to 0.54; 341 participants; three studies; I 2 = 65%; moderate-quality evidence). This translates to a number needed to treat for an additional beneficial outcome of 4 (95% CI 3 to 8). Data show no differences in exacerbation frequency between use of macrolides (OR 0.31, 95% CI 0.08 to 1.15; 43 participants; one study; moderate-quality evidence) and no intervention. Macrolides were also associated with a significantly better quality of life compared with placebo (MD -8.90, 95% CI -13.13 to -4.67; 68 participants; one study; moderate-quality evidence). We found no evidence of a reduction in hospitalisations (OR 0.56, 95% CI 0.19 to 1.62; 151 participants; two studies; I 2 = 0%; low-quality evidence), in the number of participants with serious adverse events, including pneumonia, respiratory and non-respiratory infections, haemoptysis, and gastroenteritis (OR 0.49, 95% CI 0.20 to 1.23; 326 participants; three studies; I 2 = 0%; low-quality evidence), or in the number experiencing adverse events (OR 0.83, 95% CI 0.51 to 1.35; 435 participants; five studies; I 2 = 28%) in adults with macrolides compared with placebo.In children, there were no differences in exacerbation frequency (OR 0.40, 95% CI 0.11 to 1.41; 89 children; one study; low-quality evidence); hospitalisations (OR 0.28, 95% CI 0.07 to 1.11; 89 children; one study; low-quality evidence), serious adverse events, defined within the study as exacerbations of bronchiectasis or investigations related to bronchiectasis (OR 0.43, 95% CI 0.17 to 1.05; 89 children; one study; low-quality evidence), or adverse events (OR 0.78, 95% CI 0.33 to 1.83; 89 children; one study), in those receiving macrolides compared to placebo. The same study reported an increase in macrolide-resistant bacteria (OR 7.13, 95% CI 2.13 to 23.79; 89 children; one study), an increase in resistance to Streptococcus pneumoniae (OR 13.20, 95% CI 1.61 to 108.19; 89 children; one study), and an increase in resistance to Staphylococcus aureus (OR 4.16, 95% CI 1.06 to 16.32; 89 children; one study) with macrolides compared with placebo. Quality of life was not reported in the studies with children. Long-term macrolide therapy may reduce the frequency of exacerbations and improve quality of life, although supporting evidence is derived mainly from studies of azithromycin, rather than other macrolides, and predominantly among adults rather than children. However, macrolides should be used with caution, as limited data indicate an associated increase in microbial resistance. Macrolides are associated with increased risk of cardiovascular death and other serious adverse events in other populations, and available data cannot exclude a similar risk among patients with bronchiectasis.

Solid phase microextraction of macrolide, trimethoprim, and sulfonamide antibiotics in wastewaters.

PubMed

McClure, Evelyn L; Wong, Charles S

2007-10-26

In this work, we optimize a solid phase microextraction (SPME) method for the simultaneous collection of antibiotics (sulfonamides, macrolides, and trimethoprim) present in wastewaters. The performance of the SPME method is compared to a solid phase extraction (SPE) method. Analytes in both cases were quantified by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS-MS) with electrospray ionization. The advantages offered by SPME in this application are: decreased sample volume requirements, ease of sample processing and extraction, decreased cost, and most importantly, elimination of electrospray matrix effects. Despite having higher limits of quantification (16-1380 ng/L in influent and 35-260 ng/L in effluent), nearly all of the compounds found to be present in Edmonton Gold Bar wastewater by SPE were measurable by SPME (i.e., sulfamethoxazole, trimethoprim, erythromycin, and clarithromycin), with values similar to those obtained using the former method. Limits of quantification for the SPE method for the measured compounds were 4.7-15 ng/L and 0.86-6.1 ng/L for influent and effluent, respectively.

Miniaturized solid-phase extraction of macrolide antibiotics in honey and bovine milk using mesoporous MCM-41 silica as sorbent.

PubMed

Du, Li-Jing; Yi, Ling; Ye, Li-Hong; Chen, Yu-Bo; Cao, Jun; Peng, Li-Qing; Shi, Yu-Ting; Wang, Qiu-Yan; Hu, Yu-Han

2018-02-16

A simple and effective method of miniaturized solid-phase extraction (mini-SPE) was developed for the simultaneous purification and enrichment of macrolide antibiotics (MACs) (i.e. azithromycin, clarithromycin, erythromycin, lincomycin and roxithromycin) from honey and skim milk. Mesoporous MCM-41 silica was synthesized and used as sorbent in mini-SPE. Several key parameters affecting the performance of mini-SPE procedure were thoroughly investigated, including sorbent materials, amount of sorbent and elution solvents. Under the optimized condition, satisfactory linearity (r 2  > 0.99), acceptable precision (RSDs, 0.3-7.1%), high sensitivity (limit of detection in the range of 0.01-0.76 μg/kg), and good recoveries (83.21-105.34%) were obtained. With distinct advantages of simplicity, reliability and minimal sample requirement, the proposed mini-SPE procedure coupled with ultrahigh performance liquid chromatography and quadrupole time-of-flight tandem mass spectrometry could become an alternative tool to analyze the residues of MACs in complex food matrixes. Copyright © 2018 Elsevier B.V. All rights reserved.

Rapid and selective extraction of multiple macrolide antibiotics in foodstuff samples based on magnetic molecularly imprinted polymers.

PubMed

Zhou, Yusun; Zhou, Tingting; Jin, Hua; Jing, Tao; Song, Bin; Zhou, Yikai; Mei, Surong; Lee, Yong-Ill

2015-05-01

Magnetic molecularly imprinted polymers (MMIPs) were prepared based on surface molecular imprinting using erythromycin (ERY) as template molecule and Fe3O4 nanoparticles as support substrate. The MMIPs possessed high adsorption capacity of 94.1 mg/g for ERY and the imprinting factor was 11.9 indicating good imprinted effect for ERY. Selective evaluation demonstrated favorable selectivity of MMIPs for multiple macrolide antibiotics (MACs). Using MMIPs as adsorptive material, a rapid and convenient magnetic solid-phase extraction (MSPE) procedure was established for simultaneous and selective separation of six MACs in pork, fish and shrimp samples, then the MACs was subjected to high-performance liquid chromatography-ultraviolet (HPLC-UV) analysis. At different fortified concentrations, the extraction recoveries could reach 89.1% and the relative standard deviations were lower than 12.4%. Chromatogram revealed the response signals of MACs in spiked samples were greatly enhanced and matrix interferences were effectively eliminated after treatment with MSPE. The proposed MSPE procedure coupled with HPLC-UV realized selective and sensitive determination of multiple MACs in foodstuff samples. Copyright © 2015 Elsevier B.V. All rights reserved.

Multiclass determination and confirmation of antibiotic residues in honey using LC-MS/MS.

PubMed

Lopez, Mayda I; Pettis, Jeffery S; Smith, I Barton; Chu, Pak-Sin

2008-03-12

A multiclass method has been developed for the determination and confirmation in honey of tetracyclines (chlortetracycline, doxycycline, oxytetracycline, and tetracycline), fluoroquinolones (ciprofloxacin, danofloxacin, difloxacin, enrofloxacin, and sarafloxacin), macrolides (tylosin), lincosamides (lincomycin), aminoglycosides (streptomycin), sulfonamides (sulfathiazole), phenicols (chloramphenicol), and fumagillin residues using liquid chromatography tandem mass spectrometry (LC-MS/MS). Erythromycin (a macrolide) and monensin (an ionophore) can be detected and confirmed but not quantitated. Honey samples (approximately 2 g) are dissolved in 10 mL of water and centrifuged. An aliquot of the supernatant is used to determine streptomycin. The remaining supernatant is filtered through a fine-mesh nylon fabric and cleaned up by solid phase extraction. After solvent evaporation and sample reconstitution, 15 antibiotics are assayed by LC-MS/MS using electrospray ionization (ESI) in positive ion mode. Afterward, chloramphenicol is assayed using ESI in negative ion mode. The method has been validated at the low part per billion levels for most of the drugs with accuracies between 65 and 104% and coefficients of variation less than 17%. The evaluation of matrix effects caused by honey of different floral origin is presented.

Antibiotic prescription in the treatment of odontogenic infection by health professionals: A factor to consensus

PubMed Central

González-Martínez, Raquel; Cortell-Ballester, Isidoro; Herráez-Vilas, José M.; Arnau-de Bolós, José M.

2012-01-01

Objective: To observe the attitude of dentists and family doctors in prescribing antibiotics for the treatment of dental infections. Study Design: A poll was performed to determine the differences in the prescription of antibiotics for the treatment of odontogenic infection by dentists and family doctors of the primary care department of the Catalan Health Care Service. Results: A hundred polls were distributed among family doctors, and another 100 ones among primary care dentists assigned to the Catalan Health Care Service of the Generalitat de Catalunya. Of the total of questionnaires distributed, 63 were retuned and answered from dentists and 71 from family doctors. Eighty-one percent of dentists included in the opinion poll considered amoxicillin as the first antibiotic choice for the treatment of odontogenic infections, while 73.2% of family doctors preferred the combination of amoxicillin and clavulanic acid. With regard to antibiotics of choice in patients allergic to penicillin, 67.7% of family doctors preferred macrolides (25.4% opted for clarithromycin, 25.4% for erythromycin and 16.9% for spiramycin). However, clindamycin was the antibiotic most frequently prescribed by dentists (66.7%), followed by erythromycin (28.6%). Conclusions: The results of this study show a large discrepancy in the criteria for the treatment of odontogenic infections on the part of leading professionals involved in the management of this condition. Although the most common prescription involved beta-lactam antibiotics in both groups, several significant differences have been detected with regard to the second antibiotic choice. Key words:Odontogenic infections, antibiotics, antimicrobials. PMID:22143715

Macrolide resistance and genotypic characterization of Streptococcus pneumoniae in Asian countries: a study of the Asian Network for Surveillance of Resistant Pathogens (ANSORP).

PubMed

Song, Jae-Hoon; Chang, Hyun-Ha; Suh, Ji Yoeun; Ko, Kwan Soo; Jung, Sook-In; Oh, Won Sup; Peck, Kyong Ran; Lee, Nam Yong; Yang, Yonghong; Chongthaleong, Anan; Aswapokee, Nalinee; Chiu, Cheng-Hsun; Lalitha, M K; Perera, Jennifer; Yee, Ti Teow; Kumararasinghe, Gamini; Jamal, Farida; Kamarulazaman, Adeeba; Parasakthi, Navaratnam; Van, Pham Hung; So, Thomas; Ng, Tak Keung

2004-03-01

To characterize mechanisms of macrolide resistance among Streptococcus pneumoniae from 10 Asian countries during 1998-2001. Phenotypic and genotypic characterization of the isolates and their resistance mechanisms. Of 555 isolates studied, 216 (38.9%) were susceptible, 10 (1.8%) were intermediate and 329 (59.3%) were resistant to erythromycin. Vietnam had the highest prevalence of erythromycin resistance (88.3%), followed by Taiwan (87.2%), Korea (85.1%), Hong Kong (76.5%) and China (75.6%). Ribosomal methylation encoded by erm(B) was the most common mechanism of erythromycin resistance in China, Taiwan, Sri Lanka and Korea. In Hong Kong, Singapore, Thailand and Malaysia, efflux encoded by mef(A) was the more common in erythromycin-resistant isolates. In most Asian countries except Hong Kong, Malaysia and Singapore, erm(B) was found in >50% of pneumococcal isolates either alone or in combination with mef(A). The level of erythromycin resistance among pneumococcal isolates in most Asian countries except Thailand and India was very high with MIC(90)s of >128 mg/L. Molecular epidemiological studies suggest the horizontal transfer of the erm(B) gene and clonal dissemination of resistant strains in the Asian region. Data confirm that macrolide resistance in pneumococci is a serious problem in many Asian countries.

Antibiotics in riverine runoff of the Pearl River Delta and Pearl River Estuary, China: concentrations, mass loading and ecological risks.

PubMed

Xu, Weihai; Yan, Wen; Li, Xiangdong; Zou, Yongde; Chen, Xiaoxiang; Huang, Weixia; Miao, Li; Zhang, Ruijie; Zhang, Gan; Zou, Shichun

2013-11-01

Ten antibiotics belonging to three groups (macrolides, fluoroquinolones and sulfonamides) were investigated in riverine runoff of the Pearl River Delta (PRD) and Pearl River Estuary (PRE), South China for assessing the importance of riverine runoff in the transportation of contaminants from terrestrial sources to the open ocean. All antibiotics were detected in the eight outlets with concentrations ranging from 0.7 to 127 ng L(-1). The annual mass loadings of antibiotics from the PRD to the PRE and coast were 193 tons with 102 tons from the fluoroquinolone group. It showed that antibiotics decreased from the riverine outlets to the PRE and open ocean. Risk assessment showed that most of these antibiotics showed various ecological risks to the relevant aquatic organisms, in which ofloxacin (OFL), erythromycin (ETM) and ciprofloxacin (CIP) posed high ecological risks to the studied aquatic environments. Copyright © 2013 Elsevier Ltd. All rights reserved.

Haemophilus parasuis CpxRA two-component system confers bacterial tolerance to environmental stresses and macrolide resistance.

PubMed

Cao, Qi; Feng, Fenfen; Wang, Huan; Xu, Xiaojuan; Chen, Huanchun; Cai, Xuwang; Wang, Xiangru

2018-01-01

Haemophilus parasuis is an opportunistic pathogen localized in the upper respiratory tracts of pigs, its infection begins from bacterial survival under complex conditions, like hyperosmosis, oxidative stress, phagocytosis, and sometimes antibiotics as well. The two-component signal transduction (TCST) system serves as a common stimulus-response mechanism that allows microbes to sense and respond to diverse environmental conditions via a series of phosphorylation reactions. In this study, we investigated the role of TCST system CpxRA in H. parasuis in response to different environmental stimuli by constructing the ΔcpxA and ΔcpxR single deletion mutants as well as the ΔcpxRA double deletion mutant from H. parasuis serotype 4 isolate JS0135. We demonstrated that H. parasuis TCST system CpxRA confers bacterial tolerance to stresses and bactericidal antibiotics. The CpxR was found to play essential roles in mediating oxidative stress, osmotic stresses and alkaline pH stress tolerance, as well as macrolide resistance (i.e. erythromycin), but the CpxA deletion did not decrease bacterial resistance to abovementioned stresses. Moreover, we found via RT-qPCR approach that HAPS_RS00160 and HAPS_RS09425, both encoding multidrug efflux pumps, were significantly decreased in erythromycin challenged ΔcpxR and ΔcpxRA mutants compared with wild-type strain JS0135. These findings characterize the role of the TCST system CpxRA in H. parasuis conferring stress response tolerance and bactericidal resistance, which will deepen our understanding of the pathogenic mechanism in H. parasuis. Copyright © 2017 Elsevier GmbH. All rights reserved.

Associations of antimicrobial use with antimicrobial resistance in Campylobacter coli from grow-finish pigs in Japan.

PubMed

Ozawa, M; Makita, K; Tamura, Y; Asai, T

2012-10-01

To determine associations between antimicrobial use and antimicrobial resistance in Campylobacter coli, 155 isolates were obtained from the feces of apparently healthy grow-finish pigs in Japan. In addition, data on the use of antibiotics collected through the national antimicrobial resistance monitoring system in Japan were used for the analysis. Logistic regression was used to identify risk factors to antimicrobial resistance in C. coli in pigs for the following antimicrobials: ampicillin, dihydrostreptomycin, erythromycin, oxytetracycline, chloramphenicol, and enrofloxacin. The data suggested the involvement of several different mechanisms of resistance selection. The statistical relationships were suggestive of co-selection; use of macrolides was associated with enrofloxacin resistance (OR=2.94; CI(95%): 0.997, 8.68) and use of tetracyclines was associated with chloramphenicol resistance (OR=2.37; CI(95%): 1.08, 5.19). The statistical relationships were suggestive of cross-resistance: use of macrolides was associated with erythromycin resistance (OR=9.36; CI(95%): 2.96, 29.62) and the use of phenicols was associated with chloramphenicol resistance (OR=11.83; CI(95%): 1.41, 99.44). These data showed that the use of antimicrobials in pigs selects for resistance in C. coli within and between classes of antimicrobials. Copyright © 2012 Elsevier B.V. All rights reserved.

Distribution, fate and risk assessment of antibiotics in sewage treatment plants in Hong Kong, South China.

PubMed

Leung, H W; Minh, T B; Murphy, M B; Lam, James C W; So, M K; Martin, Michael; Lam, Paul K S; Richardson, B J

2012-07-01

Occurrence, removal, consumption and environmental risks of sixteen antibiotics were investigated in several sewage treatment plants (STPs) featuring different treatment levels in Hong Kong, China. Cefalexin, ofloxacin and erythromycin-H(2)O were predominant with concentrations of 1020-5640, 142-7900 and 243-4740 ng/L in influent, respectively; their mass loads were comparable to levels reported in urban regions in China and were at the high end of the range reported for western countries. The target antibiotics behaved differently depending on the treatment level employed at the STPs and relatively higher removal efficiencies (>70%) were observed for cefalexin, cefotaxime, amoxicillin, sulfamethoxazole and chloramphenicol during secondary treatment. ß-lactams were especially susceptible to removal via the activated sludge process while macrolides were recalcitrant (<20%) in the dissolved phase. Two fluoroquinolones, ofloxacin (4%) and norfloxacin (52%), differed greatly in their removal efficiencies, probably because of disparities in their pK(a) values which resulted in different sorption behaviour in sludge. Overall antibiotic consumption in Hong Kong was back-calculated based on influent mass flows and compared with available prescription and usage data. This model was verified by a good approximation of 82% and 141% to the predicted consumption of total ofloxacin, but a less accurate estimate was obtained for erythromycin usage. Risk assessment indicated that algae are susceptible to the environmental concentrations of amoxicillin as well as the mixture of the nine detected antibiotics in receiving surface waters. Copyright © 2011 Elsevier Ltd. All rights reserved.

Revisiting the structures of several antibiotics bound to the bacterial ribosome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bulkley, David; Innis, C. Axel; Blaha, Gregor

2010-10-08

The increasing prevalence of antibiotic-resistant pathogens reinforces the need for structures of antibiotic-ribosome complexes that are accurate enough to enable the rational design of novel ribosome-targeting therapeutics. Structures of many antibiotics in complex with both archaeal and eubacterial ribosomes have been determined, yet discrepancies between several of these models have raised the question of whether these differences arise from species-specific variations or from experimental problems. Our structure of chloramphenicol in complex with the 70S ribosome from Thermus thermophilus suggests a model for chloramphenicol bound to the large subunit of the bacterial ribosome that is radically different from the prevailing model.more » Further, our structures of the macrolide antibiotics erythromycin and azithromycin in complex with a bacterial ribosome are indistinguishable from those determined of complexes with the 50S subunit of Haloarcula marismortui, but differ significantly from the models that have been published for 50S subunit complexes of the eubacterium Deinococcus radiodurans. Our structure of the antibiotic telithromycin bound to the T. thermophilus ribosome reveals a lactone ring with a conformation similar to that observed in the H. marismortui and D. radiodurans complexes. However, the alkyl-aryl moiety is oriented differently in all three organisms, and the contacts observed with the T. thermophilus ribosome are consistent with biochemical studies performed on the Escherichia coli ribosome. Thus, our results support a mode of macrolide binding that is largely conserved across species, suggesting that the quality and interpretation of electron density, rather than species specificity, may be responsible for many of the discrepancies between the models.« less

Revisiting the Structures of Several Antibiotics Bound to the Bacterial Ribosome

DOE Office of Scientific and Technical Information (OSTI.GOV)

D Bulkley; C Innis; G Blaha

2011-12-31

The increasing prevalence of antibiotic-resistant pathogens reinforces the need for structures of antibiotic-ribosome complexes that are accurate enough to enable the rational design of novel ribosome-targeting therapeutics. Structures of many antibiotics in complex with both archaeal and eubacterial ribosomes have been determined, yet discrepancies between several of these models have raised the question of whether these differences arise from species-specific variations or from experimental problems. Our structure of chloramphenicol in complex with the 70S ribosome from Thermus thermophilus suggests a model for chloramphenicol bound to the large subunit of the bacterial ribosome that is radically different from the prevailing model.more » Further, our structures of the macrolide antibiotics erythromycin and azithromycin in complex with a bacterial ribosome are indistinguishable from those determined of complexes with the 50S subunit of Haloarcula marismortui, but differ significantly from the models that have been published for 50S subunit complexes of the eubacterium Deinococcus radiodurans. Our structure of the antibiotic telithromycin bound to the T. thermophilus ribosome reveals a lactone ring with a conformation similar to that observed in the H. marismortui and D. radiodurans complexes. However, the alkyl-aryl moiety is oriented differently in all three organisms, and the contacts observed with the T. thermophilus ribosome are consistent with biochemical studies performed on the Escherichia coli ribosome. Thus, our results support a mode of macrolide binding that is largely conserved across species, suggesting that the quality and interpretation of electron density, rather than species specificity, may be responsible for many of the discrepancies between the models.« less

Influence of livestock activities on residue antibiotic levels of rivers in Hong Kong.

PubMed

Selvam, Ammaiyappan; Kwok, Katrina; Chen, Yumei; Cheung, Anna; Leung, Kelvin S Y; Wong, Jonathan W C

2017-04-01

Occurrence of 10 antibiotics in the Yuen Long (YLR), Kam Tin (KTR), and Shing Mun (SMR) rivers of Hong Kong and possible influence of livestock activities on the concentrations of antibiotics were investigated. Tetracycline (30-497 ng/L), sulfadiazine (2-80 ng/L), sulfamethoxazole (2-152 ng/L), ofloxacin (5-227 ng/L), and erythromycin (1-315 ng/L) were detected in all the three rivers; chlortetracycline (23-227 ng/L), oxytetracycline (7-104 ng/L), ciprofloxacin (12-68 ng/L), and roxithromycin (1-105 ng/L) were detected in YLR and KTR, whereas norfloxacin (3-34 ng/L) was detected in KTR only. Significant correlation between livestock population and antibiotic contamination was observed in YLR only, indicating the influences of other sources in KTR and SMR. Among the antibiotics, significant correlation was observed between tetracyclines and sulfonamides indicating the major influence of livestock farms, whereas tetracyclines/sulfonamides were negatively correlated with fluoroquinolones/macrolides implying the differential origin of the latter class of antibiotics. Water quality of KTR and YLR were highly influenced by the non-point source pollutions, while of SMR was relatively good. Particularly, Escherichia coli populations of the YLR and KTR were 3-4 logs higher than those of the SMR indicating the involvement of livestock farms and sewerages. Good correlation between tetracyclines (TCs)/sulfonamides (SAs) and number of livestock farms and a negative correlation between TCs/SAs and fluoroquinolones (FQs)/macrolides (MLs) could be used as an indicator to trace the possible source of pollution.

Macrolide drug interactions: an update.

PubMed

Pai, M P; Graci, D M; Amsden, G W

2000-04-01

To describe the current drug interaction profiles for the commonly used macrolides in the US and Europe, and to comment on the clinical impact of these interactions. A MEDLINE search (1975-1998) was performed to identify all pertinent studies, review articles, and case reports. When appropriate information was not available in the literature, data were obtained from the product manufacturers. All available data were reviewed to provide an unbiased account of possible drug interactions. Data for some of the interactions were not available from the literature, but were available from abstracts or company-supplied materials. Although the data were not always explicit, the best attempt was made to deliver pertinent information that clinical practitioners would need to formulate practice opinions. When more in-depth information was supplied in the form of a review or study report, a thorough explanation of pertinent methodology was supplied. Several clinically significant drug interactions have been identified since the approval of erythromycin. These interactions usually were related to the inhibition of the cytochrome P450 enzyme systems, which are responsible for the metabolism of many drugs. The decreased metabolism by the macrolides has in some instances resulted in potentially severe adverse events. The development and marketing of newer macrolides are hoped to improve the drug interaction profile associated with this class. However, this has produced variable success. Some of the newer macrolides demonstrated an interaction profile similar to that of erythromycin; others have improved profiles. The most success in avoiding drug interactions related to the inhibition of cytochrome P450 has been through the development of the azalide subclass, of which azithromycin is the first and only to be marketed. Azithromycin has not been demonstrated to inhibit the cytochrome P450 system in studies using a human liver microsome model, and to date has produced none of the classic drug interactions characteristic of the macrolides. Most of the available data regarding macrolide drug interactions are from studies in healthy volunteers and case reports. These data suggest that clarithromycin appears to have an interaction profile similar to that of erythromycin. Given this similarity, it is important to consider the interaction profile of clarithromycin when using erythromycin. This is especially necessary as funds for further studies of a medication available in generic form (e.g., erythromycin) are limited. Azithromycin has produced few clinically significant interactions with any agent cleared through the cytochrome P450 enzyme system. Although the available data are promising, the final test should come from studies conducted in patients who are taking potentially interacting compounds on a chronic basis.

Macrolide antibiotics differentially influence human HepG2 cytotoxicity and modulate intrinsic/extrinsic apoptotic pathways in rat hepatocellular carcinoma model.

PubMed

Abdel-Hamid, Nagwa I; El-Azab, Mona F; Moustafa, Yasser M

2017-04-01

This study was designed to examine the potential antitumor effect of some macrolides: clarithromycin, azithromycin, and erythromycin on chemically induced hepatocellular carcinoma (HCC) in rats and on human hepatoma cells (HepG2) as well. The possible underlying antiapoptotic mechanisms were investigated. Antiproliferative activity was assessed in HepG2 using Sulforhodamine-B staining method. In vivo, HCC was induced in rats by initiation-selection-promotion protocol using diethylnitrosamine (200 mg/kg, single i.p. injection)/2-acetylaminofluorene (0.03% w/w supplemented-diet for 2 weeks)/carbon tetrachloride (2 ml/kg diluted in corn oil 1:1, single intra-gastric dose)/phenobarbitone sodium (0.05% w/w supplemented-diet for 28 weeks). Macrolides were administered once daily starting from the 3rd week until the 17th week at a dose of 100 mg/kg in the current 33-week study period. Clarithromycin showed a higher efficacy in the suppression of HepG2 proliferation with lower IC50 value than doxorubicin. In vivo, chemically-induced HCC rat model proved that clarithromycin suppressed HCC via induction of apoptosis through up-regulation of both extrinsic/intrinsic apoptotic pathways' proteins (TNFR1, cleaved caspase-3, and Bax with an increased Bax/Bcl-2 ratio) along with MMP-9 normalization. Similarly, azithromycin demonstrated antitumorigenic effect through both apoptotic pathways, however, to a lesser extent compared to clarithromycin. Moreover, azithromycin suppressed the proliferation of HepG2, however, at a higher IC50 than doxorubicin. Surprisingly, erythromycin increased HepG2 proliferation in vitro, along with worsened tumorigenic effect of the carcinogenic agents in the in vivo study with ineffective apoptotic outcome. Some macrolides represent potential antitumor agents; however, this evident anticancer activity is an individual effect rather than a group effect and involves modulation of both intrinsic and extrinsic apoptotic pathways.

Fate of antibiotics from hospital and domestic sources in a sewage network.

PubMed

Dinh, QuocTuc; Moreau-Guigon, Elodie; Labadie, Pierre; Alliot, Fabrice; Teil, Marie-Jeanne; Blanchard, Martine; Eurin, Joelle; Chevreuil, Marc

2017-01-01

Investigation of domestic and hospital effluents in a sewage system of an elementary watershed showed that antibiotics belonging to eight classes were present with concentrations ranging from

Azithromycin and erythromycin ameliorate the extent of colonic damage induced by acetic acid in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mahgoub, Afaf; El-Medany, Azza; Mustafa, Ali

2005-05-15

Ulcerative colitis is a common inflammatory bowel disease (IBD) of unknown etiology. Recent studies have revealed the role of some microorganisms in the initiation and perpetuation of IBD. The role of antibiotics in the possible modulation of colon inflammation is still uncertain. In this study, we evaluated the effects of two macrolides, namely azithromycin and erythromycin, at different doses on the extent and severity of ulcerative colitis caused by intracolonic administration of 3% acetic acid in rats. The lesions and the inflammatory response were assessed by histology and measurement of myeloperoxidase (MPO) activity, nitric oxide synthetase (NOS) and tumor necrosismore » factor alpha (TNF{alpha}) in colonic tissues. Inflammation following acetic acid instillation was characterized by oedema, diffuse inflammatory cell infiltration and necrosis. Increase in MPO, NOS and TNF{alpha} was detected in the colonic tissues. Administration of either azithromycin or erythromycin at different dosage (10, 20 and 40 mg/kg orally, daily for 5 consecutive days) significantly (P < 0.05) reduced the colonic damage, MPO and NOS activities as well as TNF{alpha} level. This reduction was highly significant with azithromycin when given at a dose of 40 mg/kg. It is concluded that azithromycin and erythromycin may have a beneficial therapeutic role in ulcerative colitis.« less

Antimicrobial resistance among lower respiratory tract isolates of Streptococcus pneumoniae: results of a 1992-93 western Europe and USA collaborative surveillance study. The Alexander Project Collaborative Group.

PubMed

Goldstein, F W; Acar, J F

1996-07-01

One thousand, eight hundred and fifty-six Streptococcus pneumoniae strains, collected in 1992 and 1993 from 15 centres in Western Europe and USA were tested for susceptibility to 16 antibiotics. The overall resistance to penicillin was 23% (range 6-54%), with the highest prevalences in Madrid, Barcelona, Toulouse and Cleveland. Seven centres reported low-level penicillin resistance only. Amoxycillin was more active than ceftriaxone against strains with intermediate resistance to penicillin, and at least four-fold more active than cefuroxime; cefaclor and cefixime had poor activity. Against penicillin-resistant strains, ceftriaxone was slightly more active than amoxycillin, cefuroxime exhibited borderline activity and cefixime and cefaclor were inactive. Ten strains fully susceptible to penicillin had MICs of ceftriaxone > or = 0.1 mg/L; this may represent a first step towards the development of cephalosporin resistance. With the exception of fluoroquinolones, resistance to non-beta-lactam antibiotics (chloramphenicol, doxycycline, co-trimoxazole, erythromycin, clarithromycin and azithromycin) was considerably higher in penicillin-resistant strains compared with penicillin-susceptible isolates. Erythromycin-resistant isolates were also resistant to the other macrolides tested.

Selective labelling and eradication of antibiotic-tolerant bacterial populations in Pseudomonas aeruginosa biofilms

PubMed Central

Chua, Song Lin; Yam, Joey Kuok Hoong; Hao, Piliang; Adav, Sunil S.; Salido, May Margarette; Liu, Yang; Givskov, Michael; Sze, Siu Kwan; Tolker-Nielsen, Tim; Yang, Liang

2016-01-01

Drug resistance and tolerance greatly diminish the therapeutic potential of antibiotics against pathogens. Antibiotic tolerance by bacterial biofilms often leads to persistent infections, but its mechanisms are unclear. Here we use a proteomics approach, pulsed stable isotope labelling with amino acids (pulsed-SILAC), to quantify newly expressed proteins in colistin-tolerant subpopulations of Pseudomonas aeruginosa biofilms (colistin is a ‘last-resort' antibiotic against multidrug-resistant Gram-negative pathogens). Migration is essential for the formation of colistin-tolerant biofilm subpopulations, with colistin-tolerant cells using type IV pili to migrate onto the top of the colistin-killed biofilm. The colistin-tolerant cells employ quorum sensing (QS) to initiate the formation of new colistin-tolerant subpopulations, highlighting multicellular behaviour in antibiotic tolerance development. The macrolide erythromycin, which has been previously shown to inhibit the motility and QS of P. aeruginosa, boosts biofilm eradication by colistin. Our work provides insights on the mechanisms underlying the formation of antibiotic-tolerant populations in bacterial biofilms and indicates research avenues for designing more efficient treatments against biofilm-associated infections. PMID:26892159

Selective labelling and eradication of antibiotic-tolerant bacterial populations in Pseudomonas aeruginosa biofilms.

PubMed

Chua, Song Lin; Yam, Joey Kuok Hoong; Hao, Piliang; Adav, Sunil S; Salido, May Margarette; Liu, Yang; Givskov, Michael; Sze, Siu Kwan; Tolker-Nielsen, Tim; Yang, Liang

2016-02-19

Drug resistance and tolerance greatly diminish the therapeutic potential of antibiotics against pathogens. Antibiotic tolerance by bacterial biofilms often leads to persistent infections, but its mechanisms are unclear. Here we use a proteomics approach, pulsed stable isotope labelling with amino acids (pulsed-SILAC), to quantify newly expressed proteins in colistin-tolerant subpopulations of Pseudomonas aeruginosa biofilms (colistin is a 'last-resort' antibiotic against multidrug-resistant Gram-negative pathogens). Migration is essential for the formation of colistin-tolerant biofilm subpopulations, with colistin-tolerant cells using type IV pili to migrate onto the top of the colistin-killed biofilm. The colistin-tolerant cells employ quorum sensing (QS) to initiate the formation of new colistin-tolerant subpopulations, highlighting multicellular behaviour in antibiotic tolerance development. The macrolide erythromycin, which has been previously shown to inhibit the motility and QS of P. aeruginosa, boosts biofilm eradication by colistin. Our work provides insights on the mechanisms underlying the formation of antibiotic-tolerant populations in bacterial biofilms and indicates research avenues for designing more efficient treatments against biofilm-associated infections.

Inducible clindamycin and methicillin resistant Staphylococcus aureus in a tertiary care hospital, Kathmandu, Nepal.

PubMed

Adhikari, R P; Shrestha, S; Barakoti, A; Amatya, R

2017-07-11

Staphylococcus aureus, an important nosocomial pathogen, is frequently associated with infections in human. The management of the infections by it especially methicillin resistant ones is often difficult because methicillin resistant S. aureus is usually resistant to multiple antibiotics. Macrolide-lincosamide streptogramin B family of antibiotics is commonly used to treat such infections as an alternative to vancomycin. This study was conducted over the period of one and half year from November 2013-April 2015 in Microbiology laboratory of Nepal Medical College and Teaching Hospital, Kathmandu, Nepal to find the incidence of different phenotypes of MLS B resistance among S. aureus from clinical samples and their association with methicillin resistance. Two hundred seventy isolates of S. aureus were included in the study. Methicillin resistance was detected by cefoxitin disc diffusion method and inducible clindamycin resistance by erythromycin and clindamycin disc approximation test (D-test). Of the 270 clinical isolates of S. aureus, 25.1% (68/270) were MRSA. Erythromycin and clindamycin resistance was seen in 54.4% (147/270) and 41.8% (113/270) isolates respectively. Resistance to erythromycin and clindamycin were higher in MRSA as compared to MSSA (erythromycin-resistance: 88.2% Vs 39.1% and clindamycin-resistance: 79.4% Vs 41.8%). The overall prevalence of i MLS B and c MLS B phenotype was 11.48% (31/270) and 29.25% (79/270) respectively. Both i MLS B and c MLS B phenotypes predominated in MRSA strains. Detection rate of MRSA in our study shows the necessity to improve in healthcare practices and to formulate new policy for the control of MRSA infections. Clindamycin resistance in the form of i MLS B and c MLS B especially among MRSA emphasizes the need of D-test to be performed routinely in our set up while using clindamycin as an alternative choice to anti-staphylococcal antibiotics like vancomycin and linezolid in the treatment of staphylococcal infections.

Structure and Function of the Macrolide Biosensor Protein, MphR(A), with and without Erythromycin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Jianting; Sagar, Vatsala; Smolinsky, Adam

2009-09-02

The regulatory protein MphR(A) has recently seen extensive use in synthetic biological applications, such as metabolite sensing and exogenous control of gene expression. This protein negatively regulates the expression of a macrolide 2{prime}-phosphotransferase I resistance gene (mphA) via binding to a 35-bp DNA operator upstream of the start codon and is de-repressed by the presence of erythromycin. Here, we present the refined crystal structure of the MphR(A) protein free of erythromycin and that of the MphR(A) protein with bound erythromycin at 2.00- and 1.76-{angstrom} resolutions, respectively. We also studied the DNA binding properties of the protein and identified mutants ofmore » MphR(A) that are defective in gene repression and ligand binding in a cell-based reporter assay. The combination of these two structures illustrates the molecular basis of erythromycin-induced gene expression and provides a framework for additional applied uses of this protein in the isolation and engineered biosynthesis of polyketide natural products.« less

Enrofloxacin and Macrolides Alone or in Combination with Rifampicin as Antimicrobial Treatment in a Bovine Model of Acute Chlamydia psittaci Infection

PubMed Central

Prohl, Annette; Lohr, Markus; Ostermann, Carola; Liebler-Tenorio, Elisabeth; Berndt, Angela; Schroedl, Wieland; Rothe, Michael; Schubert, Evelyn; Sachse, Konrad; Reinhold, Petra

2015-01-01

Chlamydia psittaci is a zoonotic bacterium with a wide host range that can cause respiratory disease in humans and cattle. In the present study, effects of treatment with macrolides and quinolones applied alone or in combination with rifampicin were tested in a previously established bovine model of respiratory C. psittaci infection. Fifty animals were inoculated intrabronchially at the age of 6–8 weeks. Seven served as untreated controls, the others were assigned to seven treatment groups: (i) rifampicin, (ii) enrofloxacin, (iii) enrofloxacin + rifampicin, (iv) azithromycin, (v) azithromycin + rifampicin, (vi) erythromycin, and (vii) erythromycin + rifampicin. Treatment started 30 hours after inoculation and continued until 14 days after inoculation (dpi), when all animals were necropsied. The infection was successful in all animals and sufficient antibiotic levels were detected in blood plasma and tissue of the treated animals. Reisolation of the pathogen was achieved more often from untreated animals than from other groups. Nevertheless, pathogen detection by PCR was possible to the same extent in all animals and there were no significant differences between treated and untreated animals in terms of local (i.e. cell count and differentiation of BALF-cells) and systemic inflammation (i.e. white blood cells and concentration of acute phase protein LBP), clinical signs, and pathological findings at necropsy. Regardless of the reduced reisolation rate in treated animals, the treatment of experimentally induced respiratory C. psittaci infection with enrofloxacin, azithromycin or erythromycin alone or in combination with rifampicin was without obvious benefit for the host, since no significant differences in clinical and pathological findings or inflammatory parameters were detected and all animals recovered clinically within two weeks. PMID:25768665

Occurrence and risk assessment of antibiotics in surface water and groundwater from different depths of aquifers: A case study at Jianghan Plain, central China.

PubMed

Yao, Linlin; Wang, Yanxin; Tong, Lei; Deng, Yamin; Li, Yonggang; Gan, Yiqun; Guo, Wei; Dong, Chuangju; Duan, Yanhua; Zhao, Ke

2017-01-01

The occurrence of 14 antibiotics (fluoroquinolones, tetracyclines, macrolides and sulfonamides) in groundwater and surface water at Jianghan Plain was investigated during three seasons. The total concentrations of target compounds in the water samples were higher in spring than those in summer and winter. Erythromycin was the predominant antibiotic in surface water samples with an average value of 1.60μg/L, 0.772μg/L and 0.546μg/L respectively in spring, summer and winter. In groundwater samples, fluoroquinolones and tetracyclines accounted for the dominant proportion of total antibiotic residues. The vertical distributions of total antibiotics in groundwater samples from three different depths boreholes (10m, 25m, and 50m) exhibited irregular fluctuations. Consistently decreasing of antibiotic residues with increasing of depth was observed in four (G01, G02, G03 and G05) groundwater sampling sites over three seasons. However, at the sampling sites G07 and G08, the pronounced high concentrations of total antibiotic residues were detected in water samples from 50m deep boreholes instead of those at upper aquifer in winter sampling campaign, with the total concentrations of 0.201μg/L and 0.100μg/L respectively. The environmental risks posed by the 14 antibiotics were assessed by using the methods of risk quotient and mixture risk quotient for algae, daphnids and fish in surface water and groundwater. The results suggested that algae might be the aquatic organism most sensitive to the antibiotics, with the highest risk levels posed by erythromycin in surface water and by ciprofloxacin in groundwater among the 14 antibiotics. In addition, the comparison between detected antibiotics in groundwater samples and the reported effective concentrations of antibiotics on denitrification by denitrifying bacteria, indicating this biogeochemical process driven by microorganisms won't be inhibitory influenced by the antibiotic residues in groundwater. Copyright © 2016. Published by Elsevier Inc.

Macrolides for diffuse panbronchiolitis.

PubMed

Yang, Ming; Dong, Bi Rong; Lu, Jing; Lin, Xiufang; Wu, Hong Mei

2013-02-28

Diffuse panbronchiolitis (DPB) is a chronic airways disease predominantly affecting East Asians. Macrolides, a class of antibiotics, have been used as the main treatment for DPB, based on evidence from retrospective and non-randomised studies. To assess the efficacy and safety of macrolides for DPB. We searched CENTRAL 2012, Issue 7, MEDLINE (1966 to July week 2, 2012), EMBASE (1974 to July 2012), Chinese Biomedical Literature Database (CBM) (1978 to July 2012), China National Knowledge Infrastructure (CNKI) (1974 to July 2012), KoreaMed (1997 to July 2012) and Database of Japana Centra Revuo Medicina (1983 to July 2012). Randomised controlled trials (RCTs) or quasi-RCTs assessing the effect of macrolides for DPB. Two review authors independently assessed study quality and subsequent risk of bias according to the Cochrane Collaboration's tool for assessing risk of bias. The primary outcomes were five-year survival rate, lung function and clinical response. We used risk ratios (RR) for individual trial results in the data analysis and measured all outcomes with 95% confidence intervals (CI). Only one RCT (19 participants) with significant methodological limitations was included in this review. It found that the computerised tomography images of all participants treated with a long-term, low-dose macrolide (erythromycin) improved from baseline, while the images of 71.4% of participants in the control group (with no treatment) worsened and 28.6% remained unchanged. Adverse effects were not reported. There is little evidence for macrolides in the treatment of DPB. We are therefore unable to make any new recommendations. It may be reasonable to use low-dose macrolides soon after diagnosis is made and to continue this treatment for at least six months, according to current guidelines.

Macrolides for diffuse panbronchiolitis.

PubMed

Yang, Ming; Dong, Bi Rong; Lu, Jing; Lin, Xiufang; Wu, Hong Mei

2010-12-08

Diffuse panbronchiolitis (DPB) is a chronic airways disease predominantly affecting East Asians. Macrolides, a class of antibiotics, have been used as the main treatment for DPB, based on evidence from retrospective and non-randomised studies. To assess the efficacy and safety of macrolides for DPB. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, issue 1), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to April 2010), EMBASE (1974 to April 2010), Chinese Biomedical Literature Database (CBM) (1978 to April 2010), China National Knowledge Infrastructure (CNKI) (1974 to April 2010), KoreaMed (1997 to April 2010) and Database of Japana Centra Revuo Medicina (1983 to April 2010). Randomised controlled trials (RCTs) or quasi-RCTs assessing the effect of macrolides for DPB. Two review authors independently assessed study quality and subsequent risk of bias according to the Cochrane Collaboration's tool for assessing risk of bias. The primary outcomes were five-year survival rate, lung function and clinical response. We used risk ratios (RR) for individual trial results in the data analysis and measured all outcomes with 95% confidence intervals (CI). Only one RCT (19 participants) with significant methodological limitations was included in this review. It found that the computerised tomography images of all participants treated with a long-term, low-dose macrolide (erythromycin) improved from baseline, while the images of 71.4% of participants in the control group (with no treatment) worsened and 28.6% remained unchanged. Adverse effects were not reported. There is little evidence for macrolides in the treatment of DPB. We are therefore unable to make any new recommendations. It may be reasonable to use low-dose macrolides soon after diagnosis is made and to continue this treatment for at least six months, according to current guidelines.

Macrolides for diffuse panbronchiolitis.

PubMed

Lin, Xiufang; Lu, Jing; Yang, Ming; Dong, Bi Rong; Wu, Hong Mei

2015-01-25

Diffuse panbronchiolitis (DPB) is a chronic airways disease predominantly affecting East Asians. Macrolides, a class of antibiotics, have been used as the main treatment for DPB, based on evidence from retrospective and non-randomised studies. To assess the efficacy and safety of macrolides for DPB. We searched CENTRAL (2014, Issue 6), MEDLINE (1966 to July week 1, 2014), EMBASE (1974 to July 2014), Chinese Biomedical Literature Database (CBM) (1978 to July 2014), China National Knowledge Infrastructure (CNKI) (1974 to July 2014), KoreaMed (1997 to July 2014) and Database of Japana Centra Revuo Medicina (1983 to July 2014). Randomised controlled trials (RCTs) or quasi-RCTs assessing the effect of macrolides for DPB. Two review authors independently assessed study quality and subsequent risk of bias according to The Cochrane Collaboration's tool for assessing risk of bias. The primary outcomes were five-year survival rate, lung function and clinical response. We used risk ratios (RR) for individual trial results in the data analysis and measured all outcomes with 95% confidence intervals (CI). Only one RCT (19 participants) with significant methodological limitations was included in this review. It found that the computerised tomography images of all participants treated with a long-term, low-dose macrolide (erythromycin) improved from baseline, while the images of 71.4% of participants in the control group (with no treatment) worsened and 28.6% remained unchanged. Adverse effects were not reported. This review was previously published in 2010 and 2013. For this 2014 update, we identified no new trials for inclusion or exclusion. There is little evidence for macrolides in the treatment of DPB. We are therefore unable to make any new recommendations. It may be reasonable to use low-dose macrolides soon after diagnosis is made and to continue this treatment for at least six months, according to current guidelines.

Recent advances in the field of 16-membered macrolide antibiotics.

PubMed

Cui, W; Ma, S

2011-10-01

The continuing emergence of bacterial resistance has provided an incentive for recent intensified research on macrolide antibiotics. Belonging to the macrolide family, 16-membered macrolides also experience a renewed interest in further exploration. The medicinal potential of 16-membered macrolides in search for new antibacterials stems from some advantages over 14-membered macrolides, such as gastrointestinal tolerability, structural flexibility, and lack of inducible resistance. Thus, compared with abundant articles on various 14-membered macrolide derivatives in the literature, this review will highlight some representative 16-membered macrolide antibiotics and their recently discovered analogs. Furthermore, the action and resistance mechanisms of 16-membered macrolide antibiotics will be elucidated as well to assist the drug design.

Interlaboratory study of a liquid chromatography method for erythromycin: determination of uncertainty.

PubMed

Dehouck, P; Vander Heyden, Y; Smeyers-Verbeke, J; Massart, D L; Marini, R D; Chiap, P; Hubert, Ph; Crommen, J; Van de Wauw, W; De Beer, J; Cox, R; Mathieu, G; Reepmeyer, J C; Voigt, B; Estevenon, O; Nicolas, A; Van Schepdael, A; Adams, E; Hoogmartens, J

2003-08-22

Erythromycin is a mixture of macrolide antibiotics produced by Saccharopolyspora erythreas during fermentation. A new method for the analysis of erythromycin by liquid chromatography has previously been developed. It makes use of an Astec C18 polymeric column. After validation in one laboratory, the method was now validated in an interlaboratory study. Validation studies are commonly used to test the fitness of the analytical method prior to its use for routine quality testing. The data derived in the interlaboratory study can be used to make an uncertainty statement as well. The relationship between validation and uncertainty statement is not clear for many analysts and there is a need to show how the existing data, derived during validation, can be used in practice. Eight laboratories participated in this interlaboratory study. The set-up allowed the determination of the repeatability variance, s(2)r and the between-laboratory variance, s(2)L. Combination of s(2)r and s(2)L results in the reproducibility variance s(2)R. It has been shown how these data can be used in future by a single laboratory that wants to make an uncertainty statement concerning the same analysis.

Comparison of the effect of a single dose of erythromycin with pantoprazole on gastric content volume and acidity in elective general surgery patients

PubMed Central

Bhatia, Nidhi; Palta, Sanjeev; Arora, Kanika

2011-01-01

Introduction: Pulmonary aspiration of gastric contents remains one of the most feared complications of anesthesia. A gastric pH of 2.5 or less and a volume of 25 ml (0.4 ml/kg body weight) or more in average adult patients are considered critical factors for the development of pulmonary damage in adults. Materials and Methods: This study compared the efficacy of a single oral dose of erythromycin (a macrolide antibiotic) with oral pantoprazole (a proton pump inhibitor) on pre-operative gastric fluid volume and pH in a prospective, randomized, double-blind controlled fashion in 80 adult patients (of ASA physical status I and II) planned for elective surgery under general anesthesia. Patients were divided into two groups of 40 patients each. The pantoprazole group (Group I) received oral pantoprazole 40 mg and the erythromycin group (Group II) received oral erythromycin 250 mg at least 1 h prior to the induction of anesthesia. After tracheal intubation, gastric fluid was aspirated via a Salem Sump tube and its volume and pH were measured. Results: Although both erythromycin and pantoprazole decreased the gastric fluid volume to a similar extent, the decrease in gastric fluid acidity by pantoprazole was significantly greater than that by erythromycin. The proportion of patients at risk of pulmonary aspiration according to traditional criteria, i.e. pH ≤2.5 and volume ≥25ml, was lower in the pantoprazole group. Conclusion: Administration of pantoprazole was found to be more useful than a sub-therapeutic dose of erythromycin in decreasing both volume and acidity of gastric content. PMID:21772679

Effect of in-feed administration and withdrawal of tylosin phosphate on antibiotic resistance in enterococci isolated from feedlot steers

PubMed Central

Beukers, Alicia G.; Zaheer, Rahat; Cook, Shaun R.; Stanford, Kim; Chaves, Alexandre V.; Ward, Michael P.; McAllister, Tim A.

2015-01-01

Tylosin phosphate is a macrolide commonly administered to cattle in North America for the control of liver abscesses. This study investigated the effect of in-feed administration of tylosin phosphate to cattle at subtherapeutic levels and its subsequent withdrawal on macrolide resistance using enterococci as an indicator bacterium. Fecal samples were collected from steers that received no antibiotics and steers administered tylosin phosphate (11 ppm) in-feed for 197 days and withdrawn 28 days before slaughter. Enterococcus species isolated from fecal samples were identified through sequencing the groES-EL intergenic spacer region and subject to antimicrobial susceptibility testing, identification of resistance determinants and pulsed-field gel electrophoresis profiling. Tylosin increased (P < 0.05) the proportion of eryR and tylR enterococci within the population. Just prior to its removal, the proportion of eryR and tylR resistant enterococci began decreasing and continued to decrease after tylosin was withdrawn from the diet until there was no difference (P > 0.05) between treatments on d 225. This suggests that antibiotic withdrawal prior to slaughter contributes to a reduction in the proportion of macrolide resistant enterococci entering the food chain. Among the 504 enterococci isolates characterized, Enterococcus hirae was found to predominate (n = 431), followed by Enterococcus villorum (n = 32), Enterococcus faecium (n = 21), Enterococcus durans (n = 7), Enterococcus casseliflavus (n = 4), Enterococcus mundtii (n = 4), Enterococcus gallinarum (n = 3), Enterococcus faecalis (n = 1), and Enterococcus thailandicus (n = 1). The diversity of enterococci was greater in steers at arrival than at exit from the feedlot. Erythromycin resistant isolates harbored the erm(B) and/or msrC gene. Similar PFGE profiles of eryR E. hirae pre- and post-antibiotic treatment suggest that increased abundance of eryR enterococci after administration of tylosin phosphate reflects selection for strains that were already present within the gastrointestinal tract of cattle at arrival. PMID:26074889

A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest

NASA Astrophysics Data System (ADS)

Arenz, Stefan; Bock, Lars V.; Graf, Michael; Innis, C. Axel; Beckmann, Roland; Grubmüller, Helmut; Vaiana, Andrea C.; Wilson, Daniel N.

2016-07-01

Nascent polypeptides can induce ribosome stalling, regulating downstream genes. Stalling of ErmBL peptide translation in the presence of the macrolide antibiotic erythromycin leads to resistance in Streptococcus sanguis. To reveal this stalling mechanism we obtained 3.6-Å-resolution cryo-EM structures of ErmBL-stalled ribosomes with erythromycin. The nascent peptide adopts an unusual conformation with the C-terminal Asp10 side chain in a previously unseen rotated position. Together with molecular dynamics simulations, the structures indicate that peptide-bond formation is inhibited by displacement of the peptidyl-tRNA A76 ribose from its canonical position, and by non-productive interactions of the A-tRNA Lys11 side chain with the A-site crevice. These two effects combine to perturb peptide-bond formation by increasing the distance between the attacking Lys11 amine and the Asp10 carbonyl carbon. The interplay between drug, peptide and ribosome uncovered here also provides insight into the fundamental mechanism of peptide-bond formation.

High-throughput method for macrolides and lincosamides antibiotics residues analysis in milk and muscle using a simple liquid-liquid extraction technique and liquid chromatography-electrospray-tandem mass spectrometry analysis (LC-MS/MS).

PubMed

Jank, Louise; Martins, Magda Targa; Arsand, Juliana Bazzan; Campos Motta, Tanara Magalhães; Hoff, Rodrigo Barcellos; Barreto, Fabiano; Pizzolato, Tânia Mara

2015-11-01

A fast and simple method for residue analysis of the antibiotics classes of macrolides (erythromycin, azithromycin, tylosin, tilmicosin and spiramycin) and lincosamides (lincomycin and clindamycin) was developed and validated for cattle, swine and chicken muscle and for bovine milk. Sample preparation consists in a liquid-liquid extraction (LLE) with acetonitrile, followed by liquid chromatography-electrospray-tandem mass spectrometry analysis (LC-ESI-MS/MS), without the need of any additional clean-up steps. Chromatographic separation was achieved using a C18 column and a mobile phase composed by acidified acetonitrile and water. The method was fully validated according the criteria of the Commission Decision 2002/657/EC. Validation parameters such as limit of detection, limit of quantification, linearity, accuracy, repeatability, specificity, reproducibility, decision limit (CCα) and detection capability (CCβ) were evaluated. All calculated values met the established criteria. Reproducibility values, expressed as coefficient of variation, were all lower than 19.1%. Recoveries range from 60% to 107%. Limits of detection were from 5 to 25 µg kg(-1).The present method is able to be applied in routine analysis, with adequate time of analysis, low cost and a simple sample preparation protocol. Copyright © 2015. Published by Elsevier B.V.

Antibiotic-resistant fecal bacteria, antibiotics, and mercury in surface waters of Oakland County, Michigan, 2005-2006

USGS Publications Warehouse

Fogarty, Lisa R.; Duris, Joseph W.; Crowley, Suzanne L.; Hardigan, Nicole

2007-01-01

Water samples collected from 20 stream sites in Oakland and Macomb Counties, Mich., were analyzed to learn more about the occurrence of cephalosporin-resistant Escherichia coli (E. coli) and vancomycin-resistant enterococci (VRE) and the co-occurrence of antibiotics and mercury in area streams. Fecal indicator bacteria concentrations exceeded the Michigan recreational water-quality standard of 300 E. coli colony forming units (CFU) per 100 milliliters of water in 19 of 35 stream-water samples collected in Oakland County. A gene commonly associated with enterococci from humans was detected in samples from Paint Creek at Rochester and Evans Ditch at Southfield, indicating that human fecal waste is a possible source of fecal contamination at these sites. E. coli resistant to the cephalosporin antibiotics (cefoxitin and/ or ceftriaxone) were found at all sites on at least one occasion. The highest percentages of E. coli isolates resistant to cefoxitin and ceftriaxone were 71 percent (Clinton River at Auburn Hills) and 19 percent (Sashabaw Creek near Drayton Plains), respectively. Cephalosporin-resistant E. coli was detected more frequently in samples from intensively urbanized or industrialized areas than in samples from less urbanized areas. VRE were not detected in any sample collected in this study. Multiple antibiotics (azithromycin, erythromycin, ofloxacin, sulfamethoxazole, and trimethoprim) were detected in water samples from the Clinton River at Auburn Hills, and tylosin (an antibiotic used in veterinary medicine and livestock production that belongs to the macrolide group, along with erythromycin) was detected in one water sample from Paint Creek at Rochester. Concentrations of total mercury were as high as 19.8 nanograms per liter (Evans Ditch at Southfield). There was no relation among percentage of antibiotic-resistant bacteria and measured concentrations of antibiotics or mercury in the water. Genetic elements capable of exchanging multiple antibiotic-resistance genes (class I integrons) were detected in several samples, indicating that the resistance carried by these organisms may be transferable to other bacteria, including disease-causing bacteria.

Metagenomic profiles of antibiotic resistance genes (ARGs) between human impacted estuary and deep ocean sediments.

PubMed

Chen, Baowei; Yang, Ying; Liang, Ximei; Yu, Ke; Zhang, Tong; Li, Xiangdong

2013-11-19

Knowledge of the origins and dissemination of antibiotic resistance genes (ARGs) is essential for understanding modern resistomes in the environment. The mechanisms of the dissemination of ARGs can be revealed through comparative studies on the metagenomic profiling of ARGs between relatively pristine and human-impacted environments. The deep ocean bed of the South China Sea (SCS) is considered to be largely devoid of anthropogenic impacts, while the Pearl River Estuary (PRE) in south China has been highly impacted by intensive human activities. Commonly used antibiotics (sulfamethazine, norfloxacin, ofloxacin, tetracycline, and erythromycin) have been detected through chemical analysis in the PRE sediments, but not in the SCS sediments. In the relatively pristine SCS sediments, the most prevalent and abundant ARGs are those related to resistance to macrolides and polypeptides, with efflux pumps as the predominant mechanism. In the contaminated PRE sediments, the typical ARG profiles suggest a prevailing resistance to antibiotics commonly used in human health and animal farming (including sulfonamides, fluoroquinolones, and aminoglycosides), and higher diversity in both genotype and resistance mechanism than those in the SCS. In particular, antibiotic inactivation significantly contributed to the resistance to aminoglycosides, β-lactams, and macrolides observed in the PRE sediments. There was a significant correlation in the levels of abundance of ARGs and those of mobile genetic elements (including integrons and plasmids), which serve as carriers in the dissemination of ARGs in the aquatic environment. The metagenomic results from the current study support the view that ARGs naturally originate in pristine environments, while human activities accelerate the dissemination of ARGs so that microbes would be able to tolerate selective environmental stress in response to anthropogenic impacts.

Results from the Survey of Antibiotic Resistance (SOAR) 2011–13 in the Gulf States

PubMed Central

Jamsheer, A.; Rafay, A. M.; Daoud, Z.; Morrissey, I.; Torumkuney, D.

2016-01-01

Objectives To provide surveillance data on the susceptibility of community-acquired respiratory tract isolates from four Gulf and Near East countries from 2011 to 2013. Methods MICs were determined using Etests® for all antibiotics evaluated except erythromycin, where testing was by disc diffusion. Susceptibility was assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. Results Seven hundred and twenty-six respiratory isolates comprising 265 isolates of Streptococcus pneumoniae, 125 isolates of Streptococcus pyogenes and 336 isolates of Haemophilus influenzae were collected from Bahrain, Lebanon, Oman and the United Arab Emirates (UAE). Among S. pneumoniae, susceptibility to penicillin was low in the UAE and Bahrain. Macrolide susceptibility was ∼45%–60% in the UAE and Oman but higher in Lebanon (73.7%) and Bahrain (84%–85%). Penicillin susceptibility using CLSI intravenous breakpoints was >85% in all countries. Antibiotic susceptibility of S. pneumoniae was lower in UAE and Oman. Among S. pyogenes isolates, resistance to erythromycin was highest in Oman (31.6%) but <20% in the other countries. In H. influenzae, susceptibility to most antibiotics was high, except for ampicillin in Lebanon (70.2%) and amoxicillin in Oman (95.4%). Lebanon also had a high percentage (14.9%) of β-lactamase-positive isolates with non-susceptibility to ampicillin. Amoxicillin/clavulanic acid susceptibility was >95% in all countries. Use of EUCAST versus CLSI breakpoints demonstrated profound differences for cefaclor and cefuroxime in S. pneumoniae and H. influenzae, with EUCAST showing lower susceptibility. Conclusions There was considerable variability in susceptibility among countries in the same region. Thus, continued surveillance is necessary to track future changes in antibiotic resistance. PMID:27048582

Application of passive sampling in assessing the occurrence and risk of antibiotics and endocrine disrupting chemicals in the Yangtze Estuary, China.

PubMed

Shi, X; Zhou, J L; Zhao, H; Hou, L; Yang, Y

2014-09-01

Polar organic chemical integrative sampler (POCIS) was used in assessing the occurrence and risk of 12 widely used antibiotics and 5 most potent endocrine disrupting chemicals (EDCs) in the Yangtze Estuary, China. During laboratory validation, the kinetics of pollutant uptake by POCIS were linear, and the sampling rates of most compounds were raised by flow rate and salinity, reaching the highest values at salinity 14‰. The sampling rates varied with the target compounds with the EDCs showing the highest values (overall average=0.123Ld(-1)), followed by chloramphenicols (0.100Ld(-1)), macrolides (0.089Ld(-1)), and finally sulfonamides (0.056Ld(-1)). Validation in the Yangtze Estuary in 2013 showed that the field sampling rates were significantly greater for all compounds except bisphenol A, in comparison to laboratory results, and high-frequency spot sampling is critical for fully validating the passive sampler. The field studies show that antibiotics were widely detected in the Yangtze Estuary, with concentrations varying from below quantification to 1613ngL(-1), suggesting their widespread use and persistence in estuarine waters. The dominating pollutants in July were sulfonamides with a total concentration of 258ngL(-1) and in October were macrolides with a total concentration of 350ngL(-1). The calculation of risk quotient suggested that sulfapyridine, sulfaquinoxaline and erythromycin-H2O may have caused medium damage to sensitive organisms such as fish. Copyright © 2014. Published by Elsevier Ltd.

Antimicrobial Susceptibilities of 1,684 Streptococcus pneumoniae and 2,039 Streptococcus pyogenes Isolates and Their Ecological Relationships: Results of a 1-Year (1998–1999) Multicenter Surveillance Study in Spain

PubMed Central

Pérez-Trallero, E.; Fernández-Mazarrasa, C.; García-Rey, C.; Bouza, E.; Aguilar, L.; García-de-Lomas, J.; Baquero, F.

2001-01-01

A nationwide multicenter susceptibility surveillance study which included 1,684 Streptococcus pneumoniae and 2,039 S. pyogenes isolates was carried out over 1 year in order to assess the current resistance patterns for the two most important gram-positive microorganisms responsible for community-acquired infections in Spain. Susceptibility testing was done by a broth microdilution method according to National Committee for Clinical Laboratory Standards M100-S10 interpretative criteria. For S. pneumoniae, the prevalences of highly resistant strains were 5% for amoxicillin and amoxicillin-clavulanic acid; 7% for cefotaxime; 22% for penicillin; 31% for cefuroxime; 35% for erythromycin, clarithromycin, and azithromycin; and 42% for cefaclor. For S. pyogenes, the prevalence of erythromycin resistance was 20%. Efflux was encountered in 90% of S. pyogenes and 5% of S. pneumoniae isolates that exhibited erythromycin resistance. Erythromycin resistance was associated with clarithromycin and azithromycin in both species, regardless of phenotype. Despite the different nature of the mechanisms of resistance, a positive correlation (r = 0.612) between the two species in the prevalence of erythromycin resistance was found in site-by-site comparisons, suggesting some kind of link with antibiotic consumption. Regarding ciprofloxacin, the MIC was ≥4 μg/ml for 7% of S. pneumoniae and 3.5% of S. pyogenes isolates. Ciprofloxacin resistance (MIC, ≥4 μg/ml) was significantly (P < 0.05) associated with macrolide resistance in both S. pyogenes and S. pneumoniae and with penicillin nonsusceptibility in S. pneumoniae. PMID:11709305

[Activity of macrolides and fluoroquinolones against intracellular Legionella pneumophila].

PubMed

Yu, Ling-ling; Hu, Bi-jie; Huang, Sheng-lei; Zhou, Zhao-yan; Tao, Li-li

2011-06-01

To evaluate the activity of macrolides and fluoroquinolones against Legionella pneumophila by intracellular susceptibility testing. Minimum inhibitory concentration (MIC) was determined by standard agar dilution test according to the CLSI. For intracellular assays, legionella pneumonia was used to infect human monocytic cell line THP-1. Erythromycin, azithromycin, levofloxacin and moxifloxacin at 1 × MIC, 4 × MIC, 8 × MIC were added following phagocytosis. Number of viable bacteria was enumerated at 24 h on BCYE (buffered charcoal yeast extract) agar in duplicates using standard plate count method. The result was expressed as percentage inhibition. Mann-Whitney U test was used to determine the significant differences in mean percentage inhibition between agents. Percentage inhibition at 24 h were as follows: Erythromycin 1 × MIC (50.18 ± 27.29)%, 4 × MIC (79.48 ± 20.08)%, 8 × MIC (91.46 ± 8.70)%; Azithromycin 1 × MIC (66.77 ± 26.18)%, 4 × MIC (91.73 ± 8.72)%, 8 × MIC (97.10 ± 3.37)%; Levofloxacin 1 × MIC (99.84 ± 0.25)%, 4 × MIC (99.99 ± 0.02)%, 8 × MIC (99.99 ± 0.01)%; Moxifloxacin 1 × MIC (99.90 ± 0.10)%, 4 × MIC (99.99 ± 0.03)%, 8 × MIC (99.99 ± 0.03)%. The fluoroquinolones showed greater inhibitory activity than macrolides against legionella pneumophila(u = 1.0, 2.0, 5.0, P < 0.05). Levofloxacin and moxifloxacin had the same intracellular activity against legionella pneumophila (u = 190, 183, 217, P > 0.05). Azithromycin was more effective than erythromycin in inhibiting intracellular legionella pneumophila (u = 132, 125, 128, P < 0.05). The fluoroquinolones were more active than macrolides against legionella pneumophila. The intracellular activity of levofloxacin against legionella pneumophila appeared to be similar to moxifloxacin. Azithromycin was demonstrated to have superior activity against legionella pneumophila compared with erythromycin.

Antibiotic contamination in a typical developing city in south China: occurrence and ecological risks in the Yongjiang River impacted by tributary discharge and anthropogenic activities.

PubMed

Xue, Baoming; Zhang, Ruijie; Wang, Yinghui; Liu, Xiang; Li, Jun; Zhang, Gan

2013-06-01

The occurrence and distribution of ten selected antibiotics from three groups (sulfonamides, macrolides, and trimethoprim) were investigated in the Yongjiang River, which flows through Nanning City, a typical developing city in China. The study also assessed the ecological risks and the potential effects caused by discharge from tributaries and anthropogenic activities. Concentrations of most of the antibiotics were elevated along the section of the river in the urban area, highlighting the significant impact of high population density and human activities on the presence of antibiotics in the environment. The concentrations in the tributaries (ranged from not detected to 1336ngL(-1)) were generally higher than those in the main stream (ranged from not detected to 78.8ngL(-1)), but both areas contained the same predominant antibiotics, revealing the importance of tributary discharge as a source of antibiotic pollution. A risk assessment for the surface water contamination revealed that sulfamethoxazole and erythromycin posed high ecological risks to the most sensitive aquatic organisms (Synechococcus leopoliensis and Pseudokirchneriella subcapitata, respectively) in the midstream and some tributaries. Most of the selected antibiotics presented high ecological risks (risk quotients up to 95) in the sediments. Copyright © 2013 Elsevier Inc. All rights reserved.

Macrolides for treatment of Haemophilus ducreyi infection in sexually active adults.

PubMed

Romero, Laura; Huerfano, Cesar; Grillo-Ardila, Carlos F

2017-12-11

Chancroid is a genital ulcerative disease caused by Haemophilus ducreyi. This microorganism is endemic in Africa, where it can cause up to 10% of genital ulcers. Macrolides may be an effective alternative to treat chancroid and, based on their oral administration and duration of therapy, could be considered as first line therapy. To assess the effectiveness and safety of macrolides for treatment of H ducreyi infection in sexually active adults. We searched the Cochrane STI Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, WHO ICTRP, ClinicalTrials.gov and Web of Science to 30 October 2017. We also handsearched conference proceedings and reference lists of retrieved studies. Randomized controlled trials (RCTs) comparing macrolides in different regimens or with other therapeutic alternatives for chancroid. Two review authors independently assessed trials for inclusion, extracted data and assessed risk of bias. We resolved disagreements through consensus. We used the GRADE approach to assess the quality of the evidence. Seven RCTs (875 participants) met our inclusion criteria, of which four were funded by industry. Five studies (664 participants) compared macrolides with ceftriaxone, ciprofloxacin, spectinomycin or thiamphenicol. Low quality evidence suggested there was no difference between the groups after treatment in terms of clinical cure (risk ratio (RR) 1.09, 95% confidence interval (CI) 0.97 to 1.21; 2 studies, 340 participants with syndromic approach and RR 1.06, 95% CI 0.98 to 1.15; 5 studies, 348 participants with aetiological diagnosis) or improvement (RR 0.89, 95% CI 0.52 to 1.52; 2 studies, 340 participants with syndromic approach and RR 0.80, 95% CI 0.42 to 1.51; 3 studies, 187 participants with aetiological diagnosis). Based on low and very low quality evidence, there was no difference between macrolides and any other antibiotic treatments for microbiological cure (RR 0.93, 95% CI 0.74 to 1.16; 1 study, 45 participants) and minor adverse effects (RR 1.34, 95% CI 0.24 to 7.51; 3 studies, 412 participants).Two trials (269 participants) compared erythromycin with any other macrolide type. Low quality evidence suggested that, compared with azithromycin or rosaramicin, long courses of erythromycin did not increase clinical cure (RR 1.00, 95% CI 0.91 to 1.10; 2 studies, 269 participants with syndromic approach and RR 1.04, 95% CI 0.93 to 1.16; 2 studies, 211 participants with aetiological diagnosis), with a similar frequency of minor adverse effects between the groups (RR 1.14, 95% CI 0.63 to 2.06; 1 trial, 101 participants). For this comparison, subgroup analysis found no difference between HIV-positive participants (RR 1.02, 95% CI 0.73 to 1.43; 1 study, 38 participants) and HIV-negative participants (RR 1.04, 95% CI 0.94 to 1.14; 1 study, 89 participants). We downgraded the quality of evidence to low, because of imprecision, some limitations on risk of bias and heterogeneity.None of the trials reported serious adverse events, cost effectiveness and participant satisfaction. At present, the quality of the evidence on the effectiveness and safety of macrolides for treatment of H ducreyi infection in sexually active adults is low, implying that we are uncertain about the estimated treatment effect. There is no statistically significant difference between the available therapeutic alternatives for the treatment of sexually active adults with genital ulcers compatible with chancroid. Low quality evidence suggests that azithromycin could be considered as the first therapeutic alternative, based on their mono-dose oral administration, with a similar safety and effectiveness profile, when it is compared with long-term erythromycin use.Due to sparse available evidence about the safety and effectiveness of macrolides to treat H ducreyi infection in people with HIV, these results should be taken with caution.

A seventeen-year observation of the antimicrobial susceptibility of clinical Campylobacter jejuni and the molecular mechanisms of erythromycin-resistant isolates in Beijing, China.

PubMed

Zhou, Jiyuan; Zhang, Maojun; Yang, Wanna; Fang, Yuqing; Wang, Guiqiang; Hou, Fengqin

2016-01-01

To investigate the dynamic development of the antimicrobial resistance of Campylobacter jejuni isolated from human diarrhea in Beijing, China, between 1994 and 2010, and to further analyze the molecular mechanisms of erythromycin-resistant strains. Susceptibility tests were performed on 203 non-duplicate clinical C. jejuni strains against eight common antibiotics using the standard agar dilution method. The molecular determinants were further studied in the erythromycin (ERY) non-susceptible strains. The analysis focused on the 23S rRNA gene, the rplD and rplV ribosomal genes, the ermB gene, and the regulatory region of the CmeABC efflux pump. The rates of resistance of C. jejuni to ciprofloxacin (CIP), nalidixic acid (NAL), doxycycline (DOX), tetracycline (TET), florfenicol (FFC), and chloramphenicol (CHL) increased significantly over the period studied (all p<0.05). Similarly, the proportions of resistant patterns (CIP-NAL-DOX-TET, CIP-NAL-DOX-TET-FFC, and CIP-NAL-DOX-TET-CHL) increased remarkably. In this study, 4.4% (9/203) of C. jejuni strains were ERY non-susceptible. The A2075G mutation in the 23S rRNA was found in all of the resistant strains except cj8091, which harbored the ermB gene. Interestingly, the ermB gene was also detected in intermediately resistant isolates, and the earliest ermB-positive strain cj94473 was derived in 1994. Moreover, none of the ribosomal rplD or rplV genes harbored mutations that have been described to confer resistance to macrolides. Different mutations affecting the regulatory region of the CmeABC efflux pump were also found. This is the first comprehensive study on the recent trend in antimicrobial resistance and the molecular mechanisms of macrolide resistance in clinical C. jejuni strains isolated in China. More stringent monitoring and regulation of human and animal antimicrobial use are warranted. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Ureaplasma parvum undergoes selection in utero resulting in genetically diverse isolates colonizing the chorioamnion of fetal sheep.

PubMed

Dando, Samantha J; Nitsos, Ilias; Polglase, Graeme R; Newnham, John P; Jobe, Alan H; Knox, Christine L

2014-02-01

Ureaplasmas are the microorganisms most frequently isolated from the amniotic fluid of pregnant women and can cause chronic intrauterine infections. These tiny bacteria are thought to undergo rapid evolution and exhibit a hypermutatable phenotype; however, little is known about how ureaplasmas respond to selective pressures in utero. Using an ovine model of chronic intraamniotic infection, we investigated if exposure of ureaplasmas to subinhibitory concentrations of erythromycin could induce phenotypic or genetic indicators of macrolide resistance. At 55 days gestation, 12 pregnant ewes received an intraamniotic injection of a nonclonal, clinical Ureaplasma parvum strain followed by (i) erythromycin treatment (intramuscularly, 30 mg/kg/day, n = 6) or (ii) saline (intramuscularly, n = 6) at 100 days gestation. Fetuses were then delivered surgically at 125 days gestation. Despite injecting the same inoculum into all the ewes, significant differences between amniotic fluid and chorioamnion ureaplasmas were detected following chronic intraamniotic infection. Numerous polymorphisms were observed in domain V of the 23S rRNA gene of ureaplasmas isolated from the chorioamnion (but not the amniotic fluid), resulting in a mosaiclike sequence. Chorioamnion isolates also harbored the macrolide resistance genes erm(B) and msr(D) and were associated with variable roxithromycin minimum inhibitory concentrations. Remarkably, this variability occurred independently of exposure of ureaplasmas to erythromycin, suggesting that low-level erythromycin exposure does not induce ureaplasmal macrolide resistance in utero. Rather, the significant differences observed between amniotic fluid and chorioamnion ureaplasmas suggest that different anatomical sites may select for ureaplasma subtypes within nonclonal, clinical strains. This may have implications for the treatment of intrauterine ureaplasma infections.

Bacteriological Efficacies of Three Macrolides Compared with Those of Amoxicillin-Clavulanate against Streptococcus pneumoniae and Haemophilus influenzae

PubMed Central

Berry, Valerie; Thorburn, Christine E.; Knott, Sarah J.; Woodnutt, Gary

1998-01-01

Comparative antibacterial efficacies of erythromycin, clarithromycin, and azithromycin were examined against Streptococcus pneumoniae and Haemophilus influenzae, with amoxicillin-clavulanate used as the active control. In vitro, the macrolides at twice their MICs and at concentrations achieved in humans were bacteriostatic or reduced the numbers of viable S. pneumoniae slowly, whereas amoxicillin-clavulanate showed a rapid antibacterial effect. Against H. influenzae, erythromycin, clarithromycin, and clarithromycin plus 14-hydroxy clarithromycin at twice their MICs produced a slow reduction in bacterial numbers, whereas azithromycin was bactericidal. Azithromycin at the concentrations achieved in the serum of humans was bacteriostatic, whereas erythromycin and clarithromycin were ineffective. In experimental respiratory tract infections in rats, clarithromycin (equivalent to 250 mg twice daily [b.i.d.]) and amoxicillin-clavulanate (equivalent to 500 plus 125 mg b.i.d., respectively) were highly effective against S. pneumoniae, but azithromycin (equivalent to 500 and 250 mg once daily) was significantly less effective (P < 0.01). Against H. influenzae, clarithromycin treatment (equivalent to 250 or 500 mg b.i.d.) was similar to no treatment and was significantly less effective than amoxicillin-clavulanate treatment (P < 0.01). Azithromycin demonstrated significant in vivo activity (P < 0.05) but was significantly less effective than amoxicillin-clavulanate (P < 0.05). Overall, amoxicillin-clavulanate was effective in vitro and in vivo. Clarithromycin and erythromycin were ineffective in vitro and in vivo against H. influenzae, and azithromycin (at concentrations achieved in humans) showed unreliable activity against both pathogens. These results may have clinical implications for the utility of macrolides in the empiric therapy of respiratory tract infections. PMID:9835514

Spectrophotometric Investigations of Macrolide Antibiotics: A Brief Review

PubMed Central

Keskar, Mrudul R; Jugade, Ravin M

2015-01-01

Macrolides, one of the most commonly used class of antibiotics, are a group of drugs produced by Streptomyces species. They belong to the polyketide class of natural products. Their activity is due to the presence of a large macrolide lactone ring with deoxy sugar moieties. They are protein synthesis inhibitors and broad-spectrum antibiotics, active against both gram-positive and gram-negative bacteria. Different analytical techniques have been reported for the determination of macrolides such as chromatographic methods, flow injection methods, spectrofluorometric methods, spectrophotometric methods, and capillary electrophoresis methods. Among these methods, spectrophotometric methods are sensitive and cost effective for the analysis of various antibiotics in pharmaceutical formulations as well as biological samples. This article reviews different spectrophotometric methods for the determination of macrolide antibiotics. PMID:26609215

Effects of chlorophyll-derived efflux pump inhibitor pheophorbide a and pyropheophorbide a on erythromycin resistance of Staphylococcus aureus, Enterococcus faecalis, Salmonella Typhimurium and Escherichia coli

USDA-ARS?s Scientific Manuscript database

The purpose of this study was to validate the hypothesis that pheophorbide a and pyropheophorbide a reduce erythromycin resistance of reference strains of facultative anaerobic bacteria with multidrug or macrolide efflux pumps, as indicative of their effect on bacteria indigenous to anaerobic swine ...

The AcrAB-TolC pump is involved in macrolide resistance but not in telithromycin efflux in Enterobacter aerogenes and Escherichia coli.

PubMed

Chollet, Renaud; Chevalier, Jacqueline; Bryskier, André; Pagès, Jean-Marie

2004-09-01

The role of the AcrAB-TolC pump in macrolide and ketolide susceptibility in Escherichia coli and Enterobacter aerogenes was studied. Efflux pump inhibitor restored erythromycin, clarithromycin, and telithromycin susceptibilities to multidrug-resistant isolates. No modification of telithromycin accumulation was detected in E. aerogenes acrAB or tolC derivatives compared to that in the parental strain. Two independent efflux pumps, inhibited by phenylalanine arginine beta-naphthylamide, expel macrolides and telithromycin in E. aerogenes.

Sample preservation for the analysis of antibiotics in water.

PubMed

Llorca, Marta; Gros, Meritxell; Rodríguez-Mozaz, Sara; Barceló, Damià

2014-11-21

This paper describes a stability study performed for 56 antibiotics belonging to 9 different groups--macrolides, tetracyclines, fluoroquinolones, quinolones, penicillins, cephalosporines, lincosamides, sulfonamides and nitroimidazole antibiotics--in purified water samples fortified with the selected compounds at 10 ng/ml. For this purpose, three different sample preservation modes were tested with the aim of avoiding biotic and abiotic degradation: (i) storage at -20°C, (ii) storage at -20°C with 0.1% of EDTA and (iii) pre-concentration in a solid phase extraction cartridge (SPE), which was afterwards stored at -20°C. Concentrations of antibiotics in the samples preserved using the different protocols were monitored after 0, 1, 2 and 12 weeks. The results showed that, for the accurate determination of all compounds they should be analyzed right after sampling. However, if this is not possible, most of the antibiotics can be analyzed within the 1st week after sampling and preservation at -20°C (with or without EDTA) or in a SPE cartridges at -20°C. Nonetheless, some antibiotics found extensively in the environment, such as sulfamethoxazole, ciprofloxacin, ofloxacin, erythromycin, azithromycin and clarithromycin exhibited low stability after 1 week preservation and, therefore, they should be analyzed within this time. Copyright © 2014 Elsevier B.V. All rights reserved.

Predominant role of msr(D) over mef(A) in macrolide resistance in Streptococcus pyogenes.

PubMed

Zhang, Yan; Tatsuno, Ichiro; Okada, Ryo; Hata, Nanako; Matsumoto, Masakado; Isaka, Masanori; Isobe, Ken-ichi; Hasegawa, Tadao

2016-01-01

In Japan, the number of patients with streptococcal toxic shock syndrome is reported to be increasing. mef(A) gene-positive macrolide-resistant emm1 strains are thought to possibly contribute to the rise in the frequency of STSS. Although analyses of macrolide-resistant mechanisms, including mef(A) resistance, have been performed mainly in Streptococcus pneumoniae, the role of this gene in Streptococcus pyogenes has not been completely investigated. Therefore, to the best of our knowledge, we established the first mef(A)-knockout strain using an emm1-type S. pyogenes strain, and tested its susceptibility to erythromycin, clarithromycin and azithromycin. We found that the antimicrobial susceptibilities were almost identical to those of the parental strain. Hence, we established a knockout strain for another gene, msr(D), that is located immediately downstream of mef(A). The macrolide resistances of the resulting strain significantly decreased, and were further altered when both mef(A) and msr(D) were knocked out. The introduction of the msr(D) gene into a macrolide-sensitive strain conferred more resistance than the introduction of the mef(A) gene. The erythromycin susceptibilities of knockout strains were further dissected using two additional emm4- and emm75-type S. pyogenes strains. We found almost identical results for both strains except for the mef(A) knockout emm4 type, whose susceptibility was altered, although the change was less than that for the msr(D) knockout. These results suggest that both mef(A) and msr(D) are involved in macrolide resistance in S. pyogenes, and that the msr(D) gene plays a more predominant role in macrolide resistance than mef(A).

Dissecting and engineering of the TetR family regulator SACE_7301 for enhanced erythromycin production in Saccharopolyspora erythraea.

PubMed

Wu, Hang; Chen, Meng; Mao, Yongrong; Li, Weiwei; Liu, Jingtao; Huang, Xunduan; Zhou, Ying; Ye, Bang-Ce; Zhang, Lixin; Weaver, David T; Zhang, Buchang

2014-11-13

Saccharopolyspora erythraea was extensively utilized for the industrial-scale production of erythromycin A (Er-A), a macrolide antibiotic commonly used in human medicine. Yet, S. erythraea lacks regulatory genes in the erythromycin biosynthetic gene (ery) cluster, hampering efforts to enhance Er-A production via the engineering of regulatory genes. By the chromosome gene inactivation technique based on homologous recombination with linearized DNA fragments, we have inactivated a number of candidate TetR family transcriptional regulators (TFRs) and identified one TFR (SACE_7301) positively controlling erythromycin biosynthesis in S. erythraea A226. qRT-PCR and EMSA analyses demonstrated that SACE_7301 activated the transcription of erythromycin biosynthetic gene eryAI and the resistance gene ermE by interacting with their promoter regions with low affinities, similar to BldD (SACE_2077) previously identified to regulate erythromycin biosynthesis and morphological differentiation. Therefore, we designed a strategy for overexpressing SACE_7301 with 1 to 3 extra copies under the control of PermE* in A226. Following up-regulated transcriptional expression of SACE_7301, eryAI and ermE, the SACE_7301-overexpressed strains all increased Er-A production over A226 proportional to the number of copies. Likewise, when SACE_7301 was overexpressed in an industrial S. erythraea WB strain, Er-A yields of the mutants WB/7301, WB/2×7301 and WB/3×7301 were respectively increased by 17%, 29% and 42% relative to that of WB. In a 5 L fermentor, Er-A accumulation increased to 4,230 mg/L with the highest-yield strain WB/3×7301, an approximately 27% production improvement over WB (3,322 mg/L). We have identified and characterized a TFR, SACE_7301, in S. erythraea that positively regulated erythromycin biosynthesis, and overexpression of SACE_7301 in wild-type and industrial S. erythraea strains enhanced Er-A yields. This study markedly improves our understanding of the unusual regulatory mechanism of erythromycin biosynthesis, and provides a novel strategy towards Er-A overproduction by engineering transcriptional regulators of S. erythraea.

A platform for the discovery of new macrolide antibiotics

NASA Astrophysics Data System (ADS)

Seiple, Ian B.; Zhang, Ziyang; Jakubec, Pavol; Langlois-Mercier, Audrey; Wright, Peter M.; Hog, Daniel T.; Yabu, Kazuo; Allu, Senkara Rao; Fukuzaki, Takehiro; Carlsen, Peter N.; Kitamura, Yoshiaki; Zhou, Xiang; Condakes, Matthew L.; Szczypiński, Filip T.; Green, William D.; Myers, Andrew G.

2016-05-01

The chemical modification of structurally complex fermentation products, a process known as semisynthesis, has been an important tool in the discovery and manufacture of antibiotics for the treatment of various infectious diseases. However, many of the therapeutics obtained in this way are no longer effective, because bacterial resistance to these compounds has developed. Here we present a practical, fully synthetic route to macrolide antibiotics by the convergent assembly of simple chemical building blocks, enabling the synthesis of diverse structures not accessible by traditional semisynthetic approaches. More than 300 new macrolide antibiotic candidates, as well as the clinical candidate solithromycin, have been synthesized using our convergent approach. Evaluation of these compounds against a panel of pathogenic bacteria revealed that the majority of these structures had antibiotic activity, some efficacious against strains resistant to macrolides in current use. The chemistry we describe here provides a platform for the discovery of new macrolide antibiotics and may also serve as the basis for their manufacture.

High frequency of fluoroquinolone- and macrolide-resistant streptococci among clinically isolated group B streptococci with reduced penicillin susceptibility.

PubMed

Kimura, Kouji; Nagano, Noriyuki; Nagano, Yukiko; Suzuki, Satowa; Wachino, Jun-ichi; Shibayama, Keigo; Arakawa, Yoshichika

2013-03-01

Recently several clinical isolates of Streptococcus agalactiae [also known as group B Streptococcus (GBS)] that have acquired reduced penicillin susceptibility (PRGBS) by amino acid substitutions in the penicillin-binding protein 2X have emerged. The frequency of fluoroquinolone (FQ)- and macrolide-resistant streptococci among PRGBS is not yet known. Fifty-seven GBS [19 PRGBS and 38 penicillin-susceptible GBS (PSGBS)], isolated from different medical institutions in Japan, were studied. For GBS, the MICs of penicillin G, levofloxacin and erythromycin were determined using the agar dilution method. Nineteen PRGBS were previously confirmed as genetically diverse streptococci by PFGE. Further, the mechanisms underlying penicillin, FQ and macrolide non-susceptibility/resistance were analysed. The frequency of non-susceptibility to FQs among PSGBS was 18.4% (7/38), whereas that among PRGBS was 100% (19/19). The frequency of resistance to erythromycin among PSGBS was 7.9% (3/38), while that among PRGBS was 47.4% (9/19). Statistical significance was determined using Fisher's exact test between reduced penicillin susceptibility and FQ non-susceptibility (P ≤ 0.0001) and macrolide resistance (P=0.0012). The resistance/non-susceptibility mechanisms among PRGBS were diverse, suggesting that the PRGBS examined were not clonal. PRGBS isolates tend to show resistance to FQs and/or macrolides. Because the drug choice for treating these multidrug-resistant GBS is more limited than that for usual GBS, these strains may present future public health challenges.

Comparative analysis on antibiotic resistance characteristics of Listeria spp. and Enterococcus spp. isolated from laying hens and eggs in conventional and organic keeping systems in Bavaria, Germany.

PubMed

Schwaiger, K; Schmied, E-M V; Bauer, J

2010-05-01

By investigating the prevalence and antimicrobial resistance characteristics of Gram-positive bacteria from organic and conventional keeping systems of laying hens, it was to be determined to what extent these properties are influenced by the different systems. For this purpose, a total of 799 cloacal swabs and 800 egg samples were examined. Prevalences for all selected bacteria from cloacal swabs were much the same for both organic and caged birds: Listeria spp.1.3%[org] versus 1.6%[con]; Enterococcus spp. 95.5%[org] versus 97.5%[con]. Egg contents and eggshells were generally contaminated to a lesser extent, primarily with Enterococcus spp. Listeria isolates were susceptible to almost all tested antibiotics, only three Listeria innocua from conventional keepings were resistant to clindamycin; one isolate additionally to imipenem. High percentages of Enterococcus faecalis were resistant to doxycycline and macrolides. Enterococcus faecium proved to have high resistance rates to clindamycin, fosfomycin and erythromycin; 9.1% were even resistant to the reserve antibiotic synercid. Further, Enterococcus spp. showed higher resistance rates to doxycycline, erythromycin, fosfomycin and rifampicin. No glycopeptide resistant enterococci were detected. A correlation between keeping system and resistance/susceptibility rates could be demonstrated. In detail, E. faecalis from organic laying hen husbandries showed significant lower resistance prevalences to tylosin, streptomycin and doxycycline; susceptibility rates were higher for enrofloxacin and ciprofloxacin. Rifampicin and imipenem were more effective in isolates from conventional keepings (P < 0.05). The amounts of resistant isolates of the Enterococcus raffinosus from organic farms were significantly lower, the amounts of sensitive isolates were significantly higher than from conventional farms concerning eight antibiotics (P < 0.05). When comparing the susceptibility/resistance rates, as well as the mean minimum inhibitory concentrations values, the consistent tendency is that bacteria from organic layer flocks are more susceptible to antimicrobials. These results show that organic livestock farming plays a part in contributing to reduced antibiotic resistance.

Antimicrobial resistance mechanisms among Campylobacter.

PubMed

Wieczorek, Kinga; Osek, Jacek

2013-01-01

Campylobacter jejuni and Campylobacter coli are recognized as the most common causative agents of bacterial gastroenteritis in the world. Humans most often become infected by ingesting contaminated food, especially undercooked chicken, but also other sources of bacteria have been described. Campylobacteriosis is normally a self-limiting disease. Antimicrobial treatment is needed only in patients with more severe disease and in those who are immunologically compromised. The most common antimicrobial agents used in the treatment of Campylobacter infections are macrolides, such as erythromycin, and fluoroquinolones, such as ciprofloxacin. Tetracyclines have been suggested as an alternative choice in the treatment of clinical campylobacteriosis but in practice are not often used. However, during the past few decades an increasing number of resistant Campylobacter isolates have developed resistance to fluoroquinolones and other antimicrobials such as macrolides, aminoglycosides, and beta-lactams. Trends in antimicrobial resistance have shown a clear correlation between use of antibiotics in the veterinary medicine and animal production and resistant isolates of Campylobacter in humans. In this review, the patterns of emerging resistance to the antimicrobial agents useful in treatment of the disease are presented and the mechanisms of resistance to these drugs in Campylobacter are discussed.

Comparison of two treatments for the removal of selected organic micropollutants and bulk organic matter: conventional activated sludge followed by ultrafiltration versus membrane bioreactor.

PubMed

Sahar, E; Ernst, M; Godehardt, M; Hein, A; Herr, J; Kazner, C; Melin, T; Cikurel, H; Aharoni, A; Messalem, R; Brenner, A; Jekel, M

2011-01-01

The potential of membrane bioreactor (MBR) systems to remove organic micropollutants was investigated at different scales, operational conditions, and locations. The effluent quality of the MBR system was compared with that of a plant combining conventional activated sludge (CAS) followed by ultrafiltration (UF). The MBR and CAS-UF systems were operated and tested in parallel. An MBR pilot plant in Israel was operated for over a year at a mixed liquor suspended solids (MLSS) range of 2.8-10.6 g/L. The MBR achieved removal rates comparable to those of a CAS-UF plant at the Tel-Aviv wastewater treatment plant (WWTP) for macrolide antibiotics such as roxythromycin, clarithromycin, and erythromycin and slightly higher removal rates than the CAS-UF for sulfonamides. A laboratory scale MBR unit in Berlin - at an MLSS of 6-9 g/L - showed better removal rates for macrolide antibiotics, trimethoprim, and 5-tolyltriazole compared to the CAS process of the Ruhleben sewage treatment plant (STP) in Berlin when both were fed with identical quality raw wastewater. The Berlin CAS exhibited significantly better benzotriazole removal and slightly better sulfamethoxazole and 4-tolyltriazole removal than its MBR counterpart. Pilot MBR tests (MLSS of 12 g/L) in Aachen, Germany, showed that operating flux significantly affected the resulting membrane fouling rate, but the removal rates of dissolved organic matter and of bisphenol A were not affected.

Macrolide antibiotics for cystic fibrosis.

PubMed

Southern, Kevin W; Barker, Pierre M; Solis-Moya, Arturo; Patel, Latifa

2012-11-14

Macrolide antibiotics may have a modifying role in diseases which involve airway infection and inflammation, like cystic fibrosis. To test the hypotheses that, in people with cystic fibrosis, macrolide antibiotics: 1. improve clinical status compared to placebo or another antibiotic; 2. do not have unacceptable adverse effects. If benefit was demonstrated, we aimed to assess the optimal type, dose and duration of macrolide therapy. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings.We contacted investigators known to work in the field, previous authors and pharmaceutical companies manufacturing macrolide antibiotics for unpublished or follow-up data (May 2010).Latest search of the Group's Cystic Fibrosis Trials Register: 29 February 2012. Randomised controlled trials of macrolide antibiotics compared to: placebo; another class of antibiotic; another macrolide antibiotic; or the same macrolide antibiotic at a different dose. Two authors independently extracted data and assessed risk of bias. Seven groups were contacted and provided additional data which were incorporated into the review. Ten of 31 studies identified were included (959 patients). Five studies with a low risk of bias examined azithromycin versus placebo and demonstrated consistent improvement in forced expiratory volume in one second over six months (mean difference at six months 3.97% (95% confidence interval 1.74% to 6.19%; n = 549, from four studies)). Patients treated with azithromycin were approximately twice as likely to be free of pulmonary exacerbation at six months, odds ratio 1.96 (95% confidence interval 1.15 to 3.33). With respect to secondary outcomes, there was a significant reduction in need for oral antibiotics and greater weight gain in those taking azithromycin. Adverse events were uncommon and not obviously associated with azithromycin, although a once-weekly high dose regimen was associated with more frequent gastrointestinal adverse events. Treatment with azithromycin was associated with reduced identification of Staphylococcus aureus on respiratory culture, but also a significant increase in macrolide resistance. This review provides evidence of improved respiratory function after six months of azithromycin. Data beyond six months were less clear, although reduction in pulmonary exacerbation was sustained. Treatment appeared safe over a six-month period; however, emergence of macrolide resistance was a concern. A multi-centre trial examining long-term effects of this antibiotic treatment is needed, especially for infants recognised through newborn screening.

Effects of Subinhibitory Concentrations of Antibiotics on Alpha-Toxin (hla) Gene Expression of Methicillin-Sensitive and Methicillin-Resistant Staphylococcus aureus Isolates

PubMed Central

Ohlsen, Knut; Ziebuhr, Wilma; Koller, Klaus-Peter; Hell, Wolfgang; Wichelhaus, Thomas A.; Hacker, Jörg

1998-01-01

Concentrations of antibiotics below the MIC are able to modulate the expression of virulence-associated genes. In this study, the influence of subinhibitory doses of 31 antibiotics on the expression of the gene encoding the staphylococcal alpha-toxin (hla), a major virulence factor of Staphylococcus aureus, was investigated with a novel gene fusion protocol. The most striking observation was a strong induction of hla expression by subinhibitory concentrations of β-lactams and an almost complete inhibition of alpha-toxin expression by clindamycin. Whereas glycopeptide antibiotics had no effect, the macrolide erythromycin and several aminoglycosides reduced and fluoroquinolones slightly stimulated hla expression. Furthermore, Northern blot analysis of hla mRNA and Western blot (immunoblot) analysis of culture supernatants of both methicillin-sensitive and methicillin-resistant S. aureus strains revealed that methicillin-induced alpha-toxin expression is a common phenomenon of alpha-toxin-producing strains. Some methicillin-resistant S. aureus isolates produced up to 30-fold more alpha-toxin in the presence of 10 μg of methicillin per ml than in its absence. The results indicate that the novel gene fusion technique is a useful tool for studying the modulation of virulence gene expression by antibiotics. Moreover, the results suggest that the effects of certain antibiotics on virulence properties may be relevant for the management of S. aureus infections. PMID:9797209

New Fluorescent Macrolide Derivatives for Studying Interactions of Antibiotics and Their Analogs with the Ribosomal Exit Tunnel.

PubMed

Tereshchenkov, A G; Shishkina, A V; Karpenko, V V; Chertkov, V A; Konevega, A L; Kasatsky, P S; Bogdanov, A A; Sumbatyan, N V

2016-10-01

Novel fluorescent derivatives of macrolide antibiotics related to tylosin bearing rhodamine, fluorescein, Alexa Fluor 488, BODIPY FL, and nitrobenzoxadiazole (NBD) residues were synthesized. The formation of complexes of these compounds with 70S E. coli ribosomes was studied by measuring the fluorescence polarization depending on the ribosome amount at constant concentration of the fluorescent substance. With the synthesized fluorescent tylosin derivatives, the dissociation constants for ribosome complexes with several known antibiotics and macrolide analogs previously obtained were determined. It was found that the fluorescent tylosin derivatives containing BODIPY FL and NBD groups could be used to screen the binding of novel antibiotics to bacterial ribosomes in the macrolide-binding site.

Multiclass analysis of antibiotic residues in honey by ultraperformance liquid chromatography-tandem mass spectrometry.

PubMed

Vidal, Jose Luis Martínez; Aguilera-Luiz, María Del Mar; Romero-González, Roberto; Frenich, Antonia Garrido

2009-03-11

A method has been developed and validated for the simultaneous analysis of different veterinary drug residues (macrolides, tetracyclines, quinolones, and sulfonamides) in honey. Honey samples were dissolved with Na(2)EDTA, and veterinary residues were extracted from the supernatant by solid-phase extraction (SPE), using OASIS HLB cartridges. The separation and determination was carried out by ultraperformance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS), using an electrospay ionization source (ESI) in positive mode. Data acquisition under MS/MS was achieved by applying multiple reaction monitoring (MRM) of two ion transitions per compound to provide a high degree of sensitivity and specificity. The method was validated, and mean recoveries were evaluated at three concentration levels (10, 50, and 100 microg/kg), ranging from 70 to 120% except for doxycycline, erythromycin, and tylmicosin with recovery higher than 50% at the three levels assayed. Relative standard deviations (RSDs) of the recoveries were less than 20% within the intraday precision and less than 25% within the interday precision. The limits of quantification (LOQs) were always lower than 4 microg/kg. The developed procedure was applied to 16 honey samples, and erythromycin, sarafloxacin, and tylosin were found in a few samples.

Determination of antibiotics in sewage from hospitals, nursery and slaughter house, wastewater treatment plant and source water in Chongqing region of Three Gorge Reservoir in China

USGS Publications Warehouse

Chang, Xiaotian; Meyer, M.T.; Liu, Xiuying; Zhao, Q.; Hao, Chen; Chen, J.-a.; Qiu, Z.; Yang, L.; Cao, J.; Shu, W.

2010-01-01

Sewage samples from 4 hospitals, 1 nursery, 1 slaughter house, 1 wastewater treatment plant and 5 source water samples of Chongqing region of Three Gorge Reservoir were analyzed for macrolide, lincosamide, trimethoprim, fluorouinolone, sulfonamide and tetracycline antibiotics by online solid-phase extraction and liquid chromatography-tandem mass spectrometry. Results showed that the concentration of ofloxacin (OFX) in hospital was the highest among all water environments ranged from 1.660????g/L to 4.240????g/L and norfloxacin (NOR, 0.136-1.620????g/L), ciproflaxacin (CIP, ranged from 0.011????g/L to 0.136????g/L), trimethoprim (TMP, 0.061-0.174????g/L) were commonly detected. Removal range of antibiotics in the wastewater treatment plant was 18-100% and the removal ratio of tylosin, oxytetracycline and tetracycline were 100%. Relatively higher removal efficiencies were observed for tylosin (TYL), oxytetracycline (OXY) and tetracycline (TET)(100%), while lower removal efficiencies were observed for Trimethoprim (TMP, 1%), Epi-iso-chlorotetracycline (EICIC, 18%) and Erythromycin-H2O (ERY-H2O, 24%). Antibiotics were removed more efficiently in primary treatment compared with those in secondary treatment. ?? 2009 Elsevier Ltd. All rights reserved.

The distribution of antibiotics in water of a river basin in South China

NASA Astrophysics Data System (ADS)

Meng, T.; Cheng, W.; Wang, M.; Wan, T.; Cheng, M.; Zhang, C. C.; Jia, Z. Y.

2017-08-01

In water environment field, one of the most attractive research topics is the determination of contamination characteristics of antibiotics in water. In order to investigate the distribution of antibiotics in surface water and drinking water of a certain river basin in southern China, we determined the types and concentrations of antibiotics that contaminated the river by performing HPLC-ESI-MS/MS method. Thus, we detected 17 antibiotics in four surface water samples (B1, B2, B3, and B4). In sampling points B3 and B4, we detected 16 antibiotics separately. The detection rates of norfloxacin, ofloxacin, and erythromycin-H2O were 100%, and the antibiotic erythromycin-H2O had the maximum concentration. In six drinking water samples (A1, A2, A3, A4, A5, and A6), we detected 13 antibiotics. In A5 water samples, we detected all the 13 antibiotics. The detection rate of ofloxacin and erythromycin-H2O was 100%, and erythromycin-H2O was the antibiotic with the highest concentration. We also found that from the upstream to the downstream of the river basin, the types of antibiotics in river increased gradually. In the upstream water samples (B1), we detected three antibiotics. Erythromycin-H2O was the antibiotic with the highest concentration of 6.61 ng/L, and sulfapyridine had the lowest concentration of 2.82 ng/L. In the downstream water samples (B4), we detected 16 antibiotics. Erythromycin-H2O was the antibiotic with the highest concentration of 277.58 ng/L, and the Sulfamonomethoxine was the antibiotic with the second-highest concentration of 242.1 ng/L. In addition, different membrane treatment processes could remove different amounts of antibiotics from the water samples. The study is an important reference for providing environmental protection to river water basin.

An automated on-line turbulent flow liquid-chromatography technology coupled to a high resolution mass spectrometer LTQ-Orbitrap for suspect screening of antibiotic transformation products during microalgae wastewater treatment.

PubMed

Jaén-Gil, Adrián; Hom-Diaz, Andrea; Llorca, Marta; Vicent, Teresa; Blánquez, Paqui; Barceló, Damià; Rodríguez-Mozaz, Sara

2018-06-11

The evaluation of wastewater treatment capabilities in terms of removal of water pollutants is crucial when assessing water mitigation issues. Not only the monitoring of target pollutants becomes a critical point, but also the transformation products (TPs) generated. Since these TPs are very often unknown compounds, their study in both wastewater and natural environment is currently recognized as a tedious task and challenging research field. In this study, a novel automated suspect screening methodology was developed for a comprehensive assessment of the TPs generated from nine antibiotics during microalgae water treatment. Three macrolides (azithromycin, erythromycin, clarithromycin), three fluoroquinolones (ofloxacin, ciprofloxacin, norfloxacin) and three additional antibiotics (trimethoprim, pipemidic acid, sulfapyridine) were selected as target pollutants. The analysis of samples was carried out by direct injection in an on-line turbulent flow liquid chromatography-high resolution mass spectrometry (TFC-LC-LTQ-Orbitrap-MS/MS) system, followed by automatic data processing for compound identification. The screening methodology allowed the identification of 40 tentative TPs from a list of software predicted intermediates created automatically. Once known and unknown TPs were identified, degradation pathways were suggested considering the different mechanisms involved on their formation (biotic and abiotic). Results reveal microalgae ability for macrolide biotransformation, but not for other antibiotics such as for fluoroquinolones. Finally, the intermediates detected were included into an in-house library and applied to the identification of tentative TPs in real toilet wastewater treated in a microalgae based photobioreactor (PBR). The overall approach allowed a comprehensive overview of the performance of microalgae water treatment in a fast and reliable manner: it represents a useful tool for the rapid screening of wide range of compounds, reducing time invested in data analysis and providing reliable structural identification. Copyright © 2018 Elsevier B.V. All rights reserved.

INVESTIGATING ENVIRONMENTAL SINKS OF MACROLIDE ANTIBIOTICS WITH ANALYTICAL CHEMISTRY

EPA Science Inventory

Possible environmental sinks (wastewater effluents, biosolids, sediments) of macrolide antibiotics (i.e., azithromycin, roxithromycin and clarithromycin)are investigated using state-of-the-art analytical chemistry techniques.

Dynamics of serotype 14 Streptococcus pneumoniae population causing acute respiratory infections among children in China (1997-2012).

PubMed

He, Mingming; Yao, Kaihu; Shi, Wei; Gao, Wei; Yuan, Lin; Yu, Sangjie; Yang, Yonghong

2015-07-11

In the last decade, the Streptococcus pneumoniae population has changed, mainly due to the abuse of antibiotics. The aim of this study was to determine the genetic structure of 144 S. pneumonia serotype 14 isolates collected from children with acute respiratory infections during 1997-2012 in China. All isolated pneumococci were tested for their sensitivity to 11 kinds of antibiotics with the E-test method or disc diffusion. The macrolides resistance genes ermB and mefA, as well as the sulfamethoxazole-trimethoprim resistance gene dihydrofolate reductase (DHFR) were detected by polymerase chain reaction (PCR). The sequence types (STs) were analyzed with multilocus sequence typing (MLST). From 1997 to 2012, the percentage of serotype 14 S. pneumonia isolates in the whole isolates increased. All of the 144 serotype 14 S. pneumonia isolates were susceptible to amoxicillin-clavulanic acid, vancomycin and levofloxacin. No penicillin resistant isolate was found, and the intermediate rate was as low as 0.7 %. Erythromycin resistance was confirmed among 143 isolates. The ermB gene was determined in all erythromycin resistant isolates, and the mefA gene was positive additionally in 13 of them. The non-susceptibility rate to the tested cephalosporins increased from 1997-2012. All trimethoprim-resistant isolates contained the Ile100-Leu mutation. Overall, 30 STs were identified, among which ST876 was the most prevalent, followed by ST875. During the study period, the percentage of CC876 increased from 0 % in 1997-2000 to 96.4 % in 2010-2012, whereas CC875 decreased from 84.2 to 0 %. CC876 showed higher non-susceptibility rates to β-lactam antibiotics than CC875. The percentage of serotype 14 S. pneumonia isolates increased over time in China. The increase of resistance to β-lactam antibiotics in this serotype isolates was associated with the spread of CC876.

Macrolones Are a Novel Class of Macrolide Antibiotics Active against Key Resistant Respiratory Pathogens In Vitro and In Vivo.

PubMed

Čipčić Paljetak, Hana; Verbanac, Donatella; Padovan, Jasna; Dominis-Kramarić, Miroslava; Kelnerić, Željko; Perić, Mihaela; Banjanac, Mihailo; Ergović, Gabrijela; Simon, Nerrisa; Broskey, John; Holmes, David J; Eraković Haber, Vesna

2016-09-01

As we face an alarming increase in bacterial resistance to current antibacterial chemotherapeutics, expanding the available therapeutic arsenal in the fight against resistant bacterial pathogens causing respiratory tract infections is of high importance. The antibacterial potency of macrolones, a novel class of macrolide antibiotics, against key respiratory pathogens was evaluated in vitro and in vivo MIC values against Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, and Haemophilus influenzae strains sensitive to macrolide antibiotics and with defined macrolide resistance mechanisms were determined. The propensity of macrolones to induce the expression of inducible erm genes was tested by the triple-disk method and incubation in the presence of subinhibitory concentrations of compounds. In vivo efficacy was assessed in a murine model of S. pneumoniae-induced pneumonia, and pharmacokinetic (PK) profiles in mice were determined. The in vitro antibacterial profiles of macrolones were superior to those of marketed macrolide antibiotics, including the ketolide telithromycin, and the compounds did not induce the expression of inducible erm genes. They acted as typical protein synthesis inhibitors in an Escherichia coli transcription/translation assay. Macrolones were characterized by low to moderate systemic clearance, a large volume of distribution, a long half-life, and low oral bioavailability. They were highly efficacious in a murine model of pneumonia after intraperitoneal application even against an S. pneumoniae strain with constitutive resistance to macrolide-lincosamide-streptogramin B antibiotics. Macrolones are the class of macrolide antibiotics with an outstanding antibacterial profile and reasonable PK parameters resulting in good in vivo efficacy. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Macrolones Are a Novel Class of Macrolide Antibiotics Active against Key Resistant Respiratory Pathogens In Vitro and In Vivo

PubMed Central

Verbanac, Donatella; Padovan, Jasna; Dominis-Kramarić, Miroslava; Kelnerić, Željko; Perić, Mihaela; Banjanac, Mihailo; Ergović, Gabrijela; Simon, Nerrisa; Broskey, John; Holmes, David J.; Eraković Haber, Vesna

2016-01-01

As we face an alarming increase in bacterial resistance to current antibacterial chemotherapeutics, expanding the available therapeutic arsenal in the fight against resistant bacterial pathogens causing respiratory tract infections is of high importance. The antibacterial potency of macrolones, a novel class of macrolide antibiotics, against key respiratory pathogens was evaluated in vitro and in vivo. MIC values against Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, and Haemophilus influenzae strains sensitive to macrolide antibiotics and with defined macrolide resistance mechanisms were determined. The propensity of macrolones to induce the expression of inducible erm genes was tested by the triple-disk method and incubation in the presence of subinhibitory concentrations of compounds. In vivo efficacy was assessed in a murine model of S. pneumoniae-induced pneumonia, and pharmacokinetic (PK) profiles in mice were determined. The in vitro antibacterial profiles of macrolones were superior to those of marketed macrolide antibiotics, including the ketolide telithromycin, and the compounds did not induce the expression of inducible erm genes. They acted as typical protein synthesis inhibitors in an Escherichia coli transcription/translation assay. Macrolones were characterized by low to moderate systemic clearance, a large volume of distribution, a long half-life, and low oral bioavailability. They were highly efficacious in a murine model of pneumonia after intraperitoneal application even against an S. pneumoniae strain with constitutive resistance to macrolide-lincosamide-streptogramin B antibiotics. Macrolones are the class of macrolide antibiotics with an outstanding antibacterial profile and reasonable PK parameters resulting in good in vivo efficacy. PMID:27353268

Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children.

PubMed

Korpela, Katri; Salonen, Anne; Virta, Lauri J; Kekkonen, Riina A; Forslund, Kristoffer; Bork, Peer; de Vos, Willem M

2016-01-26

Early-life antibiotic use is associated with increased risk for metabolic and immunological diseases, and mouse studies indicate a causal role of the disrupted microbiome. However, little is known about the impacts of antibiotics on the developing microbiome of children. Here we use phylogenetics, metagenomics and individual antibiotic purchase records to show that macrolide use in 2-7 year-old Finnish children (N=142; sampled at two time points) is associated with a long-lasting shift in microbiota composition and metabolism. The shift includes depletion of Actinobacteria, increase in Bacteroidetes and Proteobacteria, decrease in bile-salt hydrolase and increase in macrolide resistance. Furthermore, macrolide use in early life is associated with increased risk of asthma and predisposes to antibiotic-associated weight gain. Overweight and asthmatic children have distinct microbiota compositions. Penicillins leave a weaker mark on the microbiota than macrolides. Our results support the idea that, without compromising clinical practice, the impact on the intestinal microbiota should be considered when prescribing antibiotics.

Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children

PubMed Central

Korpela, Katri; Salonen, Anne; Virta, Lauri J.; Kekkonen, Riina A.; Forslund, Kristoffer; Bork, Peer; de Vos, Willem M.

2016-01-01

Early-life antibiotic use is associated with increased risk for metabolic and immunological diseases, and mouse studies indicate a causal role of the disrupted microbiome. However, little is known about the impacts of antibiotics on the developing microbiome of children. Here we use phylogenetics, metagenomics and individual antibiotic purchase records to show that macrolide use in 2–7 year-old Finnish children (N=142; sampled at two time points) is associated with a long-lasting shift in microbiota composition and metabolism. The shift includes depletion of Actinobacteria, increase in Bacteroidetes and Proteobacteria, decrease in bile-salt hydrolase and increase in macrolide resistance. Furthermore, macrolide use in early life is associated with increased risk of asthma and predisposes to antibiotic-associated weight gain. Overweight and asthmatic children have distinct microbiota compositions. Penicillins leave a weaker mark on the microbiota than macrolides. Our results support the idea that, without compromising clinical practice, the impact on the intestinal microbiota should be considered when prescribing antibiotics. PMID:26811868

Susceptibility of bacterial isolates from community-acquired infections in sub-Saharan Africa and Asia to macrolide antibiotics.

PubMed

Lubell, Yoel; Turner, Paul; Ashley, Elizabeth A; White, Nicholas J

2011-10-01

To review the literature on the susceptibility of common community pathogens in sub-Saharan Africa and Asia to the macrolide antibiotics. Inclusion criteria required that isolates were collected since 2004 to ensure results were of contemporary relevance. The data were aggregated by region, age group and sterility of site of culture sample. A total of 51 studies were identified, which reported the macrolide antimicrobial susceptibilities of common bacterial pathogens isolated since 2004. In general, there was less macrolide resistance in African than in Asian isolates. Most African studies reported high levels of macrolide susceptibility in Streptococcus pneumoniae, whereas most Chinese studies reported high levels of resistance. There was very little information available for Gram-negative organisms. Susceptibility of the pneumococcus to macrolides in SSA remains high in many areas, and good activity of azithromycin has been shown against Salmonellae spp. in Asia. In urban areas where high antibiotic consumption is prevalent, there was evidence of increased resistance to macrolides. However, there is no information on susceptibility from large areas in both continents. © 2011 Blackwell Publishing Ltd.

SUSCEPTIBILITY OF RESPIRATORY ISOLATES OF STREPTOCOCCUS PNEUMONIAE ISOLATED FROM CHILDREN HOSPITALIZED IN THE CLINICAL CENTER NIS.

PubMed

Dinić, Marina M; Mladenović Antić, Snezana; Kocić, Branislava; Stanković Dordević, Dobrila; Vrbić, Miodrag; Bogdanović, Milena

2016-01-01

Streptococcus pneumoniae is one of the most common causes of respiratory infections. The aim was to study the susceptibility to antimicrobial agents of respiratory isolates ofStreptococcus pneumoniae obtained from hospitalized children. A total of 190 respiratory pneumococcal isolates obtained from children aged from 0 to 14 years were isolated and identified by using standard microbiological methods. Susceptibility to oxacillin, erythromycin, clindamycin, tetracycline, cotrimoxazole, ofloxacin and rifampicin was tested by disc diffusion method. Minimal inhibitory concentrations for amoxicillin and ceftriaxone were determined by means of E test. The macrolide-resistant phenotype was detected by double disc diffusion test. All tested isolates were susceptible to amoxicillin and ceftriaxone. The minimal amoxicillin concentration inhibiting the growth of 50% of isolates and of 90% of isolates was 0.50 microg/ml and 1.0 microg/ml, respectively and the minimal ceftriaxone concentration inhibiting the growth of 50% of isolates and of 90% of isolates was 0.25 microg/ml and 0.50 microg/ml, respectively. Susceptibility to erythromycin and clindamycin was observed in 21.6% and 29.47% of isolates, respectively. The resistence to macrolides-M phenotype was detected in 10.07% of isolates and constitutive macrolide-lincosamide-streptogramin phenotype (constitutive MLS phenotype) was found in 89.93% of isolates. All tested isolates were susceptible to ofloxacin and rifampicin. Amoxicillin could be the therapy of choice in pediatric practice. The macrolides should not be recommended for the empirical therapy of pneumococcal respiratory tract infection in our local area.

Ultraviolet reduction of erythromycin and tetracycline resistant heterotrophic bacteria and their resistance genes in municipal wastewater.

PubMed

Guo, Mei-Ting; Yuan, Qing-Bin; Yang, Jian

2013-11-01

Antibiotic resistance in wastewater is becoming a major public health concern, but poorly understood about impact of disinfection on antibiotic resistant bacteria and antibiotic resistance genes. The UV disinfection of antibiotic resistant heterotrophic bacteria and their relevant genes in the wastewater of a municipal wastewater treatment plant has been evaluated. Two commonly used antibiotics, erythromycin and tetracycline were selected because of their wide occurrences in regard to the antibiotic resistance problem. After UV treatment at a fluence of 5mJcm(-2), the log reductions of heterotrophic bacteria resistant to erythromycin and tetracycline in the wastewater were found to be 1.4±0.1 and 1.1±0.1, respectively. The proportion of tetracycline-resistant bacteria (5%) was nearly double of that before UV disinfection (3%). Tetracycline-resistant bacteria exhibited more tolerance to UV irradiation compared to the erythromycin-resistant bacteria (p<0.05). Gene copy numbers were quantified via qPCR and normalized to the volume of original sample. The total concentrations of erythromycin- and tetracycline-resistance genes were (3.6±0.2)×10(5) and (2.5±0.1)×10(5) copies L(-1), respectively. UV treatment at a fluence of 5mJcm(-2) removed the total erythromycin- and tetracycline-resistance genes by 3.0±0.1 log and 1.9±0.1 log, respectively. UV treatment was effective in reducing antibiotic resistance in the wastewater. Copyright © 2013 Elsevier Ltd. All rights reserved.

Decision and cost analysis of empirical antibiotic therapy of acute sinusitis in the era of increasing antimicrobial resistance: do we have an additional tool for antibiotic policy decisions?

PubMed

Babela, Robert; Jarcuska, Pavol; Uraz, Vladimir; Krčméry, Vladimír; Jadud, Branislav; Stevlik, Jan; Gould, Ian M

2017-11-01

No previous analyses have attempted to determine optimal therapy for upper respiratory tract infections on the basis of cost-minimization models and the prevalence of antimicrobial resistance among respiratory pathogens in Slovakia. This investigation compares macrolides and cephalosporines for empirical therapy and look at this new tool from the aspect of potential antibiotic policy decision-making process. We employed a decision tree model to determine the threshold level of macrolides and cephalosporines resistance among community respiratory pathogens that would make cephalosporines or macrolides cost-minimising. To obtain information on clinical outcomes and cost of URTIs, a systematic review of the literature was performed. The cost-minimization model of upper respiratory tract infections (URTIs) treatment was derived from the review of literature and published models. We found that the mean cost of empirical treatment with macrolides for an URTIs was €93.27 when the percentage of resistant Streptococcus pneumoniae in the community was 0%; at 5%, the mean cost was €96.45; at 10%, €99.63; at 20%, €105.99, and at 30%, €112.36. Our model demonstrated that when the percentage of macrolide resistant Streptococcus pneumoniae exceeds 13.8%, use of empirical cephalosporines rather than macrolides minimizes the treatment cost of URTIs. Empirical macrolide therapy is less expensive than cephalosporines therapy for URTIs unless macrolide resistance exceeds 13.8% in the community. Results have important antibiotic policy implications, since presented model can be use as an additional decision-making tool for new guidelines and reimbursement processes by local authorities in the era of continual increase in antibiotic resistance.

Oxyrase, a method which avoids CO2 in the incubation atmosphere for anaerobic susceptibility testing of antibiotics affected by CO2.

PubMed

Spangler, S K; Appelbaum, P C

1993-02-01

The Oxyrase agar dilution method, with exclusion of CO2 from the environment, was compared with the reference agar dilution method recommended by the National Committee for Clinical Laboratory Standards (anaerobic chamber with 10% CO2) to test the susceptibility of 51 gram-negative and 43 gram-positive anaerobes to azithromycin and erythromycin. With the Oxyrase method, anaerobiosis was achieved by incorporation of the O2-binding enzyme Oxyrase in addition to susceptibility test medium, antibiotic, and enzyme substrates into the upper level of a biplate. Plates were covered with a Brewer lid and incubated in ambient air. With azithromycin, Oxyrase yielded an MIC for 50% of strains tested (MIC50) and MIC90 of 2.0 and 8.0 micrograms/ml, compared to 8.0 and > 32.0 micrograms/ml in standard anaerobic conditions. At a breakpoint of 8.0 micrograms/ml, 90.4% of strains were susceptible to azithromycin with Oxyrase, compared to 53.2% in the chamber. The corresponding erythromycin MIC50 and MIC90 were 1.0 and 8.0 micrograms/ml with Oxyrase, compared to 4.0 and > 32.0 micrograms/ml by the reference method, with 89.3% of strains susceptible at a breakpoint of 4 micrograms/ml with Oxyrase, compared to 60.6% in CO2. Exclusion of CO2 from the anaerobic atmosphere when testing for susceptibility to azalides and macrolides yielded lower MICs, which may lead to a reconsideration of the role played by these compounds in treatment of infections caused by these strains.

Erythromycin

MedlinePlus

... is used to treat certain infections caused by bacteria, such as infections of the respiratory tract, including ... antibiotics. It works by stopping the growth of bacteria.Antibiotics such as erythromycin will not work for ...

Novel spectrophotometric method for determination of some macrolide antibiotics in pharmaceutical formulations using 1,2-naphthoquinone-4-sulphonate

NASA Astrophysics Data System (ADS)

Ashour, Safwan; Bayram, Roula

2012-12-01

New, simple and rapid spectrophotometric method has been developed and validated for the assay of two macrolide drugs, azithromycin (AZT) and erythromycin (ERY) in pure and pharmaceutical formulations. The proposed method was based on the reaction of AZT and ERY with sodium 1,2-naphthoquinone-4-sulphonate (NQS) in alkaline medium at 25 °C to form an orange-colored product of maximum absorption peak at 452 nm. All variables were studied to optimize the reaction conditions and the reaction mechanism was postulated. Beer's law was obeyed in the concentration range 1.5-33.0 and 0.92-8.0 μg mL-1 with limit of detection values of 0.026 and 0.063 μg mL-1 for AZT and ERY, respectively. The calculated molar absorptivity values are 4.3 × 104 and 12.3 × 104 L mol-1 cm-1 for AZT and ERY, respectively. The proposed methods were successfully applied to the determination of AZT and ERY in formulations and the results tallied well with the label claim. The results were statistically compared with those of an official method by applying the Student's t-test and F-test. No interference was observed from the concomitant substances normally added to preparations.

Antibiotics as immunomodulant agents in COPD.

PubMed

Blasi, Francesco; Mantero, Marco; Aliberti, Stefano

2012-06-01

It is widely accepted that some antibiotics have activities beyond their direct antibacterial effects. Macrolide is the antibiotic class with more convincing studies and evidence on its immunomodulatory and anti-inflammatory activities. Different clinical studies have shown that macrolide prophylaxis in patients with moderate-severe chronic obstructive pulmonary disease (COPD) can have a significant impact on the exacerbation rate reducing morbidity and, potentially, mortality of the disease. Other antibiotics, such as fluoroquinolones, demonstrate a variety of immunomodulatory effects but only few clinical data are available in COPD. New macrolide derivatives devoid of antibacterial activity have been synthetized. This review analyses the relevance of immunomodulatory and anti-inflammatory effects of antibiotics in the management of COPD. Copyright © 2012 Elsevier Ltd. All rights reserved.

Identification and quantification of five macrolide antibiotics in several tissues, eggs and milk by liquid chromatography-electrospray tandem mass spectrometry.

PubMed

Dubois, M; Fluchard, D; Sior, E; Delahaut, P

2001-04-05

We present an electrospray high-performance liquid chromatographic tandem mass spectrometric (HPLC-MS-MS) method capable of determining in several tissues (muscle, kidney, liver), eggs and milk the following five macrolides: tylosin, tilmicosin, spiramycin, josamycin, erythromycin. Roxithromycin was used as an internal standard. The method uses extraction in a Tris buffer at pH 10.5, followed by protein precipitation with sodium tungstate and clean-up on an Oasis solid-phase extraction column. The HPLC separation was performed on a Purospher C18 column (125 x 3 mm I.D.) protected by a guard column, with a gradient of aqueous 0.1 M ammonium acetate-acetonitrile as the mobile phase at a flow-rate of 0.7 ml min(-1). Protonated molecules served as precursor ions for electrospray ionisation in the positive ion mode and four product ions were chosen for each analyte for multiple reaction monitoring (MRM). A validation study was conducted to confirm the five macrolides by MRM HPLC-MS-MS analysis of a negative control and fortified samples. All of the samples analysed were confirmed with four ions. The ion ratio reproducibility limit ranged from 2.4 to 15%. All compounds could be detected and quantified at half-maximum residue limits (MRLs). The method is specific, quantitative and reproducible enough to conform to European Union recommendations within the concentration range 0.5 MRL-2 MRL (accuracy: 80 to 110%, relative standard deviation: 2 to 13%). This whole method allows extraction and analysis of up to 50 samples per day.

Genotypes of macrolide-resistant pneumococci from children in southwestern Japan: raised incidence of strains that have both erm(B) and mef(A) with serotype 6B clones.

PubMed

Ikenaga, Masaaki; Kosowska-Shick, Klaudia; Gotoh, Kenji; Hidaka, Hidenobu; Koga, Hiroyasu; Masunaga, Kenji; Nagai, Kensuke; Tsumura, Naoki; Appelbaum, Peter C; Matsuishi, Toyojiro

2008-09-01

MICs of penicillin G, erythromycin, clarithromycin, clindamycin, azithromycin, and telithromycin were tested for 189 clinical isolates collected during 2002 to 2005 from children in southwestern Japan. Serotyping and polymerase chain reaction for presence of erm(B) and mef(A) were performed. All strains with erm(B) + mef(A) were analyzed by pulsed-field gel electrophoresis (PFGE) and compared to 3 global clones: Spain(23F)-1; Spain(9V)-3 and its variant -14; a South Korean strain same as Taiwan (19F)-14 clone and 5 strains with erm(B) + mef(A) from other countries. Of the 173 macrolide-resistant (erythromycin MIC > or =0.5 microg/mL) strains, 104 (60.1%) had erm(B), 47 (27.2%) had mef(A), and 22 (12.7%) had erm(B) + mef(A). Strains expressing erm(B) or both erm(B) and mef(A) had high macrolide MIC(90)s (>64 microg/mL), except telithromycin (MIC(90), 0.25 microg/mL). Of the 22 erm(B) + mef(A) strains, 10 had 4 distinct PFGE patterns and were mainly serotype 6B clones, which differed from those described in previous reports; 5 other strains had unique profiles.

A comparative uncertainty study of the calibration of macrolide antibiotic reference standards using quantitative nuclear magnetic resonance and mass balance methods.

PubMed

Liu, Shu-Yu; Hu, Chang-Qin

2007-10-17

This study introduces the general method of quantitative nuclear magnetic resonance (qNMR) for the calibration of reference standards of macrolide antibiotics. Several qNMR experimental conditions were optimized including delay, which is an important parameter of quantification. Three kinds of macrolide antibiotics were used to validate the accuracy of the qNMR method by comparison with the results obtained by the high performance liquid chromatography (HPLC) method. The purities of five common reference standards of macrolide antibiotics were measured by the 1H qNMR method and the mass balance method, respectively. The analysis results of the two methods were compared. The qNMR is quick and simple to use. In a new medicine research and development process, qNMR provides a new and reliable method for purity analysis of the reference standard.

Effect of spiramycin and tulathromycin on abomasal emptying rate in milk-fed calves

PubMed Central

Rashnavadi, Mehdi; Nouri, Mohammad; Haji Hajikolaei, Mohammad R.; Najafzadeh, Housain; Constable, Peter D.

2014-01-01

Impaired abomasal motility is common in cattle with abomasal disorders. The macrolide erythromycin has been demonstrated to be an effective prokinetic agent in healthy calves and in adult cattle with abomasal volvulus or left displaced abomasum. We hypothesized that 2 structurally related macrolides, spiramycin and tulathromycin, would also be effective prokinetic agents in cattle. Six milk-fed, male, Holstein-Friesian calves were administered each of the following 4 treatments: spiramycin, 75 000 IU/kg BW, IM, this dose approximates 25 mg/kg BW, IM; tulathromycin, 2.5 mg/kg BW, SC; 2 mL of 0.9% NaCl (negative control); and erythromycin, 8.8 mg/kg BW, IM (positive control). Calves were fed 2 L of cow’s milk containing acetaminophen (50 mg/kg body weight) 30 min after each treatment was administered and jugular venous blood samples were obtained periodically after the start of sucking. Abomasal emptying rate was assessed by the time to maximal plasma acetaminophen concentration. Spiramycin, tulathromycin, and the positive control erythromycin increased abomasal emptying rate compared to the negative control. We conclude that the labeled antimicrobial dose of spiramycin and tulathromycin increases the abomasal emptying rate in healthy milk-fed calves. Additional studies investigating whether spiramycin and tulathromycin exert a prokinetic effect in adult cattle with abomasal hypomotility appear indicated. PMID:24396182

Ureaplasma urealyticum and Ureaplasma parvum in women of reproductive age.

PubMed

Hunjak, Blaženka; Sabol, Ivan; Vojnović, Gordana; Fistonić, Ivan; Erceg, Andrea Babić; Peršić, Zdenka; Grce, Magdalena

2014-02-01

To determine the incidence of Ureaplasma urealyticum and Ureaplasma parvum (UP) in symptomatic and asymptomatic women of reproductive age and to estimate antibiotic susceptibility of ureaplasma isolates. This study included 424 ureaplasma positive women of 1,370 tested women who visited gynecological practices during 2010. Cervicovaginal or urethral swab specimens from each patient were obtained for cultivation and molecular typing by RT-PCR. Ureaplasma spp. was identified by cultivation in 424 (34.4 %) cases, of which 79.0 % were from women with symptoms and 21.0 % from women without symptoms. Among ureaplasma positive women, 121 (28.5 %) were pregnant. Genotyping was successful in 244 strains, and the majority of samples were identified as UP (92.6 %). Among genotyped isolates, there were 79.5 % from symptomatic and 20.5 % from asymptomatic women; 29.9 % from pregnant and 70.1 % from non-pregnant women. There was no difference in the incidence of ureaplasma type regarding symptoms. Antibiotic susceptibility of 424 ureaplasma isolates identified by cultivation showed that all strains were susceptible to doxycycline, josamycin, erythromycin, tetracycline, clarithromycin and pristinamycin, but there was lower susceptibility to quinolone antibiotics, i.e., 42.9 and 24.5 % isolates were susceptible to ofloxacin and ciprofloxacin, respectively. This study shows that UP was the most frequent isolated ureaplasma species (92.6 %). Regarding antibiotic susceptibility, quinolones are not the best choice for the treatment of ureaplasma infections, while macrolides and tetracyclines are still effective.

Prophylactic antibiotic therapy for chronic obstructive pulmonary disease (COPD).

PubMed

Herath, Samantha C; Poole, Phillippa

2013-11-28

There has been renewal of interest in the use of prophylactic antibiotics to reduce the frequency of exacerbations and improve quality of life in chronic obstructive pulmonary disease (COPD). To determine whether or not regular treatment of COPD patients with prophylactic antibiotics reduces exacerbations or affects quality of life. We searched the Cochrane Airways Group Trials Register and bibliographies of relevant studies. The latest literature search was August 2013. Randomised controlled trials (RCTs) that compared prophylactic antibiotics with placebo in patients with COPD. We used the standard methods of The Cochrane Collaboration. Data were extracted and analysed by two independent review authors. Seven RCTs involving 3170 patients were included in this systematic review. All studies were published between 2001 and 2011. Five studies were of continuous antibiotics and two studies were of intermittent antibiotic prophylaxis (termed 'pulsed' for this review). The antibiotics investigated were azithromycin, erythromycin, clarithromycin and moxifloxacin. Azithromycin, erythromycin and clarithromycin are macrolides while moxifloxacin is a fourth-generation synthetic fluoroquinolone antibacterial agent. The study duration varied from three months to 36 months and all used intention-to-treat analysis. Most of the results were of moderate quality. The risk of bias of the included studies was generally low, and we did not downgrade the quality of evidence for risk of bias.The trials recruited participants with a mean age of 66 years and with at least a moderate severity of COPD. Three trials included participants with frequent exacerbations and two trials recruited participants requiring systemic steroids or antibiotics, or both, or who were at the end stage of their disease and required oxygen.The primary outcomes for this review were the number of exacerbations and quality of life.With use of continuous prophylactic antibiotics the number of patients experiencing an exacerbation was reduced (odds ratio (OR) 0.55; 95% confidence interval (CI) 0.39 to 0.77, 3 studies, 1262 participants, high quality). This represented a reduction from 69% of participants in the control group compared to 54% in the treatment group (95% CI 46% to 63%) and the number needed to treat to prevent one exacerbation (NNTb) was therefore 8 (95% CI 5 to 18). The frequency of exacerbations was also reduced with continuous prophylactic antibiotic treatment (rate ratio 0.73; 95% CI 0.58 to 0.91).Use of pulsed antibiotic treatment showed a non-significant reduction in the number of people with exacerbations (OR 0.87; 95% CI 0.69 to 1.09, 1 study, 1149 participants, moderate quality) and the test for interaction showed that this result was significantly different from the effect on exacerbations with continuous antibiotics.There was a statistically significant improvement in quality of life with both continuous and pulsed antibiotic treatment but this was smaller than the four unit improvement that is regarded as being clinically significant (MD -1.78; 95% CI -2.95 to -0.61, 2 studies, 1962 participants, moderate quality).Neither pulsed nor continuous antibiotics showed a significant effect on the secondary outcomes of frequency of hospital admissions, change in lung function, serious adverse events or all-cause mortality (moderate quality evidence).The adverse events that were recorded varied among the trials depending on the different antibiotics used. Azithromycin was associated with a significant hearing loss in the treatment group. The moxifloxacin pulsed study reported a significantly higher number of adverse events in the treatment arm due to the marked increase in gastrointestinal adverse events (P < 0.001). Some adverse events that led to drug discontinuation, such as development of long QTc or tinnitus, were not significantly more frequent in the treatment group than the placebo group but pose important considerations in clinical practice.The development of antibiotic resistance in the community is of major concern. One study found newly colonised patients to have higher rates of antibiotic resistance. Patients colonised with moxifloxacin-sensitive pseudomonas at initiation of therapy rapidly became resistant with the quinolone treatment. Use of continuous prophylactic antibiotics results in a clinically significant benefit in reducing exacerbations in COPD patients. All trials of continuous antibiotics used macrolides hence the noted benefit applies only to the use of continuous macrolide antibiotics. The impact of pulsed antibiotics remains uncertain and requires further research.The trials in this review included patients who were frequent exacerbators and needed treatment with antibiotics or systemic steroids, or who were on supplemental oxygen. There were also older individuals with a mean age of 66 years. The results of these trials apply only to the group of patients who were studied in these trials and may not be generalisable to other groups.Because of concerns about antibiotic resistance and specific adverse effects, consideration of prophylactic antibiotic use should be mindful of the balance between benefits to individual patients and the potential harms to society created by antibiotic overuse.

Role of long term antibiotics in chronic respiratory diseases.

PubMed

Suresh Babu, K; Kastelik, J; Morjaria, J B

2013-06-01

Antibiotics are commonly used in the management of respiratory disorders such as cystic fibrosis (CF), non-CF bronchiectasis, asthma and COPD. In those conditions long-term antibiotics can be delivered as nebulised aerosols or administered orally. In CF, nebulised colomycin or tobramycin improve lung function, reduce number of exacerbations and improve quality of life (QoL). Oral antibiotics, such as macrolides, have acquired wide use not only as anti-microbial agents but also due to their anti-inflammatory and pro-kinetic properties. In CF, macrolides such as azithromycin have been shown to improve the lung function and reduce frequency of infective exacerbations. Similarly macrolides have been shown to have some benefits in COPD including reduction in a number of exacerbations. In asthma, macrolides have been reported to improve some subjective parameters, bronchial hyperresponsiveness and airway inflammation; however have no benefits on lung function or overall asthma control. Macrolides have also been used with beneficial effects in less common disorders such as diffuse panbronchiolitis or post-transplant bronchiolitis obliterans syndrome. In this review we describe our current knowledge the use of long-term antibiotics in conditions such as CF, non-CF bronchiectasis, asthma and COPD together with up-to-date clinical and scientific evidence to support our understanding of the use of antibiotics in those conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Antibiotic resistance of streptococcus pneumoniae among healthy nasopharyngeal carriers in seven regions of Peru].

PubMed

Torres, Nancy; Velásquez, Ricardo; Mercado, Erik H; Egoavil, Martha; Horna, Gertrudis; Mejía, Lida; Castillo, María E; Chaparro, Eduardo; Hernández, Roger; Silva, Wilda; Campos, Francisco E; Sáenz, Andrés; Hidalgo, Félix; Letona, Carolina; Valencia, Angel G; Cerpa, Rosario; López-de-Romaña, Bernardo; Torres, Berenice; Castillo, Fiorella; Calle, Andrea; Rabanal, Synthia; Pando, Jackeline; Lacroix, Elizabeth; Reyes, Isabel; Guerra, Humberto; Ochoa, Theresa J

2013-01-01

To determine the pattern of antibiotic susceptibility of isolated Streptococcus pneumoniae strains of healthy nasopharyngeal carriers younger than 2 years in seven regions of Peru. Between 2007 and 2009, nasopharyngeal swab samples were collected among 2123 healthy children aged 2-24 months in growth and development medical practices (CRED) and vaccination offices of hospitals and health centers in Lima, Piura, Cusco, Abancay, Arequipa, Huancayo, and Iquitos. The resistance to ten antibiotics through disk diffusion sensitivity testing of isolated pneumococcus strains was determined. 572 strains were isolated. High rates of resistance to co-trimoxazole (58%), penicillin (52.2% non-sensitive); tetracycline (29,1%); azithromycin (28,9%), and erythromycin (26,3%). Resistance to chloramphenicol was low (8.8%). Multiresistance was found at 29.5%. Resistance to azithromycin and penicillin was different in all seven regions (p<0,05), the highest percentage of non-sensitive strains being found in Arequipa (63,6%), whereas the lowest percentage was found in Cusco (23.4%). High levels of resistance found to penicillin, co-trimoxasole and macrolides in isolated pneumococcus strains of healthy carriers in all studied regions, and their association to a previous use of antibiotics, represent a significant public health problem in our country. This emphasizes the need to implement nationwide strategies to reduce the irrational use of antibiotics, especially among children. It is necessary to complement data of resistance to penicillin with the determination of minimal inhibitory concentration to make proper therapeutic recommendations.

Update on the combination effect of macrolide antibiotics in community-acquired pneumonia.

PubMed

Emmet O'Brien, M; Restrepo, Marcos I; Martin-Loeches, Ignacio

2015-09-01

Community-acquired pneumonia (CAP) is a leading cause of death from an infectious cause worldwide. Guideline-concordant antibiotic therapy initiated in a timely manner is associated with improved treatment responses and patient outcomes. In the post-antibiotic era, much of the morbidity and mortality of CAP is as a result of the interaction between bacterial virulence factors and host immune responses. In patients with severe CAP, or who are critically ill, there is a lot of emerging observational evidence demonstrating improved survival rates when treatment using combination therapy with a β-lactam and a macrolide is initiated, as compared to other antibiotic regimes without a macrolide. Macrolides in combination with a β-lactam antibiotic provide broader coverage for the atypical organisms implicated in CAP, and may contribute to antibacterial synergism. However, it has been postulated that the documented immunomodulatory effects of macrolides are the primary mechanism for improved patient outcomes through attenuation of bacterial virulence factors and host systemic inflammatory responses. Despite concerns regarding the limitations of observational evidence and the lack of confirmatory randomized controlled trials, the potential magnitude of mortality benefits estimated at 20-50% cannot be overlooked. In light of recent data from a number of trials showing that combination treatment with a macrolide and a suitable second agent is justified in all patients with severe CAP, such treatment should be obligatory for those admitted to an intensive care setting. Copyright © 2015 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Intracellular multiplication of Legionnaires' disease bacteria (Legionella pneumophila) in human monocytes is reversibly inhibited by erythromycin and rifampin.

PubMed Central

Horwitz, M A; Silverstein, S C

1983-01-01

We have previously reported that virulent egg yolk-grown Legionella pneumophila, Philadelphia 1 strain, multiplies intracellularly in human blood monocytes and only intracellularly under tissue culture conditions. In this paper, we have investigated the effect of erythromycin and rifampin on L. pneumophila-monocyte interaction in vitro; erythromycin and rifampin are currently the drugs of choice for the treatment of Legionnaires' disease. The intracellular multiplication of L. pneumophila is inhibited by erythromycin and rifampin, as measured by colony-forming units, whether the antibiotics are added just before or just after infection of monocytes with L. pneumophila, or 2 d after infection when L. pneumophila is in the logarithmic phase of growth in monocytes. Intracellular multiplication of L. pneumophila is inhibited by 1.25 microgram/ml but not less than or equal to 0.125 microgram/ml erythromycin and 0.01 microgram/ml but not less than or equal to 0.001 microgram/ml rifampin. These concentrations of antibiotics are comparable to those that inhibit extracellular multiplication of L. pneumophila under cell-free conditions in artificial medium; the minimal inhibitory concentration is 0.37 microgram/ml for erythromycin and 0.002 microgram/ml for rifampin. Multiplication of L. pneumophila in the logarithmic phase of growth in monocytes is inhibited within 1 h of the addition of antibiotics. Intracellular bacteria inhibited from multiplying by antibiotics are not killed. By electron microscopy, the bacteria appear intact within membrane-bound vacuoles, studded with ribosomelike structures. L. pneumophila multiplying extracellularly on artificial medium is killed readily by relatively low concentrations of erythromycin and rifampin; the minimal bactericidal concentration is 1 microgram/ml for erythromycin and 0.009 microgram/ml for rifampin. In contrast, L. pneumophila multiplying intracellularly is resistant to killing by these concentrations of erythromycin and rifampin or by concentrations equal to or greater than peak serum levels in humans. Extracellular L. pneumophila in stationary phase is also resistant to killing by erythromycin and rifampin. These findings, taken together with our previous work, indicate that, in vivo, L. pneumophila is resistant to killing by erythromycin and rifampin. Inhibition of L. pneumophila multiplication in monocytes by antibiotics is reversible; when the antibiotics are removed from infected monocyte cultures after 2 d, L. pneumophila resumes multiplication. This study indicates that patients with Legionnaires' disease under treatment with erythromycin and rifampin require host defenses to eliminate L. pneumophila, and that inadequate host defenses may result in relapse after cessation of therapy. PMID:6848556

Functional Repertoire of Antibiotic Resistance Genes in Antibiotic Manufacturing Effluents and Receiving Freshwater Sediments

PubMed Central

González-Plaza, Juan J.; Šimatović, Ana; Milaković, Milena; Bielen, Ana; Wichmann, Fabienne; Udiković-Kolić, Nikolina

2018-01-01

Environments polluted by direct discharges of effluents from antibiotic manufacturing are important reservoirs for antibiotic resistance genes (ARGs), which could potentially be transferred to human pathogens. However, our knowledge about the identity and diversity of ARGs in such polluted environments remains limited. We applied functional metagenomics to explore the resistome of two Croatian antibiotic manufacturing effluents and sediments collected upstream of and at the effluent discharge sites. Metagenomic libraries built from an azithromycin-production site were screened for resistance to macrolide antibiotics, whereas the libraries from a site producing veterinary antibiotics were screened for resistance to sulfonamides, tetracyclines, trimethoprim, and beta-lactams. Functional analysis of eight libraries identified a total of 82 unique, often clinically relevant ARGs, which were frequently found in clusters and flanked by mobile genetic elements. The majority of macrolide resistance genes identified from matrices exposed to high levels of macrolides were similar to known genes encoding ribosomal protection proteins, macrolide phosphotransferases, and transporters. Potentially novel macrolide resistance genes included one most similar to a 23S rRNA methyltransferase from Clostridium and another, derived from upstream unpolluted sediment, to a GTPase HflX from Emergencia. In libraries deriving from sediments exposed to lower levels of veterinary antibiotics, we found 8 potentially novel ARGs, including dihydrofolate reductases and beta-lactamases from classes A, B, and D. In addition, we detected 7 potentially novel ARGs in upstream sediment, including thymidylate synthases, dihydrofolate reductases, and class D beta-lactamase. Taken together, in addition to finding known gene types, we report the discovery of novel and diverse ARGs in antibiotic-polluted industrial effluents and sediments, providing a qualitative basis for monitoring the dispersal of ARGs from environmental hotspots such as discharge sites of pharmaceutical effluents. PMID:29387045

Fate of Antibiotic Resistant Bacteria and Genes during Wastewater Chlorination: Implication for Antibiotic Resistance Control

PubMed Central

Yuan, Qing-Bin; Guo, Mei-Ting; Yang, Jian

2015-01-01

This study investigated fates of nine antibiotic-resistant bacteria as well as two series of antibiotic resistance genes in wastewater treated by various doses of chlorine (0, 15, 30, 60, 150 and 300 mg Cl2 min/L). The results indicated that chlorination was effective in inactivating antibiotic-resistant bacteria. Most bacteria were inactivated completely at the lowest dose (15 mg Cl2 min/L). By comparison, sulfadiazine- and erythromycin-resistant bacteria exhibited tolerance to low chlorine dose (up to 60 mg Cl2 min/L). However, quantitative real-time PCRs revealed that chlorination decreased limited erythromycin or tetracycline resistance genes, with the removal levels of overall erythromycin and tetracycline resistance genes at 0.42 ± 0.12 log and 0.10 ± 0.02 log, respectively. About 40% of erythromycin-resistance genes and 80% of tetracycline resistance genes could not be removed by chlorination. Chlorination was considered not effective in controlling antimicrobial resistance. More concern needs to be paid to the potential risk of antibiotic resistance genes in the wastewater after chlorination. PMID:25738838

A new mosaic integrative and conjugative element from Streptococcus agalactiae carrying resistance genes for chloramphenicol (catQ) and macrolides [mef(I) and erm(TR)].

PubMed

Morici, Eleonora; Simoni, Serena; Brenciani, Andrea; Giovanetti, Eleonora; Varaldo, Pietro E; Mingoia, Marina

2017-01-01

To investigate the genetic basis of catQ-mediated chloramphenicol resistance in Streptococcus agalactiae. Two clinical strains of catQ-positive chloramphenicol-resistant S. agalactiae (Sag236 and Sag403) were recently isolated, typed (MLST, PFGE pulsotypes, capsular types) and their antibiotic resistances investigated by phenotypic and genotypic approaches. Several molecular methods (PCR mapping, restriction assays, Southern blotting, sequencing and sequence analysis, conjugal transfer assays) were used to determine the genetic context of catQ and characterize a genetic element detected in the isolates. Sag236 and Sag403 shared the same ST (ST19), but exhibited a different capsular type (III and V, respectively) and pulsotype. Both harboured the macrolide resistance genes mef(I) and erm(TR) and the tetracycline resistance gene tet(M). Accordingly, they were resistant to chloramphenicol, erythromycin and tetracycline. catQ and mef(I) were associated in an IQ module that was indistinguishable in Sag236 and Sag403. In mating assays, chloramphenicol and erythromycin resistance proved transferable, at low frequency, only from Sag236. Transconjugants carried not only catQ and mef(I), but also erm(TR), suggesting a linkage of the three resistance genes in a mobile element, which, though seemingly non-mobile, was also detected in Sag403. The new element (designated ICESag236, ∼110 kb) results from recombination of two integrative and conjugative elements (ICEs) originally described in different streptococcal species: S. agalactiae ICESagTR7, carrying erm(TR); and Streptococcus pneumoniae ICESpn529IQ, carrying the prototype IQ module. These findings strengthen the notion that widespread streptococcal ICEs may form mosaics that enhance their diversity and spread, broaden their host range and carry new cargo genes. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Drug safety of macrolide and quinolone antibiotics in a tertiary care hospital: administration of interacting co-medication and QT prolongation.

PubMed

Niedrig, David; Maechler, Sarah; Hoppe, Liesa; Corti, Natascia; Kovari, Helen; Russmann, Stefan

2016-07-01

Some macrolide and quinolone antibiotics (MQABs) are associated with QT prolongation and life-threatening torsade de pointes (TdP) arrhythmia. MQAB may also inhibit cytochrome P450 isoenzymes and thereby cause pharmacokinetic drug interactions (DDIs). There is limited data on the frequency and management of such risks in clinical practice. We aimed to quantify co-administration of MQAB with interacting drugs and associated adverse drug reactions. We conducted an observational study within our pharmacoepidemiological database derived from electronic medical records of a tertiary care hospital. Among all users of MQAB associated with TdP, we determined the prevalence of additional QT-prolonging drugs and risk factors and identified contraindicated co-administrations of simvastatin, atorvastatin, or tizanidine. Electrocardiographic (ECG) monitoring and associated adverse events were validated in medical records. Among 3444 administered courses of clarithromycin, erythromycin, azithromycin, ciprofloxacin, levofloxacin, or moxifloxacin, there were 1332 (38.7 %) with concomitant use of additional QT-prolonging drugs. Among those, we identified seven cases of drug-related QT prolongation, but 49.1 % had no ECG monitoring. Of all MQAB users, 547 (15.9 %) had hypokalemia. Forty-four MQAB users had contraindicated co-administrations of simvastatin, atorvastatin, or tizanidine and three of those related adverse drug reactions. In the studied real-life setting, we found a considerable number of MQAB users with additional risk factors for TdP but no ECG monitoring. However, adverse drug reactions were rarely found, and costs vs. benefits of ECG monitoring have to be weighted. In contrast, avoidable risk factors and selected contraindicated pharmacokinetic interactions are clear targets for implementation as automated alerts in electronic prescribing systems.

Treatment failure rates and health care utilization and costs among patients with community-acquired pneumonia treated with levofloxacin or macrolides in an outpatient setting: a retrospective claims database analysis.

PubMed

Ye, Xin; Sikirica, Vanja; Schein, Jeffrey R; Grant, Richard; Zarotsky, Victoria; Doshi, Dilesh; Benson, Carmela Janagap; Riedel, Aylin A

2008-02-01

Macrolide antibiotics and fluoroquinolones are extensively used in the treatment of community-acquired pneumonia (CAP). This analysis was conducted to compare treatment failure rates and health care utilization and cost outcomes among patients with CAP treated with levo-floxacin (500 or 750 mg) or macrolides (azithromycin, clarithromycin, or erythromycin) in an outpatient setting. This was a retrospective analysis of claims data from a large US health plan. Patients were aged > or =18 years and had a primary diagnosis of CAP that was treated with oral levofloxacin or a macrolide in an outpatient setting (including physicians' offices, outpatient clinics, urgent care centers, and large ambulatory health centers). Patients were followed for 30 days after the index drug date to measure study outcomes. Multivariate regression analysis and a propensity score technique were used to compare rates of treatment failure and CAP-related health care utilization and costs. Two post hoc subgroup analyses were conducted in patients aged > or =50 and > or =65 years. Of the 7526 patients meeting the inclusion criteria, 2968 (39.4%) were treated with levofloxacin and 4558 (60.6%) with a macrolide. Unadjusted rates of treatment failure were 21.1% and 22.7% in the levofloxacin and macrolide cohorts, respectively. After adjustment for demographic characteristics, baseline comorbidities, and severity of illness, levofloxacin recipients were significantly less likely to experience treatment failure than macrolide recipients (odds ratio [OR] = 0.84; 95% CI, 0.75-0.94, P = 0.003). The likelihood of treatment failure was significantly lower in levofloxacin recipients aged > or =50 years (OR = 0.79; 95% CI, 0.66-0.94; P = 0.007) and > or =65 years (OR = 0.65; 95% CI, 0.43-1.00; P = 0.049) compared with the corresponding subgroups of macrolide recipients. The magnitude of this difference was greatest in the subgroup aged > or =65 years, which had a 35% reduced risk of treatment failure compared with the corresponding group of macrolide-treated patients. The rate of CAP-related emergency department visits was significantly lower among patients receiving levofloxa-cin (OR = 0.68; 95% CI, 0.51-0.91; P = 0.009); there were no differences in CAP-related hospitalizations or total CAP-related health care costs between levofloxa-cin and macrolide recipients. Multivariate-adjusted rates of treatment failure in outpatients with CAP were significantly lower in those treated with levofloxacin relative to those treated with a macrolide. The lower rates of treatment failure with levofloxacin were consistently observed across all patients and in the subgroups aged > or =50 and > or =65 years. Rates of emergency department visits were also significantly lower among levofloxacin-treated patients, whereas overall CAP-related hospitali-zations and costs did not differ significantly between the 2 treatment groups.

Whole Genome Sequence Analysis of Pig Respiratory Bacterial Pathogens with Elevated Minimum Inhibitory Concentrations for Macrolides.

PubMed

Dayao, Denise Ann Estarez; Seddon, Jennifer M; Gibson, Justine S; Blackall, Patrick J; Turni, Conny

2016-10-01

Macrolides are often used to treat and control bacterial pathogens causing respiratory disease in pigs. This study analyzed the whole genome sequences of one clinical isolate of Actinobacillus pleuropneumoniae, Haemophilus parasuis, Pasteurella multocida, and Bordetella bronchiseptica, all isolated from Australian pigs to identify the mechanism underlying the elevated minimum inhibitory concentrations (MICs) for erythromycin, tilmicosin, or tulathromycin. The H. parasuis assembled genome had a nucleotide transition at position 2059 (A to G) in the six copies of the 23S rRNA gene. This mutation has previously been associated with macrolide resistance but this is the first reported mechanism associated with elevated macrolide MICs in H. parasuis. There was no known macrolide resistance mechanism identified in the other three bacterial genomes. However, strA and sul2, aminoglycoside and sulfonamide resistance genes, respectively, were detected in one contiguous sequence (contig 1) of A. pleuropneumoniae assembled genome. This contig was identical to plasmids previously identified in Pasteurellaceae. This study has provided one possible explanation of elevated MICs to macrolides in H. parasuis. Further studies are necessary to clarify the mechanism causing the unexplained macrolide resistance in other Australian pig respiratory pathogens including the role of efflux systems, which were detected in all analyzed genomes.

Overview of antimicrobial options for Mycoplasma pneumoniae pneumonia: focus on macrolide resistance.

PubMed

Cao, Bin; Qu, Jiu-Xin; Yin, Yu-Dong; Eldere, Johan Van

2017-07-01

Community-acquired pneumonia (CAP) is a common infectious disease affecting children and adults of any age. Mycoplasma pneumoniae has emerged as leading causative agent of CAP in some region, and the abrupt increasing resistance to macrolide that widely used for management of M. pneumoniae has reached to the level that it often leads to treatment failures. We aim to discuss the drivers for development of macrolide-resistant M. pneumoniae, antimicrobial stewardship and also the potential treatment options for patients infected with macrolide-resistant M. pneumonia. The articles in English and Chinese published in Pubmed and in Asian medical journals were selected for the review. M. pneumoniae can develop macrolide resistance by point mutations in the 23S rRNA gene. Inappropriate and overuse of macrolides for respiratory tract infections may induce the resistance rapidly. A number of countries have introduced the stewardship program for restricting the use of macrolide. Tetracyclines and fluoroquinolones are highly effective for macrolide-resistant strains, which may be the substitute in the region of high prevalence of macrolide-resistant M. pneumoniae. The problem of macrolide resistant M. pneumonia is emerging. Antibiotic stewardship is needed to inhibit the inappropriate use of macrolide and new antibiotics with a more acceptable safety profile for all ages need to be explored. © 2015 John Wiley & Sons Ltd.

Pathogen- and host-directed anti-inflammatory activities of macrolide antibiotics.

PubMed

Steel, Helen C; Theron, Annette J; Cockeran, Riana; Anderson, Ronald; Feldman, Charles

2012-01-01

Macrolide antibiotics possess several, beneficial, secondary properties which complement their primary antimicrobial activity. In addition to high levels of tissue penetration, which may counteract seemingly macrolide-resistant bacterial pathogens, these agents also possess anti-inflammatory properties, unrelated to their primary antimicrobial activity. Macrolides target cells of both the innate and adaptive immune systems, as well as structural cells, and are beneficial in controlling harmful inflammatory responses during acute and chronic bacterial infection. These secondary anti-inflammatory activities of macrolides appear to be particularly effective in attenuating neutrophil-mediated inflammation. This, in turn, may contribute to the usefulness of these agents in the treatment of acute and chronic inflammatory disorders of both microbial and nonmicrobial origin, predominantly of the airways. This paper is focused on the various mechanisms of macrolide-mediated anti-inflammatory activity which target both microbial pathogens and the cells of the innate and adaptive immune systems, with emphasis on their clinical relevance.

Pathogen- and Host-Directed Anti-Inflammatory Activities of Macrolide Antibiotics

PubMed Central

Steel, Helen C.; Theron, Annette J.; Cockeran, Riana; Anderson, Ronald; Feldman, Charles

2012-01-01

Macrolide antibiotics possess several, beneficial, secondary properties which complement their primary antimicrobial activity. In addition to high levels of tissue penetration, which may counteract seemingly macrolide-resistant bacterial pathogens, these agents also possess anti-inflammatory properties, unrelated to their primary antimicrobial activity. Macrolides target cells of both the innate and adaptive immune systems, as well as structural cells, and are beneficial in controlling harmful inflammatory responses during acute and chronic bacterial infection. These secondary anti-inflammatory activities of macrolides appear to be particularly effective in attenuating neutrophil-mediated inflammation. This, in turn, may contribute to the usefulness of these agents in the treatment of acute and chronic inflammatory disorders of both microbial and nonmicrobial origin, predominantly of the airways. This paper is focused on the various mechanisms of macrolide-mediated anti-inflammatory activity which target both microbial pathogens and the cells of the innate and adaptive immune systems, with emphasis on their clinical relevance. PMID:22778497

Susceptibility to antimicrobial agents among bovine mastitis pathogens isolated from North American dairy cattle, 2002-2010.

PubMed

Lindeman, Cynthia J; Portis, Ellen; Johansen, Lacie; Mullins, Lisa M; Stoltman, Gillian A

2013-09-01

Approximately 8,000 isolates of Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus uberis, Staphylococcus aureus, and Escherichia coli, isolated by 25 veterinary laboratories across North America between 2002 and 2010, were tested for in vitro susceptibility to beta-lactam, macrolide, and lincosamide drugs. The minimal inhibitory concentrations (MICs) of the beta-lactam drugs remained low against most of the Gram-positive strains tested, and no substantial changes in the MIC distributions were seen over time. Of the beta-lactam antimicrobial agents tested, only ceftiofur showed good in vitro activity against E. coli. The MICs of the macrolides and lincosamides also remained low against Gram-positive mastitis pathogens. While the MIC values given by 50% of isolates (MIC50) for erythromycin and pirlimycin and the streptococci were all low (≤0.5 µg/ml), the MIC values given by 90% of isolates (MIC90) were higher and more variable, but with no apparent increase over time. Staphylococcus aureus showed little change in erythromycin susceptibility over time, but there may be a small, numerical increase in pirlimycin MIC50 and MIC90 values. Overall, the results suggest that mastitis pathogens in the United States and Canada have not shown any substantial changes in the in vitro susceptibility to beta-lactam, macrolide, and lincosamide drugs tested over the 9 years of the study.

Occurrence and partitioning of antibiotic compounds found in the water column and bottom sediments from a stream receiving two wastewater treatment plant effluents in northern New Jersey, 2008.

PubMed

Gibs, Jacob; Heckathorn, Heather A; Meyer, Michael T; Klapinski, Frank R; Alebus, Marzooq; Lippincott, Robert L

2013-08-01

An urban watershed in northern New Jersey was studied to determine the presence of four classes of antibiotic compounds (macrolides, fluoroquinolones, sulfonamides, and tetracyclines) and six degradates in the water column and bottom sediments upstream and downstream from the discharges of two wastewater treatment plants (WWTPs) and a drinking-water intake (DWI). Many antibiotic compounds in the four classes not removed by conventional WWTPs enter receiving waters and partition to stream sediments. Samples were collected at nine sampling locations on 2 days in September 2008. Two of the nine sampling locations were background sites upstream from two WWTP discharges on Hohokus Brook. Another background site was located upstream from a DWI on the Saddle River above the confluence with Hohokus Brook. Because there is a weir downstream of the confluence of Hohokus Brook and Saddle River, the DWI receives water from Hohokus Brook at low stream flows. Eight antibiotic compounds (azithromycin (maximum concentration 0.24 μg/L), ciprofloxacin (0.08 μg/L), enrofloxacin (0.015 μg/L), erythromycin (0.024 μg/L), ofloxacin (0.92 μg/L), sulfamethazine (0.018 μg/L), sulfamethoxazole (0.25 μg/L), and trimethoprim (0.14 μg/L)) and a degradate (erythromycin-H2O (0.84 μg/L)) were detected in the water samples from the sites downstream from the WWTP discharges. The concentrations of six of the eight detected compounds and the detected degradate compound decreased with increasing distance downstream from the WWTP discharges. Azithromycin, ciprofloxacin, ofloxacin, and trimethoprim were detected in stream-bottom sediments. The concentrations of three of the four compounds detected in sediments were highest at a sampling site located downstream from the WWTP discharges. Trimethoprim was detected in the sediments from a background site. Pseudo-partition coefficients normalized for streambed sediment organic carbon concentration were calculated for azithromycin, ciprofloxacin, and ofloxacin. Generally, there was good agreement between the decreasing order of the pseudo-partition coefficients in this study and the order reported in the literature. Published by Elsevier B.V.

Occurence of antibiotic compounds found in the water column and bottom sediments from a stream receiving two waste water treatment plant effluents in northern New Jersey, 2008

USGS Publications Warehouse

Gibs, Jacob; Heckathorn, Heather A.; Meyer, Michael T.; Klapinski, Frank R.; Alebus, Marzooq; Lippincott, Robert

2013-01-01

An urban watershed in northern New Jersey was studied to determine the presence of four classes of antibiotic compounds (macrolides, fluoroquinolones, sulfonamides, and tetracyclines) and six degradates in the water column and bottom sediments upstream and downstream from the discharges of two wastewater treatment plants (WWTPs) and a drinking-water intake (DWI). Many antibiotic compounds in the four classes not removed by conventional WWTPs enter receiving waters and partition to stream sediments. Samples were collected at nine sampling locations on 2 days in September 2008. Two of the nine sampling locations were background sites upstream from two WWTP discharges on Hohokus Brook. Another background site was located upstream from a DWI on the Saddle River above the confluence with Hohokus Brook. Because there is a weir downstream of the confluence of Hohokus Brook and Saddle River, the DWI receives water from Hohokus Brook at low stream flows. Eight antibiotic compounds (azithromycin (maximum concentration 0.24 μg/L), ciprofloxacin (0.08 μg/L), enrofloxacin (0.015 μg/L), erythromycin (0.024 μg/L), ofloxacin (0.92 μg/L), sulfamethazine (0.018 μg/L), sulfamethoxazole (0.25 μg/L), and trimethoprim (0.14 μg/L)) and a degradate (erythromycin-H2O (0.84 μg/L)) were detected in the water samples from the sites downstream from the WWTP discharges. The concentrations of six of the eight detected compounds and the detected degradate compound decreased with increasing distance downstream from the WWTP discharges. Azithromycin, ciprofloxacin, ofloxacin, and trimethoprim were detected in stream-bottom sediments. The concentrations of three of the four compounds detected in sediments were highest at a sampling site located downstream from the WWTP discharges. Trimethoprim was detected in the sediments from a background site. Pseudo-partition coefficients normalized for streambed sediment organic carbon concentration were calculated for azithromycin, ciprofloxacin, and ofloxacin. Generally, there was good agreement between the decreasing order of the pseudo-partition coefficients in this study and the order reported in the literature.

Appropriate antibiotic therapy improves Ureaplasma sepsis outcome in the neonatal mouse.

PubMed

Weisman, Leonard E; Leeming, Angela H; Kong, Lingkun

2012-11-01

Ureaplasma causes sepsis in human neonates. Although erythromycin has been the standard treatment, it is not always effective. No published reports have evaluated Ureaplasma sepsis in a neonatal model. We hypothesized that appropriate antibiotic treatment improves Ureaplasma sepsis in a neonatal mouse model. Two ATCC strains and two clinical strains of Ureaplasma were evaluated in vitro for antibiotic minimum inhibitory concentration (MIC). In addition, FVB albino mice pups infected with Ureaplasma were randomly assigned to saline, erythromycin, or azithromycin therapy and survival, quantitative blood culture, and growth were evaluated. MICs ranged from 0.125 to 62.5 µg/ml and 0.25 to 1.0 µg/ml for erythromycin and azithromycin, respectively. The infecting strain and antibiotic selected for treatment appeared to affect survival and bacteremia, but only the infecting strain affected growth. Azithromycin improved survival and bacteremia against each strain, whereas erythromycin was effective against only one of four strains. We have established a neonatal model of Ureaplasma sepsis and observed that treatment outcome is related to infecting strain and antibiotic treatment. We speculate that appropriate antibiotic selection and dosing are required for effective treatment of Ureaplasma sepsis in neonates, and this model could be used to further evaluate these relationships.

Activities of two novel macrolides, GW 773546 and GW 708408, compared with those of telithromycin, erythromycin, azithromycin, and clarithromycin against Haemophilus influenzae.

PubMed

Kosowska, Klaudia; Credito, Kim; Pankuch, Glenn A; Hoellman, Dianne; Lin, Gengrong; Clark, Catherine; Dewasse, Bonifacio; McGhee, Pamela; Jacobs, Michael R; Appelbaum, Peter C

2004-11-01

The MIC at which 50% of strains are inhibited (MIC(50)) and the MIC(90) of GW 773546, a novel macrolide, were 1.0 and 2.0 microg/ml, respectively, for 223 beta-lactamase-positive, beta-lactamase-negative, and beta-lactamase-negative ampicillin-resistant Haemophilus influenzae strains. The MIC(50)s and MIC(90)s of GW 708408, a second novel macrolide, and telithromycin, an established ketolide, were 2.0 and 4.0 microg/ml, respectively, while the MIC(50) and MIC(90) of azithromycin were 1.0 and 2.0 microg/ml, respectively. The MIC(50) and MIC(90) of erythromycin were 4.0 and 8.0 microg/ml, respectively; and those of clarithromycin were 4.0 and 16.0 microg/ml, respectively. All compounds except telithromycin were bactericidal (99.9% killing) against nine strains at two times the MIC after 24 h. Telithromycin was bactericidal against eight of the nine strains. In addition, both novel macrolides and telithromycin at two times the MIC showed 99% killing of all nine strains after 12 h and 90% killing of all strains after 6 h. After 24 h, all drugs were bactericidal against four to seven strains when they were tested at the MIC. Ten of 11 strains tested by multistep selection analysis yielded resistant clones after 14 to 43 passages with erythromycin. Azithromycin gave resistant clones of all strains after 20 to 50 passages, and clarithromycin gave resistant clones of 9 of 11 strains after 14 to 41 passages. By comparison, GW 708408 gave resistant clones of 9 of 11 strains after 14 to 44 passages, and GW 773546 gave resistant clones of 10 of 11 strains after 14 to 45 passages. Telithromycin gave resistant clones of 7 of 11 strains after 18 to 45 passages. Mutations mostly in the L22 and L4 ribosomal proteins and 23S rRNA were detected in resistant strains selected with all compounds, with alterations in the L22 protein predominating. Single-step resistance selection studies at the MIC yielded spontaneous resistant mutants at frequencies of 1.5 x 10(-9) to 2.2 x 10(-6) with GW 773546, 1.5 x 10(-9) to 6.0 x 10(-4) with GW 708408, and 7.1 x 10(-9) to 3.8 x 10(-4) with telithromycin, whereas the frequencies were 1.3 x 10(-9) to 6.0 x 10(-4) with erythromycin and azithromycin and 2.0 x 10(-9) to 2.0 x 10(-3) with clarithromycin. Alterations in the L22 protein (which were predominant) and the L4 protein were present in mutants selected by the single-step selection process. The postantibiotic effects of GW 773546, GW 708408, and telithromycin for seven H. influenzae strains were 6.6 h (range, 5.2 to 8.8 h), 4.7 h (range, 2.6 to 6.9 h), and 6.4 h (range, 3.8 to 9.7 h), respectively. The results of in vitro studies obtained with both novel macrolides were similar to those obtained with telithromycin and better than those obtained with older macrolides.

Activities of Two Novel Macrolides, GW 773546 and GW 708408, Compared with Those of Telithromycin, Erythromycin, Azithromycin, and Clarithromycin against Haemophilus influenzae

PubMed Central

Kosowska, Klaudia; Credito, Kim; Pankuch, Glenn A.; Hoellman, Dianne; Lin, Gengrong; Clark, Catherine; Dewasse, Bonifacio; McGhee, Pamela; Jacobs, Michael R.; Appelbaum, Peter C.

2004-01-01

The MIC at which 50% of strains are inhibited (MIC50) and the MIC90 of GW 773546, a novel macrolide, were 1.0 and 2.0 μg/ml, respectively, for 223 β-lactamase-positive, β-lactamase-negative, and β-lactamase-negative ampicillin-resistant Haemophilus influenzae strains. The MIC50s and MIC90s of GW 708408, a second novel macrolide, and telithromycin, an established ketolide, were 2.0 and 4.0 μg/ml, respectively, while the MIC50 and MIC90 of azithromycin were 1.0 and 2.0 μg/ml, respectively. The MIC50 and MIC90 of erythromycin were 4.0 and 8.0 μg/ml, respectively; and those of clarithromycin were 4.0 and 16.0 μg/ml, respectively. All compounds except telithromycin were bactericidal (99.9% killing) against nine strains at two times the MIC after 24 h. Telithromycin was bactericidal against eight of the nine strains. In addition, both novel macrolides and telithromycin at two times the MIC showed 99% killing of all nine strains after 12 h and 90% killing of all strains after 6 h. After 24 h, all drugs were bactericidal against four to seven strains when they were tested at the MIC. Ten of 11 strains tested by multistep selection analysis yielded resistant clones after 14 to 43 passages with erythromycin. Azithromycin gave resistant clones of all strains after 20 to 50 passages, and clarithromycin gave resistant clones of 9 of 11 strains after 14 to 41 passages. By comparison, GW 708408 gave resistant clones of 9 of 11 strains after 14 to 44 passages, and GW 773546 gave resistant clones of 10 of 11 strains after 14 to 45 passages. Telithromycin gave resistant clones of 7 of 11 strains after 18 to 45 passages. Mutations mostly in the L22 and L4 ribosomal proteins and 23S rRNA were detected in resistant strains selected with all compounds, with alterations in the L22 protein predominating. Single-step resistance selection studies at the MIC yielded spontaneous resistant mutants at frequencies of 1.5 × 10−9 to 2.2 × 10−6 with GW 773546, 1.5 × 10−9 to 6.0 × 10−4 with GW 708408, and 7.1 × 10−9 to 3.8 × 10−4 with telithromycin, whereas the frequencies were 1.3 × 10−9 to 6.0 × 10−4 with erythromycin and azithromycin and 2.0 × 10−9 to 2.0 × 10−3 with clarithromycin. Alterations in the L22 protein (which were predominant) and the L4 protein were present in mutants selected by the single-step selection process. The postantibiotic effects of GW 773546, GW 708408, and telithromycin for seven H. influenzae strains were 6.6 h (range, 5.2 to 8.8 h), 4.7 h (range, 2.6 to 6.9 h), and 6.4 h (range, 3.8 to 9.7 h), respectively. The results of in vitro studies obtained with both novel macrolides were similar to those obtained with telithromycin and better than those obtained with older macrolides. PMID:15504829

Macrolides versus azalides: a drug interaction update.

PubMed

Amsden, G W

1995-09-01

To describe the current drug interaction profiles for all approved and investigational macrolide and azalide antimicrobials, and to comment on the clinical impact of these interactions when appropriate. MEDLINE was searched to identify all pertinent studies, review articles, and case reports from 1975 to 1995. When appropriate information was not available in the literature, data were obtained from the product manufacturers. All available data were reviewed to give an unbiased account of possible drug interactions. Data for some of the interactions were not available from the literature, but were available from abstracts or from company-supplied materials. Although the data were not always entirely explicative, the best attempt was made to deliver the pertinent information that clinical practitioners would need to formulate practice opinions. When more in-depth information was supplied in the form of a review or study report, a thorough explanation of pertinent methodology was supplied. Since the introduction of erythromycin into clinical practice, there have been several clinically significant drug interactions identified throughout the literature associated with this drug. These interactions have been caused mostly by inhibition of the CYP3A subclass of hepatic enzymes, thereby decreasing the metabolism of any other agent given concurrently that is also cleared through this mechanism. With the development and marketing of several new macrolides, it was hoped that the drug interaction profile associated with this class would improve. This has been met with variable success. Although some of the extensions of the 14-membered ring macrolides have shown an incidence of interactions equal to that of erythromycin, others have shown improved profiles. In contrast, the 16-membered ring macrolides have demonstrated a much improved, though not absent, interaction profile. The most success in avoiding drug interactions through structure modification has been accomplished with the development of the azalide class, of which azithromycin is the first to be approved for marketing. This agent has to date produced none of the classic drug interactions that most macrolides have demonstrated in patient care. The introduction of new 14- and 16-membered ring macrolides appears to have had a variable effect in modifying the incidence of drug interactions associated with this class. Azithromycin, a member of the new azalide class, has to date produced fewer clinically significant interactions than other azalides with any agent that is cleared through the CYP3A system.(ABSTRACT TRUNCATED AT 250 WORDS)

[Antibiotic resistance to erythromycin, clindamycin and tetracycline of 573 strains of Streptococcus pyogenes (1992-1994)].

PubMed

Orden, B; Martínez, R; López de los Mozos, A; Franco, A

1996-02-01

The aim of this study was to know the antibiotic resistence of Streptococcus pyogenes to erythromycine, clindamycine and/or tetracycline in community samples. The second aim was to determine the existence of multiresistant strains and to know the relationship between resistant strains, clinical samples and age of the patient. A retrospective analysis was performed in all the strains of S. pyogenes isolated from January 1992 to December 1994. Antibiotic sensitivity was studied by MIC by the microdilution method using the Pasco semiautomatic system. During the study period 573 beta hemolytic streptococci were identified as S. pyogenes. The global resistance to erythromycine (2.8%), clindamycine (1.4%) and tetracycline (7.3%) remains at low levels but has significantly increased in the case of erythromycine (p < 0.05) and tetracycline (p < 0.05) over these 3 years. The incidence of strains resistant to clindamycine has also increased slowly although this rise is not significant. Five strains (0.9%) were not sensitive to the three antibiotics studied, 4 being isolated in the last trimester of 1994 in pharyngeal exudates. S. pyogenes resistant to erythromycine was most frequently isolated from cutaneous lesions and in pediatric patients (under the age of 14 years). These results confirm the trend towards an increase in the number of strains of S. pyogenes resistant to erythromycine, clindamycine and/or tetracycline, being most often found in cutaneous lesions and pediatric patients.

Synthesis and antibacterial activity of novel 15-membered macrolide derivatives: 4''-carbamate, 11,12-cyclic carbonate-4''-carbamate and 11,4''-di-O-arylcarbamoyl analogs of azithromycin.

PubMed

Ma, Shutao; Ma, Ruixin; Liu, Zhaopeng; Ma, Chenchen; Shen, Xuecui

2009-10-01

4''-Carbamate, 11,12-cyclic carbonate-4''-carbamate and 11,4''-di-O-arylcarbamoyl analogs of azithromycin were designed, synthesized and evaluated. The 4''-carbamate analogs retained excellent activity against erythromycin-susceptible Staphylococcus pneumoniae and showed improved activity against erythromycin-resistant Staphylococcus pneumoniae. Compared with 4''-carbamate analogs, 11,12-cyclic carbonate-4''-carbamate analogs exhibited improved activity against erythromycin-resistant Staphylococcus pneumoniae encoded by the mef gene or the erm and mef genes, and 11,4''-di-O-arylalkylcarbamoyl analogs showed greatly improved activity (0.25-0.5 microg/mL) against erythromycin-resistant Staphylococcus pneumoniae encoded by the erm gene. Among them, the novel series of 11,4''-di-O-arylalkylcarbamoyl analogs 7a-k exhibited potent and balanced activity against susceptible and resistant bacteria. In particular, compounds 7f and 7k were the most effective against susceptible bacteria and resistant bacteria encoded by the erm gene or the mef gene.

A CASE STUDY: CROP (LETTUCE, SPINACH, AND CARROTS) UPTAKE OF THREE MACROLIDE ANTIBIOTICS (AZITHROMYCIN, CLINDAMYCIN AND ROXITHROMYCIN) AND OTHER DRUGS

EPA Science Inventory

It has been shown that human-use macrolide antibiotics (azithromycin, clindamycin, and roxithromycin) are environmentally available in wastewaters, source waters, and biosolids. In order to better understand the fate of these compounds into food crops via root migration, we condu...

Microbial selectivity of UV treatment on antibiotic-resistant heterotrophic bacteria in secondary effluents of a municipal wastewater treatment plant.

PubMed

Guo, Mei-Ting; Yuan, Qing-Bin; Yang, Jian

2013-10-15

Little is known about the microbial selectivity of UV treatment for antibiotic resistant bacteria, and the results of limited studies are conflicting. To understand the effect of UV disinfection on antibiotic resistant bacteria, both total heterotrophic bacteria and antibiotic resistant bacteria (including cephalexin-, ciprofloxacin-, erythromycin-, gentamicin-, vancomycin-, sulfadiazine-, rifampicin-, tetracycline- and chloramphenicol-resistant bacteria) were examined in secondary effluent samples from a municipal wastewater treatment plant. Bacteria resistant to both erythromycin and tetracycline were chosen as the representative of multiple-antibiotic-resistant bacteria and their characteristics after UV treatment were also investigated. UV disinfection results in effective inactivation for total heterotrophic bacteria, as well as all antibiotic resistant bacteria. After UV treatment at a fluence of 5 mJ/cm(2), the log reductions of nine types of antibiotic resistant bacteria varied from 1.0 ± 0.1 to 2.4 ± 0.1. Bacteria resistant to both erythromycin and tetracycline had a similar fluence response as did total heterotrophic bacteria. The findings suggest that UV disinfection could eliminate antibiotic resistance in wastewater treatment effluents and thus ensure public health security. Our experimental results indicated that UV disinfection led to enrichment of bacteria with resistance to sulfadiazine, vancomycin, rifampicin, tetracycline and chloramphenicol, while the proportions of cephalexin-, erythromycin-, gentamicin- and ciprofloxacin-resistant bacteria in the wastewater decreased. This reveals the microbial selectivity of UV disinfection for antibiotic resistant bacteria. Copyright © 2013 Elsevier Ltd. All rights reserved.

Macrolide antibiotic interaction and resistance on the bacterial ribosome.

PubMed

Poehlsgaard, Jacob; Douthwaite, Stephen

2003-02-01

Our understanding of the fine structure of many antibiotic target sites has reached a new level of enlightenment in the last couple of years due to the advent, by X-ray crystallography, of high-resolution structures of the bacterial ribosome. Many classes of clinically useful antibiotics bind to the ribosome to inhibit bacterial protein synthesis. Macrolide, lincosamide and streptogramin B (MLSB) antibiotics form one of the largest groups, and bind to the same site on the 50S ribosomal subunit. Here, we review the molecular details of the ribosomal MLSB site to put into perspective the main points from a wealth of biochemical and genetic data that have been collected over several decades. The information is now available to understand, at atomic resolution, how macrolide antibiotics interact with their ribosomal target, how the target is altered to confer resistance, and in which directions we need to look if we are to rationally design better drugs to overcome the extant resistance mechanisms.

Macrolide therapy is associated with reduced mortality in acute respiratory distress syndrome (ARDS) patients.

PubMed

Simonis, Fabienne D; de Iudicibus, Gianfranco; Cremer, Olaf L; Ong, David S Y; van der Poll, Tom; Bos, Lieuwe D; Schultz, Marcus J

2018-01-01

Macrolides have been associated with favorable immunological effects in various inflammatory disease states. We investigated the association between macrolide therapy and mortality in patients with the acute respiratory distress syndrome (ARDS). This was an unplanned secondary analysis of patients with ARDS within a large prospective observational study of critically ill patients in the intensive care units (ICUs) of two university-affiliated hospitals in the Netherlands. The exposure of interest was low-dose macrolide use prescribed for another reason than infection; we excluded patients who received high-dose macrolides for an infection. The primary endpoint was 30-day mortality. The association between macrolide therapy and mortality was determined in the whole cohort, as well as in a propensity score matched cohort; the association was compared between pulmonary versus non-pulmonary ARDS, and between two biological phenotypes based on plasma levels of 20 biomarkers. In total, 873 patients with ARDS were analyzed, of whom 158 patients (18%) received macrolide therapy during stay in ICU for a median duration of 3 (interquartile range, 1-4) days. Erythromycin was the most frequent prescribed macrolide (97%). Macrolide therapy was associated with reduced 30-day mortality in the whole cohort [22.8% vs. 31.6%; crude odds ratio (OR), 0.64 (interquartile range, 0.43-0.96), P=0.03]. The association in the propensity score matched cohort remained significant [22.8% vs. 32.9%; OR, 0.62 (interquartile range, 0.39-0.96), P=0.03]. Propensity matched associations with mortality were different in patients with non-pulmonary ARDS vs. pulmonary ARDS and also varied by biological phenotype. These data together show that low-dose macrolide therapy prescribed for another reason than infection is associated with decreased mortality in patients with ARDS.

Macrolide therapy is associated with reduced mortality in acute respiratory distress syndrome (ARDS) patients

PubMed Central

de Iudicibus, Gianfranco; Cremer, Olaf L.; Ong, David S. Y.; van der Poll, Tom; Bos, Lieuwe D.; Schultz, Marcus J.

2018-01-01

Background Macrolides have been associated with favorable immunological effects in various inflammatory disease states. We investigated the association between macrolide therapy and mortality in patients with the acute respiratory distress syndrome (ARDS). Methods This was an unplanned secondary analysis of patients with ARDS within a large prospective observational study of critically ill patients in the intensive care units (ICUs) of two university-affiliated hospitals in the Netherlands. The exposure of interest was low-dose macrolide use prescribed for another reason than infection; we excluded patients who received high-dose macrolides for an infection. The primary endpoint was 30-day mortality. The association between macrolide therapy and mortality was determined in the whole cohort, as well as in a propensity score matched cohort; the association was compared between pulmonary versus non-pulmonary ARDS, and between two biological phenotypes based on plasma levels of 20 biomarkers. Results In total, 873 patients with ARDS were analyzed, of whom 158 patients (18%) received macrolide therapy during stay in ICU for a median duration of 3 (interquartile range, 1–4) days. Erythromycin was the most frequent prescribed macrolide (97%). Macrolide therapy was associated with reduced 30-day mortality in the whole cohort [22.8% vs. 31.6%; crude odds ratio (OR), 0.64 (interquartile range, 0.43–0.96), P=0.03]. The association in the propensity score matched cohort remained significant [22.8% vs. 32.9%; OR, 0.62 (interquartile range, 0.39–0.96), P=0.03]. Propensity matched associations with mortality were different in patients with non-pulmonary ARDS vs. pulmonary ARDS and also varied by biological phenotype. Conclusions These data together show that low-dose macrolide therapy prescribed for another reason than infection is associated with decreased mortality in patients with ARDS. PMID:29430441

Comparison of the activity of three antibiotic regimens in severe Legionnaires' disease.

PubMed

Dournon, E; Mayaud, C; Wolff, M; Schlemmer, B; Samuel, D; Sollet, J P; Levasseur-Rajagopalan, P

1990-10-01

Comparison of the activity of different antibiotic regimens in Legionnaire's disease has never been made because of the rarity of well documented cases of that disease. We have retrospectively compared severe cases of Legionnaires' disease treated with pefloxacin alone or in combination with erythromycin and/or rifampicin using computer-matched cases treated either with erythromycin or with erythromycin in combination with rifampicin. This study suggests that: (1) combined therapy including erythromycin, rifampicin and/or pefloxacin is superior to therapy with erythromycin alone; (2) combinations including pefloxacin may be the most active ones; and (3) pefloxacin alone may be as active as combination therapy. Although these results are in agreement with data obtained in cell and in animal models of legionella infection they need to be further confirmed by the study of larger number of patients.

Macrolide resistance mechanisms in Enterobacteriaceae: Focus on azithromycin.

PubMed

Gomes, Cláudia; Martínez-Puchol, Sandra; Palma, Noemí; Horna, Gertrudis; Ruiz-Roldán, Lidia; Pons, Maria J; Ruiz, Joaquim

2017-02-01

From its introduction in 1952 onwards, the clinical use of macrolides has been steadily increasing, both in human and veterinary medicine. Although initially designed to the treatment of Gram-positive microorganisms, this antimicrobial family has also been used to treat specific Gram-negative bacteria. Some of them, as azithromycin, are considered in the armamentarium against Enterobacteriaceae infections. However, the facility that this bacterial genus has to gain or develop mechanisms of antibiotic resistance may compromise the future usefulness of these antibiotics to fight against Enterobacteriaceae infections. The present review is focused on the mechanisms of macrolide resistance, currently described in Enterobacteriaceae.

Removal of antibiotics and antibiotic resistance genes from domestic sewage by constructed wetlands: Effect of flow configuration and plant species.

PubMed

Chen, Jun; Ying, Guang-Guo; Wei, Xiao-Dong; Liu, You-Sheng; Liu, Shuang-Shuang; Hu, Li-Xin; He, Liang-Ying; Chen, Zhi-Feng; Chen, Fan-Rong; Yang, Yong-Qiang

2016-11-15

This study aims to investigate the removal of antibiotics and antibiotic resistance genes (ARGs) in raw domestic wastewater by various mesocosm-scale constructed wetlands (CWs) with different flow configurations or plant species including the constructed wetland with or without plant. Six mesocosm-scale CWs with three flow types (surface flow, horizontal subsurface flow and vertical subsurface flow) and two plant species (Thaliadealbata Fraser and Iris tectorum Maxim) were set up in the outdoor. 8 antibiotics including erythromycin-H2O (ETM-H2O), monensin (MON), clarithromycin (CTM), leucomycin (LCM), sulfamethoxazole (SMX), trimethoprim (TMP), sulfamethazine (SMZ) and sulfapyridine (SPD) and 12 genes including three sulfonamide resistance genes (sul1, sul2 and sul3), four tetracycline resistance genes (tetG, tetM, tetO and tetX), two macrolide resistance genes (ermB and ermC), two chloramphenicol resistance genes (cmlA and floR) and 16S rRNA (bacteria) were determined in different matrices (water, particle, substrate and plant phases) from the mesocosm-scale systems. The aqueous removal efficiencies of total antibiotics ranged from 75.8 to 98.6%, while those of total ARGs varied between 63.9 and 84.0% by the mesocosm-scale CWs. The presence of plants was beneficial to the removal of pollutants, and the subsurface flow CWs had higher pollutant removal than the surface flow CWs, especially for antibiotics. According to the mass balance analysis, the masses of all detected antibiotics during the operation period were 247,000, 4920-10,600, 0.05-0.41 and 3500-60,000μg in influent, substrate, plant and effluent of the mesocosm-scale CWs. In the CWs, biodegradation, substrate adsorption and plant uptake all played certain roles in reducing the loadings of nutrients, antibiotics and ARGs, but biodegradation was the most important process in the removal of these pollutants. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparison of the effect of penicillins versus erythromycin in preventing neonatal group B streptococcus infection in active carriers following preterm prelabor rupture of membranes.

PubMed

Yeung, Sik Wing; Sahota, Daljit Singh; Leung, Tak Yeung

2014-06-01

To compare the incidence of neonatal group B streptococcus (GBS) infection in active GBS carriers with preterm prelabor rupture of membranes (PPROMs) after penicillins and erythromycin prophylaxis. Patients diagnosed to have PPROM between 2004 and 2009 inclusive were treated using erythromycin (erythromycin group), ampicillin, amoxicillin or co-amoxiclav (penicillin group), or no antibiotics (control group) according to department protocols depending on their gestation and their GBS status at the time of presentation. Patients receiving both erythromycin and penicillins were included in the penicillin group. The incidence of neonatal GBS infection was compared between groups categorized according to the antibiotic regime received. A total of 680 women were diagnosed to have PPROM of which 85 (12.5%) were active GBS carriers. GBS isolates were 100% sensitive to penicillins but only 35% were sensitive to erythromycin. There were 16, 22, and 47 patients in the penicillin, erythromycin, and control groups, respectively. The incidence of neonatal GBS infection in the three groups was 0%, 36%, and 13%, respectively, and was statistically significant (p = 0.023). Penicillins are more effective than erythromycin in preventing neonatal GBS infection in women with PPROM who were active GBS carriers. Because most women do not know their GBS status at the time of PPROM and it is practically difficult to identify the active carriers before delivery, ampicillin/amoxicillin should be used as a prophylactic antibiotic for active GBS carriers and women with unknown GBS carriage status to prevent neonatal GBS infection following PPROM. Copyright © 2014. Published by Elsevier B.V.

Low-Dose Nocturnal Tegaserod or Erythromycin Delays Symptom Recurrence After Treatment of Irritable Bowel Syndrome Based on Presumed Bacterial Overgrowth

PubMed Central

Morales, Walter; Lezcano, Sheila; Sun-Chuan, Dai; Low, Kimberly; Yang, Janet

2009-01-01

Our group previously demonstrated a deficiency of migrating motor complexes in irritable bowel syndrome (IBS) patients with small intestinal bacterial overgrowth (SIBO). Based on disturbed fasting motility, we tested whether low-dose nocturnal erythromycin or tegaserod can prevent the recurrence of IBS symptoms after successful antibiotic treatment. Methods: 203 patient charts were reviewed to find IBS patients with SIBO, and treatment cycles were assessed to identify subjects with clinical and breath test resolution. The charts of those who met the inclusion criteria were reviewed to determine the method of prevention of symptom recurrence and the length of remission. The two preventive agents used were erythromycin (50 mg) or tegaserod (2–6 mg) orally at bedtime. Results: 64 patients met the inclusion criteria. Subjects receiving no prevention (n=6) after successful antibiotic treatment experienced symptom recurrence after 59.7±47.4 days. Prevention using erythromycin (n=42) demonstrated 138.5±132.2 symptom-free days (P=.08 vs no prevention) compared to 241.6±162.2 days with tegaserod (n=16; P=.003 vs no prevention; P=.004 vs erythromycin). Switching from erythromycin to tegaserod (n=20) extended resolution from 105.8±73.3 days to 199.7±162.9 days (P=.04). Changing from no therapy to erythromycin or tegaserod (n=6) extended recurrence from 41.0±44.8 days to 195.6±153.5 days (P=.06). Conclusion: Tegaserod significantly prevents the recurrence of IBS symptoms after antibiotic treatment compared to erythromycin or no prevention. PMID:20574504

Valosin containing protein (VCP) interacts with macrolide antibiotics without mediating their anti-inflammatory activities.

PubMed

Nujić, Krunoslav; Smith, Marjorie; Lee, Michael; Belamarić, Daniela; Tomašković, Linda; Alihodžić, Sulejman; Malnar, Ivica; Polančec, Denis; Schneider, Klaus; Eraković Haber, Vesna

2012-02-29

In addition to antibacterial activity, some macrolide antibiotics, such as azithromycin and clarithromycin, also exhibit anti-inflammatory properties in vitro and in vivo, although the targets and mechanism(s) of action remain unknown. The aim of the present study was to identify protein targets of azithromycin and clarithromycin which could potentially explain their anti-inflammatory effects. Using chemical proteomics approach, based on compound-immobilized affinity chromatography, valosin containing protein (VCP) was identified as a potential target of the macrolides. Validation studies confirmed the interaction of macrolides and VCP and gave some structural characteristics of this interaction. Cell based assays however, including the use of gene silencing and the study of VCP specific cellular functions in J774.A1 (murine macrophage) and IB3-1 (human cystic fibrotic epithelial) cell lines, failed to confirm an association between the binding of the macrolides to VCP and anti-inflammatory effects. These findings suggest the absence of an abundant high affinity protein target and the potential involvement of other biological molecules in the anti-inflammatory activity of macrolides. Copyright © 2011 Elsevier B.V. All rights reserved.

Explaining the accelerated degradation of ciprofloxacin, sulfamethazine, and erythromycin in different soil exposure scenarios by their aqueous extractability.

PubMed

Goulas, Anaïs; Sabourin, Lyne; Asghar, Farah; Haudin, Claire-Sophie; Benoit, Pierre; Topp, Edward

2018-06-01

Antibiotics are frequently introduced into agricultural soils with the application of sewage sludge or farm organic fertilizers. Repeated exposure of soils to a pollutant can enrich for microbial populations that metabolize the chemical, reducing its environmental persistence. In London, Canada, soils from a long-term field experiment have received different concentrations of antibiotics annually for several years. The purpose of the present study was to assess the bioavailability of sulfamethazine, erythromycin, or ciprofloxacin through aqueous extractions with borax or EDTA solutions and their biodegradation following different soil exposure scenarios. Control soils and soils treated annually in the field with 10 mg antibiotics per kg were sampled, supplemented in the laboratory with radiolabeled antibiotic either added directly or carried in dairy manure. Sulfamethazine and erythromycin were initially more bioavailable than ciprofloxacin, with aqueous extractabilities representing 60, 36, and 8%, respectively. Sulfamethazine and erythromycin were degraded in soils, with a larger fraction mineralized in the long-term exposed soil (20 and 65%, respectively) than in control soil (0.4 and 3%, respectively) after 7 days of incubation. In contrast, ciprofloxacin was not mineralized neither in control nor long-term exposed soils. The mineralized fractions were similar for antibiotics added directly to soil or carried in dairy manure.

Macrolide, lincosamide, and streptogramin B resistance in lipophilic Corynebacteria inhabiting healthy human skin.

PubMed

Szemraj, Magdalena; Kwaszewska, Anna; Pawlak, Renata; Szewczyk, Eligia M

2014-10-01

Corynebacteria exist as part of human skin microbiota. However, under some circumstances, they can cause opportunistic infections. The subject of the study was to examine the macrolide-lincosamide-streptogramin B (MLSB) antibiotic resistance in 99 lipophilic strains of Corynebacterium genus isolated from the skin of healthy men. Over 70% of the tested strains were resistant to erythromycin and clindamycin. All of which demonstrated a constitutive type of MLSB resistance mechanism. In all strains, there were being investigated the erm(A), erm(B), erm(C), erm(X), lin(A), msr(A), and mph(C) genes that could be responsible for the different types of resistance to marcolides, lincosamides, and streptogramin B. In all strains with the MLSB resistance phenotype, the erm(X) gene was detected. None of the other tested genes were discovered. Strains harboring the erm(X) gene were identified using a phenotypic method based on numerous biological and biochemical tests. Identification of the chosen strains was compared with the results of API Coryne, MALDI-TOF MS, and 16S rDNA sequencing methods. Only 7 out of the 23 investigated resistant strains provided successful results in all the used methods, showing that identification of this group of bacteria is still a great challenge. The MLSB resistance mechanism was common in most frequently isolated from healthy human skin Corynebacterium tuberculostearicum and Corynebacterium jeikeium strains. This represents a threat as these species are also commonly described as etiological factors of opportunistic infections.

Effect of Erythromycin on Chronic Respiratory Infection Caused by Pseudomonas aeruginosa with Biofilm Formation in an Experimental Murine Model

PubMed Central

Nagata, Towako; Mukae, Hiroshi; Kadota, Junichi; Hayashi, Tomayoshi; Fujii, Takeshi; Kuroki, Misuzu; Shirai, Ryo; Yanagihara, Katsunori; Tomono, Kazunori; Koji, Takehiko; Kohno, Shigeru

2004-01-01

Diffuse panbronchiolitis (DPB) is a chronic lower respiratory tract infection commonly associated with persistent late-stage Pseudomonas aeruginosa infection. However, low-dose long-term therapy with certain macrolides is effective in most patients with DPB. The present study was designed to examine the effects of long-term erythromycin (ERY) therapy by using our established murine model of chronic respiratory P. aeruginosa infection. ERY or saline was administered from day 80 after intubation with a P. aeruginosa-precoated tube for the subsequent 10, 20, 40, and 80 days. Bacteriologic and histologic analyses of the murine lungs and electron microscopy of the intubated tube were performed. In the murine model, treatment with ERY for 80 days significantly reduced the number of viable P. aeruginosa organisms in the lungs (P < 0.05). The biofilm formed in situ by P. aeruginosa on the inner wall of the inoculation tube placed into the murine bronchus became significantly thinner after 80 days of ERY treatment. We conclude that the clinical efficacy of macrolides in DPB may be due at least in part to the reduction in P. aeruginosa biofilm formation. PMID:15155229

Exploring the association between resistance and outpatient antibiotic use expressed as DDDs or packages.

PubMed

Bruyndonckx, Robin; Hens, Niel; Aerts, Marc; Goossens, Herman; Cortiñas Abrahantes, José; Coenen, Samuel

2015-04-01

The objective of this study was to explore the association between resistance and outpatient antibiotic use, expressed as either DDDs per 1000 inhabitants per day (DID) or packages per 1000 inhabitants per day (PID). IMS Health data on outpatient penicillin and cephalosporin (β-lactam) and tetracycline, macrolide, lincosamide and streptogramin (TMLS) use, aggregated at the level of the active substance (WHO version 2011) expressed as DID and PID (2000-07) were linked to European Antimicrobial Resistance Surveillance System (EARSS) data on proportions of penicillin-non-susceptible Streptococcus pneumoniae (PNSP) and erythromycin-non-susceptible S. pneumoniae (ENSP) (2000-09). Combined data for 27 European countries were analysed with a generalized linear mixed model. Model fit for use in DID, PID or both and 0, 1 or 2 year time lags between use and resistance was assessed and predictions of resistance were made for decreasing use expressed as DID, PID or both. When exploring the association between β-lactam use and PNSP, the best model fit was obtained for use in PID without time lag. For the association between TMLS use and ENSP, the best model fit was obtained for use in both PID and DID with a 1 year time lag. PNSP and ENSP are predicted to decrease when use decreases in PID, but not when use decreases in DID. Associations between outpatient antibiotic use and resistance and predictions of resistance were inconsistent whether expressing antibiotic use as DID or PID. We recommend that data on antibiotic use be expressed as PID and that time lags between use and resistance be considered when exploring these associations. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Analysis of 27 antibiotic residues in raw cow's milk and milk-based products--validation of Delvotest® T.

PubMed

Bion, Cindy; Beck Henzelin, Andrea; Qu, Yajuan; Pizzocri, Giuseppe; Bolzoni, Giuseppe; Buffoli, Elena

2016-01-01

Delvotest® T was evaluated for its capability at detecting residues of 27 antibiotics in raw cow's milk and in some dairy ingredients (skimmed and full-cream milk powders). The kit was used as a screening tool for the qualitative determination of antibiotics from different families in a single test. Results delivered by such a method are expressed as 'positive' or 'negative', referring to the claimed screening target concentration (STC). Validation was conducted according to the European Community Reference Laboratories' (CRLs) residues guidelines of 20 January 2010 and performed by two laboratories, one located in Europe and the other in Asia. Five criteria were evaluated including detection capability at STC, false-positive (FP) rate, false-negative (FN) rate, robustness and cross-reactivity using visual reading and Delvoscan®. STCs were set at or below the corresponding maximum residue limit (MRL), as fixed by European Regulation EC No. 37/2010. Four antibiotics (nafcillin, oxytetracycline, tetracycline and rifaximin) out of 27 had a false-negative rate ranging from 1.7% to 4.9%; however, it was still compliant with the CRLs' requirements. Globally, Delvotest T can be recommended for the analysis of the surveyed antibiotics in raw cow's milk, skimmed and full-cream milk powders. Additional compounds were tested such as sulfamethazine, spiramycin and erythromycin; however, detection at the corresponding MRL was not achievable and these compounds were removed from the validation. Other drugs from the sulfonamide, aminoglycoside or macrolide families not detected by the test at the MRL were not evaluated in this study. Regarding the reliability of this rapid test to milk-based preparations, additional experiments should be performed on a larger range of compounds and samples to validate the Delvotest T in such matrices.

ORACLE--antibiotics for preterm prelabour rupture of the membranes: short-term and long-term outcomes.

PubMed

Kenyon, S; Taylor, D J; Tarnow-Mordi, W O

2002-01-01

Preterm prelabour rupture of the foetal membranes (pPROM) is the most common antecedent of preterm birth and can lead to death, neonatal disease and long-term disability. Previous small trials of antibiotics for pPROM suggested some health benefits for the neonate, but the results were inconclusive. A large, randomized, multicentre trial was undertaken to try to resolve this issue. In total, 4826 women with pPROM were randomized to one of four treatments: 325 mg co-amoxiclav plus 250 mg erythromycin, co-amoxiclav plus erythromycin placebo, erythromycin plus co-amoxiclav placebo, or co-amoxiclav placebo plus erythromycin placebo, four times daily for 10 d or until delivery. The primary outcome measure was a composite of neonatal death, chronic lung disease or major cerebral abnormality on ultrasonography before discharge from hospital. The analysis was undertaken by intention to treat. Indications of short-term respiratory function, chronic lung disease and major neonatal cerebral abnormality were reduced with the prescription of erythromycin. In contrast, the use of co-amoxiclav was associated with a significant increase in the occurrence of neonatal necrotizing enterocolitis. Prophylactic antibiotics can play a role in preterm prelabour rupture of the membranes in reducing infant morbidity.

Removal of antibiotics and antibiotic resistance genes from domestic sewage by constructed wetlands: Optimization of wetland substrates and hydraulic loading.

PubMed

Chen, Jun; Wei, Xiao-Dong; Liu, You-Sheng; Ying, Guang-Guo; Liu, Shuang-Shuang; He, Liang-Ying; Su, Hao-Chang; Hu, Li-Xin; Chen, Fan-Rong; Yang, Yong-Qiang

2016-09-15

This study aimed to assess removal potential of antibiotics and antibiotic resistance genes (ARGs) in raw domestic wastewater by various mesocosm-scale horizontal subsurface-flow constructed wetlands (CWs) planted Cyperus alternifolius L. with different design parameters. Twelve CWs with three hydraulic loading rates (HLR 10, 20 and 30cm/day) and four substrates (oyster shell, zeolite, medical stone and ceramic) were set up in order to select the best optimized wetland. The result showed that 7 target antibiotics compounds including erythromycin-H2O, lincomycin, monensin, ofloxacin, sulfamerazine, sulfamethazine and novobiocin were detected, and all selected 18 genes (three sulfonamide resistance genes (sul1, sul2 and sul3), four tetracycline resistance genes (tetG, tetM, tetO and tetX), two macrolide resistance genes (ermB and ermC), three quinolone resistance genes (qnrB, qnrD and qnrS) and four chloramphenicol resistance genes (cmlA, fexA, fexB and floR)) and two integrase genes (int1 and int2) were positively detected in the domestic wastewaters. The aqueous removal rates of the total antibiotics ranged from17.9 to 98.5%, while those for the total ARGs varied between 50.0 and 85.8% by the mesocosm-scale CWs. After considering their aqueous removal rates in combination with their mass removals, the CW with zeolite as the substrate and HLR of 20cm/day was selected as the best choice. Combined chemical and biological analyses indicate that both microbial degradation and physical sorption processes were responsible for the fate of antibiotics and ARGs in the wetlands. The findings from this study suggest constructed wetlands could be a promising technology for the removal of emerging contaminants such as antibiotics and ARGs in domestic wastewater. Copyright © 2015 Elsevier B.V. All rights reserved.

Production of macrolide antibiotics from a cytotoxic soil Streptomyces sp. strain ZDB.

PubMed

Dame, Zerihun T; Ruanpanun, Pornthip

2017-07-01

Crude extract from a culture of a soil Streptomyces sp. strain ZDB showed toxicity towards Artemia salina and antimicrobial activity against Escherichia coli, Bacillus subtilis, Staphylococcus aureus, Chlorella vulgaris, and Chlorella sorokiniana. Large scale fermentation of the strain led to the isolation of the macrolide antibiotics, bafilomycins A1 (1), B1 (2), and D (3) together with nonactic acid (4) and bostrycoidin-9-methyl ether (5). Structures of the antibiotics were determined based on spectral data analysis. We describe the isolation of the compounds and characterization of the producing strain.

Phenotypic and Molecular Antibiotic Resistance Determination of Airborne Coagulase Negative Staphylococcus spp. Strains from Healthcare Facilities in Southern Poland.

PubMed

Lenart-Boroń, Anna; Wolny-Koładka, Katarzyna; Stec, Joanna; Kasprowic, Andrzej

2016-10-01

This study assessed the antimicrobial resistance of airborne Staphylococcus spp. strains isolated from healthcare facilities in southern Poland. A total of 55 isolates, belonging to 10 coagulase-negative staphylococci (CoNS) species, isolated from 10 healthcare facilities (including hospitals and outpatient units) were included in the analysis. The most frequently identified species were Staphylococcus saprophyticus and Staphylococcus warneri, which belong to normal human skin flora, but can also be the cause of common and even severe nosocomial infections. Disk diffusion tests showed that the bacterial strains were most frequently resistant to erythromycin and tetracycline and only 18% of strains were susceptible to all tested antimicrobials. Polymerase chain reaction amplification of specific gene regions was used to determine the presence of the Macrolide-Lincosamide-Streptogramin resistance mechanisms in CoNS. The molecular analysis, conducted using specific primer pairs, identified the msrA1 gene, encoding active efflux pumps in bacterial cells, as the most frequent resistance gene. As many as seven antibiotic resistance genes were found in one isolate, whereas the most common number of resistance genes per isolate was five (n = 17). It may be concluded that drug resistance was widely spread among the tested strains, but the resulting antimicrobial resistance profile indicates that in the case of infection, the use of antibiotics from the basic antibiogram group will be effective in therapy. However, before administering treatment, determination of the specific antimicrobial resistance should be conducted, particularly in the case of hospitalized patients.

In vitro activity of pazufloxacin, tosufloxacin and other quinolones against Legionella species.

PubMed

Higa, Futoshi; Akamine, Morikazu; Haranaga, Shusaku; Tohyama, Masato; Shinzato, Takashi; Tateyama, Masao; Koide, Michio; Saito, Atsushi; Fujita, Jiro

2005-12-01

The activities of pazufloxacin and tosufloxacin against Legionella spp. were evaluated in vitro and compared with those of other quinolones, macrolides and azithromycin. The conventional MICs were determined by the microbroth dilution method. Intracellular activities of drugs were evaluated by a cfu count. The minimal extracellular concentration inhibiting intracellular growth of bacteria (MIEC) was determined by a colorimetric cytopathic assay. MICs of pazuloxacin and tosufloxacin at which 90% (MIC90) of isolates are inhibited in 76 different Legionella spp. strains (38 ATCC strains and 38 clinical isolates) were 0.032 and 0.016 mg/L, whereas the MIC90s of levofloxacin, ciprofloxacin, garenoxacin, erythromycin, clarithromycin and azithromycin were 0.032, 0.032, 0.032, 2.0, 0.125 and 2.0 mg/L, respectively. Pazufloxacin and tosufloxacin at 4x MIC inhibited intracellular growth of Legionella pneumophila SG1 (80-045 strain), as did other quinolones, clarithromycin and azithromycin, whereas erythromycin at 4x MIC did not. MIECs of pazufloxacin, tosufloxacin, levofloxacin, ciprofloxacin and garenoxacin for the strain were 0.063, 0.004, 0.016, 0.032 and 0.008 mg/L respectively, which were superior to those of macrolides and azithromycin. Pazufloxacin showed potent activity against three additional clinical isolates of L. pneumophila SG1, one clinical isolate each of L. pneumophila SG3 and SG5, as well as Legionella micdadei, Legionella dumoffii and Legionella longbeachae SG1. Pazufloxacin and tosufloxacin, as well as other quinolones, were more potent than macrolides and an azalide. Present data warrant further study on the efficacy of these drugs in the treatment of Legionella infections.

Multidrug-resistant enterococci in animal meat and faeces and co-transfer of resistance from an Enterococcus durans to a human Enterococcus faecium.

PubMed

Vignaroli, Carla; Zandri, Giada; Aquilanti, Lucia; Pasquaroli, Sonia; Biavasco, Francesca

2011-05-01

Forty-eight isolates resistant to at least two antibiotics were selected from 53 antibiotic-resistant enterococci from chicken and pig meat and faeces and analysed for specific resistance determinants. Of the 48 multidrug-resistant (MDR) strains, 31 were resistant to two antibiotics (29 to erythromycin and tetracycline, 1 to erythromycin and vancomycin, 1 to vancomycin and tetracycline), 14 to three (erythromycin, tetracycline and vancomycin or ampicillin) and 3 to four (erythromycin, vancomycin, ampicillin and gentamicin). erm(B), tet(M), vanA and aac (6')-Ie aph (2'')-Ia were the antibiotic resistance genes most frequently detected. All 48 MDR enterococci were susceptible to linezolid and daptomycin. Enterococcus faecalis (16), Enterococcus faecium (8), Enterococcus mundtii (2) and Enterococcus gallinarum (1) were identified in meat, and E. faecium (13) and Enterococcus durans (13) in faeces. Clonal spread was not detected, suggesting a large role of gene transfer in the dissemination of antibiotic resistance. Conjugative transfer of resistance genes was more successful when donors were enterococcal strains isolated from faeces; co-transfer of vanA and erm(B) to a human E. faecium occurred from both E. faecium and E. durans pig faecal strains. These data show that multidrug resistance can be found in food and animal species other than E. faecium and E. faecalis, and that these species can efficiently transfer antibiotic resistance to human strains in inter-specific matings. In particular, the occurrence of MDR E. durans in the animal reservoir could have a role in the emergence of human enterococcal infections difficult to eradicate with antibiotics.

Macrolide Antibiotics Exhibit Cytotoxic Effect under Amino Acid-Depleted Culture Condition by Blocking Autophagy Flux in Head and Neck Squamous Cell Carcinoma Cell Lines

PubMed Central

Hirasawa, Kazuhiro; Moriya, Shota; Miyahara, Kana; Kazama, Hiromi; Hirota, Ayako; Takemura, Jun; Abe, Akihisa; Inazu, Masato; Hiramoto, Masaki; Tsukahara, Kiyoaki

2016-01-01

Autophagy, a self-digestive system for cytoplasmic components, is required to maintain the amino acid pool for cellular homeostasis. We previously reported that the macrolide antibiotics azithromycin (AZM) and clarithromycin (CAM) have an inhibitory effect on autophagy flux, and they potently enhance the cytocidal effect of various anticancer reagents in vitro. This suggests that macrolide antibiotics can be used as an adjuvant for cancer chemotherapy. Since cancer cells require a larger metabolic demand than normal cells because of their exuberant growth, upregulated autophagy in tumor cells has now become the target for cancer therapy. In the present study, we examined whether macrolides exhibit cytotoxic effect under an amino acid-starving condition in head and neck squamous cancer cell lines such as CAL 27 and Detroit 562 as models of solid tumors with an upregulated autophagy in the central region owing to hypovascularity. AZM and CAM induced cell death under the amino acid-depleted (AAD) culture condition in these cell lines along with CHOP upregulation, although they showed no cytotoxicity under the complete culture medium. CHOP knockdown by siRNA in the CAL 27 cells significantly suppressed macrolide-induced cell death under the AAD culture condition. CHOP-/- murine embryonic fibroblast (MEF) cell lines also attenuated AZM-induced cell death compared with CHOP+/+ MEF cell lines. Using a tet-off atg5 MEF cell line, knockout of atg5, an essential gene for autophagy, also induced cell death and CHOP in the AAD culture medium but not in the complete culture medium. This suggest that macrolide-induced cell death via CHOP induction is dependent on autophagy inhibition. The cytotoxicity of macrolide with CHOP induction was completely cancelled by the addition of amino acids in the culture medium, indicating that the cytotoxicity is due to the insufficient amino acid pool. These data suggest the possibility of using macrolides for “tumor-starving therapy”. PMID:27977675

Antibiotics in typical marine aquaculture farms surrounding Hailing Island, South China: occurrence, bioaccumulation and human dietary exposure.

PubMed

Chen, Hui; Liu, Shan; Xu, Xiang-Rong; Liu, Shuang-Shuang; Zhou, Guang-Jie; Sun, Kai-Feng; Zhao, Jian-Liang; Ying, Guang-Guo

2015-01-15

The occurrence, bioaccumulation, and human dietary exposure via seafood consumption of 37 antibiotics in six typical marine aquaculture farms surrounding Hailing Island, South China were investigated in this study. Sulfamethoxazole, salinomycin and trimethoprim were widely detected in the water samples (0.4-36.9 ng/L), while oxytetracycline was the predominant antibiotic in the water samples of shrimp larvae pond. Enrofloxacin was widely detected in the feed samples (16.6-31.8 ng/g) and erythromycin-H2O was the most frequently detected antibiotic in the sediment samples (0.8-4.8 ng/g). Erythromycin-H2O was the dominant antibiotic in the adult Fenneropenaeus penicillatus with concentrations ranging from 2498 to 15,090 ng/g. In addition, trimethoprim was found to be bioaccumulative in young Lutjanus russelli with a median bioaccumulation factor of 6488 L/kg. Based on daily intake estimation, the erythromycin-H2O in adult F. penicillatus presented a potential risk to human safety. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of levofloxacin, erythromycin or rifampicin pretreatment on growth of Legionella pneumophila in human monocytes.

PubMed

Smith, R P; Baltch, A L; Franke, M; Hioe, W; Ritz, W; Michelsen, P

1997-11-01

Opsonophagocytic killing of some bacteria (Staphylococcus aureus, Pseudomonas aeruginosa) by phagocytes is enhanced by previous brief exposure of the organism to antibiotics. We studied the regrowth of Legionella pneumophila previously pretreated with levofloxacin, erythromycin and/or rifampicin in human monocytes. The MIC for the L. pneumophila isolate of levofloxacin, erythromycin and rifampicin was 0.03, 0.5 and 0.001 mg/L, respectively. Growth of L. pneumophila from buffered charcoal yeast extract (BCYE) agar for 24 h was subcultured into BYE broth containing from 0 to 4x MIC of levofloxacin, erythromycin or rifampicin. After incubation at 35 degrees C in 5% CO2 for 18 h, the organisms were washed and opsonized with 20% heat inactivated pooled normal human serum. Thereafter, L. pneumophila was exposed to human monocytes (5:1 ratio) previously adhered to wells in tissue culture plates containing RPMI and 10% fetal calf serum. After 0, 24, 48 and 72 h of incubation, quantitative cultures of lysed human monocytes were done on BCYE agar. Our results indicate effective inhibition on L. pneumophila at 0 h regardless of the antibiotic (levofloxacin, rifampicin or erythromycin) or their concentrations (1x, 2x or 4x MIC). At 24, 48 and 72 h, recovery and regrowth of L. pneumophila were both antibiotic- and concentration-dependent. In comparison with controls (no antibiotic pretreatment), peak regrowth of L. pneumophila pretreated with either 1x MIC of levofloxacin or erythromycin was delayed (48 versus 24 h) and reduced (30% of control peak regrowth). Regrowth of L. pneumophila pretreated with 1x MIC of rifampicin continued beyond 72 h. Pretreatment with levofloxacin at 4x MIC caused the greatest degree of growth inhibition (2 log10). In contrast, at 72 h, regrowth of organisms pretreated with 4x MIC of erythromycin or rifampicin was less than peak control (P < 0.01) but greater than that seen with levofloxacin (P < 0.01). The rate and degree of regrowth of L. pneumophila pretreated with combinations of levofloxacin or erythromycin with rifampicin, or levofloxacin with erythromycin (all at 1x MIC) was similar to that seen with single drugs. Thus, significant delay and reduction of regrowth in this phagocytic system occurred with levofloxacin only. Prolonged exposure of the organism at 4x MIC levofloxacin concentrations was effective in suppressing regrowth of pretreated L. pneumophila in human monocytes.

How good is the evidence for the recommended empirical antimicrobial treatment of patients hospitalized because of community-acquired pneumonia? A systematic review.

PubMed

Oosterheert, J J; Bonten, M J M; Hak, E; Schneider, M M E; Hoepelman, I M

2003-10-01

For years, monotherapy with a beta-lactam antibiotic (penicillin, amoxicillin or second-generation cephalosporin) was recommended as empirical therapy for patients with community-acquired pneumonia (CAP). A combination of a beta-lactam and a macrolide antibiotic was only recommended for patients with severe CAP needing intensive care treatment or when atypical pathogens, i.e. Legionella pneumophila, Mycoplasma pneumoniae and Chlamydia pneumoniae, were strongly suspected. However, new guidelines recommend a combination of a beta-lactam antibiotic plus a macrolide or monotherapy with a fluoroquinolone for all patients hospitalized with CAP. We evaluated whether treatment with a beta-lactam plus macrolide or quinolone monotherapy is truly superior to beta-lactam treatment alone. We systematically reviewed available studies, retrieved from MEDLINE and by hand-searching reference lists from recent reviews and guidelines on the effectiveness of recommended empirical antimicrobial treatment of patients hospitalized because of CAP. Eight relevant studies were selected. In six studies significant reductions in mortality were found, in one study a reduction in hospital length of stay was found and in one study no beneficial effects could be demonstrated for treatment regimens with fluoroquinolone monotherapy or combinations of beta-lactams and macrolides. The beneficial value of macrolides or fluoroquinolones might be the result of a large and mainly unrecognized role of atypical pathogens in the aetiology of CAP, anti-inflammatory effects of macrolides or resistance to beta-lactams of the most important pathogens. However, the studies supporting the recommended treatment regimen were designed as non-experimental cohort studies. As a consequence, the results may have been influenced by confounding by indication. In addition, the outcomes showed several inconsistencies. A randomized controlled trial is warranted to circumvent the methodological flaws in the designs of the currently available studies. Since the addition of macrolides or treatment with fluoroquinolones may lead to enhanced antibiotic resistance, increased side effects and healthcare-related costs, such a fundamental change in the treatment of CAP should be based on valid data.

Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment

PubMed Central

Nobel, Yael R.; Cox, Laura M.; Kirigin, Francis F.; Bokulich, Nicholas A.; Yamanishi, Shingo; Teitler, Isabel; Chung, Jennifer; Sohn, Jiho; Barber, Cecily M.; Goldfarb, David S.; Raju, Kartik; Abubucker, Sahar; Zhou, Yanjiao; Ruiz, Victoria E.; Li, Huilin; Mitreva, Makedonka; Alekseyenko, Alexander V.; Weinstock, George M.; Sodergren, Erica; Blaser, Martin J.

2015-01-01

Mammalian species have co-evolved with intestinal microbial communities that can shape development and adapt to environmental changes, including antibiotic perturbation or nutrient flux. In humans, especially children, microbiota disruption is common, yet the dynamic microbiome recovery from early-life antibiotics is still uncharacterized. Here we use a mouse model mimicking paediatric antibiotic use and find that therapeutic-dose pulsed antibiotic treatment (PAT) with a beta-lactam or macrolide alters both host and microbiota development. Early-life PAT accelerates total mass and bone growth, and causes progressive changes in gut microbiome diversity, population structure and metagenomic content, with microbiome effects dependent on the number of courses and class of antibiotic. Whereas control microbiota rapidly adapts to a change in diet, PAT slows the ecological progression, with delays lasting several months with previous macrolide exposure. This study identifies key markers of disturbance and recovery, which may help provide therapeutic targets for microbiota restoration following antibiotic treatment. PMID:26123276

Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment.

PubMed

Nobel, Yael R; Cox, Laura M; Kirigin, Francis F; Bokulich, Nicholas A; Yamanishi, Shingo; Teitler, Isabel; Chung, Jennifer; Sohn, Jiho; Barber, Cecily M; Goldfarb, David S; Raju, Kartik; Abubucker, Sahar; Zhou, Yanjiao; Ruiz, Victoria E; Li, Huilin; Mitreva, Makedonka; Alekseyenko, Alexander V; Weinstock, George M; Sodergren, Erica; Blaser, Martin J

2015-06-30

Mammalian species have co-evolved with intestinal microbial communities that can shape development and adapt to environmental changes, including antibiotic perturbation or nutrient flux. In humans, especially children, microbiota disruption is common, yet the dynamic microbiome recovery from early-life antibiotics is still uncharacterized. Here we use a mouse model mimicking paediatric antibiotic use and find that therapeutic-dose pulsed antibiotic treatment (PAT) with a beta-lactam or macrolide alters both host and microbiota development. Early-life PAT accelerates total mass and bone growth, and causes progressive changes in gut microbiome diversity, population structure and metagenomic content, with microbiome effects dependent on the number of courses and class of antibiotic. Whereas control microbiota rapidly adapts to a change in diet, PAT slows the ecological progression, with delays lasting several months with previous macrolide exposure. This study identifies key markers of disturbance and recovery, which may help provide therapeutic targets for microbiota restoration following antibiotic treatment.

Trace analysis of trimethoprim and sulfonamide, macrolide, quinolone, and tetracycline antibiotics in chlorinated drinking water using liquid chromatography electrospray tandem mass spectrometry

USGS Publications Warehouse

Ye, Z.; Weinberg, H.S.; Meyer, M.T.

2007-01-01

A multirun analytical method has been developed and validated for trace determination of 24 antibiotics including 7 sulfonamides, 3 macrolides, 7 quinolones, 6 tetracyclines, and trimethoprim in chlorine-disinfected drinking water using a single solid-phase extraction method coupled to liquid chromatography with positive electrospray tandem mass spectrometry detection. The analytes were extracted by a hydrophilic-lipophilic balanced resin and eluted with acidified methanol (0.1% formic acid), resulting in analyte recoveries generally above 90%. The limits of quantitation were mostly below 10 ng/L in drinking water. Since the concentrated sample matrix typically caused ion suppression during electrospray ionization, the method of standard addition was used for quantitation. Chlorine residuals in drinking water can react with some antibiotics, but ascorbic acid was found to be an effective chlorine quenching agent without affecting the analysis and stability of the antibiotics in water. A preliminary occurrence study using this method revealed the presence of some antibiotics in drinking waters, including sulfamethoxazole (3.0-3.4 ng/L), macrolides (1.4-4.9 ng/L), and quinolones (1.2-4.0 ng/L). ?? 2007 American Chemical Society.

Multicenter cross-sectional observational study of antibiotic resistance and the genotypes of Propionibacterium acnes isolated from Chinese patients with acne vulgaris.

PubMed

Fan, Yukun; Hao, Fei; Wang, Weizhen; Lu, Yonghong; He, Li; Wang, Gang; Chen, Wenchieh

2016-04-01

Antibiotics are widely applied in management of acne vulgaris, which raises the issue of antibiotic resistance. Due to improper application and supervision of antibiotics, antibiotic resistance has become a serious problem in China. So, the efficacy of antimicrobial therapy in acne is unclear without an objective monitor of antibiotic resistance of Propionibacterium acnes. This cross-sectional, multicenter observational study is aimed at understanding the status of antibiotic resistance in P. acnes, investigating the measures of acne management in China and analyzing the genotypes of antibiotic-resistant strains of P. acnes. Altogether, 312 strains of P. acnes were collected from patients in five medical centers across central China after reviewing the corresponding medical history in detail. The samples underwent antibiotic susceptibility assays by agar dilution method with a total of 11 classes of antibiotics being tested. The antibiotic-resistant strains were screened and further analyzed by investigation of the genotypes regarding 23S rRNA, 16S rRNA and erm(X). The predominant resistance occurred in macrolides and lincomycin with an overall resistance rate of 47.8%. The resistance to tetracyclines was scarce with only two cases identified. The emergence of minimum inhibitory concentration elevation for tetracyclines is associated with its application history (P < 0.005). The genotypes of the reported macrolide-lincosamide-streptogramin B resistance strains were also spotted in Chinese subjects while other resistance determinants may also exist. The tetracyclines have been proved to be vastly susceptible while macrolides and lincomycin face a serious resistance status in China. © 2015 Japanese Dermatological Association.

[Liquid chromatography-tandem mass spectrometry method for determination of 10 macrolide antibiotics in pork samples using on-line solid phase extraction purification].

PubMed

Zhang, Xiaoguang; Liu, Dong; Liu, Hongran; Li, Qiang; Li, Lili; Wang, Lixia; Zhang, Yan

2017-10-08

A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method based on-line solid phase extraction (SPE) purification was established to determine 10 macrolide antibiotics in pork samples. The samples were extracted with acetonitrile, and the extracts were dried with rotary evaporator at 40℃, then the analytes were dissolved with 2 mL phosphate buffer. The solutions were purified and concentrated by on-line SPE with HLB cartridges. The analytes were eluted with methanol, and then transferred to XBridge BEH C18 column, separated with the mobile phases of 10 mmol/L ammonium acetate aqueous solution and acetonitrile. Finally, the target analytes were detected by tandem mass spectrometry. The results showed that good linearity was obtained in the range of 0.1-200 μg/L for the 10 macrolide antibiotics with correlation coefficients better than 0.990. The limits of detection were in range of 0.05-0.30 μg/kg and the limits of quantitation were in range of 0.10-1.00 μg/kg. The recoveries of the method were in range of 69.6%-115.2% at the spiked levels of 0.10-10.0 μg/kg for all analytes, with the relative standard deviations less than 10%. The developed method can be used for the determination of the 10 macrolide antibiotics in pork samples.

The extinction of topical erythromycin therapy for acne vulgaris and concern for the future of topical clindamycin.

PubMed

Austin, Brett A; Fleischer, Alan B

2017-03-01

This study aims to evaluate changes in topical antibiotic prescribing trends for acne. We retrospectively reviewed the National Ambulatory Medical Care Survey data from 1993 to 2012 for all visits in which acne vulgaris was the primary diagnosis. Acne vulgaris represented an estimated 94.5 million (92.3, 96.8) visits during the 20-year study period. Bivariate analysis showed that over time erythromycin use declined (p < 0.001) and clindamycin use rose (p = 0.10). Multivariate analysis showed that the likelihood of erythromycin use declined to near zero (p < 0.001), whereas clindamycin utilization increased (p < 0.05). PubMed searches of "erythromycin AND resistance" and "clindamycin AND resistance" demonstrated increasing publication frequency by year, fit with sigmoidal functions (erythromycin: R 2  =   0.93 and clindamycin: R 2  =   0.94). Yearly publications consistently exceeded 100 papers for erythromycin and clindamycin resistance in 1983 and 2003, respectively, roughly corresponding to the interval between reports of their utility in acne. Our findings suggest topical erythromycin use for acne has essentially ceased. By contrast, clindamycin use is increasing. Current recommendations discourage topical antibiotic monotherapy in favor of combination therapy with benzoyl peroxide and topical retinoids. Our group's previous work demonstrated that this trend is indeed occurring.

Mapping of chloroplast mutations conferring resistance to antibiotics in Chlamydomonas: evidence for a novel site of streptomycin resistance in the small subunit rRNA.

PubMed

Gauthier, A; Turmel, M; Lemieux, C

1988-10-01

A major obstacle to our understanding of the mechanisms governing the inheritance, recombination and segregation of chloroplast genes in Chlamydomonas is that the majority of antibiotic resistance mutations that have been used to gain insights into such mechanisms have not been physically localized on the chloroplast genome. We report here the physical mapping of two chloroplast antibiotic resistance mutations: one conferring cross-resistance to erythromycin and spiramycin in Chlamydomonas moewusii (er-nM1) and the other conferring resistance to streptomycin in the interfertile species C. eugametos (sr-2). The er-nM1 mutation results from a C to G transversion at a well-known site of macrolide resistance within the peptidyl transferase loop region of the large subunit rRNA gene. This locus, designated rib-2 in yeast mitochondrial DNA, corresponds to residue C-2611 in the 23 S rRNA of Escherichia coli. The sr-2 locus maps within the small subunit (SSU) rRNA gene at a site that has not been described previously. The mutation results from an A to C transversion at a position equivalent to residue A-523 in the E. coli 16 S rRNA. Although this region of the E. coli SSU rRNA has no binding affinity for streptomycin, it binds to ribosomal protein S4, a protein that has long been associated with the response of bacterial cells to this antibiotic. We propose that the sr-2 mutation indirectly affects the nearest streptomycin binding site through an altered interaction between a ribosomal protein and the SSU rRNA.

[Identification of lactic acid bacteria in commercial yogurt and their antibiotic resistance].

PubMed

Qin, Yuxuan; Li, Jing; Wang, Qiuya; Gao, Kexin; Zhu, Baoli; Lv, Na

2013-08-04

To identify lactic acid bacteria (LAB) in commercial yogurts and investigate their antibiotic resistance. LABs were cultured from 5 yogurt brands and the isolates were identified at the species level by 16S rRNA sequence. Genotyping was performed by repetitive extragenic palindromic PCR (rep-PCR). The sensitivity to 7 antibiotics was tested for all LAB isolates by Kirby-Bauer paper diffusion (K-B method). Meanwhile, 9 antibiotic resistance genes (ARGs), including erythromycin resistance genes (ermA and ermB) and tetracycline resistance genes (tetM, tetK, tetS, tetQ, tetO, tetL and tetW), were detected by PCR amplification in the identified LAB isolates. The PCR products were confirmed by sequencing. Total 100 LABs were isolated, including 23 Lactobacillus delbrueckii ssp. bulgaricus, 26 Lactobacillus casei, 30 Streptococcus thermophilus, 5 Lactobacillus acidophilus, 6 Lactobacillus plantarum, and 10 Lactobacillus paracasei. The drug susceptibility test shows that all 100 isolates were resistant to gentamicin and streptomycin, 42 isolates were resistant to vancomycin, and on the contrary all were sensitive to cefalexin, erythromycin, tetracycline and oxytetracycline. Moreover, 5 ARGs were found in the 28 sequencing confirmed isolates, ermB gene was detected in 8 isolates, tet K in 4 isolates, tetL in 2 isolates, tetM in 4 isolates, tetO in 2 isolates. erm A, tet S, tet Q and tet W genes were not detected in the isolates. Antibiotic resistance genes were found in 53.57% (15/28) sequenced isolates, 2 -3 antibiotic resistance genes were detected in 4 isolates of L. delbrueckii ssp. bulgaricus. Some LABs were not labeled in commercial yogurt products. Antibiotic resistance genes tend to be found in the starter culture of L. delbrueckii ssp. Bulgaricus and S. thermophilus. All the LAB isolates were sensitive to erythromycin and tetracycline, even though some carried erythromycin and/or tetracycline resistance genes. We proved again that LAB could carry antibiotic resistance gene(s) though it is sensitive to antibiotics.

High Prevalence of Macrolide-resistance and Molecular Characterization of Streptococcus pyogenes Isolates Circulating in China from 2009 to 2016

PubMed Central

Lu, Binghuai; Fang, Yujie; Fan, Yanyan; Chen, Xingchun; Wang, Junrui; Zeng, Ji; Li, Yi; Zhang, Zhijun; Huang, Lei; Li, Hongxia; Li, Dong; Zhu, Fengxia; Cui, Yanchao; Wang, Duochun

2017-01-01

Streptococcus pyogenes, or group A Streptococcus, is a pathogen responsible for a wide range of clinical manifestations, from mild skin and soft tissue infections and pharyngitis to severe diseases. Its epidemiological characteristics should be comprehensively under surveillance for regulating the national prevention and treatment practice. Herein, a total of 140 S. pyogenes, including 38 invasive and 102 noninvasive isolates, were collected from infected patients in 10 tertiary general hospitals from 7 cities/provinces in China during the years 2009–2016. All strains were characterized by classical and molecular techniques for its emm types/subtypes, virulent factors and antibiotic resistance profiling. Of 140 isolates, 15 distinct emm types and 31 subtypes were detected, dominated by emm12 (60 isolates, 42.9%), emm1(43, 30.7%), and emm89 (10, 7.1%), and 8 new emm variant subtypes were identified. All strains, invasive or not, harbored the superantigenic genes, speB and slo. The other virulence genes, smeZ, speF, and speC accounted for 96.4, 91.4, and 87.1% of collected isolates, respectively. Further multilocus sequence typing (MLST) placed all strains into 22 individual sequence types (STs), including 4 newly-identified STs (11, 7.9%). All isolates were phenotypically susceptible to penicillin, ampicillin, cefotaxime, and vancomycin, whereas 131(93.5%), 132(94.2%), and 121(86.4%) were resistant to erythromycin, clindamycin, and tetracycline, respectively. Our study highlights high genotypic diversity and high prevalence of macrolide resistance of S. pyogenes among clinical isolates circulating in China. PMID:28642756

The etiology of community-acquired pneumonia in Australia: why penicillin plus doxycycline or a macrolide is the most appropriate therapy.

PubMed

Charles, Patrick G P; Whitby, Michael; Fuller, Andrew J; Stirling, Robert; Wright, Alistair A; Korman, Tony M; Holmes, Peter W; Christiansen, Keryn J; Waterer, Grant W; Pierce, Robert J P; Mayall, Barrie C; Armstrong, John G; Catton, Michael G; Nimmo, Graeme R; Johnson, Barbara; Hooy, Michelle; Grayson, M L

2008-05-15

Available data on the etiology of community-acquired pneumonia (CAP) in Australia are very limited. Local treatment guidelines promote the use of combination therapy with agents such as penicillin or amoxycillin combined with either doxycycline or a macrolide. The Australian CAP Study (ACAPS) was a prospective, multicenter study of 885 episodes of CAP in which all patients underwent detailed assessment for bacterial and viral pathogens (cultures, urinary antigen testing, serological methods, and polymerase chain reaction). Antibiotic agents and relevant clinical outcomes were recorded. The etiology was identified in 404 (45.6%) of 885 episodes, with the most frequent causes being Streptococcus pneumoniae (14%), Mycoplasma pneumoniae (9%), and respiratory viruses (15%; influenza, picornavirus, respiratory syncytial virus, parainfluenza virus, and adenovirus). Antibiotic-resistant pathogens were rare: only 5.4% of patients had an infection for which therapy with penicillin plus doxycycline would potentially fail. Concordance with local antibiotic recommendations was high (82.4%), with the most commonly prescribed regimens being a penicillin plus either doxycycline or a macrolide (55.8%) or ceftriaxone plus either doxycycline or a macrolide (36.8%). The 30-day mortality rate was 5.6% (50 of 885 episodes), and mechanical ventilation or vasopressor support were required in 94 episodes (10.6%). Outcomes were not compromised by receipt of narrower-spectrum beta-lactams, and they did not differ on the basis of whether a pathogen was identified. The vast majority of patients with CAP can be treated successfully with narrow-spectrum beta-lactam treatment, such as penicillin combined with doxycycline or a macrolide. Greater use of such therapy could potentially reduce the emergence of antibiotic resistance among common bacterial pathogens.

Determination of macrolide antibiotics in chicken tissues by liquid chromatography-electrospray mass spectrometry

NASA Astrophysics Data System (ADS)

Salikin, Jamilah; Abdullah, Aminah

2013-11-01

A methodusingliquid chromatography-electrospray mass spectrometry (LC-(ESI)MS) for the simultaneous determination of three macrolides (tylosin, spiramycin and tilmicosin) in poultry muscle has been developed. The drugs were extracted with EDTA McIlvaine buffer, filter through celite 545 and the extracts were cleaned up by SPE Oasis HLB cartridge. Separation was carried out in end-capped silica-based C18 column and mobile phases containing trifluoroacetic acid-acetonitrile with a binary gradient system at a flow rate 0.5 ml/min. Detection was performed by single mass spectrometry with electrospray ionization in the positive mode. Several parameters affecting the mass spectra were studied. Chicken samples from the market were analyzed to check the residue of macrolide antibiotics.

A new evolutionary variant of the streptogramin A resistance protein, Vga(A)LC, from Staphylococcus haemolyticus with shifted substrate specificity towards lincosamides.

PubMed

Novotna, G; Janata, J

2006-12-01

We found a new variant of the streptogramin A resistance gene, vga(A)LC, in clinical isolates of Staphylococcus haemolyticus resistant to lincomycin and clindamycin but susceptible to erythromycin and in which no relevant lincosamide resistance gene was detected. The gene vga(A)LC, differing from the gene vga(A) at the protein level by seven amino acid substitutions, was present exclusively in S. haemolyticus strains resistant to both lincosamides and streptogramin A (LS(A) phenotype). Antibiotic resistance profiles of the ATP-binding cassette (ABC) proteins Vga(A)(LC) and Vga(A) in the antibiotic-susceptible host S. aureus RN4220 were compared. It was shown that Vga(A)LC conferred resistance to both lincosamides and streptogramin A, while Vga(A) conferred significant resistance to streptogramin A only. Detailed analysis of the seven amino acid substitutions, distinguishing the two related ABC proteins with different substrate specificities, identified the substrate-recognizing site: four clustered substitutions (L212S, G219V, A220T, and G226S) in the spacer between the two ATP-binding cassettes altered the substrate specificity and constituted the lincosamide-streptogramin A resistance phenotype. A transport experiment with radiolabeled lincomycin demonstrated that the mechanism of lincosamide resistance in S. haemolyticus was identical to that of the reported macrolide-streptogramin B resistance conferred by Msr(A).

A New Evolutionary Variant of the Streptogramin A Resistance Protein, Vga(A)LC, from Staphylococcus haemolyticus with Shifted Substrate Specificity towards Lincosamides▿

PubMed Central

Novotna, G.; Janata, J.

2006-01-01

We found a new variant of the streptogramin A resistance gene, vga(A)LC, in clinical isolates of Staphylococcus haemolyticus resistant to lincomycin and clindamycin but susceptible to erythromycin and in which no relevant lincosamide resistance gene was detected. The gene vga(A)LC, differing from the gene vga(A) at the protein level by seven amino acid substitutions, was present exclusively in S. haemolyticus strains resistant to both lincosamides and streptogramin A (LSA phenotype). Antibiotic resistance profiles of the ATP-binding cassette (ABC) proteins Vga(A)LC and Vga(A) in the antibiotic-susceptible host S. aureus RN4220 were compared. It was shown that Vga(A)LC conferred resistance to both lincosamides and streptogramin A, while Vga(A) conferred significant resistance to streptogramin A only. Detailed analysis of the seven amino acid substitutions, distinguishing the two related ABC proteins with different substrate specificities, identified the substrate-recognizing site: four clustered substitutions (L212S, G219V, A220T, and G226S) in the spacer between the two ATP-binding cassettes altered the substrate specificity and constituted the lincosamide-streptogramin A resistance phenotype. A transport experiment with radiolabeled lincomycin demonstrated that the mechanism of lincosamide resistance in S. haemolyticus was identical to that of the reported macrolide-streptogramin B resistance conferred by Msr(A). PMID:17015629

Comparative genomics analyses revealed two virulent Listeria monocytogenes strains isolated from ready-to-eat food.

PubMed

Lim, Shu Yong; Yap, Kien-Pong; Thong, Kwai Lin

2016-01-01

Listeria monocytogenes is an important foodborne pathogen that causes considerable morbidity in humans with high mortality rates. In this study, we have sequenced the genomes and performed comparative genomics analyses on two strains, LM115 and LM41, isolated from ready-to-eat food in Malaysia. The genome size of LM115 and LM41 was 2,959,041 and 2,963,111 bp, respectively. These two strains shared approximately 90% homologous genes. Comparative genomics and phylogenomic analyses revealed that LM115 and LM41 were more closely related to the reference strains F2365 and EGD-e, respectively. Our virulence profiling indicated a total of 31 virulence genes shared by both analysed strains. These shared genes included those that encode for internalins and L. monocytogenes pathogenicity island 1 (LIPI-1). Both the Malaysian L. monocytogenes strains also harboured several genes associated with stress tolerance to counter the adverse conditions. Seven antibiotic and efflux pump related genes which may confer resistance against lincomycin, erythromycin, fosfomycin, quinolone, tetracycline, and penicillin, and macrolides were identified in the genomes of both strains. Whole genome sequencing and comparative genomics analyses revealed two virulent L. monocytogenes strains isolated from ready-to-eat foods in Malaysia. The identification of strains with pathogenic, persistent, and antibiotic resistant potentials from minimally processed food warrant close attention from both healthcare and food industry.

Antimicrobial Susceptibility Patterns of Enterococcus faecalis and Enterococcus faecium Isolated from Poultry Flocks in Germany.

PubMed

Maasjost, J; Mühldorfer, K; Cortez de Jäckel S; Hafez, H M

2015-03-01

Between 2010 and 2011, 145 Enterococcus isolates (Enterococcus faecalis, n = 127; Enterococcus faecium, n = 18) were collected during routine bacteriologic diagnostics from broilers, layers, and fattening turkeys in Germany showing various clinical signs. The susceptibility to 24 antimicrobial agents was investigated by broth microdilution test to determine minimum inhibitory concentrations (MICs). All E. faecalis isolates (n = 127) were susceptible to the beta-lactam antibiotics ampicillin, amoxicillin-clavulanic acid, and penicillin. Corresponding MIC with 50% inhibition (MIC50) and MIC with 90% inhibition (MIC90) values of these antimicrobial agents were at the lower end of the test range (≤ 4 μg/ml). In addition, no vancomycin-resistant enterococci (VRE) were found. High resistance rates were identified in both Enterococcus species for lincomycin (72%-99%) and tetracycline (67%-82%). Half or more than half of Enterococcus isolates were resistant to gentamicin (54%-72%) and the macrolide antibiotics erythromycin (44%-61%) and tylosin-tartate (44%-56%). Enterococcus faecalis isolated from fattening turkeys showed the highest prevalence of antimicrobial resistance compared to other poultry production systems. Eighty-nine out of 145 Enterococcus isolates were resistant to three or more antimicrobial classes. Again, turkeys stood out with 42 (8 1%) multiresistant isolates. The most-frequent resistance patterns of E. faecalis were gentamicin, lincomycin, and tetracycline in all poultry production systems.

[Pharmacological availability of erythromycin granules for children's use].

PubMed

Korenev, S V; Garsheva, G B; Nesterova, L Ia; Grakovskaia, L K; Tentsova, A I

1990-08-01

Pharmaceutical availability of erythromycin granules with polymeric coating of different composition+ was studied. With an account of the ++anatomo-physiological features of a child organism and the properties of the antibiotic, acetylphthalyl cellulose in combination with hydroxypropyl methylcellulose or methyl cellulose was used as a film forming agent. The coated granules were estimated by such parameters as the time of disintegration and the rate of dissolution in various media. The results of the study showed that coating of the erythromycin granules with the film composed of acetylphthalyl cellulose and hydroxypropyl methylcellulose in the ratio of 8 to 2 provided the required protection of the antibiotic in acid media and high pharmaceutical availability of the drug.

Prevalence of the Antibiotic Resistance Genes in Coagulase-Positive-and Negative-Staphylococcus in Chicken Meat Retailed to Consumers

PubMed Central

Osman, Kamelia; Badr, Jihan; Al-Maary, Khalid S.; Moussa, Ihab M. I.; Hessain, Ashgan M.; Girah, Zeinab M. S. Amin; Abo-shama, Usama H.; Orabi, Ahmed; Saad, Aalaa

2016-01-01

The use of antibiotics in farm management (growing crops and raising animals) has become a major area of concern. Its implications is the consequent emergence of antibiotic resistant bacteria (ARB) and accordingly their access into the human food chain with passage of antibiotic resistance genes (ARG) to the normal human intestinal microbiota and hence to other pathogenic bacteria causative human disease. Therefore, we pursued in this study to unravel the frequency and the quinolone resistance determining region, mecA and cfr genes of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), methicillin-resistant coagulase-negative staphylococci (MRCNS) and methicillin-susceptible coagulase-negative staphylococci (MSCNS) isolated from the retail trade of ready-to-eat raw chicken meat samples collected during 1 year and sold across the Great Cairo area. The 50 Staphylococcus isolated from retail raw chicken meat were analyzed for their antibiotic resistance phenotypic profile on 12 antibiotics (penicillin, oxacillin, methicillin, ampicillin-sulbactam, erythromycin, tetracycline, clindamycin, gentamicin, ciprofloxacin, chloramphenicol, sulfamethoxazole-trimethoprim, and vancomycin) and their endorsement of the quinolone resistance determining region, mecA and cfr genes. The isolation results revealed 50 isolates, CPS (14) and CNS (36), representing ten species (S. aureus, S. hyicus, S. epidermedius, S. lugdunensis, S. haemolyticus, S. hominus, S. schleiferi, S. cohnii, S. intermedius, and S. lentus). Twenty seven isolates were methicillin-resistant. Out of the characterized 50 staphylococcal isolates, three were MRSA but only 2/3 carried the mecA gene. The ARG that bestows resistance to quinolones, β-lactams, macrolides, lincosamides, and streptogramin B [MLS(B)] in MRSA and MR-CNS were perceived. According to the available literature, the present investigation was a unique endeavor into the identification of the quinolone-resistance-determining-regions, the identification of MRSA and MR-CNS from retail chicken meat in Egypt. In addition, these isolates might indicate the promulgation of methicillin, oxacillin and vancomycin resistance in the community and imply food safety hazards. PMID:27920760

A multiple antibiotic-resistant enterobacter cloacae strain isolated from a bioethanol fermentation facility.

PubMed

Murphree, Colin A; Li, Qing; Heist, E Patrick; Moe, Luke A

2014-09-17

An Enterobacter cloacae strain (E. cloacae F3S3) that was collected as part of a project to assess antibiotic resistance among bacteria isolated from bioethanol fermentation facilities demonstrated high levels of resistance to antibiotics added prophylactically to bioethanol fermentors. PCR assays revealed the presence of canonical genes encoding resistance to penicillin (ampC) and erythromycin (ermG). Assays measuring biofilm formation under antibiotic stress indicated that erythromycin induced biofilm formation in E. cloacae F3S3. Planktonic growth and biofilm formation were observed at a high ethanol content, indicating E. cloacae F3S3 can persist in a bioethanol fermentor under the highly variable environmental conditions found in fermentors.

Bactericidal activity of antibiotics against Legionella micdadei (Pittsburgh pneumonia agent).

PubMed Central

Dowling, J N; Weyant, R S; Pasculle, A W

1982-01-01

The bactericidal activity of five antibiotics for Legionella micdadei was determined by the construction of time-kill curves. Erythromycin, rifampin, penicillin G, cephalothin, and gentamicin were bactericidal for L. micdadei at readily achievable concentrations. The minimal bactericidal concentrations, defined as those producing 99.9% killing within 24 h, were: erythromycin, 4.6; rifampin, 0.13; penicillin G, 0.25; cephalothin, 2.5; and gentamicin, 0.25 micrograms/ml. The ratios of the minimal bactericidal to minimal inhibitory concentrations for these antibiotics ranged from 1 to 8. Thus, the poor in vivo activity of beta-lactam and aminoglycoside antibiotics against L. micdadei cannot be ascribed to a lack of killing by these agents. PMID:6927637

Hydrolysis of amphenicol and macrolide antibiotics: Chloramphenicol, florfenicol, spiramycin, and tylosin.

PubMed

Mitchell, Shannon M; Ullman, Jeffrey L; Teel, Amy L; Watts, Richard J

2015-09-01

Antibiotics that enter the environment can present human and ecological health risks. An understanding of antibiotic hydrolysis rates is important for predicting their environmental persistence as biologically active contaminants. In this study, hydrolysis rates and Arrhenius constants were determined as a function of pH and temperature for two amphenicol (chloramphenicol and florfenicol) and two macrolide (spiramycin and tylosin) antibiotics. Antibiotic hydrolysis rates in pH 4-9 buffer solutions at 25°C, 50°C, and 60°C were quantified, and degradation products were characterized. All of the antibiotics tested remained stable and exhibited no observable hydrolysis under ambient conditions typical of aquatic ecosystems. Acid- and base-catalyzed hydrolysis occurred at elevated temperatures (50-60°C), and hydrolysis rates increased considerably below pH 5 and above pH 8. Hydrolysis rates also increased approximately 1.5- to 2.9-fold for each 10°C increase in temperature. Based on the degradation product masses found, the functional groups that underwent hydrolysis were alkyl fluoride, amide, and cyclic ester (lactone) moieties; some of the resultant degradation products may remain bioactive, but to a lesser extent than the parent compounds. The results of this research demonstrate that amphenicol and macrolide antibiotics persist in aquatic systems under ambient temperature and pH conditions typical of natural waters. Thus, these antibiotics may present a risk in aquatic ecosystems depending on the concentration present. Copyright © 2015. Published by Elsevier Ltd.

Simultaneous determination of five tetracycline and macrolide antibiotics in feeds using HPCE.

PubMed

Tong, Jing; Rao, Qinxiong; Zhu, Kui; Jiang, Zhigang; Ding, Shuangyang

2009-12-01

This work demonstrates the potential of HPCE in the analysis of antibiotics in a complex matrix such as feedstuffs. Using 20 mM citric acid-40 mM Na(2)HPO(4) buffer (pH 2.65), the five antibiotics, tetracycline, oxytetracycline, doxycycline, tilmicosin, and tylosin were successfully separated at 30 kV in a 64.5 cm x 75 microm id capillary. Good repeatability, stability, and reliability of the method were supported by <10% CV with mean recoveries of >70%, and the limit of detection of the five analytes was 0.5-1 mg/kg. It was for the first time that a capillary electrophoretic method was employed to simultaneously detect five tetracycline and macrolide antibiotics in animal feeds.

Solvent effect on the synthesis of clarithromycin: A molecular dynamics study

NASA Astrophysics Data System (ADS)

Duran, Dilek; Aviyente, Viktorya; Baysal, Canan

2004-02-01

Clarithromycin (6- O-methylerythromycin A) is a 14-membered macrolide antibiotic which is active in vitro against clinically important gram-positive and gram-negative bacteria. The selectivity of the methylation of the C-6 OH group is studied on erythromycin A derivatives. To understand the effect of the solvent on the methylation process, detailed molecular dynamics (MD) simulations are performed in pure DMSO, pure THF and DMSO:THF (1:1) mixture by using the anions at the C-6, C-11 and C-12 positions of 2',4''-[ O-bis(TMS)]erythromycin A 9-[ O-(dimethylthexylsilyl)oxime] under the assumption that the anions are stable on the sub-nanosecond time scale. The conformations of the anions are not affected by the presence of the solvent mixture. The radial distribution functions are computed for the distribution of different solvent molecules around the `O-' of the anions. At distances shorter than 5 Å, DMSO molecules are found to cluster around the C-11 anion, whereas the anion at the C-12 position is surrounded by the THF molecules. The anion at the C-6 position is not blocked by the solvent molecules. The results are consistent with the experimental finding that the methylation yield at the latter position is increased in the presence of a DMSO:THF (1:1) solvent mixture. Thus, the effect of the solvent in enhancing the yield during the synthesis is not by changing the conformational properties of the anions, but rather by creating a suitable environment for methylation at the C-6 position.

A comparison of erythromycin and cefadroxil in the prevention of flare-ups from asymptomatic teeth with pulpal necrosis and associated periapical pathosis.

PubMed

Morse, D R; Furst, M L; Lefkowitz, R D; D'Angelo, D; Esposito, J V

1990-05-01

In a previous study by our group with patients having asymptomatic teeth with pulpal necrosis and an associated periapical radiolucent lesion (PN/PL), it was shown that prophylactic administration of penicillin V or erythromycin (high-dose, 1-day regimen) resulted in a low incidence of flare-up (mean = 2.2%) and a low incidence of swelling and pain not associated with flare-up. No hypersensitivity responses occurred, and gastrointestinal side effects were found primarily with the erythromycins. To ascertain whether a single-dose administration of a long-acting 1-gm tablet of the cephalosporin antibiotic cefadroxil would result in a similar outcome, the present study was undertaken with 200 patients having quiescent PN/PL. The patients were randomly given either cefadroxil or erythromycin (base or stearate). Evaluations of flare-up were done 1 day, 1 week, and 2 months after endodontic treatment. A 2.0% flare-up incidence was found, with no statistically significant differences for cefadroxil (1.0%), stearate (2.0%), or base (4.0%). No hypersensitivity responses occurred. Gastrointestinal side effects were found primarily with the erythromycins (19.0%). The results showed that a 1-gm, single-dose regimen of cefadroxil was as effective as erythromycin and penicillin in preventing flare-ups and serious sequelae. A comparative analysis of the data from our first study (no peritreatment antibiotics) and the pooled data from our last three investigations (including the current trial) showed that peritreatment antibiotic coverage significantly reduced flare-ups and serious sequelae after endodontic treatment of asymptomatic PN/PL (p less than 0.001).

Small bugs, big business: the economic power of the microbe.

PubMed

Demain, A L

2000-10-01

The versatility of microbial biosynthesis is enormous. The most industrially important primary metabolites are the amino acids, nucleotides, vitamins, solvents, and organic acids. Millions of tons of amino acids are produced each year with a total multibillion dollar market. Many synthetic vitamin production processes are being replaced by microbial fermentations. In addition to the multiple reaction sequences of fermentations, microorganisms are extremely useful in carrying out biotransformation processes. These are becoming essential to the fine chemical industry in the production of single-isomer intermediates. Microbially produced secondary metabolites are extremely important to our health and nutrition. As a group, they have tremendous economic importance. The antibiotic market amounts to almost 30 billion dollars and includes about 160 antibiotics and derivatives such as the beta-lactam peptide antibiotics, the macrolide polyketide erythromycin, tetracyclines, aminoglycosides and others. Other important pharmaceutical products produced by microrganisms are hypocholesterolemic agents, enzyme inhibitors, immunosuppressants and antitumor compounds, some having markets of over 1 billion dollars per year. Agriculturally important secondary metabolites include coccidiostats, animal growth promotants, antihelmintics and biopesticides. The modern biotechnology industry has made a major impact in the business world, biopharmaceuticals (recombinant protein drugs, vaccines and monoclonal antibodies) having a market of 15 billion dollars. Recombinant DNA technology has also produced a revolution in agriculture and has markedly increased markets for microbial enzymes. Molecular manipulations have been added to mutational techniques as means of increasing titers and yields of microbial procresses and in discovery of new drugs. Today, microbiology is a major participant in global industry. The best is yet to come as microbes move into the environmental and energy sectors.

Serotype distribution and antibiotic susceptibility of Streptococcus pneumoniae strains in the south of Tunisia: A five-year study (2012-2016) of pediatric and adult populations.

PubMed

Ktari, Sonia; Jmal, Ikram; Mroua, Manel; Maalej, Sonda; Ben Ayed, Nour ElHouda; Mnif, Basma; Rhimi, Faouzia; Hammami, Adnene

2017-12-01

To analyze the serotype distribution of Streptococcus pneumoniae clinical isolates collected in the south of Tunisia over a 5-year period in different age groups and to assess their antimicrobial susceptibility patterns. A total of 305 non-duplicate S. pneumoniae isolates were collected between January 2012 and December 2016 at the university hospital in Sfax, Tunisia. All isolates were serotyped by multiplex PCR. The antibiotic susceptibility of all isolates was determined using the disk diffusion test or Etest assay. Among the 305 pneumococcal isolates, 76 (24.9%) were invasive and 229 (75.1%) were non-invasive. The most common serotypes were 19F (20%), 14 (16.7%), 3 (9.2%), 23F (7.5%), 19A (5.9%), and 6B (5.9%). Potential immunization coverage rates for pneumococcal conjugate vaccines PCV7, PCV10, and PCV13 were 58%, 59.3%, and 78.7%, respectively. Three-quarters (75.3%) of pneumococcal isolates were non-susceptible to penicillin. The resistance rate to erythromycin was 71.4%. Only two isolates were resistant to levofloxacin. 19F and 14 were the most prevalent serotypes in the south of Tunisia. The inclusion of a PCV in the immunization program could be useful for reducing the burden of pneumococcal diseases. The high resistance rate to penicillin and macrolides is alarming. Prudent use of antibiotics is crucial to prevent the selection of multidrug-resistant pneumococci. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Antibacterial Effects of Levofloxacin, Erythromycin, and Rifampin in a Human Monocyte System against Legionella pneumophila

PubMed Central

Baltch, Aldona L.; Smith, Raymond P.; Franke, Mary A.; Michelsen, Phyllis B.

1998-01-01

The antibacterial activities of levofloxacin, erythromycin, and rifampin against intracellular Legionella pneumophila L-1033, serogroup 1, were studied. In an in vitro system utilizing adherent human monocytes, L. pneumophila L-1033, a phagocytosis time period of 1 h, and antibiotic (levofloxacin, erythromycin, and/or rifampin) at 1 to 10 times the MIC, the CFU/ml values for the monocyte lysate were determined during 0- to 4-day time periods. The decrease in CFU/ml with levofloxacin at pH 7.4 was rapid, occurring within 24 h, and was drug concentration dependent (P < 0.01). The decrease in CFU with rifampin was first observed at 48 h (P < 0.01), while only a minimal decrease in CFU/ml was observed with erythromycin. Combination of levofloxacin and rifampin and of levofloxacin and erythromycin at ten times their MICs significantly decreased the CFU/ml value (P < 0.01), to the value attained by levofloxacin alone, while combination of rifampin and erythromycin did not. Removal of levofloxacin after 24 h of incubation resulted in regrowth of L. pneumophila L-1033, while a continued slow decrease in CFU/ml was seen following rifampin removal; CFU/ml values were unaffected by the removal of erythromycin. At 4 days, and even in assays performed following antibiotic removal, the CFU/ml value continued to be lower in the levofloxacin and rifampin assays than in the assays with erythromycin. Levofloxacin had a significantly higher bactericidal activity against L. pneumophila L-1033 than erythromycin or rifampin. In these assays, the addition of erythromycin or rifampin did not affect the antibacterial activity of levofloxacin. PMID:9835507

Proliferation of antibiotic resistance genes in microbial consortia of sequencing batch reactors (SBRs) upon exposure to trace erythromycin or erythromycin-H2O.

PubMed

Fan, Caian; He, Jianzhong

2011-05-01

A variety of antibiotics and their metabolites at sub-inhibitory level concentrations are suspected to expand resistance genes in the environment. However, knowledge is limited on the causal correlation of trace antibiotics or their metabolites with resistance proliferation. In this study, erythromycin (ERY) resistance genes were screened on microbial consortia of sequencing batch reactors (SBRs) after one year acclimation to ERY (100 μg/L) or dehydrated erythromycin (ERY-H(2)O, 50 μg/L). The identified esterase gene ereA explains that ERY could be degraded to six products by microbes acclimated to ERY (100 μg/L). However, ERY could not be degraded by microbes acclimated to ERY-H(2)O (50 μg/L), which may be due to the less proliferated ereA gene. Biodegradation of ERY required the presence of exogenous carbon source (e.g., glucose) and nutrients (e.g., nitrogen, phosphorus) for assimilation, but overdosed ammonium-N (>40 mg/L) inhibited degradation of ERY. Zoogloea, a kind of biofilm formation bacteria, became predominant in the ERY degradation consortia, suggesting that the input of ERY could induce biofilm resistance to antibiotics. Our study highlights that lower μg/L level of ERY or ERY-H(2)O in the environment encourages expansion of resistance genes in microbes. Copyright © 2011 Elsevier Ltd. All rights reserved.

Childhood outcomes after prescription of antibiotics to pregnant women with spontaneous preterm labour: 7-year follow-up of the ORACLE II trial.

PubMed

Kenyon, S; Pike, K; Jones, D R; Brocklehurst, P; Marlow, N; Salt, A; Taylor, D J

2008-10-11

The ORACLE II trial compared the use of erythromycin and/or amoxicillin-clavulanate (co-amoxiclav) with that of placebo for women in spontaneous preterm labour and intact membranes, without overt signs of clinical infection, by use of a factorial randomised design. The aim of the present study--the ORACLE Children Study II--was to determine the long-term effects on children after exposure to antibiotics in this clinical situation. We assessed children at age 7 years born to the 4221 women who had completed the ORACLE II study and who were eligible for follow-up with a structured parental questionnaire to assess the child's health status. Functional impairment was defined as the presence of any level of functional impairment (severe, moderate, or mild) derived from the mark III Multi-Attribute Health Status classification system. Educational outcomes were assessed with national curriculum test results for children resident in England. Outcome was determined for 3196 (71%) eligible children. Overall, a greater proportion of children whose mothers had been prescribed erythromycin, with or without co-amoxiclav, had any functional impairment than did those whose mothers had received no erythromycin (658 [42.3%] of 1554 children vs 574 [38.3%] of 1498; odds ratio 1.18, 95% CI 1.02-1.37). Co-amoxiclav (with or without erythromycin) had no effect on the proportion of children with any functional impairment, compared with receipt of no co-amoxiclav (624 [40.7%] of 1523 vs 608 [40.0%] of 1520; 1.03, 0.89-1.19). No effects were seen with either antibiotic on the number of deaths, other medical conditions, behavioural patterns, or educational attainment. However, more children whose mothers had received erythromycin or co-amoxiclav developed cerebral palsy than did those born to mothers who received no erythromycin or no co-amoxiclav, respectively (erythromycin: 53 [3.3%] of 1611 vs 27 [1.7%] of 1562, 1.93, 1.21-3.09; co-amoxiclav: 50 [3.2%] of 1587 vs 30 [1.9%] of 1586, 1.69, 1.07-2.67). The number needed to harm with erythromycin was 64 (95% CI 37-209) and with co-amoxiclav 79 (42-591). The prescription of erythromycin for women in spontaneous preterm labour with intact membranes was associated with an increase in functional impairment among their children at 7 years of age. The risk of cerebral palsy was increased by either antibiotic, although the overall risk of this condition was low. UK Medical Research Council.

Detection of tetQ and ermF antibiotic resistance genes in Prevotella and Porphyromonas isolates from clinical specimens and resident microbiota of humans.

PubMed

Arzese, A R; Tomasetig, L; Botta, G A

2000-05-01

Gram-negative anaerobes belonging to the genera Fusobacterium, Prevotella and Porphyromonas were investigated for the presence of tetQ and ermF, which have been shown to be spread by conjugal elements. One hundred isolates from either sites of infection or various body sites in healthy subjects were studied. PCR was used to detect tetQ, and DNA-DNA hybridization studies on EcoRI chromosomal digests were undertaken to detect the presence of tetQ and ermF. Antibiotic sensitivity assays were performed on selected isolates to detect tetracycline, erythromycin and penicillin resistance. Twenty Fusobacterium isolates lacked tetQ, and were tetracycline sensitive. Twenty per cent of Prevotella spp. isolates both from clinical specimens and from healthy subjects were found to possess tetQ. Of 20 Porphyromonas isolates tested, one (Porphyromonas levii) from a case of bacterial vaginosis was shown to possess tetQ in the chromosome. The presence of tetQ was always associated with tetracycline resistance. Four isolates of Prevotella melaninogenica and one isolate of Prevotella were ermF-positive, although expression of erythromycin resistance was not consistently associated with detection of this gene. Antibiotic resistance phenotypes of Prevotella isolates were shown to be related to specific chromosomal restriction patterns by hybridization studies: tetracycline resistance and tetracycline/erythromycin resistance are conferred by Bacteroides tetracycline-resistant ERL elements, whereas the tetracycline/penicillin resistance phenotype could be due to spread of elements identified in Prevotella only. Tetracycline/erythromycin-resistant and tetracycline/erythromycin/penicillin-resistant P. melaninogenica isolates were found in this study. It appeared that the presence of tetQ and ermF in Bacteroides and Prevotella contributed to the persistence of antibiotic resistance isolates within the host and to potential spread to other organisms through conjugal elements.

Fate and transport of tylosin and macrolide-resistance genes following manure applications in tile-drained landscapes

USDA-ARS?s Scientific Manuscript database

The use of antibiotics in swine production leads to antibiotic-resistance in gastrointestinal bacteria. Application of swine manure to drained agricultural fields introduces elevated levels of antibiotic-resistant bacteria and residual antibiotics. The persistence and transport of these agents are g...

Use of natural antimicrobials to increase antibiotic susceptibility of drug resistant bacteria.

PubMed

Palaniappan, Kavitha; Holley, Richard A

2010-06-15

Plant-derived antibacterial compounds may be of value as a novel means for controlling antibiotic resistant zoonotic pathogens which contaminate food animals and their products. Individual activity of natural antimicrobials (eugenol, thymol, carvacrol, cinnamaldehyde, allyl isothiocyanate (AIT)) and activity when paired with an antibiotic was studied using broth microdilution and checkerboard methods. In the latter assays, fractional inhibitory concentration (FIC) values were calculated to characterize interactions between the inhibitors. Bacteria tested were chosen because of their resistance to at least one antibiotic which had a known genetic basis. Substantial susceptibility of these bacteria toward the natural antimicrobials and a considerable reduction in the minimum inhibitory concentrations (MIC's) of the antibiotics were noted when paired combinations of antimicrobial and antibiotic were used. In the interaction study, thymol and carvacrol were found to be highly effective in reducing the resistance of Salmonella Typhimurium SGI 1 (tet A) to ampicillin, tetracycline, penicillin, bacitracin, erythromycin and novobiocin (FIC<0.4) and resistance of Streptococcus pyogenes ermB to erythromycin (FIC<0.5). With Escherichia coli N00 666, thymol and cinnamaldehyde were found to have a similar effect (FIC<0.4) in reducing the MIC's of ampicillin, tetracycline, penicillin, erythromycin and novobiocin. Carvacrol, thymol (FIC<0.3) and cinnamaldehyde (FIC<0.4) were effective against Staphylococcus aureus blaZ and in reducing the MIC's of ampicillin, penicillin and bacitracin. Allyl isothiocyanate (AIT) was effective in reducing the MIC of erythromycin (FIC<0.3) when tested against S. pyogenes. Fewer combinations were found to be synergistic when the decrease in viable population (log DP) was calculated. Together, fractional inhibitory concentrations < or = 0.5 and log DP<-1 indicated synergistic action between four natural antimicrobials and as many as three antibiotics to which these bacteria were normally resistant. Copyright 2010 Elsevier B.V. All rights reserved.

Use of antibiotics during pregnancy and risk of spontaneous abortion.

PubMed

Muanda, Flory T; Sheehy, Odile; Bérard, Anick

2017-05-01

Although antibiotics are widely used during pregnancy, evidence regarding their fetal safety remains limited. Our aim was to quantify the association between antibiotic exposure during pregnancy and risk of spontaneous abortion. We conducted a nested case-control study within the Quebec Pregnancy Cohort (1998-2009). We excluded planned abortions and pregnancies exposed to fetotoxic drugs. Spontaneous abortion was defined as having a diagnosis or procedure related to spontaneous abortion before the 20th week of pregnancy. The index date was defined as the calendar date of the spontaneous abortion. Ten controls per case were randomly selected and matched by gestational age and year of pregnancy. Use of antibiotics was defined by filled prescriptions between the first day of gestation and the index date and was compared with (a) non-exposure and (b) exposure to penicillins or cephalosporins. We studied type of antibiotics separately using the same comparator groups. After adjustment for potential confounders, use of azithromycin (adjusted odds ratio [OR] 1.65, 95% confidence interval [CI] 1.34-2.02; 110 exposed cases), clarithromycin (adjusted OR 2.35, 95% CI 1.90-2.91; 111 exposed cases), metronidazole (adjusted OR 1.70, 95% CI 1.27-2.26; 53 exposed cases), sulfonamides (adjusted OR 2.01, 95% CI 1.36-2.97; 30 exposed cases), tetracyclines (adjusted OR 2.59, 95% CI 1.97-3.41; 67 exposed cases) and quinolones (adjusted OR 2.72, 95% CI 2.27-3.27; 160 exposed cases) was associated with an increased risk of spontaneous abortion. Similar results were found when we used penicillins or cephalosporins as the comparator group. After adjustment for potential confounders, use of macro-lides (excluding erythromycin), quinolones, tetracyclines, sulfonamides and metronidazole during early pregnancy was associated with an increased risk of spontaneous abortion. Our findings may be of use to policy-makers to update guidelines for the treatment of infections during pregnancy. © 2017 Canadian Medical Association or its licensors.

Use of antibiotics during pregnancy and risk of spontaneous abortion

PubMed Central

Muanda, Flory T.; Sheehy, Odile; Bérard, Anick

2017-01-01

BACKGROUND: Although antibiotics are widely used during pregnancy, evidence regarding their fetal safety remains limited. Our aim was to quantify the association between antibiotic exposure during pregnancy and risk of spontaneous abortion. METHODS: We conducted a nested case–control study within the Quebec Pregnancy Cohort (1998–2009). We excluded planned abortions and pregnancies exposed to fetotoxic drugs. Spontaneous abortion was defined as having a diagnosis or procedure related to spontaneous abortion before the 20th week of pregnancy. The index date was defined as the calendar date of the spontaneous abortion. Ten controls per case were randomly selected and matched by gestational age and year of pregnancy. Use of antibiotics was defined by filled prescriptions between the first day of gestation and the index date and was compared with (a) non-exposure and (b) exposure to penicillins or cephalosporins. We studied type of antibiotics separately using the same comparator groups. RESULTS: After adjustment for potential confounders, use of azithromycin (adjusted odds ratio [OR] 1.65, 95% confidence interval [CI] 1.34–2.02; 110 exposed cases), clarithromycin (adjusted OR 2.35, 95% CI 1.90–2.91; 111 exposed cases), metronidazole (adjusted OR 1.70, 95% CI 1.27–2.26; 53 exposed cases), sulfonamides (adjusted OR 2.01, 95% CI 1.36–2.97; 30 exposed cases), tetracyclines (adjusted OR 2.59, 95% CI 1.97–3.41; 67 exposed cases) and quinolones (adjusted OR 2.72, 95% CI 2.27–3.27; 160 exposed cases) was associated with an increased risk of spontaneous abortion. Similar results were found when we used penicillins or cephalosporins as the comparator group. INTERPRETATION: After adjustment for potential confounders, use of macro-lides (excluding erythromycin), quinolones, tetracyclines, sulfonamides and metronidazole during early pregnancy was associated with an increased risk of spontaneous abortion. Our findings may be of use to policy-makers to update guidelines for the treatment of infections during pregnancy. PMID:28461374

Inactivation of SACE_3446, a TetR family transcriptional regulator, stimulates erythromycin production in Saccharopolyspora erythraea.

PubMed

Wu, Hang; Wang, Yansheng; Yuan, Li; Mao, Yongrong; Wang, Weiwei; Zhu, Lin; Wu, Panpan; Fu, Chengzhang; Müller, Rolf; Weaver, David T; Zhang, Lixin; Zhang, Buchang

2016-03-01

Erythromycin A is a widely used antibiotic produced by Saccharopolyspora erythraea ; however, its biosynthetic cluster lacks a regulatory gene, limiting the yield enhancement via regulation engineering of S. erythraea . Herein, six TetR family transcriptional regulators (TFRs) belonging to three genomic context types were individually inactivated in S. erythraea A226, and one of them, SACE_3446, was proved to play a negative role in regulating erythromycin biosynthesis. EMSA and qRT-PCR analysis revealed that SACE_3446 covering intact N-terminal DNA binding domain specifically bound to the promoter regions of erythromycin biosynthetic gene eryAI , the resistant gene ermE and the adjacent gene SACE_3447 (encoding a long-chain fatty-acid CoA ligase), and repressed their transcription. Furthermore, we explored the interaction relationships of SACE_3446 and previously identified TFRs (SACE_3986 and SACE_7301) associated with erythromycin production. Given demonstrated relatively independent regulation mode of SACE_3446 and SACE_3986 in erythromycin biosynthesis, we individually and concomitantly inactivated them in an industrial S. erythraea WB. Compared with WB, the WBΔ 3446 and WBΔ 3446 Δ 3986 mutants respectively displayed 36% and 65% yield enhancement of erythromycin A, following significantly elevated transcription of eryAI and ermE . When cultured in a 5 L fermentor, erythromycin A of WBΔ 3446 and WBΔ 3446 Δ 3986 successively reached 4095 mg/L and 4670 mg/L with 23% and 41% production improvement relative to WB. The strategy reported here will be useful to improve antibiotics production in other industrial actinomycete.

The genetic diversity and phenotypic characterisation of Streptococcus agalactiae isolates from Rio de Janeiro, Brazil.

PubMed

Corrêa, Ana Beatriz de Almeida; Silva, Lígia Guedes da; Pinto, Tatiana de Castro Abreu; Oliveira, Ivi Cristina Menezes de; Fernandes, Flávio Gimenis; Costa, Natalia Silva da; Mattos, Marcos Corrêa de; Fracalanzza, Sergio Eduardo Longo; Benchetrit, Leslie Claude

2011-12-01

Streptococcus agalactiae isolates are more common among pregnant women, neonates and nonpregnant adults with underlying diseases compared to other demographic groups. In this study, we evaluate the genetic and phenotypic diversity in S. agalactiae strains from Rio de Janeiro (RJ) that were isolated from asymptomatic carriers. We analysed these S. agalactiae strains using pulsed-field gel electrophoresis (PFGE), serotyping and antimicrobial susceptibility testing, as well as by determining the macrolide resistance phenotype, and detecting the presence of the ermA/B, mefA/E and lnuB genes. The serotypes Ia, II, III and V were the most prevalent serotypes observed. The 60 strains analysed were susceptible to penicillin, vancomycin and levofloxacin. Resistance to clindamycin, chloramphenicol, erythromycin, rifampin and tetracycline was observed. Among the erythromycin and/or clindamycin resistant strains, the ermA, ermB and mefA/E genes were detected and the constitutive macrolides, lincosamides and streptogramin B-type resistance was the most prevalent phenotype observed. The lnuB gene was not detected in any of the strains studied. We found 56 PFGE electrophoretic profiles and only 22 of them were allocated in polymorphism patterns. This work presents data on the genetic diversity and prevalent capsular serotypes among RJ isolates. Approximately 85% of these strains came from pregnant women; therefore, these data may be helpful in developing future prophylaxis and treatment strategies for neonatal syndromes in RJ.

Metal and antibiotic resistance of bacteria isolated from the Baltic Sea.

PubMed

Moskot, Marta; Kotlarska, Ewa; Jakóbkiewicz-Banecka, Joanna; Gabig-Cimińska, Magdalena; Fari, Karolina; Wegrzyn, Grzegorz; Wróbel, Borys

2012-09-01

The resistance of 49 strains of bacteria isolated from surface Baltic Sea waters to 11 antibiotics was analyzed and the resistance of selected strains to three metal ions (Ni2+, Mn2+, Zn2+) was tested. Most isolates belonged to Gammaproteobacteria (78%), while Alphaproteobacteria (8%), Actinobacteria (10%), and Bacteroidetes (4%) were less abundant. Even though previous reports suggested relationships between resistance and the presence of plasmids or the ability to produce pigments, no compelling evidence for such relationships was obtained for the strains isolated in this work. In particular, strains resistant to multiple antibiotics did not carry plasmids more frequently than sensitive strains. A relation between resistance and the four aminoglycosides tested (gentamycin, kanamycin, neomycin, and streptomycin), but not to spectinomycin, was demonstrated. This observation is of interest given that spectinomycin is not always classified as an aminoglycoside because it lacks a traditional sugar moiety. Statistical analysis indicated relationships between resistance to some antibiotics (ampicillin and erythromycin, chloramphenicol and erythromycin, chloramphenicol and tetracycline, erythromycin and tetracycline), suggesting the linkage of resistance genes for antibiotics belonging to different classes. The effects of NiSO4, ZnCl2 and MnCl2 on various media suggested that the composition of Marine Broth might result in low concentrations of Mn2+ due to chemical interactions that potentially lead to precipitation.

Nonantibiotic macrolides prevent human neutrophil elastase-induced mucus stasis and airway surface liquid volume depletion.

PubMed

Tarran, Robert; Sabater, Juan R; Clarke, Tainya C; Tan, Chong D; Davies, Catrin M; Liu, Jia; Yeung, Arthur; Garland, Alaina L; Stutts, M Jackson; Abraham, William M; Phillips, Gary; Baker, William R; Wright, Clifford D; Wilbert, Sibylle

2013-06-01

Mucus clearance is an important component of the lung's innate defense system. A failure of this system brought on by mucus dehydration is common to both cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). Mucus clearance rates are regulated by the volume of airway surface liquid (ASL) and by ciliary beat frequency (CBF). Chronic treatment with macrolide antibiotics is known to be beneficial to both CF and COPD patients. However, chronic macrolide usage may induce bacterial resistance. We have developed a novel macrolide, 2'-desoxy-9-(S)-erythromycylamine (GS-459755), that has significantly diminished antibiotic activity against Staphylococcus aureus, Streptococcus pneumonia, Moraxella catarrhalis, and Haemophilus influenzae. Since neutrophilia frequently occurs in chronic lung disease and human neutrophil elastase (HNE) induces mucus stasis by activating the epithelial sodium channel (ENaC), we tested the ability of GS-459755 to protect against HNE-induced mucus stasis. GS-459755 had no effect on HNE activity. However, GS-459755 pretreatment protected against HNE-induced ASL volume depletion in human bronchial epithelial cells (HBECs). The effect of GS-459755 on ASL volume was dose dependent (IC₅₀ ~3.9 μM) and comparable to the antibacterial macrolide azithromycin (IC₅₀ ~2.4 μM). Macrolides had no significant effect on CBF or on transepithelial water permeability. However, the amiloride-sensitive transepithelial voltage, a marker of ENaC activity, was diminished by macrolide pretreatment. We conclude that GS-459755 may limit HNE-induced activation of ENaC and may be useful for the treatment of mucus dehydration in CF and COPD without inducing bacterial resistance.

Pathological Studies on the Protective Effect of a Macrolide Antibiotic, Roxithromycin, against Sulfur Mustard Inhalation Toxicity in a Rat Model

DTIC Science & Technology

2011-01-01

placed in a water-jacketed (37C) glass vapor generator custom fabri - cated by Atmar Glass (Kennett Square, PA). Spontaneously breathing rats were...bronchiectasis, and pul- monary fibrosis (Emad and Rezaian 1997). Macrolide antibio- tics have shown effectiveness in a variety of chronic respiratory diseases ...observed in clinical studies of chronic inflammatory airway diseases (e.g., DPB) after long-term treatment with low dose of macrolides (Rubin 2004). For

Efficacy of azithromycin or clarithromycin for prophylaxis of viridans group streptococcus experimental endocarditis.

PubMed Central

Rouse, M S; Steckelberg, J M; Brandt, C M; Patel, R; Miro, J M; Wilson, W R

1997-01-01

The efficacy of azithromycin or clarithromycin was compared to that of amoxicillin, clindamycin, or erythromycin for the prevention of viridans group streptococcus experimental endocarditis. Rabbits with catheter-induced aortic valve vegetations were given no antibiotics or two doses of amoxicillin at 25 mg/kg of body weight, azithromycin at 10 mg/kg, clarithromycin at 10 mg/kg, clindamycin at 40 mg/kg followed by clindamycin at 20 mg/kg, or erythromycin at 10 mg/kg. Antibiotics were administered 0.5 h before and 5.5 h after intravenous infusion of 5 x 10(5) CFU of Streptococcus milleri. Forty-eight hours after bacterial inoculation, the rabbits were killed and aortic valve vegetations were aseptically removed and cultured for bacteria. Infective endocarditis occurred in 88% of untreated animals, 1% of animals receiving amoxicillin, 9% of animals receiving erythromycin, 0% of animals receiving clindamycin, 2.5% of animals receiving clarithromycin, and 1% of animals receiving azithromycin. All five regimens were more effective (P < 0.001) than no prophylaxis. Erythromycin was less effective (P < 0.05) than amoxicillin or clindamycin. Azithromycin or clarithromycin was as effective as amoxicillin, clindamycin, or erythromycin for the prevention of viridans group streptococcus experimental endocarditis in this model. PMID:9257739

Cost-effectiveness of antibiotic treatment strategies for community-acquired pneumonia: results from a cluster randomized cross-over trial.

PubMed

van Werkhoven, Cornelis H; Postma, Douwe F; Mangen, Marie-Josee J; Oosterheert, Jan Jelrik; Bonten, Marc J M

2017-01-10

To determine the cost-effectiveness of strategies of preferred antibiotic treatment with beta-lactam/macrolide combination or fluoroquinolone monotherapy compared to beta-lactam monotherapy. Costs and effects were estimated using data from a cluster-randomized cross-over trial of antibiotic treatment strategies, primarily from the reduced third payer perspective (i.e. hospital admission costs). Cost-minimization analysis (CMA) and cost-effectiveness analysis (CEA) were performed using linear mixed models. CMA results were expressed as difference in costs per patient. CEA results were expressed as incremental cost-effectiveness ratios (ICER) showing additional costs per prevented death. A total of 2,283 patients were included. Crude average costs within 90 days from the reduced third payer perspective were €4,294, €4,392, and €4,002 per patient for the beta-lactam monotherapy, beta-lactam/macrolide combination, and fluoroquinolone monotherapy strategy, respectively. CMA results were €106 (95% CI €-697 to €754) for the beta-lactam/macrolide combination strategy and €-278 (95%CI €-991 to €396) for the fluoroquinolone monotherapy strategy, both compared to the beta-lactam monotherapy strategy. The ICER was not statistically significantly different between the strategies. Other perspectives yielded similar results. There were no significant differences in cost-effectiveness of strategies of preferred antibiotic treatment of CAP on non-ICU wards with either beta-lactam monotherapy, beta-lactam/macrolide combination therapy, or fluoroquinolone monotherapy. The trial was registered with ClinicalTrials.gov, number NCT01660204 , on May 2nd, 2012.

Immuno-modulation and anti-inflammatory benefits of antibiotics: the example of tilmicosin.

PubMed

Buret, André G

2010-01-01

Exaggerated immune responses, such as those implicated in severe inflammatory reactions, are costly to the metabolism. Inflammation and pro-inflammatory mediators negatively affect production in the food animal industry by reducing growth, feed intake, reproduction, milk production, and metabolic health. An ever-increasing number of findings have established that antibiotics, macrolides in particular, may generate anti-inflammatory effects, including the modulation of pro-inflammatory cytokines and the alteration of neutrophil function. The effects are time- and dose-dependent, and the mechanisms responsible for these phenomena remain incompletely understood. Recent studies, mostly using the veterinary macrolide tilmicosin, may have shed new light on the mode of action of some macrolides and their anti-inflammatory properties. Indeed, research findings demonstrate that this compound, amongst others, induces neutrophil apoptosis, which in turn provides anti-inflammatory benefits. Studies using tilmicosin model systems in vitro and in vivo demonstrate that this antibiotic has potent immunomodulatory effects that may explain why at least parts of its clinical benefits are independent of anti-microbial effects. More research is needed, using this antibiotic and others that may have similar properties, to clarify the biological mechanisms responsible for antibiotic-induced neutrophil apoptosis, and how this, in turn, may provide enhanced clinical benefits. Such studies may help establish a rational basis for the development of novel, efficacious, anti-microbial compounds that generate anti-inflammatory properties in addition to their antibacterial effects.

Immuno-modulation and anti-inflammatory benefits of antibiotics: The example of tilmicosin

PubMed Central

Buret, André G.

2010-01-01

Exagerated immune responses, such as those implicated in severe inflammatory reactions, are costly to the metabolism. Inflammation and pro-inflammatory mediators negatively affect production in the food animal industry by reducing growth, feed intake, reproduction, milk production, and metabolic health. An ever-increasing number of findings have established that antibiotics, macrolides in particular, may generate anti-inflammatory effects, including the modulation of pro-inflammatory cytokines and the alteration of neutrophil function. The effects are time- and dose-dependent, and the mechanisms responsible for these phenomena remain incompletely understood. Recent studies, mostly using the veterinary macrolide tilmicosin, may have shed new light on the mode of action of some macrolides and their anti-inflammatory properties. Indeed, research findings demonstrate that this compound, amongst others, induces neutrophil apoptosis, which in turn provides anti-inflammatory benefits. Studies using tilmicosin model systems in vitro and in vivo demonstrate that this antibiotic has potent immunomodulatory effects that may explain why at least parts of its clinical benefits are independent of anti-microbial effects. More research is needed, using this antibiotic and others that may have similar properties, to clarify the biological mechanisms responsible for antibiotic-induced neutrophil apoptosis, and how this, in turn, may provide enhanced clinical benefits. Such studies may help establish a rational basis for the development of novel, efficacious, anti-microbial compounds that generate anti-inflammatory properties in addition to their antibacterial effects. PMID:20357951

Distribution of macrolide resistance mechanisms in Bulgarian clinical isolates of Streptococcus pyogenes during the years of 2013-2016.

PubMed

Muhtarova, Adile A; Gergova, Raina T; Mitov, Ivan G

2017-09-01

Streptococcus pyogenes, or group A streptococcus (GAS), is the main etiological agent of bacterial tonsillopharyngitis and a common cause of a wide variety of other mild to severe infections. Objectives of the present study was to determine and evaluate the distribution of genetic mechanisms associated with certain phenotypes of macrolide resistance in Bulgarian GAS isolated during the years of 2013-2016. All GAS strains were screened for the macrolide resistance genes erm(A), erm(B) and mef(A), using multiplex polymerase chain reaction (PCR). The minimal inhibitory concentrations (MICs) of erythromycin, azithromycin, clarithromycin, clindamycin were determined by E-tests. Almost 23% of GAS isolates obtained in 2013-2014 and near 40% of them in 2015-2016 contained various elements of resistance. The predominant gene was mef(A), which encodes an efflux pump (M-phenotype), identified in 57.84% of the macrolide-resistant strains. The next frequently prevalent mechanism was a combination of mef(A) and erm(B) in 22.55%, which determined high-level inducible or constitutive resistance to macrolides, lincosamides and streptogramins (iMLSB or cMLSB). The highest MIC value (>256mg/L) was detected in association with erm(B) (p<0.05). The MIC range was observed to be much higher in the isolates with combinations of resistance genes vs. those with mef genes alone (p<0.05). The data about the distribution and prevalence of macrolide resistance mechanisms obtained in this study can help in the treatment of persistent and recurrent GAS infections and in the correct choice of empiric therapy. Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

Ultratrace analysis of nine macrolides, including tulathromycin A (Draxxin), in edible animal tissues with minicolumn liquid chromatography tandem mass spectrometry.

PubMed

Martos, Perry A; Lehotay, Steven J; Shurmer, Bryn

2008-10-08

The analysis of nine macrolides is presented, including tulathromycin A (Draxxin), in beef, poultry, and pork muscle with a simple multiresidue extraction and analysis method using high-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry. The sample preparation method involves extraction with acetonitrile and defatting with hexane followed by dilution of the extracts for analysis. Separation of the nine macrolides was performed using an Atlantis dC 18, 3 mum, 3.9 mm x 20 mm minicolumn (guard column). Detection was carried out with two multiple reaction monitoring experiments per macrolide. The method detection limits (MDLs) were based on three times standard deviation of eight repeat spikes at 3.0 ng/g of a mix of the nine macrolides in the various tissues. The MDLs and retention times for the macrolides were as follows: lincomycin, 0.19 ng/g (t R = 5.00 min); tulathromycin, 0.46 ng/g (t R = 5.63 min); spiramycin, 0.21 ng/g (t R = 6.06 min); pirlimycin, 0.10 ng/g (t R = 6.04 min); clindamycin, 0.16 ng/g (t R = 6.20 min); tilmicosin, 0.29 ng/g (t R = 6.38 min); erythromycin, 0.19 ng/g (t R = 6.62 min); tylosin, 0.10 ng/g (t R = 6.72 min); and josamycin, 0.09 ng/g (t R = 6.98 min). Precision at 25 ng/g (n = 4) ranged from 2.3 to 9.4% for the compounds from beef muscle. Of interest is the detection of incurred residues of tulathromycin A in edible calf tissue at 0.10-7 mug/g, which is presented here for the first time.

Macrolides: a promising pharmacologic therapy for chronic obstructive pulmonary disease

PubMed Central

Qiu, Shilin; Zhong, Xiaoning

2016-01-01

Chronic inflammation plays a central role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, there are no effective anti-inflammatory pharmacologic therapies available for COPD so far. Recent evidence suggests that an immunologic mechanism has a role in the pathogenesis of COPD. Macrolides possess anti-inflammatory and immune-modulating effects may be helpful in the treatment of COPD. Several clinical studies have shown that long-term use of macrolides reduces the frequency of COPD exacerbations. However, the subgroups that most effectively respond to long-term treatment of macrolides still need to be determined. The potential adverse events to individuals and the microbial resistance in community populations raises great concern on the long-term use of macrolides. Thus, novel macrolides have anti-inflammatory and immuno-modulating effects, but without antibiotic effects, and are promising as an anti-inflammatory agent for the treatment of COPD. In addition, the combination of macrolides and other anti-inflammatory pharmacologic agents may be a new strategy for the treatment of COPD. PMID:28030992

Macrolides selectively inhibit mutant KCNJ5 potassium channels that cause aldosterone-producing adenoma

PubMed Central

Scholl, Ute I.; Abriola, Laura; Zhang, Chengbiao; Reimer, Esther N.; Plummer, Mark; Zhang, Junhui; Hoyer, Denton; Merkel, Jane S.; Wang, Wenhui; Lifton, Richard P.

2017-01-01

Aldosterone-producing adenomas (APAs) are benign tumors of the adrenal gland that constitutively produce the salt-retaining steroid hormone aldosterone and cause millions of cases of severe hypertension worldwide. Either of 2 somatic mutations in the potassium channel KCNJ5 (G151R and L168R, hereafter referred to as KCNJ5MUT) in adrenocortical cells account for half of APAs worldwide. These mutations alter channel selectivity to allow abnormal Na+ conductance, resulting in membrane depolarization, calcium influx, aldosterone production, and cell proliferation. Because APA diagnosis requires a difficult invasive procedure, patients often remain undiagnosed and inadequately treated. Inhibitors of KCNJ5MUT could allow noninvasive diagnosis and therapy of APAs carrying KCNJ5 mutations. Here, we developed a high-throughput screen for rescue of KCNJ5MUT-induced lethality and identified a series of macrolide antibiotics, including roxithromycin, that potently inhibit KCNJ5MUT, but not KCNJ5WT. Electrophysiology demonstrated direct KCNJ5MUT inhibition. In human aldosterone-producing adrenocortical cancer cell lines, roxithromycin inhibited KCNJ5MUT-induced induction of CYP11B2 (encoding aldosterone synthase) expression and aldosterone production. Further exploration of macrolides showed that KCNJ5MUT was similarly selectively inhibited by idremcinal, a macrolide motilin receptor agonist, and by synthesized macrolide derivatives lacking antibiotic or motilide activity. Macrolide-derived selective KCNJ5MUT inhibitors thus have the potential to advance the diagnosis and treatment of APAs harboring KCNJ5MUT. PMID:28604387

Macrolides selectively inhibit mutant KCNJ5 potassium channels that cause aldosterone-producing adenoma.

PubMed

Scholl, Ute I; Abriola, Laura; Zhang, Chengbiao; Reimer, Esther N; Plummer, Mark; Kazmierczak, Barbara I; Zhang, Junhui; Hoyer, Denton; Merkel, Jane S; Wang, Wenhui; Lifton, Richard P

2017-06-30

Aldosterone-producing adenomas (APAs) are benign tumors of the adrenal gland that constitutively produce the salt-retaining steroid hormone aldosterone and cause millions of cases of severe hypertension worldwide. Either of 2 somatic mutations in the potassium channel KCNJ5 (G151R and L168R, hereafter referred to as KCNJ5MUT) in adrenocortical cells account for half of APAs worldwide. These mutations alter channel selectivity to allow abnormal Na+ conductance, resulting in membrane depolarization, calcium influx, aldosterone production, and cell proliferation. Because APA diagnosis requires a difficult invasive procedure, patients often remain undiagnosed and inadequately treated. Inhibitors of KCNJ5MUT could allow noninvasive diagnosis and therapy of APAs carrying KCNJ5 mutations. Here, we developed a high-throughput screen for rescue of KCNJ5MUT-induced lethality and identified a series of macrolide antibiotics, including roxithromycin, that potently inhibit KCNJ5MUT, but not KCNJ5WT. Electrophysiology demonstrated direct KCNJ5MUT inhibition. In human aldosterone-producing adrenocortical cancer cell lines, roxithromycin inhibited KCNJ5MUT-induced induction of CYP11B2 (encoding aldosterone synthase) expression and aldosterone production. Further exploration of macrolides showed that KCNJ5MUT was similarly selectively inhibited by idremcinal, a macrolide motilin receptor agonist, and by synthesized macrolide derivatives lacking antibiotic or motilide activity. Macrolide-derived selective KCNJ5MUT inhibitors thus have the potential to advance the diagnosis and treatment of APAs harboring KCNJ5MUT.

Wastewater treatment plants as a pathway for aquatic contamination by pharmaceuticals in the ebro river basin (northeast Spain).

PubMed

Gros, Meritxell; Petrović, Mira; Barceló, Damià

2007-08-01

The occurrence of 28 pharmaceuticals of major human consumption in Spain, including analgesics and anti-inflammatories, lipid regulators, psychiatric drugs, antibiotics, antihistamines, and beta-blockers, was assessed along the Ebro river basin, one of the biggest irrigated lands in that country. Target compounds were simultaneously analyzed by off-line solid-phase extraction, followed by liquid chromatography-tandem mass spectrometry. The loads of detected pharmaceuticals and their removal rates were studied in seven wastewater treatment plants (WWTPs) located in the main cities along the basin. Total loads ranged from 2 to 5 and from 0.5 to 1.5 g/d/1,000 inhabitants in influent and effluent wastewaters, respectively. High removal rates (60-90%) were achieved mainly for analgesics and anti-inflammatories. The other groups showed lower rates, ranging from 20 to 60%, and in most cases, the antiepileptic carbamazepine, macrolide antibiotics, and trimethoprim were not eliminated at all. Finally, the contribution of WWTP effluents to the presence of pharmaceuticals in receiving river waters was surveyed. In receiving surface water, the most ubiquitous compounds were the analgesics and anti-inflammatories ibuprofen, diclofenac, and naproxen; the lipid regulators bezafibrate and gemfibrozil; the antibiotics erythromycin, azithromycin, sulfamethoxazole, trimethoprim, and less frequently, ofloxacin; the antiepileptic carbamazepine; the antihistamine ranitidine; and the beta-blockers atenolol and sotalol. Although levels found in WWTP effluents ranged from low microg/L to high ng/L, pharmaceuticals in river waters occurred at levels at least one order of magnitude lower (low ng/L range) because of dilution effect. From the results obtained, it was proved that WWTP are hot spots of aquatic contamination concerning pharmaceuticals of human consumption.

Metagenomic Assembly Reveals Hosts of Antibiotic Resistance Genes and the Shared Resistome in Pig, Chicken, and Human Feces.

PubMed

Ma, Liping; Xia, Yu; Li, Bing; Yang, Ying; Li, Li-Guan; Tiedje, James M; Zhang, Tong

2016-01-05

The risk associated with antibiotic resistance disseminating from animal and human feces is an urgent public issue. In the present study, we sought to establish a pipeline for annotating antibiotic resistance genes (ARGs) based on metagenomic assembly to investigate ARGs and their co-occurrence with associated genetic elements. Genetic elements found on the assembled genomic fragments include mobile genetic elements (MGEs) and metal resistance genes (MRGs). We then explored the hosts of these resistance genes and the shared resistome of pig, chicken and human fecal samples. High levels of tetracycline, multidrug, erythromycin, and aminoglycoside resistance genes were discovered in these fecal samples. In particular, significantly high level of ARGs (7762 ×/Gb) was detected in adult chicken feces, indicating higher ARG contamination level than other fecal samples. Many ARGs arrangements (e.g., macA-macB and tetA-tetR) were discovered shared by chicken, pig and human feces. In addition, MGEs such as the aadA5-dfrA17-carrying class 1 integron were identified on an assembled scaffold of chicken feces, and are carried by human pathogens. Differential coverage binning analysis revealed significant ARG enrichment in adult chicken feces. A draft genome, annotated as multidrug resistant Escherichia coli, was retrieved from chicken feces metagenomes and was determined to carry diverse ARGs (multidrug, acriflavine, and macrolide). The present study demonstrates the determination of ARG hosts and the shared resistome from metagenomic data sets and successfully establishes the relationship between ARGs, hosts, and environments. This ARG annotation pipeline based on metagenomic assembly will help to bridge the knowledge gaps regarding ARG-associated genes and ARG hosts with metagenomic data sets. Moreover, this pipeline will facilitate the evaluation of environmental risks in the genetic context of ARGs.

Molecular characterization of invasive Streptococcus dysgalactiae subsp. equisimilis. Multicenter study: Argentina 2011-2012.

PubMed

Traverso, Fernando; Blanco, Alejandra; Villalón, Pilar; Beratz, Noelia; Sáez Nieto, Juan Antonio; Lopardo, Horacio

Streptococcus dysgalactiae subsp. equisimilis (SDSE) has virulence factors similar to those of Streptococcus pyogenes. Therefore, it causes pharyngitis and severe infections indistinguishable from those caused by the classic pathogen. The objectives of this study were: to know the prevalence of SDSE invasive infections in Argentina, to study the genetic diversity, to determine the presence of virulence genes, to study antibiotic susceptibility and to detect antibiotic resistance genes. Conventional methods of identification were used. Antibiotic susceptibility was determined by the disk diffusion and the agar dilution methods and the E-test. Twenty eight centers from 16 Argentinean cities participated in the study. Twenty three isolates (16 group G and 7 group C) were obtained between July 1 2011 and June 30 2012. Two adult patients died (8.7%). Most of the isolates were recovered from blood (60.9%). All isolates carried speJ and ssa genes. stG62647, stG653 and stG840 were the most frequent emm types. Nineteen different PFGE patterns were detected. All isolates were susceptible to penicillin and levofloxacin, 6 (26.1%) showed resistance or reduced susceptibility to erythromycin [1 mef(A), 3 erm(TR), 1 mef(A)+erm(TR) and 1 erm(TR)+erm(B)] and 7 (30.4%) were resistant or exhibited reduced susceptibility to tetracycline [2 tet(M), 5 tet(M)+tet(O)]. The prevalence in Argentina was of at least 23 invasive infections by SDSE. A wide genetic diversity was observed. All isolates carried speJ and ssa genes. Similarly to other studies, macrolide resistance (26.1%) was mainly associated to the MLS B phenotype. Copyright © 2016 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

A human health risk assessment for macrolide-resistant Campylobacter associated with the use of macrolides in Danish pig production.

PubMed

Alban, Lis; Nielsen, Elisabeth Okholm; Dahl, Jan

2008-02-01

In 2006, macrolides were withdrawn from the list of antibiotics recommended for veterinary treatment of diarrhoea in Danish pigs. The motive was to lower the antibiotic consumption in general and to mitigate the risk related to human infection with macrolide-resistant (Mres) Campylobacter. We subsequently conducted a risk assessment following international guidelines to address the risk for human health associated with usage of macrolides in Danish pigs. Data originated from surveillance programs, published papers, reports and statistics. Furthermore, an exposure model was built in @Risk. Mres Campylobacter is the hazard of interest. Data from different EU countries show that beef contains a very low prevalence (typically 0.1-1.1%) of Campylobacter; moreover, Mres is uncommon in Campylobacter isolates from cattle (between 0% and 6%). Beef was therefore left out of further analysis. For pork at retail, a high variation in the prevalence of Campylobacter has been reported within EU; but generally the prevalence is <10%, and the isolates are often Mres. EU data indicate that poultry meat harbor a high prevalence of Campylobacter (more more than 10%) with Mres at prevalence ranging from 0% to 8%. According to the exposure model - that included origin of meat as well as consumption patterns - most human cases of Mres campylobacteriosis (157 out of 186) was ascribed to imported meat. Only seven cases could be explained by veterinary usage of macrolides in Danish pigs. In general, human cases of campylobacteriosis are self-limiting, and it is questionable whether there is any excess risk related to infection with Mres Campylobacter compared to sensitive Campylobacter. In conclusion, the risk associated with veterinary use of macrolides in Danish pigs for the human health of Danes seemed to be low.

Nonantibiotic macrolides prevent human neutrophil elastase-induced mucus stasis and airway surface liquid volume depletion

PubMed Central

Sabater, Juan R.; Clarke, Tainya C.; Tan, Chong D.; Davies, Catrin M.; Liu, Jia; Yeung, Arthur; Garland, Alaina L.; Stutts, M. Jackson; Abraham, William M.; Phillips, Gary; Baker, William R.; Wright, Clifford D.; Wilbert, Sibylle

2013-01-01

Mucus clearance is an important component of the lung's innate defense system. A failure of this system brought on by mucus dehydration is common to both cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). Mucus clearance rates are regulated by the volume of airway surface liquid (ASL) and by ciliary beat frequency (CBF). Chronic treatment with macrolide antibiotics is known to be beneficial to both CF and COPD patients. However, chronic macrolide usage may induce bacterial resistance. We have developed a novel macrolide, 2′-desoxy-9-(S)-erythromycylamine (GS-459755), that has significantly diminished antibiotic activity against Staphylococcus aureus, Streptococcus pneumonia, Moraxella catarrhalis, and Haemophilus influenzae. Since neutrophilia frequently occurs in chronic lung disease and human neutrophil elastase (HNE) induces mucus stasis by activating the epithelial sodium channel (ENaC), we tested the ability of GS-459755 to protect against HNE-induced mucus stasis. GS-459755 had no effect on HNE activity. However, GS-459755 pretreatment protected against HNE-induced ASL volume depletion in human bronchial epithelial cells (HBECs). The effect of GS-459755 on ASL volume was dose dependent (IC50 ∼3.9 μM) and comparable to the antibacterial macrolide azithromycin (IC50 ∼2.4 μM). Macrolides had no significant effect on CBF or on transepithelial water permeability. However, the amiloride-sensitive transepithelial voltage, a marker of ENaC activity, was diminished by macrolide pretreatment. We conclude that GS-459755 may limit HNE-induced activation of ENaC and may be useful for the treatment of mucus dehydration in CF and COPD without inducing bacterial resistance. PMID:23542952

Antimicrobial activity of topical agents against Propionibacterium acnes: an in vitro study of clinical isolates from a hospital in Shanghai, China.

PubMed

Ma, Ying; Zhang, Nanxue; Wu, Shi; Huang, Haihui; Cao, Yanpei

2016-12-01

This study aimed to compare the antimicrobial activities of topical agents against Propionibacterium acnes isolated from patients admitted to a hospital in Shanghai, China. The minimal inhibitory concentrations of the cultured P. acnes were determined in accordance with the Clinical and Laboratory Standards Institute. Susceptibilities to clindamycin and erythromycin were compared in terms of gender, age, disease duration, previous treatment, and disease severity. A total of 69 P. acnes strains were isolated from 98 patients (70.41%). The susceptibility to triple antibiotic ointment (neomycin/bacitracin/polymyxin B) and bacitracin was 100%. The susceptibility to fusidic acid was 92.7%. The resistance rates to neomycin sulfate, erythromycin, and clindamycin were 11.7%, 49.3%, and 33.4%, respectively. The high resistance rate to clindamycin and erythromycin was significantly affected by gender, previous treatment, and disease severity rather than by age and disease duration. Topical antibiotics should not be used separately for long-term therapy to avoid multiresistance. The use of topical antibiotics should be determined by clinicians on the basis of clinical conditions.

Comparative Treatment Failure Rates of Respiratory Fluoroquinolones or β-Lactam + Macrolide Versus β-Lactam Alone in the Treatment for Community-Acquired Pneumonia in Adult Outpatients

PubMed Central

Lee, Meng-Tse Gabriel; Lee, Shih-Hao; Chang, Shy-Shin; Chan, Ya-Lan; Pang, Laura; Hsu, Sue-Ming; Lee, Chien-Chang

2015-01-01

Abstract No comparative effectiveness study has been conducted for the following 3 antibiotics: respiratory fluoroquinolone, β-lactam, and β-lactam + advanced macrolide. To gain insights into the real-world clinical effectiveness of these antibiotics for community-acquired pneumonia in adult outpatients, our study investigated the treatment failure rates in 2 million representative participants from the National Health Informatics Project (NHIP) of Taiwan. A new-user cohort design was used to follow NHIP participants from January 2000 until December 2009. Treatment failure was defined by either one of the following events: a second antibiotic prescription, hospitalization due to CAP, an emergency department visit with a diagnosis of CAP, or 30-day nonaccident-related mortality. From 2006 to 2009, we identified 9256 newly diagnosed CAP outpatients, 1602 of whom were prescribed levofloxacin, 2100 were prescribed moxifloxacin, 5049 were prescribed β-lactam alone, and 505 were prescribed advanced macrolide + β-lactam. Compared with the β-lactam-based regimen, the propensity score-matched odds ratio for composite treatment failure was 0.81 (95% CI, 0.67–0.97) for moxifloxacin, 1.10 (95% CI, 0.90–1.35) for levofloxacin, and 0.95 (95% CI, 0.67–1.35) for macrolide +β-lactam. Moxifloxacin was associated with lower treatment failure rates compared with β-lactam alone, or levofloxacin in Taiwanese CAP outpatients. However, due to inherent limitations in our claims database, more randomized controlled trials are required before coming to a conclusion on which antibiotic is more effective for Taiwanese CAP outpatients. More population-based comparative effectiveness studies are also encouraged and should be considered as an integral piece of evidence in local CAP treatment guidelines. PMID:26426664

Antibiotics for ureaplasma in the vagina in pregnancy.

PubMed

Raynes-Greenow, C H; Roberts, C L; Bell, J C; Peat, B; Gilbert, G L

2004-01-01

Preterm birth is a significant obstetric problem in high-income countries. Genital infection including ureaplasmas are suspected of playing a role in preterm birth and preterm rupture of the membranes. Antibiotics are used to treat women with preterm prelabour rupture of the membranes and results in prolongation of pregnancy and lowers the risks of maternal and neonatal infection. However, antibiotics may be beneficial earlier in pregnancy to eradicate potentially causative agents. The objective of this review is to assess whether antibiotic treatment of pregnant women with ureaplasma in the vagina reduces the incidence of preterm birth and other adverse pregnancy outcomes. We searched the Cochrane Pregnancy and Childbirth Group trials register (April 2003). All randomised controlled trials that compared any antibiotic regimen with placebo or no treatment in pregnant women with ureaplasma detected in the vagina. Three reviewers independently assessed eligibility and trial quality and extracted data. One trial involving 1071 women was included. Of these, 644 randomly received antibiotic treatment (174 erythromycin estolate, 224 erythromycin sterate, and 246 clindamycin hydrochloride) and 427 received placebo. This trial did not report data on preterm birth. Incidence of low birthweight less than 2500 grams was only evaluated for erythromycin (combined) (n = 398 ) compared to placebo (n = 427) and there was no statistically significant difference between those treated and those not treated (relative risk (RR) 0.70, 95% confidence interval (CI) 0.46 to 1.07). In regards to side-effects sufficient to stop treatment, data were available for all women, and there were no statistically significant differences between any antibiotic (combined) and the placebo group (RR 1.25, 95% CI 0.85 to 1.85). There is insufficient evidence to show whether giving antibiotics to women with ureaplasma in the vagina will prevent preterm birth.

Immunomodulatory effects of macrolide antibiotics - part 2: advantages and disadvantages of long-term, low-dose macrolide therapy.

PubMed

Altenburg, J; de Graaff, C S; van der Werf, T S; Boersma, W G

2011-01-01

The available evidence for long-term, low-dose treatment with 14- and 15-membered ring macrolides in non-cystic fibrosis (CF) bronchiectasis, COPD, chronic sinusitis, and asthma is reviewed with special attention to possible adverse effects and the emergence of resistance during long-term macrolide treatment. Macrolide maintenance therapy has been proven to be of benefit in diffuse panbronchiolitis and CF, presumably due to an anti-inflammatory mechanism of action in addition to its direct antimicrobial effect. Solid evidence to justify this treatment regimen for non-CF bronchiectasis, asthma, or sinusitis is still lacking, although a beneficial effect of long-term macrolide therapy has been found in small clinical trials on these subjects. Data from randomized trials of long-term macrolide treatment in COPD are conflicting. A sufficiently long duration of treatment and the careful selection of patients appears to be crucial. Aside from its beneficial effects, possible side effects of macrolide treatment should be taken into account, the most important of these being gastrointestinal upset and cardiac arrhythmias. Development of macrolide resistance among respiratory pathogens is very common during long-term macrolide treatment. Whether this finding is clinically significant is a matter of debate. Copyright © 2010 S. Karger AG, Basel.

Antibiotics in the human food chain: establishing no effect levels of tetracycline, neomycin, and erythromycin using a chemostat model of the human colonic microflora.

PubMed

Carman, Robert J; Simon, Mary Alice; Petzold, H Earl; Wimmer, Robert F; Batra, Monica R; Fernández, A Haydée; Miller, Margaret A; Bartholomew, Mary

2005-11-01

A chemostat model of the healthy human large bowel ecosystem was used to establish no effect levels for tetracycline, neomycin, and erythromycin. For each compound, the equivalent to four oral doses (0, 1.5, 15, and 150 mg/60 kg person/d) was studied. Concentrations of the test compounds in the chemostat medium were intended to simulate fecal levels that might be expected following consumption of food containing antibiotic residue and were based on published oral doses and fecal levels. We monitored the following parameters: short chain fatty acids, bile acids, sulfate reduction, azoreductase and nitroreductase activities, beta-glucosidase and beta-glucuronidase activities, a range of bacterial counts and, lastly, the susceptibility among sentinel bacteria to each test compound. Neomycin and erythromycin reduced bile acid metabolism. Neomycin elevated propionate levels and caused a marginal diminution in azoreductase activity. Based on our results, the no observed effect level (NOEL) of both tetracycline and erythromycin was 15 mg/60 kg person/d. The NOEL for neomycin was 1.5 mg/60 kg person/d.

Francisella tularensis Susceptibility to Antibiotics: A Comprehensive Review of the Data Obtained In vitro and in Animal Models

PubMed Central

Caspar, Yvan; Maurin, Max

2017-01-01

The antibiotic classes that are recommended for tularaemia treatment are the aminoglycosides, the fluoroquinolones and the tetracyclines. However, cure rates vary between 60 and 100% depending on the antibiotic used, the time to appropriate antibiotic therapy setup and its duration, and the presence of complications, such as lymph node suppuration. Thus, antibiotic susceptibility testing (AST) of F. tularensis strains remains of primary importance for detection of the emergence of antibiotic resistances to first-line drugs, and to test new therapeutic alternatives. However, the AST methods reported in the literature were poorly standardized between studies and AST data have not been previously evaluated in a comprehensive and comparative way. The aim of the present review was to summarize experimental data on antibiotic susceptibilities of F. tularensis obtained in acellular media, cell models and animal models since the introduction of fluoroquinolones in the treatment of tularaemia in 1989. We compiled MIC data of 33 antibiotics (including aminoglycosides, fluoroquinolones, tetracyclines, macrolides, β-lactams, chloramphenicol, rifampicin, and linezolid) against 900 F. tularensis strains (504 human strains), including 107 subsp. tularensis (type A), 789 subsp. holarctica (type B) and four subsp. mediasiatica strains, using various AST methods. Specific culture media were identified or confirmed as unsuitable for AST of F. tularensis. Overall, MICs were the lowest for ciprofloxacin (≤ 0.002–0.125 mg/L) and levofloxacin, and ranged from ≤ 0.016 to 2 mg/L for gentamicin, and 0.064 to 4 mg/L for doxycycline. No resistant strain to any of these antibiotics was reported. Fluoroquinolones also exhibited a bactericidal activity against intracellular F. tularensis and lower relapse rates in animal models when compared with the bacteriostatic compound doxycycline. As expected, lower MIC values were found for macrolides against type A and biovar I type B strains, compared to biovar II type B strains. The macrolides were more effective against F. tularensis grown in phagocytic cells than in acellular media. PMID:28443249

Antimicrobial activity of Manuka honey against antibiotic-resistant strains of the cell wall-free bacteria Ureaplasma parvum and Ureaplasma urealyticum.

PubMed

Hillitt, K L; Jenkins, R E; Spiller, O B; Beeton, M L

2017-03-01

The susceptibility of the cell wall-free bacterial pathogens Ureaplasma spp. to Manuka honey was examined. The minimum inhibitory concentration (MIC) of Manuka honey for four Ureaplasma urealyticum and four Ureaplasma parvum isolates was determined. Sensitivity to honey was also compared to clinical isolates with resistance to tetracycline, macrolide and fluoroquinolone antibiotics. Finally step-wise resistance training was utilized in an attempt to induce increased tolerance to honey. The MIC was dependent on the initial bacterial load with 7·5 and 18·0% w/v honey required to inhibit U. urealyticum at 1 and 10 6 colour changing units (CCU), respectively, and 4·8 and 15·3% w/v required to inhibit U. parvum at 1 and 10 6  CCU respectively. MIC values were consistently lower for U. parvum compared with U. urealyticum. Antimicrobial activity was seen against tetracycline-resistant, erythromycin-resistant and ciprofloxacin-resistant isolates at 10 5  CCU. No resistance to honey was observed with 50 consecutive challenges at increasing concentrations of honey. This is the first report of the antimicrobial activity of Manuka honey against a cell wall-free bacterial pathogen. The antimicrobial activity was retained against antibiotic-resistant strains and it was not possible to generate resistant mutants. Manuka honey is known to have a broad spectrum of antimicrobial activity, with the bacterial cell wall being suggested as a predominant site of action. This study has demonstrated that Manuka honey has activity against Ureaplasma spp., a genus of cell wall-free bacteria which are intrinsically resistant to many available antibiotics making treatment inherently difficult. This is the first report of the antimicrobial activity of Manuka honey against a bacterial pathogen, in the absence of a cell well and opens scope for the use of components of Manuka honey as a therapeutic among Ureaplasma infections. © 2016 The Society for Applied Microbiology.

Determination of antibiotic resistance of lactic acid bacteria isolated from traditional Turkish fermented dairy products.

PubMed

Erginkaya, Z; Turhan, E U; Tatlı, D

2018-01-01

In this study, the antibiotic resistance (AR) of lactic acid bacteria (LAB) isolated from traditional Turkish fermented dairy products was investigated. Yogurt, white cheese, tulum cheese, cokelek, camız cream and kefir as dairy products were collected from various supermarkets. Lactic acid bacteria such as Lactobacillus spp., Streptococcus spp., Bifidobacterium spp., and Enterecoccus spp. were isolated from these dairy products. Lactobacillus spp. were resistant to vancomycin (58%), erythromycin (10.8%), tetracycline (4.3%), gentamicin (28%), and ciprofloxacin (26%). Streptococcus spp. were resistant to vancomycin (40%), erythromycin (10%), chloramphenicol (10%), gentamicin (20%), and ciprofloxacin (30%). Bifidobacterium spp. were resistant to vancomycin (60%), E 15 (6.6%), gentamicin (20%), and ciprofloxacin (33%). Enterococcus spp. were resistant to vancomycin (100%), erythromycin (100%), rifampin (100%), and ciprofloxacin (100%). As a result, LAB islated from dairy products in this study showed mostly resistance to vancomycin.

Clinical significance of serotype V among infants with invasive group B streptococcal infections in South Korea.

PubMed

Yoon, In Ae; Jo, Dae Sun; Cho, Eun Young; Choi, Eun Hwa; Lee, Hoan Jong; Lee, Hyunju

2015-09-01

Group B Streptococcus (GBS) strains are classified by the polysaccharide capsule, which is an important virulence factor and stimulator of antibody-associated immunity. As GBS infections in neonates may be life-threatening, GBS screening and intrapartum antibiotic prophylaxis have been implemented for prevention. In Korea, there are few reports on the GBS serotype distribution and antibiotic resistance patterns because GBS screening and intrapartum prophylaxis are not done routinely. The serotype distribution and antibiotic resistance of GBS in infants in Korea with invasive bacterial infections were examined for the 19-year period 1995-2013. Isolates obtained previously from hospitals located in three different regions were analyzed for capsular serotype by PCR and sequencing and for antimicrobial susceptibility. Among 56 isolates serotyped, the most common serotypes were III (44.6%) and V (28.6%), followed by Ia (14.3%), Ib (10.7%), and VI (1.8%). No penicillin-resistant strains were detected, however 51.8% of the strains had resistance to erythromycin and 55.4% showed clindamycin resistance. Resistance was highest (93.8%) to both erythromycin and clindamycin for serotype V; all 15 isolates resistant to erythromycin were cMLSB phenotype and had a high level of resistance to both erythromycin and clindamycin with MIC levels >256μg/ml, and all but one were positive for ermB. In this study in Korea, serotype V was identified in a relatively large proportion of GBS isolates and this serotype showed a high level of resistance to erythromycin and clindamycin in a statistically significant majority. Continuous monitoring of changes in clinical disease and molecular characteristics is important for the treatment and prevention of invasive GBS disease in infants. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effect of Periodontal Therapy With Amoxicillin-Metronidazole on Pharyngeal Carriage of Penicillin- and Erythromycin-Resistant Viridans Streptococci.

PubMed

Mombelli, Andrea; Cionca, Norbert; Almaghlouth, Adnan; Cherkaoui, Abdessalam; Schrenzel, Jacques; Giannopoulou, Catherine

2016-05-01

Previous studies have focused on antibiotic resistance of Gram-negative bacteria before and after periodontal therapy. The purpose of this analysis is to assess changes in resistance patterns of the commensal Gram-positive microbiota. The viridans group streptococci (VGS) have been suggested to serve as reservoirs of resistance genes for more pathogenic streptococci and may be implicated in some non-oral infections. In this randomized clinical trial, 80 patients with periodontitis are distributed randomly into two groups. In group A, patients received 375 mg amoxicillin and 500 mg metronidazole three times per day for 7 days during the non-surgical treatment phase (T1). In group B, the antibiotics were administered during the surgical phase (T2). Resistance of VGS to penicillin and erythromycin was determined by the epsilometer test. At baseline, VGS from 12.5% (group A) and 11.8% (group B) of patients had a minimum inhibitory concentration (MIC) >2 μg/mL to penicillin. Three months after T1, VGS from 15.6% and 16.7% of patients had an MIC >2 μg/mL, respectively. Six months after T2 VGS from 5.9% and 5.9% and 12 months after T2 VGS from 6.1% and 6.3% patients had an MIC >2 μg/mL. There was no effect of therapy with antibiotics, administered either in T1 or T2, on the carriage of penicillin-resistant VGS. Erythromycin resistance was high at baseline and remained unchanged throughout the study. MICs for penicillin and erythromycin were correlated (P <0.05). Amoxicillin plus metronidazole did not significantly affect the resistance pattern of the VGS to penicillin or erythromycin.

Occurrence and distribution of antibiotics in surface water impacted by crab culturing: a case study of Lake Guchenghu, China.

PubMed

Wang, Wenxia; Zhou, Lijun; Gu, Xiaohong; Chen, Huihui; Zeng, Qingfei; Mao, Zhigang

2018-05-30

The objective of this study was to evaluate the occurrence, distribution, potential sources, and ecological risk of antibiotics in aqueous phase of Lake Guchenghu, China. Target antibiotics in surface water of Lake Guchenghu, adjacent streams, and crab ponds were detected seasonally. The results showed that erythromycin-H 2 O (1.60-2450 ng/L), sulfadiazine (ND-654 ng/L), and florfenicol (ND-919 ng/L) were the predominant antibiotics in Lake Guchenghu. The concentrations of antibiotics in Lake Guchenghu Basin showed obvious seasonal variation, with the highest concentration in summer. In general, the concentrations of antibiotics in crab ponds and streams were higher than those in the lake and spatial distributions of antibiotics were affected by pollution sources. The types and origins of antibiotics indicated that wastewater from ponds was the main source of antibiotics in the lake. Risk assessment suggested that as individual compound, erythromycin-H 2 O and clarithromycin posed a high risk to algae while other compounds might pose low or no risk. The mixture of antibiotics may pose a high risk to aquatic organisms in Lake Guchenghu. Overall, our study revealed the occurrence and spatiotemporal variation of antibiotics in Lake Guchenghu, which was related with crab culturing.

Antibiotics in the coastal environment of the Hailing Bay region, South China Sea: Spatial distribution, source analysis and ecological risks.

PubMed

Chen, Hui; Liu, Shan; Xu, Xiang-Rong; Zhou, Guang-Jie; Liu, Shuang-Shuang; Yue, Wei-Zhong; Sun, Kai-Feng; Ying, Guang-Guo

2015-06-15

In this study, the occurrence and spatial distribution of 38 antibiotics in surface water and sediment samples of the Hailing Bay region, South China Sea, were investigated. Twenty-one, 16 and 15 of 38 antibiotics were detected with the concentrations ranging from <0.08 (clarithromycin) to 15,163ng/L (oxytetracycline), 2.12 (methacycline) to 1318ng/L (erythromycin-H2O), <1.95 (ciprofloxacin) to 184ng/g (chlortetracycline) in the seawater, discharged effluent and sediment samples, respectively. The concentrations of antibiotics in the water phase were correlated positively with chemical oxygen demand and nitrate. The source analysis indicated that untreated domestic sewage was the primary source of antibiotics in the study region. Fluoroquinolones showed strong sorption capacity onto sediments due to their high pseudo-partitioning coefficients. Risk assessment indicated that oxytetracycline, norfloxacin and erythromycin-H2O posed high risks to aquatic organisms. Copyright © 2015 Elsevier Ltd. All rights reserved.

Occurrence of antibiotics in water, sediments, aquatic plants, and animals from Baiyangdian Lake in North China.

PubMed

Li, Wenhui; Shi, Yali; Gao, Lihong; Liu, Jiemin; Cai, Yaqi

2012-11-01

This study investigated the presence and distribution of 22 antibiotics, including eight quinolones, nine sulfonamides and five macrolides, in the water, sediments, and biota samples from Baiyangdian Lake, China. A total of 132 samples were collected in 2008 and 2010, and laboratory analyses revealed that antibiotics were widely distributed in the lake. Sulfonamides were the dominant antibiotics in the water (0.86-1563 ng L(-1)), while quinolones were prominent in sediments (65.5-1166 μg kg(-1)) and aquatic plants (8.37-6532 μg kg(-1)). Quinolones (17.8-167 μg kg(-1)) and macrolides [from below detection limit (BDL) to 182 μg kg(-1)] were often found in aquatic animals and birds. Salvinia natans exhibited the highest bioaccumulation capability for quinolones among three species of aquatic plants. Geographical differences of antibiotic concentrations were greatly due to anthropogenic activities. Sewage discharged from Baoding City was likely the main source of antibiotics in the lake. Risk assessment of antibiotics on aquatic organisms suggested that algae and aquatic plants might be at risk in surface water, while animals were likely not at risk. Copyright © 2012 Elsevier Ltd. All rights reserved.

The antibiotic azithromycin is a motilin receptor agonist in human stomach: comparison with erythromycin

PubMed Central

Broad, John; Sanger, Gareth J

2013-01-01

Background and Purpose The antibiotic azithromycin is a suggested alternative to erythromycin for treating patients with delayed gastric emptying. However, although hypothesized to activate motilin receptors, supportive evidence is unavailable. This was investigated using recombinant and naturally expressed motilin receptors in human stomach, comparing azithromycin with erythromycin. Experimental Approach [125I]-motilin binding and calcium flux experiments were conducted using human recombinant motilin receptors in CHO cells. Neuromuscular activities were studied using circular muscle of human gastric antrum, after electrical field stimulation (EFS) of intrinsic nerves. Key Results Azithromycin (1–100 μM) and erythromycin (3–30 μM) concentration-dependently displaced [125I]-motilin binding to the motilin receptor (52 ± 7 and 58 ± 18% displacement at 100 and 30 μM respectively). Azithromycin, erythromycin and motilin concentration-dependently caused short-lived increases in intracellular [Ca2+] in cells expressing the motilin receptor. EC50 values were, respectively, 2.9, 0.92 and 0.036 μM (n = 3 each); and maximal activities were similar. In human stomach, EFS evoked cholinergically mediated contractions, attenuated by simultaneous nitrergic activation. Azithromycin and erythromycin lactobionate (30–300 μM each) facilitated these contractions (apparent Emax values of 2007 ± 396 and 1924 ± 1375%, n = 3–4 each concentration, respectively). These actions were slow in onset and faded slowly. The higher concentrations also evoked short-lived muscle contraction. Contractions to a submaximally effective concentration of carbachol were unaffected by either drug. Conclusions and Implications Azithromcyin activates human recombinant motilin receptors in therapeutically relevant concentrations, similar to erythromycin. In humans, gastric antrum azithromycin caused long-lasting facilitation of cholinergic activity. These actions explain the gastric prokinetic activity of azithromycin. PMID:23190027

Arrangement and number of clustered regularly interspaced short palindromic repeat spacers are associated with erythromycin susceptibility in emm12, emm75 and emm92 of group A streptococcus.

PubMed

Zheng, P-X; Chiang-Ni, C; Wang, S-Y; Tsai, P-J; Kuo, C-F; Chuang, W-J; Lin, Y-S; Liu, C-C; Wu, J-J

2014-06-01

Clustered regularly interspaced short palindromic repeats (CRISPR) are composed of numerous repeat-spacer units and are considered a prokaryotic defence system against foreign nucleic acids. Since antibiotic-resistant genes are frequently encoded in foreign nucleic acids, the aim of this study was to test whether erythromycin susceptibility in group A streptococcus (Streptococcus pyogenes) is associated with characteristics of CRISPR elements. Erythromycin susceptibility of 330 isolates collected between 1997 and 2003 was analysed. Among 29 emm types, emm12, emm75 and emm92 showed significant changes in erythromycin-resistance rates. By sequencing the spacers from two CRISPR loci, spacer contents in emm12, emm75 and emm92 strains were associated with erythromycin susceptibility. Strains with fewer spacers were more resistant to erythromycin. Moreover, in emm4 strains, which showed no significant change in their annual erythromycin-resistance rate, CRISPR type and number of spacers were not correlated with erythromycin susceptibility. These results highlight a novel association between CRISPR spacer content and erythromycin susceptibility in group A streptococcus. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

Antibiotics for whooping cough (pertussis).

PubMed

Altunaiji, S; Kukuruzovic, R; Curtis, N; Massie, J

2007-07-18

Whooping cough is a highly contagious disease. Infants are at highest risk of severe disease and death. Erythromycin for 14 days is currently recommended for treatment and contact prophylaxis, but is of uncertain benefit. To study the benefits and risks of antibiotic treatment of and contact prophylaxis against whooping cough. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library Issue 1, 2007); MEDLINE (January 1966 to March 2007); EMBASE (January 1974 to March 2007). All randomised and quasi-randomised controlled trials of antibiotics for treatment of, and contact prophylaxis against, whooping cough. Three to four review authors independently extracted data and assessed the quality of each trial. Thirteen trials with 2197 participants met the inclusion criteria: 11 trials investigated treatment regimens; 2 investigated prophylaxis regimens. The quality of the trials was variable.Short-term antibiotics (azithromycin for three to five days, or clarithromycin or erythromycin for seven days) were as effective as long-term (erythromycin for 10 to 14 days) in eradicating Bordetella pertussis (B. pertussis) from the nasopharynx (relative risk (RR) 1.02, 95% confidence interval (CI) 0.98 to 1.05), but had fewer side effects (RR 0.66, 95% CI 0.52 to 0.83). Trimethoprim/sulfamethoxazole for seven days was also effective. Nor were there differences in clinical outcomes or microbiological relapse between short and long-term antibiotics. Contact prophylaxis of contacts older than six months of age with antibiotics did not significantly improve clinical symptoms or the number of cases developing culture-positive B. pertussis. Although antibiotics were effective in eliminating B. pertussis, they did not alter the subsequent clinical course of the illness. There is insufficient evidence to determine the benefit of prophylactic treatment of pertussis contacts.

[Interrelation of the antibiotic sensitivity (resistance) of staphylococci, clinical forms of the infection and production of protein A].

PubMed

Fomenko, G A

1984-06-01

Two hundred and thirty-two strains of Staph. aureus isolated from patients with staphylococcal infections were studied. The strains were isolated from the blood of patients with sepsis, from the purulent foci on the skin and in the subcutaneous fat, from the nasopharyngeal mucosa of patients with tonsillitis and inflammation of the upper respiratory tract, from the sputum of patients with the pneumonia signs and from the pus of patients with otitis. The pathogens were identified with the routine methods. The quantitative content of protein A in the strains was determined by the method of indirect hemagglutination with red blood cells sensitized with the hemolytic serum. The data obtained were analysed with regard to the strain group and characteristics of the strain resistance or sensitivity to benzylpenicillin, erythromycin, oleandomycin, chloramphenicol, streptomycin, neomycin, kanamycin, monomycin, ristomycin and furagin K. Statistically significant differences in the protein A content in certain strain groups were observed. These differences might be correlated with the strain antibiotic resistance but not sensitivity. Pronounced changes in the levels of protein A were detected in the staphylococcal hemocultures resistant to erythromycin and streptomycin. The cultures resistant to erythromycin were characterized by decreased content of protein A and those resistant to streptomycin were characterized by increased content of protein A. Comparison of the antibiotic sensitivity of the strains of 5 groups by variation statistics revealed significant differences in the levels of sensitivity to streptomycin, neomycin, kanamycin, monomycin, ristomycin and furagin K but not to erythromycin, oleandomycin and chloramphenicol in the strains of certain groups. The staphylococcal hemocultures isolated from patients with sepsis proved to be the most sensitive to the antibiotics.

Interference of the antimicrobial peptide lactoferricin B with the action of various antibiotics against Escherichia coli and Staphylococcus aureus.

PubMed

Vorland, L H; Osbakk, S A; Perstølen, T; Ulvatne, H; Rekdal, O; Svendsen, J S; Gutteberg, T J

1999-01-01

The antimicrobial peptide, lactoferricin, can be generated upon gastric pepsin cleavage of lactoferrin. We have examined the interaction of lactoferricin of bovine origin, Lf-cin B, with the antibiotics penicillin G, vancomycin, gentamicin, colistin, D-cycloserine and erythromycin against E. coli ATCC 25922 and Staphylococcus aureus ATCC 25923. We demonstrated synergism between Lf-cin B and erythromycin against E. coli, and partial synergism between Lf-cin B and penicillin G, vancomycin and gentamicin against E. coli. Only penicillin G acted in partial synergism with Lf-cin B against S. aureus. Lf-cin B antagonized vancomycin and gentamicin against S. aureus in low concentration. We conclude that Lf-cin B may facilitate the uptake of antibiotics across the cell envelope.

Analysis of antibiotic resistance pattern of S. aureus strains isolated from the Orthopedics-Traumatology Section of "Sf. Spiridon" Clinical Emergency Hospital, Iaşi.

PubMed

Tucaliuc, D; Alexa, O; Tuchiluş, Cristina Gabriela; Ursu, Ramona Gabriela; Tucaliuc, Elena Simona; Iancu, Luminiţa Smaranda

2014-01-01

The retrospective analysis of antibiotic sensibility of S. aureus strains isolated from infected patients from the Orthopedics-Traumatology Clinic of "Sf. Spiridon" Clinical Emergency Hospital, Iaşi during January 2003-December 2013, in view of determining the evolution trend of the resistance phenomenon and of pinpointing the most useful treatment for these strains. The antibiotic sensitivity test was carried out using two methods: diffusimetric-Kirby-Bauer and the MIC determination by E-test (for the strains isolated in 2013); the interpretation of the sensitivity was made in a standardized manner, in compliance with the CLSI (Clinical and Laboratory Standards Institute) standard for antibiotics testing in force. The sensitivity testing for beta-lactams proved that during the 11 years of the study, the average value of the frequency of resistant strains was of 41.59% +/- 8.68. The highest frequency of MRSA (Methicillin Restant S. aureus) strains was noticed in 2012 (58.6%), followed by 2004 (50.7%). Even if in 2013 it dropped to 38.9%, the trend calculated for 2003-2013 is slightly rising (y = 0.0073x + 0.372). Out of the total of 495 S. aureus strains that were isolated, 164 (33.13%) were completely sensitive to the tested antibiotics and 26 (5.25%) were resistant only to beta-lactams. The other MRSA strains associated multiple resistance and MIC for vancomycin varied between 0.5-2 mg/ml. Two strains whose MIC was of 0.5 mg/ml were sensitive to most classes of tested antibiotics, including beta-lactams, except for macrolides (erythromycin), and the strain whose MIC was of 2 mg/ml, was resistant to all classes of tested antibiotics, except for glycopeptides and oxazolidiones. The other tested strains had a MIC for vancomycin equal to 1 mg/ml. Due to the fact that there are infections with SAMR strains in a rather worrying percentage (53.9%) that are resistant to the other classes of antibiotics, the only therapeutic solution being the vancomycin treatment, its use should be limited solely to those cases when it is really necessary. Fortunately, no vancomycin resistant MRSA strains have been identified in our country, but this phenomenon should be kept under close surveillance.

Effects of national antibiotic stewardship and infection control strategies on hospital-associated and community-associated meticillin-resistant Staphylococcus aureus infections across a region of Scotland: a non-linear time-series study.

PubMed

Lawes, Timothy; Lopez-Lozano, José-María; Nebot, Cesar A; Macartney, Gillian; Subbarao-Sharma, Rashmi; Dare, Ceri Rj; Wares, Karen D; Gould, Ian M

2015-12-01

Restriction of antibiotic consumption to below predefined total use thresholds might remove the selection pressure that maintains antimicrobial resistance within populations. We assessed the effect of national antibiotic stewardship and infection prevention and control programmes on prevalence density of meticillin-resistant Staphylococcus aureus (MRSA) infections across a region of Scotland. This non-linear time-series analysis and quasi-experimental study explored ecological determinants of MRSA epidemiology among 1,289,929 hospital admissions and 455,508 adults registered in primary care in northeast Scotland. Interventions included antibiotic stewardship to restrict use of so-called 4C (cephalosporins, co-amoxiclav, clindamycin, and fluoroquinolones) and macrolide antibiotics; a hand hygiene campaign; hospital environment inspections; and MRSA admission screening. Total effects were defined as the difference between scenarios with intervention (observed) and without intervention (predicted from time-series models). The primary outcomes were prevalence density of MRSA infections per 1000 occupied bed days (OBDs) in hospitals or per 10,000 inhabitants per day (IDs) in the community. During antibiotic stewardship, use of 4C and macrolide antibiotics fell by 47% (mean decrease 224 defined daily doses [DDDs] per 1000 OBDs, 95% CI 154-305, p=0·008) in hospitals and 27% (mean decrease 2·52 DDDs per 1000 IDs, 0·65-4·55, p=0·031) in the community. Hospital prevalence densities of MRSA were inversely related to intensified infection prevention and control, but positively associated with MRSA rates in neighbouring hospitals, importation pressures, bed occupancy, and use of fluoroquinolones, co-amoxiclav, and third-generation cephalosporins, or macrolide antibiotics that exceeded hospital-specific thresholds. Community prevalence density was predicted by hospital MRSA rates and above-threshold use of macrolides, fluoroquinolones, and clindamycin. MRSA prevalence density decreased during antibiotic stewardship by 54% (mean reduction 0·60 per 1000 OBDs, 0·01-1·18, p=0·049) in hospital and 37% (mean reduction 0·017 per 10,000 IDs, 0·004-0·029, p=0·012) in the community. Combined with infection prevention and control measures, MRSA prevalence density was reduced by 50% (absolute difference 0·94 cases per 1000 OBDs, 0·27-1·62, p=0·006) in hospitals and 47% (absolute difference 0·033 cases per 10,000 IDs, 0·018-0·048, p<0·0001) in the community. Alongside infection control measures, removal of key antibiotic selection pressures during a national antibiotic stewardship intervention predicted large and sustained reductions in hospital-associated and community-associated MRSA. NHS Grampian Research & Development Fund. Copyright © 2015 Elsevier Ltd. All rights reserved.

Trends and patterns of antibiotic consumption in China's tertiary hospitals: Based on a 5 year surveillance with sales records, 2011-2015.

PubMed

Wushouer, Haishaerjiang; Tian, Ye; Guan, Xiao-Dong; Han, Sheng; Shi, Lu-Wen

2017-01-01

The consumption of antibiotics is a major driver in the development of antimicrobial resistance. This study aims to identify the trends and patterns of the total antibiotic consumption in China's tertiary hospitals from 2011 to 2015 by retrospectively analyzing aggregated monthly surveillance data on antibiotic sales made to 468 hospitals from 28 provinces. Antibiotic consumption was expressed in DDD per 1,000 inhabitants per day (DID). We compared population weighted antibiotic consumption patterns in China with European countries using indicators from the European Surveillance of Antimicrobial Consumption (ESAC). Total antibiotic consumption, including all the specific antibiotic class except for aminoglycoside antibacterials, were significantly increased during the study period from an average of 7.97 DID in 2011 to 10.08 DID in 2015. In 2015, the eastern regions of China consumed the most antibiotics using population denominator while the western regions consumed the most using inpatient denominator. Cephalosporins accounted for 28.6% of total DID, followed by beta-lactam-beta-lactamase inhibitor combinations (20.0%), macrolides (17.4%), and fluoroquinolones (10.5%). Antibiotic in parenteral form accounted for nearly half of all antibiotics. Although over the past few years major efforts had been made to reduce the risks of excessive antibiotic use through antibiotic stewardship, total antibiotic consumption showed a significant upward trend during the study period. A consistent preference for cephalosporins, macrolides, beta-lactam-beta-lactamase inhibitor combinations, as well as parenteral preparations was observed.

[A comparative evaluation of modern antibacterial preparations in the treatment of a severe degree of periodontitis at a stage of exacerbation].

PubMed

Dmitrieva, L A; Tsarev, V N; Romanov, A E; Filatova, N A; Chernyshova, S B; Sechko, O N

1998-01-01

Sensitivities of peptostreptococci, streptococci, Actinomyces, bacteroid, and fusobacterial strains pathogenic for the periodontium to wide-spectrum penicillines, cephalosporines, lincomycin, macrolides, metronidasole, and nitasole are compared. New macrolide antibiotics rulide. Macropene, gramicidin C, levomycetin, and rifampicin are highly effective. Some narrow-spectrum drugs, e.g. augmentin, cephalexin, and vancomycin (towards actinomycetes) were highly effective, too.

Association between Antibiotic Prescribing in Pregnancy and Cerebral Palsy or Epilepsy in Children Born at Term: A Cohort Study Using The Health Improvement Network

PubMed Central

Meeraus, Wilhelmine Hadler; Petersen, Irene; Gilbert, Ruth

2015-01-01

Background Between 19%-44% pregnant women are prescribed antibiotics during pregnancy. A single, large randomised-controlled-trial (ORACLE Childhood Study II) found an increased risk of childhood cerebral palsy and possibly epilepsy following prophylactic antibiotic use in pregnant women with spontaneous preterm labour. We ascertained whether this outcome could be reproduced across the population of babies delivered at term and prospectively followed in primary-care using data from The Health Improvement Network. Methods We determined the risk of cerebral palsy or epilepsy in children whose mothers were prescribed antibiotics during pregnancy using a cohort of 195,909 women linked to their live, term-born, singleton children. We compared the effect of antibiotic class, number of courses and timing of prescribing in pregnancy. Analyses were adjusted for maternal risk factors (e.g. recorded infection, age, chronic conditions, social deprivation, smoking status). Children were followed until age seven years or cessation of registration with the primary-care practitioner. Results In total, 64,623 (33.0%) women were prescribed antibiotics in pregnancy and 1,170 (0.60%) children had records indicating cerebral palsy or epilepsy. Adjusted analyses showed no association between prescribing of any antibiotic and cerebral palsy or epilepsy (adj.HR 1.04, 95%CI 0.91–1.19). However, compared with penicillins, macrolides were associated with an increased risk of cerebral palsy or epilepsy (adj.HR 1.78, 95%CI 1.18–2.69; number needed to harm 153, 95%CI 71–671). Conclusions We found no overall association between antibiotic prescribing in pregnancy and cerebral palsy and/or epilepsy in childhood. However, our finding of an increased risk of cerebral palsy or epilepsy associated with macrolide prescribing in pregnancy adds to evidence that macrolide use is associated with serious harm. PMID:25807115

Assessing antibiotic sorption in soil: a literature review and new case studies on sulfonamides and macrolides

PubMed Central

2014-01-01

The increased use of veterinary antibiotics in modern agriculture for therapeutic uses and growth promotion has raised concern regarding the environmental impacts of antibiotic residues in soil and water. The mobility and transport of antibiotics in the environment depends on their sorption behavior, which is typically predicted by extrapolating from an experimentally determined soil-water distribution coefficient (Kd). Accurate determination of Kd values is important in order to better predict the environmental fate of antibiotics. In this paper, we examine different analytical approaches in assessing Kd of two major classes of veterinary antibiotics (sulfonamides and macrolides) and compare the existing literature data with experimental data obtained in our laboratory. While environmental parameters such as soil pH and organic matter content are the most significant factors that affect the sorption of antibiotics in soil, it is important to consider the concentrations used, the analytical method employed, and the transformations that can occur when determining Kd values. Application of solid phase extraction and liquid chromatography/mass spectrometry can facilitate accurate determination of Kd at environmentally relevant concentrations. Because the bioavailability of antibiotics in soil depends on their sorption behavior, it is important to examine current practices in assessing their mobility in soil. PMID:24438473

Tylosin sorption to diatomaceous earth described by Langmuir isotherm and Freundlich isotherm models

USDA-ARS?s Scientific Manuscript database

Tylosin, an antibiotic used for livestock, is a macrolide structurally similar to a number of important, often prescribed human antibiotics. Because of this relationship, tylosin presents a potential threat of antimicrobial resistance from environmental buildup. This work investigated tylosin sorpti...

Predictors for individual patient antibiotic treatment effect in hospitalized community-acquired pneumonia patients.

PubMed

Simonetti, A F; van Werkhoven, C H; Schweitzer, V A; Viasus, D; Carratalà, J; Postma, D F; Oosterheert, J J; Bonten, M J M

2017-10-01

Our objective was to identify clinical predictors of antibiotic treatment effects in hospitalized patients with community-acquired pneumonia (CAP) who were not in the intensive care unit (ICU). Post-hoc analysis of three prospective cohorts (from the Netherlands and Spain) of adult patients with CAP admitted to a non-ICU ward having received either β-lactam monotherapy, β-lactam + macrolide, or a fluoroquinolone-based therapy as empirical antibiotic treatment. We evaluated candidate clinical predictors of treatment effects in multiple mixed-effects models by including interactions of the predictors with empirical antibiotic choice and using 30-day mortality, ICU admission and length of hospital stay as outcomes. Among 8562 patients, empirical treatment was β-lactam in 4399 (51.4%), fluoroquinolone in 3373 (39.4%), and β-lactam + macrolide in 790 (9.2%). Older age (interaction OR 1.67, 95% CI 1.23-2.29, p 0.034) and current smoking (interaction OR 2.36, 95% CI 1.34-4.17, p 0.046) were associated with lower effectiveness of fluoroquinolone on 30-day mortality. Older age was also associated with lower effectiveness of β-lactam + macrolide on length of hospital stay (interaction effect ratio 1.14, 95% CI 1.06-1.22, p 0.008). Older age and smoking could influence the response to specific antibiotic regimens. The effect modification of age and smoking should be considered hypothesis generating to be evaluated in future trials. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Membrane-active macromolecules kill antibiotic-tolerant bacteria and potentiate antibiotics towards Gram-negative bacteria

PubMed Central

Uppu, Divakara S. S. M.; Konai, Mohini M.; Sarkar, Paramita; Samaddar, Sandip; Fensterseifer, Isabel C. M.; Farias-Junior, Celio; Krishnamoorthy, Paramanandam; Shome, Bibek R.; Franco, Octávio L.

2017-01-01

Chronic bacterial biofilms place a massive burden on healthcare due to the presence of antibiotic-tolerant dormant bacteria. Some of the conventional antibiotics such as erythromycin, vancomycin, linezolid, rifampicin etc. are inherently ineffective against Gram-negative bacteria, particularly in their biofilms. Here, we report membrane-active macromolecules that kill slow dividing stationary-phase and antibiotic tolerant cells of Gram-negative bacteria. More importantly, these molecules potentiate antibiotics (erythromycin and rifampicin) to biofilms of Gram-negative bacteria. These molecules eliminate planktonic bacteria that are liberated after dispersion of biofilms (dispersed cells). The membrane-active mechanism of these molecules forms the key for potentiating the established antibiotics. Further, we demonstrate that the combination of macromolecules and antibiotics significantly reduces bacterial burden in mouse burn and surgical wound infection models caused by Acinetobacter baumannii and Carbapenemase producing Klebsiella pneumoniae (KPC) clinical isolate respectively. Colistin, a well-known antibiotic targeting the lipopolysaccharide (LPS) of Gram-negative bacteria fails to kill antibiotic tolerant cells and dispersed cells (from biofilms) and bacteria develop resistance to it. On the contrary, these macromolecules prevent or delay the development of bacterial resistance to known antibiotics. Our findings emphasize the potential of targeting the bacterial membrane in antibiotic potentiation for disruption of biofilms and suggest a promising strategy towards developing therapies for topical treatment of Gram-negative infections. PMID:28837596

Combinations of Macrolide Resistance Determinants in Field Isolates of Mannheimia haemolytica and Pasteurella multocida▿

PubMed Central

Desmolaize, Benoit; Rose, Simon; Wilhelm, Cornelia; Warrass, Ralf; Douthwaite, Stephen

2011-01-01

Respiratory tract infections in cattle are commonly associated with the bacterial pathogens Mannheimia haemolytica and Pasteurella multocida. These infections can generally be successfully treated in the field with one of several groups of antibiotics, including macrolides. A few recent isolates of these species exhibit resistance to veterinary macrolides with phenotypes that fall into three distinct classes. The first class has type I macrolide, lincosamide, and streptogramin B antibiotic resistance and, consistent with this, the 23S rRNA nucleotide A2058 is monomethylated by the enzyme product of the erm(42) gene. The second class shows no lincosamide resistance and lacks erm(42) and concomitant 23S rRNA methylation. Sequencing of the genome of a representative strain from this class, P. multocida 3361, revealed macrolide efflux and phosphotransferase genes [respectively termed msr(E) and mph(E)] that are arranged in tandem and presumably expressed from the same promoter. The third class exhibits the most marked drug phenotype, with high resistance to all of the macrolides tested, and possesses all three resistance determinants. The combinations of erm(42), msr(E), and mph(E) are chromosomally encoded and intermingled with other exogenous genes, many of which appear to have been transferred from other members of the Pasteurellaceae. The presence of some of the exogenous genes explains recent reports of resistance to additional drug classes. We have expressed recombinant versions of the erm(42), msr(E), and mph(E) genes within an isogenic Escherichia coli background to assess their individually contributions to resistance. Our findings indicate what types of compounds might have driven the selection for these resistance determinants. PMID:21709086

Fate and transport of tylosin-resistant bacteria and macrolide resistance genes in artificially drained agricultural fields receiving swine manure

USDA-ARS?s Scientific Manuscript database

Application of manure from swine treated with antibiotics introduces antibiotics and antibiotic resistance genes to soil with the potential for further movement in drainage water. Manure concentrations for ermB, ermC and ermF were all >109 copy g-1. Manure contained 1.76 x 105 CFUg-1 enterococci w...

Tracing the Sources of Macrolide Antibiotics and Illicit Drugs into the Lower Colorado River Basin

EPA Science Inventory

A number of pharmaceuticals have been detected in surface waters across the United States. Antibiotics present in the environment can produce resistance in microorganisms, which could potentially have adverse effects on human health. In addition, while the ecotoxicological signif...

Engineering of an Lrp family regulator SACE_Lrp improves erythromycin production in Saccharopolyspora erythraea.

PubMed

Liu, Jing; Chen, Yunfu; Wang, Weiwei; Ren, Min; Wu, Panpan; Wang, Yansheng; Li, Changrun; Zhang, Lixin; Wu, Hang; Weaver, David T; Zhang, Buchang

2017-01-01

Leucine-responsive regulatory proteins (Lrps) are a group of transcriptional regulators that regulate diverse cellular processes in bacteria and archaea. However, the regulatory role of Lrps in antibiotic biosynthesis remains poorly understood. In this study, we show that SACE_5388, an Lrp family regulator named as SACE_Lrp, is an efficient regulator for transporting and catabolizing branched-chain amino acids (BCAAs), playing an important role in regulating erythromycin production in Saccharopolyspora erythraea. SACE_Lrp directly controlled the expression of the divergently transcribed SACE_5387-5386 operon putatively encoding a BCAA ABC transporter by interacting with the intergenic region between SACE_Lrp and SACE_5387 (SACE_Lrp-5387-int), and indirectly controlled the expression of ilvE putatively encoding an aminotransferase catabolizing BCAAs. BCAA catabolism is one source of the precursors for erythromycin biosynthesis. Lysine and arginine promoted the dissociation of SACE_Lrp from SACE_Lrp -5387-int, whereas histidine increased their binding. Gene disruption of SACE_Lrp (ΔSACE_Lrp) in S. erythraea A226 resulted in a 25% increase in erythromycin production, while overexpression of SACE_5387-5386 in A226 enhanced erythromycin production by 36%. Deletion of SACE_Lrp (WBΔSACE_Lrp) in the industrial strain S. erythraea WB enhanced erythromycin production by 19%, and overexpression of SACE_5387-5386 in WBΔSACE_Lrp (WBΔSACE_Lrp/5387-5386) increased erythromycin production by 41% compared to WB. Additionally, supplement of 10mM valine to WBΔSACE_Lrp/5387-5386 culture further increased total erythromycin production up to 48%. In a 5-L fermenter, the erythromycin accumulation in the engineered strain WBΔSACE_Lrp/5387-5386 with 10mM extra valine in the industrial culture media reached 5001mg/L, a 41% increase over 3503mg/L of WB. These insights into the molecular regulation of antibiotic biosynthesis by SACE_Lrp in S. erythraea are instrumental in increasing industrial production of secondary metabolites. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

The analysis of animal faeces as a tool to monitor antibiotic usage.

PubMed

Berendsen, Bjorn J A; Wegh, Robin S; Memelink, Joost; Zuidema, Tina; Stolker, Linda A M

2015-01-01

The analysis of antibiotics in animal faeces is important to obtain more insight in the possible formation of bacterial resistance in the animals׳ gut, to learn about the dissemination of antibiotics to the environment, to monitor trends in antibiotic usage and to detect the illegal and off-label use of antibiotics. To facilitate these studies a comprehensive method for the analysis of trace levels of 44 antibiotic compounds including tetracyclines, quinolones, macrolides and sulfonamides in animal faeces by liquid chromatography in combination with tandem mass spectrometric (LC-MS/MS) detection is reported. The method is fully validated according to European regulation and showed satisfactory quantitative performance according to the stringent criteria adopted, with the exception of some of the macrolide compounds, which can be analysed with somewhat high measurement uncertainty. A large survey was carried out monitoring swine and cattle faeces and the outcomes were striking. In 55% of the swines, originating from 80% of the swine farms and in 75% of the calves, originating from 95% of the cattle farms, antibiotics were detected. Oxytetracycline, doxycycline and sulfadiazine were the most detected antibiotics, followed by tetracycline, flumequine, lincomycin and tylosin. Over 34% of the faeces samples contained two or more different antibiotics with a maximum of eight. Possible explanations for these findings are given and the effects are discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

Antibiotic susceptibility of Legionella strains isolated from public water sources in Macau and Guangzhou.

PubMed

Xiong, Lina; Yan, He; Shi, Lei; Mo, Ziyao

2016-12-01

The purpose of this study was to investigate the susceptibility of waterborne strains of Legionella to eight antimicrobials commonly used in legionellosis therapy. The minimum inhibitory concentrations (MICs) of 66 environmental Legionella strains, isolated from fountains and cooling towers of public facilities (hotels, schools, and shopping malls) in Macau and Guangzhou, were tested using the microdilution method in buffered yeast extract broth. The MIC 50 /MIC 90 values for erythromycin, cefotaxime (CTX), doxycycline (DOC), minocycline (MIN), azithromycin, ciprofloxacin, levofloxacin (LEV), and moxifloxacin were 0.125/0.5 mg/L, 4/8 mg/L, 8/16 mg/L, 4/8 mg/L, 0.125/0.5 mg/L, 0.031/0.031 mg/L, 0.031/0.031 mg/L, and 0.031/0.062 mg/L, respectively. Legionella isolates were inhibited by either low concentrations of macrolides and fluoroquinolones, or high concentrations of CTX and tetracycline drugs. LEV was the most effective drug against different Legionella species and serogroups of L. pneumophila isolates. The latter were inhibited in decreasing order by MIN > CTX >DOC, while non-L. pneumophila isolates were inhibited by CTX> MIN >DOC. In this study, we evaluated drug resistance of pathogenic bacteria from the environment. This may help predict the emergence of drug resistance, improve patient outcomes, and reduce hospitalization costs.

Occurrence and transport of tetracycline, sulfonamide, quinolone, and macrolide antibiotics in the Haihe River Basin, China.

PubMed

Luo, Yi; Xu, Lin; Rysz, Michal; Wang, Yuqiu; Zhang, Hao; Alvarez, Pedro J J

2011-03-01

The occurrence and transport of 12 antibiotics (from the tetracycline, sulfonamide, quinolone, and macrolide families) was studied in a 72-km stretch of the Haihe River, China, and in six of its tributaries. Aqueous and sediment samples were analyzed by HPLC-MS/MS. Sulfonamides were detected at the highest concentrations (24-385 ng/L) and highest frequencies (76-100%). Eight of the 12 antibiotics likely originated from veterinary applications in swine farms and fishponds, and concentrations at these sources (0.12-47 μg/L) were 1-2 orders of magnitude higher than in the effluent of local wastewater treatment plants. Sulfachloropyridazine (SCP) was detected in all swine farm and fishpond samples (maximum concentration 47 μg/L), which suggests its potential usefulness to indicate livestock source pollution in the Haihe River basin. Hydrological and chemical factors that may influence antibiotic distribution in the Haihe River were considered by multiple regression analysis. River flow rate exerted the most significant effect on the first-order attenuation coefficient (K) for sulfonamides, quinolones, and macrolides, with higher flow rates resulting in higher K, probably due to dilution. For tetracyclines, sediment total organic matter and cation exchange capacity exerted a greater impact on K than flow rate, indicating that adsorption to sediments plays an important role in attenuating tetracycline migration. Overall, the predominance of sulfonamides in the Haihe River underscores the need to consider regulating their veterinary use and improving the management and treatment of associated releases.

Novel Tn916-like elements confer aminoglycoside/macrolide co-resistance in clinical isolates of Streptococcus gallolyticus ssp. gallolyticus.

PubMed

Kambarev, Stanimir; Pecorari, Frédéric; Corvec, Stéphane

2018-02-09

Streptococcus gallolyticus ssp. gallolyticus (Sgg) is a commensal bacterium and an opportunistic pathogen. In humans it has been clinically associated with the incidence of colorectal cancer (CRC) and epidemiologically recognized as an emerging cause of infective endocarditis (IE). The standard therapy of Sgg includes the administration of a penicillin in combination with an aminoglycoside. Even though penicillin-resistant isolates have still not been reported, epidemiological studies have shown that this microbe is a reservoir of multiple acquired genes, conferring resistance to tetracyclines, aminoglycosides, macrolides and glycopeptides. However, the underlying antibiotic resistance mobilome of Sgg remains poorly understood. To investigate the mobile genetic basis of antibiotic resistance in multiresistant clinical Sgg. Isolate NTS31106099 was recovered from a patient with IE and CRC at Nantes University Hospital, France and studied by Illumina WGS and comparative genomics. Molecular epidemiology of the identified mobile element(s) was performed using antibiotic susceptibility testing (AST), PCR, PFGE and WGS. Mobility was investigated by PCR and filter mating. Two novel conjugative transposons, Tn6263 and Tn6331, confer aminoglycoside/macrolide co-resistance in clinical Sgg. They display classical family Tn916/Tn1545 modular architecture and harbour an aph(3')-III→sat4→ant(6)-Ia→erm(B) multiresistance gene cluster, related to pRE25 of Enterococcus faecium. These and/or closely related elements are highly prevalent among genetically heterogeneous clinical isolates of Sgg. Previously unknown Tn916-like mobile genetic elements conferring aminoglycoside/macrolide co-resistance make Sgg, collectively with other gut Firmicutes such as enterococci and eubacteria, a potential laterally active reservoir of these antibiotic resistance determinants among the mammalian gastrointestinal microbiota. © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Quantification of tylosin and tylosin antibiotic resistance genes in cattle waste

USDA-ARS?s Scientific Manuscript database

Presented is the development of a solid phase extraction (SPE) procedure and a liquid chromatography-mass spectrometry (LC-MS/MS) method for quantifying tylosin in cattle waste samples. Tylosin is a macrolide antibiotic found naturally as a fermentation product of Streptomyces fradiae and is mainly ...

Fluorescence quenching effects of antibiotics on the main components of dissolved organic matter.

PubMed

Yan, Peng-Fei; Hu, Zhen-Hu; Yu, Han-Qing; Li, Wei-Hua; Liu, Li

2016-03-01

Dissolved organic matter (DOM) in wastewater can be characterized using fluorescence excitation-emission matrix and parallel factor (EEM-PARAFAC) analysis. Wastewater from animal farms or pharmaceutical plants usually contains high concentration of antibiotics. In this study, the quenching effect of antibiotics on the typical components of DOM was explored using fluorescence EEM-PARAFAC analysis. Four antibiotics (roxarsone, sulfaquinoxaline sodium, oxytetracycline, and erythromycin) at the concentration of 0.5∼4.0 mg/L and three typical components of DOM (tyrosine, tryptophan, and humic acid) were selected. Fluorescence quenching effects were observed with the addition of antibiotics. Among these four antibiotics, roxarsone (2.9∼20.2 %), sulfaquinoxaline sodium (0∼32.0 %), and oxytetracycline (0∼41.8 %) led to a stronger quenching effect than erythromycin (0∼8.0 %). From the side of DOM, tyrosine and tryptophan (0.5∼41.8 %) exhibited a similar quenching effect, but they were higher than humic acids (0∼20.2 %) at the same concentration of antibiotics. For humic acid, a significant quenching effect was observed only with the addition of roxarsone. This might be the first report about the fluorescence quenching effect caused by antibiotics. The results from this study confirmed the interference of antibiotics on the fluorescence intensity of the main components of DOM and highlighted the importance of correcting fluorescence data in the wastewater containing antibiotics.

Spatial and seasonal distribution of selected antibiotics in surface waters of the Pearl Rivers, China.

PubMed

Yang, Ji-Feng; Ying, Guang-Guo; Zhao, Jian-Liang; Tao, Ran; Su, Hao-Chang; Liu, You-Sheng

2011-01-01

The distribution and occurrence of 15 antibiotics in surface water of the Pearl River System (Liuxi River, Shijing River and Zhujiang River) and effluents of four wastewater treatment plants (WWTPs) were investigated in two sampling events representing wet season and dry season by using rapid resolution liquid chromatography-electrospray tandem mass spectrometry (RRLC-MS/MS) in positive ionization mode. Only eight antibiotics (sulfadiazine, sulfapyridine, sulfamethazine, sulfamethoxazole, trimethoprim, roxithromycin, erythromycin-H₂O and norfloxacin) were detected in the water samples of the three rivers and the effluents. The detection frequencies and levels of antibiotics in the dry season were higher than those in the wet season. This could be attributed to the dilution effects in the wet season and relatively lower temperature in the dry season under which antibiotics could persist for a longer period. The levels of the detected antibiotics in different sites are generally in a decreasing order as follows: Shijing River ≥WWTP effluent ≥Zhujiang River ≥ Liuxi River. Risk assessment based on the calculated risk quotients showed that only erythromycin-H₂O and roxithromycin detected in the Pearl Rivers might have adverse effects on aquatic organisms.

Broad-spectrum antibiotics for spontaneous preterm labour: the ORACLE II randomised trial. ORACLE Collaborative Group.

PubMed

Kenyon, S L; Taylor, D J; Tarnow-Mordi, W

2001-03-31

Preterm birth after spontaneous preterm labour is associated with death, neonatal disease, and long-term disability. Previous small trials of antibiotics for spontaneous preterm labour have reported inconclusive results. We did a randomised multicentre trial to resolve this issue. 6295 women in spontaneous preterm labour with intact membranes and without evidence of clinical infection were randomly assigned 250 mg erythromycin (n=1611), 325 mg co-amoxiclav (250 mg amoxicillin and 125 mg clavulanic acid; n=1550), both (n=1565), or placebo (n=1569) four times daily for 10 days or until delivery, whichever occurred earlier. The primary outcome measure was a composite of neonatal death, chronic lung disease, or major cerebral abnormality on ultrasonography before discharge from hospital. Analysis was by intention to treat. None of the trial antibiotics was associated with a lower rate of the composite primary outcome than placebo (erythromycin 90 [5.6%], co-amoxiclav 76 [5.0%], both antibiotics 91 [5.9%], vs placebo 78 [5.0%]). However, antibiotic prescription was associated with a lower occurrence of maternal infection. This trial provides evidence that antibiotics should not be routinely prescribed for women in spontaneous preterm labour without evidence of clinical infection.

Characterisation of antibiotic prescriptions for acute respiratory tract infections in Danish general practice: a retrospective registry based cohort study.

PubMed

Aabenhus, Rune; Hansen, Malene Plejdrup; Saust, Laura Trolle; Bjerrum, Lars

2017-05-19

Inappropriate use of antibiotics is contributing to the increasing rates of antimicrobial resistance. Several Danish guidelines on antibiotic prescribing for acute respiratory tract infections in general practice have been issued to promote rational prescribing of antibiotics, however it is unclear if these recommendations are followed. We aimed to characterise the pattern of antibiotic prescriptions for patients diagnosed with acute respiratory tract infections, by means of electronic prescriptions, labeled with clinical indications, from Danish general practice. Acute respiratory tract infections accounted for 456,532 antibiotic prescriptions issued between July 2012 and June 2013. Pneumonia was the most common indication with 178,354 prescriptions (39%), followed by acute tonsillitis (21%) and acute otitis media (19%). In total, penicillin V accounted for 58% of all prescriptions, followed by macrolides (18%) and amoxicillin (15%). The use of second-line agents increased with age for all indications, and comprised more than 40% of the prescriptions in patients aged >75 years. Women were more often prescribed antibiotics regardless of clinical indication. This is the first Danish study to characterise antibiotic prescription patterns for acute respiratory tract infections by data linkage of clinical indications. The findings confirm that penicillin V is the most commonly prescribed antibiotic agent for treatment of patients with an acute respiratory tract infection in Danish general practice. However, second-line agents like macrolides and amoxicillin with or without clavulanic acid are overused. Strategies to improve the quality of antibiotic prescribing especially for pneumonia, acute otitis media and acute rhinosinusitis are warranted. TRACKING THE OVERUSE OF ANTIBIOTICS: Better adherence to guidelines for prescribing antibiotics for different respiratory tract infections are warranted in Danish general practice. The over-use of antibiotics, particularly so-called 'second-line' agents such as amoxicillin, increases resistance and may lead to a potentially catastrophic scenario where antibiotics are no longer effective. Exactly how widespread the over-use of antibiotics is for different infections, however, is not clear. Rune Aabenhus at the University of Copenhagen and co-workers analyzed primary care data regarding antibiotic prescriptions for acute respiratory tract infections including pneumonia and ear infections in Denmark. They found that penicillin V-the current recommended first-line drug in Scandinavian countries-accounted for 58 per cent of prescriptions, a figure which should be improved. Amoxicillin and macrolides were over-prescribed, particularly in elderly patients. The team also call for further analysis of prescriptions given by out-of-hours clinics.

Practical implications of erythromycin resistance gene diversity on surveillance and monitoring of resistance

USDA-ARS?s Scientific Manuscript database

Use of antibiotics in human and animal medicine has applied selective pressure for the global dissemination of antibiotic-resistant bacteria. Therefore, it is of interest to develop strategies to mitigate the continued amplification and transmission of resistance genes in environmental reservoirs s...

Occurrence, distribution, and potential sources of antibiotics pollution in the water-sediment of the northern coastline of the Persian Gulf, Iran.

PubMed

Kafaei, Raheleh; Papari, Fatemeh; Seyedabadi, Mohammad; Sahebi, Soleyman; Tahmasebi, Rahim; Ahmadi, Mehdi; Sorial, George A; Asgari, Ghorban; Ramavandi, Bahman

2018-06-15

Occurrence and frequency of six most prescribed antibiotics (tetracycline, norfloxacin, azithromycin, anhydro erythromycin, cephalexin, and amoxicillin) were assessed in three wastewater treatment plants (WWTPs), and in water and sediments of the Persian Gulf at Bushehr coastline, Iran. The antibiotics concentration in the influent and effluent of septic tank (the hospital WWTP), activated sludge (the hospital WWTP), and stabilization pond (municipal WWTP) ranged between 7.89 and 149.63, 13.49-198.47, 6.55-16.37 ng/L, respectively. Conventional treatment resulted in incomplete removal of most of the studied antibiotics. Furthermore, the activated sludge was more effective in terms of antibiotic elimination compared to the stabilization pond or septic tank. The mean concentration of antibiotics ranged 1.21-51.50 ng/L in seawater and 1.40-25.32 ng/g in sediments during summer and winter. Norfloxacin was the dominant detected antibiotic in seawater, sediments, and influent of two hospital WWTPs. Seasonal comparisons showed significant differences for erythromycin and amoxicillin concentrations in seawater. Spatial variation indicated the role of physicochemical properties on distribution of antibiotics in seawater and sediments. The results emphasize the need to pay attention to antibiotic contamination in water and sediments of the Persian Gulf. Copyright © 2018 Elsevier B.V. All rights reserved.

Genital mycoplasmas in women attending a family planning clinic in Guiné-Bissau and their susceptibility to antimicrobial agents.

PubMed

Domingues, D; Távora Tavira, L; Duarte, A; Sanca, A; Prieto, E; Exposto, F

2003-04-01

A study on the prevalence of genital mycoplasmas and their susceptibility to the most common antimicrobial agents used for treating the infection was conducted on 94 women attending a family planning clinic in Guiné-Bissau. Fifty-four women (57.4%) were positive for Mycoplasma hominis and/or Ureaplasma urealyticum. M. hominis and U. urealyticum separately isolated from infected women yielded frequencies of 31.5 and 27.8%, respectively, the remainder were infected with both species. No strain was found to be resistant to all three commonly employed antibiotics for the management of these infections (erythromycin, tetracycline and ofloxacin), although multiple resistance to two antibiotics was frequent, especially when both genital mycoplasmas were present. Some 90.7 and 24.1% of all isolates were resistant to erythromycin and tetracycline, respectively. No resistance was observed to ofloxacin, although 50% of the strains had intermediate resistance. The high prevalence of genital mycoplasmas in women attending a family planning clinic in Guiné-Bissau, as demonstrated in this study, appears to be associated with trichomonosis and bacterial vaginosis. These infections were also found to be highly resistant to erythromycin and tetracycline and to have intermediate resistance to ofloxacin. However, further studies are necessary to establish the burden of infection due to antibiotic resistant genital mycoplasmas.

Infectious flare-ups and serious sequelae following endodontic treatment: a prospective randomized trial on efficacy of antibiotic prophylaxis in cases of asymptomatic pulpal-periapical lesions.

PubMed

Morse, D R; Furst, M L; Belott, R M; Lefkowitz, R D; Spritzer, I B; Sideman, B H

1987-07-01

Without peritreatment antibiotics, infectious flare-ups (about 15% incidence) and serious sequelae follow endodontic treatment of asymptomatic teeth with necrotic pulps and associated periapical lesions. Antibiotics administered after endodontic treatment (4-day regimen) reduce the flare-up incidence to about 2%, but hypersensitivity responses, sensitization, resistant microbes, and drug-taking compliance are potential problems. To ascertain whether a specific prophylactic antibiotic (high-dose, 1-day regimen) would preferentially maintain this low flare-up incidence while overcoming antibiotic-related problems, 315 patients with quiescent pulpal necrosis and an associated periapical lesion were randomly given either penicillin V or erythromycin (base or stearate). Evaluations of flare-up after endodontic treatment were done at 1 day, 1 week, and 2 months. A 2.2% flare-up incidence was found, with no statistically significant differences for penicillin (0.0%), base (2.9%), and stearate (3.8%). No hypersensitivity responses occurred. Gastrointestinal side effects were found primarily with the erythromycins (12.4%). A comparative analysis of the data from our first study (no peritreatment antibiotics) and the pooled data from our last two investigations (including the current trial) showed that peritreatment antibiotic coverage significantly reduced flare-ups and serious sequelae after endodontic treatment (p less than 0.001).

Antibiotic resistance among clinical isolates of Haemophilus influenzae in the United States in 1994 and 1995 and detection of beta-lactamase-positive strains resistant to amoxicillin-clavulanate: results of a national multicenter surveillance study.

PubMed

Doern, G V; Brueggemann, A B; Pierce, G; Holley, H P; Rauch, A

1997-02-01

A total of 1,537 clinical isolates of Haemophilus influenzae were recovered in 30 U.S. medical center laboratories between 1 November 1994 and 30 April 1995 and were characterized in a central laboratory with respect to serotype and beta-lactamase production and the in vitro activities of 15 oral antimicrobial agents. Overall, 36.4% of the isolates were found to produce beta-lactamase. The rank order of activity of six cephalosporins on the basis of MICs was cefixime > cefpodoxime > cefuroxime > loracarbef > or = cefaclor > cefprozil. On the basis of current National Committee for Clinical Laboratory Standards (NCCLS) breakpoints ages of isolates found to be resistant or intermediate to these agents were as follows: 0.1, 0.3, 6.4, 16.3, 18.3, and 29.8, respectively (National Committee for Clinical Laboratory Standards. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 4th ed. M7-A4, 1995). Azithromycin was, on a weight basis, the most potent of the macrolides tested in this study, followed by erythromycin and then clarithromycin. Azithromycin was typically fourfold more active than erythromycin, which was, in turn, slightly more active than clarithromycin. However, when compared on the basis of the frequency of resistance determined by using current NCCLS breakpoints, there was essentially no difference between azithromycin and clarithromycin, i.e., 0.5 and 1.9%, respectively (P = 0.086). Interpretive breakpoints for erythromycin MIC tests versus H. influenzae have not been developed. Resistance to other non- beta-lactam agents was variable, as follows: trimethoprim-sulfamethoxazole, 9.0%; chloramphenicol, 0.2%; tetracycline, 1.3%; and rifampin, 0.3%. Two conspicuous findings in this study were the identification of 39 strains H. influenzae that were beta-lactamase negative but ampicillin intermediate or resistant (BLNAR) and, even more surprisingly, 17 beta-lactamase-positive isolates that were resistant to amoxicillin-clavulanate (BLPACR). Strains of H. influenzae in the first group have heretofore been very uncommon; organisms in the second group have not previously been described in the literature. The percentages of all study isolates comprised of BLNAR and BLPACR organisms were 2.5 and 1.1, respectively. Overall resistance to ampicillin was thus 38.9%, and that to amoxicillin-clavulanate was 4.5%.

Calibration and controlled flume evaluation of polar organic chemical integrative samplers (POCIS) for tylosin

USDA-ARS?s Scientific Manuscript database

In recent years, the occurrence and fate of emerging contaminants such as antibiotics in the environment have become a concern. One of these is tylosin, a macrolide antibiotic that is used extensively in the swine industry as a growth promoter. The monitoring of these emerging contaminants for asses...

Macrolide Hybrid Compounds: Drug Discovery Opportunities in Anti- Infective and Anti-inflammatory Area.

PubMed

Paljetak, Hana Cipcic; Tomaskovic, Linda; Matijasic, Mario; Bukvic, Mirjana; Fajdetic, Andrea; Verbanac, Donatella; Peric, Mihaela

2017-01-01

Macrolides, polyketide natural products, and their 15-membered semi-synthetic derivatives are composed of substituted macrocyclic lactone ring and used primarily as potent antibiotics. Recently their usefulness was extended to antimalarial and anti-inflammatory area. Hybrid macrolides presented in this article are the next generation semi-synthetic compounds that combine pharmacophores from antibacterial, antimalarial and anti-inflammatory area with 14- and 15-membered azalide scaffolds. Antibacterial azalide hybrids with sulphonamides showed improved activity against resistant streptococci while quinolone conjugates demonstrated full coverage of respiratory pathogens including macrolide resistant strains and their efficacy was confirmed in mouse pneumonia model. Antimalarial macrolide hybrids, mainly involving (chloro)quinoline pharmacophores, showed outstanding activity against chloroquine resistant strains, favourable pharmacokinetics, promising in vivo efficacy as well as encouraging developmental potential. Anti-inflammatory hybrids were obtained by combining macrolides with corticosteroid and non-steroidal anti-inflammatory drugs. They were found active in in vivo animal models of locally induced inflammation, asthma, inflammatory bowel disease and rheumatoid arthritis and demonstrated improved safety over parent steroid drugs. Overall, macrolide hybrids possess significant potential to be developed as potent novel medicines in therapeutic areas of utmost pharmaceutical interest. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Sensitivity of microbial associations of periodontal lesions to antibacterial agents].

PubMed

Makeeva, I M; Daurova, F Yu; Byakova, S F; Ippolitov, E V; Gostev, M S; Polikushina, A O; Shubin, E V

2016-01-01

The aim of the study was the development of approaches to improve the effectiveness of antibiotic therapy in dental practice on the basis of determining the sensitivity of pathogenic microorganisms to antibiotics of different groups. The study included determination of the sensitivity of the microbial complexes from wound exudate of periodontal pocket and apical abscess to macrolides, quinolones, penicillins, lincosamides and 5-nitroimidazole. A survey of dentists and dental clinics patients to identify the cause and frequency of use of antibiotics and to identify possible adverse reactions was also conducted. Dentists prefer macrolide antibiotics, protected penicillins, and fluoroquinolone combined with 5-nitroimidazole. All patients have taken antibiotics themselves at least once a year. Microbial complexes in patients with acute and exacerbated apical periodontitis in 79% of cases are susceptible to amoxicillin/clavulanic acid, to azithromycin - 52%, lincomycin - 36%, 5-nitroimidazole - 68%, ciprofloxacin - 73.7%. In patients with apical abscess high rates of resistance of microbial complexes to all types of antibiotics was revealed (33% for lincomycin 76,1% for ciprofloxacin, 28,6% for 5-nitroimidazole). Patients with moderate to severe periodontitis in 90.5% are sensitive to amoxicillin/clavulanic acid and azithromycin, in 62.4% to lincomycin. Sensitivity to ciprofloxacin was detected in 85.7% of patients, in 14.3% - moderate resistance.

SACE_3986, a TetR family transcriptional regulator, negatively controls erythromycin biosynthesis in Saccharopolyspora erythraea.

PubMed

Wu, Panpan; Pan, Hui; Zhang, Congming; Wu, Hang; Yuan, Li; Huang, Xunduan; Zhou, Ying; Ye, Bang-ce; Weaver, David T; Zhang, Lixin; Zhang, Buchang

2014-07-01

Erythromycin, a medically important antibiotic, is produced by Saccharopolyspora erythraea. Unusually, the erythromycin biosynthetic gene cluster lacks a regulatory gene, and the regulation of its biosynthesis remains largely unknown. In this study, through gene deletion, complementation and overexpression experiments, we identified a novel TetR family transcriptional regulator SACE_3986 negatively regulating erythromycin biosynthesis in S. erythraea A226. When SACE_3986 was further inactivated in an industrial strain WB, erythromycin A yield of the mutant was increased by 54.2 % in average compared with that of its parent strain, displaying the universality of SACE_3986 as a repressor for erythromycin production in S. erythraea. qRT-PCR analysis indicated that SACE_3986 repressed the transcription of its adjacent gene SACE_3985 (which encodes a short-chain dehydrogenase/reductase), erythromycin biosynthetic gene eryAI and the resistance gene ermE. As determined by EMSA analysis, purified SACE_3986 protein specifically bound to the intergenic region between SACE_3985 and SACE_3986, whereas it did not bind to the promoter regions of eryAI and ermE. Furthermore, overexpression of SACE_3985 in A226 led to enhanced erythromycin A yield by at least 32.6 %. These findings indicate that SACE_3986 is a negative regulator of erythromycin biosynthesis, and the adjacent gene SACE_3985 is one of its target genes. The present study provides a basis to increase erythromycin production by engineering of SACE_3986 and SACE_3985 in S. erythraea.

Antibiotics for ureaplasma in the vagina in pregnancy.

PubMed

Raynes Greenow, Camille H; Roberts, Christine L; Bell, Jane C; Peat, Brian; Gilbert, Gwendolyn L; Parker, Sharon

2011-09-07

Preterm birth is a significant perinatal problem contributing to perinatal morbidity and mortality. Heavy vaginal ureaplasma colonisation is suspected of playing a role in preterm birth and preterm rupture of the membranes. Antibiotics are used to treat infections and have been used to treat pregnant women with preterm prelabour rupture of the membranes, resulting in some short-term improvements. However, the benefit of using antibiotics in early pregnancy to treat heavy vaginal colonisation is unclear. To assess whether antibiotic treatment of pregnant women with heavy vaginal ureaplasma colonisation reduces the incidence of preterm birth and other adverse pregnancy outcomes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2011). Randomised controlled trials comparing any antibiotic regimen with placebo or no treatment in pregnant women with ureaplasma detected in the vagina. Three review authors independently assessed eligibility and trial quality and extracted data. We included one trial, involving 1071 women. Of these, 644 women between 22 weeks and 32 weeks' gestation were randomly assigned to one of three groups of antibiotic treatment (n = 174 erythromycin estolate, n = 224 erythromycin stearate, and n = 246 clindamycin hydrochloride) or a placebo (n = 427). Preterm birth data was not reported in this trial. Incidence of low birthweight less than 2500 grams was only evaluated for erythromycin (combined, n = 398) compared to placebo (n = 427) and there was no statistically significant difference between the two groups (risk ratio (RR) 0.70, 95% confidence interval (CI) 0.46 to 1.07). There were no statistically significant differences in side effects sufficient to stop treatment between either group (RR 1.25, 95% CI 0.85 to 1.85). There is insufficient evidence to assess whether pregnant women who have vaginal colonisation with ureaplasma should be treated with antibiotics to prevent preterm birth.Preterm birth is a significant perinatal problem. Upper genital tract infections, including ureaplasmas, are suspected of playing a role in preterm birth and preterm rupture of the membranes. Antibiotics are used to treat women with preterm prelabour rupture of the membranes; this may result in prolongation of pregnancy and lowers the risks of maternal and neonatal infection. However, antibiotics may be beneficial earlier in pregnancy to eradicate potentially causative agents.

In Vitro Antibiotic Susceptibilities of Burkholderia mallei (Causative Agent of Glanders) Determined by Broth Microdilution and E-Test

PubMed Central

Heine, Henry S.; England, Marilyn J.; Waag, David M.; Byrne, W. Russell

2001-01-01

In vitro susceptibilities to 28 antibiotics were determined for 11 strains of Burkholderia mallei by the broth microdilution method. The B. mallei strains demonstrated susceptibility to aminoglycosides, macrolides, quinolones, doxycycline, piperacillin, ceftazidime, and imipenem. For comparison and evaluation, 17 antibiotic susceptibilities were also determined by the E-test. E-test values were always lower than the broth dilution values. Establishing and comparing antibiotic susceptibilities of specific B. mallei strains will provide reference information for assessing new antibiotic agents. PMID:11408233

Comparing two types of macrolide antibiotics for the purpose of assessing population-based drug interactions

PubMed Central

Fleet, Jamie L; Shariff, Salimah Z; Bailey, David G; Gandhi, Sonja; Juurlink, David N; Nash, Danielle M; Mamdani, Muhammad; Gomes, Tara; Patel, Amit M; Garg, Amit X

2013-01-01

Objective Clarithromycin strongly inhibits enzyme cytochrome P450 3A4, preventing the metabolism of some other drugs, while azithromycin is a weak inhibitor. Accordingly, blood concentrations of other drugs increase with clarithromycin coprescription leading to adverse events. These macrolide antibiotics also differ on other properties that may impact outcomes. In this study, we compared outcomes in two groups of macrolide antibiotic users in the absence of potentially interacting drugs. Design Population-based retrospective cohort study. Setting Ontario, Canada, from 2003 to 2010. Patients Patients (mean 74 years) prescribed clarithromycin (n=52 251) or azithromycin (referent group, n=46 618). Main outcomes The primary outcomes were hospital admission within 30 days of a new antibiotic prescription with any of the 12 conditions examined separately (acute kidney injury, acute myocardial infarction, neuroimaging (proxy for delirium), hypotension, syncope, hyperkalaemia, hyponatraemia, hyperglycaemia, arrhythmia, ischaemic stroke, gastrointestinal bleeding and sepsis). The secondary outcome was mortality. Results The baseline characteristics of the two groups, including patient demographics, comorbid conditions, infection type and prescribing physician specialty, were nearly identical. The median daily dose was 1000 mg for clarithromycin and 300 mg for azithromycin and the median duration of dispensing antibiotics was 10 and 5 days, respectively. There was no difference between the groups in the risk of hospitalisation for any condition studied (relative risk ranged from 0.67 to 1.23). Compared with azithromycin, clarithromycin was associated with a slightly higher risk of all-cause mortality (0.46% vs 0.37%, relative risk 1.25, 95% CI 1.03 to 1.52). Conclusions Clarithromycin can be used to assess drug interactions in population-based studies with azithromycin serving as a control group. However, any differences in mortality observed between the two antibiotic groups in the setting of other drug use may be partially attributable to factors beyond the inhibition of drug metabolising enzymes and transporters, as the difference for this outcome was significant. PMID:23847265

Transfer of antibiotics from wastewater or animal manure to soil and edible crops.

PubMed

Pan, Min; Chu, L M

2017-12-01

Antibiotics are added to agricultural fields worldwide through wastewater irrigation or manure application, resulting in antibiotic contamination and elevated environmental risks to terrestrial environments and humans. Most studies focused on antibiotic detection in different matrices or were conducted in a hydroponic environment. Little is known about the transfer of antibiotics from antibiotic-contaminated irrigation wastewater and animal manure to agricultural soil and edible crops. In this study, we evaluated the transfer of five different antibiotics (tetracycline, sulfamethazine, norfloxacin, erythromycin, and chloramphenicol) to different crops under two levels of antibiotic-contaminated wastewater irrigation and animal manure fertilization. The final distribution of tetracycline (TC), norfloxacin (NOR) and chloramphenicol (CAP) in the crop tissues under these four treatments were as follows: fruit > leaf/shoot > root, while an opposite order was found for sulfamethazine (SMZ) and erythromycin (ERY): root > leaf/shoot > fruit. The growth of crops could accelerate the dissipation of antibiotics by absorption from contaminated soil. A higher accumulation of antibiotics was observed in crop tissues under the wastewater treatment than under manure treatment, which was due to the continual irrigation that increased adsorption in soil and uptake by crops. The translocation of antibiotics in crops mainly depended on their physicochemical properties (e.g. log K ow ), crop species, and the concentrations of antibiotics applied to the soil. The levels of antibiotics ingested through the consumption of edible crops under the different treatments were much lower than the acceptable daily intake (ADI) levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

Streptococcus pneumoniae non-susceptibility and outpatient antimicrobial prescribing rates at the Alaska Native Medical Center

PubMed Central

Stevens, Ryan W.; Wenger, Jay; Bulkow, Lisa; Bruce, Michael G.

2013-01-01

Background American Indian/Alaska Native (AI/AN) people suffer substantially higher rates of invasive pneumococcal disease (IPD) than the general US population. We evaluated antimicrobial prescribing data and their association with non-susceptibility in Streptococcus pneumoniae causing IPD in AI/AN people between 1992 and 2009. Methods Antimicrobial use data were gathered from the electronic patient management system and included all prescriptions dispensed to Alaska Native patients aged 5 years and older from outpatient pharmacies at the Alaska Native Medical Center (ANMC). Antimicrobial susceptibility data were gathered from pneumococcal isolates causing IPD among Anchorage Service Unit AI/AN residents aged 5 years and older. Data were restricted to serotypes not contained in the pneumococcal vaccine (PCV7). Results Over the study period, overall antimicrobial prescribing increased 59% (285/1,000 persons/year in 1992 to 454/1,000 persons per year in 2009, p<0.001). Trimethoprim/sulfamethoxazole prescribing increased (43/1,000 persons/year in 1992 to 108/1,000 persons/year in 2009, p<0.001) and non-susceptibility to trimethoprim/sulfamethoxazole in AI/AN patients ≥5 years of age increased in non-PCV7 serotypes (0–12%, p<0.05). Similarly, prescribing rates increased for macrolide antibiotics (46/1,000 persons/year in 1992 to 84/1,000 persons/year in 2009, p<0.05). We observed no statistically significant change over time in erythromycin non-susceptibility among non-PCV7 serotypes in AI/AN patients aged 5 years or greater (0–7%, p=0.087). Conclusion Antimicrobial prescribing patterns of some antibiotics in the AI/AN population corresponded to increased antimicrobial resistance in clinical isolates. This study highlights the on-going threat of antimicrobial resistance, the critical importance of judicious prescribing of antibiotics and the potential utility of prescribing data for addressing this issue. PMID:24358456

Contamination profiles and mass loadings of macrolide antibiotics and illicit drugs from a small urban wastewater treatment plant.

PubMed

Loganathan, Bommanna; Phillips, Malia; Mowery, Holly; Jones-Lepp, Tammy L

2009-03-01

Information is limited regarding sources, distribution, environmental behavior, and fate of prescribed and illicit drugs. Wastewater treatment plant (WWTP) effluents can be one of the sources of pharmaceutical and personal care products (PPCP) into streams, rivers and lakes. The objective of this study was to determine the contamination profiles and mass loadings of urobilin (a chemical marker of human waste), macrolide antibiotics (azithromycin, clarithromycin, roxithromycin), and two drugs of abuse (methamphetamine and ecstasy), from a small (<19 mega liters day(-1), equivalent to <5 million gallons per day) wastewater treatment plant in southwestern Kentucky. The concentrations of azithromycin, clarithromycin, methamphetamine and ecstasy in wastewater samples varied widely, ranging from non-detects to 300 ng L(-1). Among the macrolide antibiotics analyzed, azithromycin was consistently detected in influent and effluent samples. In general, influent samples contained relatively higher concentrations of the analytes than the effluents. Based on the daily flow rates and an average concentration of 17.5 ng L(-1) in the effluent, the estimated discharge of azithromycin was 200 mg day(-1) (range 63-400 mg day(-1)). Removal efficiency of the detected analytes from this WWTP were in the following order: urobilin>methamphetamine>azithromycin with percentages of removal of 99.9%, 54.5% and 47%, respectively, indicating that the azithromycin and methamphetamine are relatively more recalcitrant than others and have potential for entering receiving waters.

Association of macrolides with overall mortality and cardiac death among patients with various infections: A meta-analysis.

PubMed

Li, Xiang; Wang, Min; Liu, Guiyang; Ma, Jianli; Li, Chuntong

2016-03-01

A large body of evidences suggested that macrolide therapy could improve the survival of patients with various infections. While in the same time, macrolides are known to increase fatal arrhythmogenic risks and cause cardiac death. To assess the risks and benefits of macrolide therapy, we systematically reviewed all studies of macrolide use, cardiac death and mortality among patients with various infections. We searched Pubmed, Embase and Cochrane library and reviewed reference lists from 1980 through April 2015. Studies were included if they compared macrolides to other antibiotics in adults with various infections. The outcome measures were the overall mortality and the risk of cardiac death. Overall, macrolide use was associated with a statistically significant mortality reduction compared with nonmacrolide use (OR: 0.65, 95% CI: 0.46-0.92). There was no difference in the risk of cardiac death between macrolide and nonmacrolide regimes (OR: 1.43, 95% CI: 0.86-2.40). In subgroup analyses, macrolide use was found to be associated with the decreased risk of mortality in a population of older individuals (age>48 years, OR: 0.69; 95% CI: 0.66-0.72). While in a general population of young and middle-aged adults, the use of macrolide-based regimens could not decrease the risk of death from any cause (age<48 years, OR: 0.42; 95% CI: 0.02-11.01). As for cardiac death, macrolide use was found to be associated with increased risk of cardiac death in a population of older individuals (age>48 years, OR: 1.99; 95% CI: 1.53-2.59). Despite the potential cardiotoxic effects, there is a net benefit associated with macrolide use in older patients with various infections and macrolide use except roxithromycin was found to be associated with increased risk of cardiac death in a population of adults aged > 48 years. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Fidaxomicin

MedlinePlus

... by Clostridium difficile (C. difficile; a type of bacteria that my cause severe or life-threatening diarrhea.) ... medications called macrolide antibiotics. It works by killing bacteria in the intestines.Fidaxomicin will not treat infections ...

Aeromedical Aspects of CH-47C Helicopter Self-Deployment (Operation Northern Leap),

DTIC Science & Technology

1980-03-01

layover at Loring AFB. He was treated with erythromycin, pseudoephedrine and a cough prep- aration, and was restricted from performing pilot duties...tab- lets, pseudoephedrine tablets, and throat lozenges. Erythromycin was the only antibiotic dispensed in significant quantities and most emer- gency...medi(al supplies were not used. The fliqht surgeon obtained one refill of his stock of pseudoephedrine tablets in Goose Bay after his first stoc; was

Antibiotic prescribing practice for acute, uncomplicated respiratory tract infections in primary care settings in New Delhi, India.

PubMed

Kotwani, Anita; Holloway, Kathleen

2014-07-01

To obtain information on prescribing rates and choice of antibiotics for acute, uncomplicated respiratory tract infections (RTIs) in the community. Antibiotic use in acute, uncomplicated RTIs consisting of common cold/sore throat/cough for not more than five days was surveyed in the community (December 2007-November 2008) using patient exit interviews at public and private facilities from four localities in New Delhi. Data were collected from 10 public sector facilities and 20 private clinics over one year. The percentage of acute, uncomplicated RTIs patients receiving antibiotics in general and using the Anatomical Therapeutic Chemical classification and the Defined Daily Dose (ATS/DDD) were analysed. At public and private facilities, 45% (746/1646) and 57% (259/457) of acute, uncomplicated RTI patients were prescribed at least one antibiotic, respectively. The main antibiotic class calculated as percentage of total antibiotics DDDs/1000 prescribed to acute, uncomplicated RTI patients at private clinics was cephalosporins, J01DA (39%), followed by fluoroquinolones, J01MA (24%), penicillins, J01C (19%) and macrolides, J01FA (15%). Newer members from each class were prescribed; older antibiotics such as co-trimoxazole or tetracyclines were rarely prescribed. At public facilities, the main class of antibiotic prescribed was penicillins (31%), followed by macrolides (25%), fluoroquinolones (20%) and cephalosporins (10%). Study clearly shows overuse and inappropriate choice of antibiotics for the treatment of acute, uncomplicated RTIs which are mainly due to virus and do not require antibiotic treatment. Results of the study warrant interventional strategies to promote rational use of antibiotics to decrease the overgrowing threat of antibiotic resistance. © 2014 John Wiley & Sons Ltd.

Antibiotic prescriptions for outpatient acute rhinosinusitis in Canada, 2007-2013.

PubMed

Sharma, Prateek; Finley, Rita; Weese, Scott; Glass-Kaastra, Shiona; McIsaac, Warren

2017-01-01

Acute rhinosinusitis (ARS) is a respiratory disease commonly caused by viral infections. Physicians regularly prescribe antibiotics despite bacterial etiologies being uncommon. This is of concern, as this use adds to the selection pressure for resistance. Here we present the descriptive epidemiology of acute rhinosinusitis and corresponding antibiotic prescribing practices by Canadian outpatient physicians from 2007-2013. Diagnosis and antibiotic prescription data for ARS were extracted from the Canadian Disease and Therapeutic Index for 2007 to 2013, and population data were acquired from Statistics Canada. ARS diagnosis and antibiotic prescription rates and frequencies of antibiotic classes were calculated. Eighty-eight percent of patients diagnosed with ARS in 2013 were adults, with a greater rate of antibiotic prescriptions observed among the adults relative to the pediatric patients (1632.9 and 468.6 antibiotic prescriptions per 10,000 inhabitants). Between 2007 and 2013, the ARS diagnosis rate decreased from 596 to 464 diagnoses per 10,000 inhabitants, while the percentage of diagnoses with antibiotic prescriptions at the national level remained stable (87% to 84%). From 2007 to 2013, prescription rates for macrolides decreased from 203.5 to 105.4 prescriptions per 10,000 inhabitants. In 2013, penicillins with extended spectrum were more commonly prescribed compared to macrolides among adult patients (153.5 and 105.4 prescriptions per 10,000 inhabitants, respectively). This study is the first to describe physician antibiotic prescribing practices for treatment of ARS in Canada. Results show that antibiotic treatment for ARS represents an area for implementing antimicrobial stewardship, and through it, managing antibiotic resistance. Further work is required to better understand diagnosing practices and treatment criteria for ARS, and use this information to further assist physicians to limit unnecessary antibiotic prescribing practices.

Antibiotic prescriptions for outpatient acute rhinosinusitis in Canada, 2007-2013

PubMed Central

Weese, Scott; Glass-Kaastra, Shiona; McIsaac, Warren

2017-01-01

Introduction Acute rhinosinusitis (ARS) is a respiratory disease commonly caused by viral infections. Physicians regularly prescribe antibiotics despite bacterial etiologies being uncommon. This is of concern, as this use adds to the selection pressure for resistance. Here we present the descriptive epidemiology of acute rhinosinusitis and corresponding antibiotic prescribing practices by Canadian outpatient physicians from 2007–2013. Materials/Methods Diagnosis and antibiotic prescription data for ARS were extracted from the Canadian Disease and Therapeutic Index for 2007 to 2013, and population data were acquired from Statistics Canada. ARS diagnosis and antibiotic prescription rates and frequencies of antibiotic classes were calculated. Results Eighty-eight percent of patients diagnosed with ARS in 2013 were adults, with a greater rate of antibiotic prescriptions observed among the adults relative to the pediatric patients (1632.9 and 468.6 antibiotic prescriptions per 10,000 inhabitants). Between 2007 and 2013, the ARS diagnosis rate decreased from 596 to 464 diagnoses per 10,000 inhabitants, while the percentage of diagnoses with antibiotic prescriptions at the national level remained stable (87% to 84%). From 2007 to 2013, prescription rates for macrolides decreased from 203.5 to 105.4 prescriptions per 10,000 inhabitants. In 2013, penicillins with extended spectrum were more commonly prescribed compared to macrolides among adult patients (153.5 and 105.4 prescriptions per 10,000 inhabitants, respectively). Conclusion This study is the first to describe physician antibiotic prescribing practices for treatment of ARS in Canada. Results show that antibiotic treatment for ARS represents an area for implementing antimicrobial stewardship, and through it, managing antibiotic resistance. Further work is required to better understand diagnosing practices and treatment criteria for ARS, and use this information to further assist physicians to limit unnecessary antibiotic prescribing practices. PMID:28750020

Molecular characterization and antibiotic resistance of clinical Streptococcus dysgalactiae subsp. equisimilis in Beijing, China.

PubMed

Lu, Binghuai; Fang, Yujie; Huang, Lei; Diao, Baowei; Du, Xiaoli; Kan, Biao; Cui, Yanchao; Zhu, Fengxia; Li, Dong; Wang, Duochun

2016-06-01

Streptococcus dysgalactiae subsp. equisimilis (SDSE) is presently considered as a human pathogen associated with clinical infection. We characterized 56 SDSE isolates collected from two tertiary hospitals in Beijing, China. Sixteen distinct emm types/subtypes were detected, dominated by stG245.0 (32.1%), stG652.0 (10.7%), stG6.1 (10.7%) and stG485.0 (10.7%), and a novel stG840.0 variant type was identified. All isolates possessed virulence genes of sagA and scpA, and most carried slo (98.2%), ska (98.2%) and speG(dys) (35.7%). By multilocus sequence typing (MLST) analysis, 17 individual sequence types (STs) were distinguished, including 7 newly-identified STs (26.8% of isolates), of which ST127 (30.4%), ST7 (12.5%) and ST44 (10.7%) dominated. Meanwhile, pulsed-field gel electrophoresis (PFGE) analysis revealed 33 pattern types (PTs), which were further combined into 16 pattern clusters (PCs), and 59.3% of isolates were distributed into 2 dominant PCs. Notably, emm types had both close relationship and consistency with STs and PFGE PCs. Furthermore, of 56 SDSE isolates, the predominant antibiotic resistances were erythromycin (71.4%), clindamycin (71.4%) and tetracycline (60.7%). Correspondingly, the prevalent resistance genes of macrolide and tetracycline were erm(B) (78.6%) and tet(M) (73.2%). In addition, multiple point mutations of parC, one of fluoroquinolone resistance genes, were observed (accounting for 75%), and were divided into 12 types, with parC 07 as the predominant type. Our data suggested the wide molecular diversity and distinctive regional features of SDSE from clinical infection in Beijing, China. Copyright © 2016 Elsevier B.V. All rights reserved.

Antimicrobial Use and Indication-based Prescribing Among General Practitioners in Eastern Croatia: Comparison with Data from the European Surveillance of Antimicrobial Consumption Project

PubMed Central

Vojvodić, Željko

2010-01-01

Aim To investigate antibiotic consumption in a sample of physicians from Osijek-Baranja county in Eastern Croatia and to determine the volume of prescribed antimicrobials and assess the appropriateness of prescribing practices. Methods Analysis of routine prescribing data was carried out in 30 primary care practices in both urban and rural communities of eastern Croatia, corresponding to a total population of 48 000 patients. Prescribing practices were studied over a period of 3 years, from 2003 to 2005. Both the quantity of antimicrobials and differences and similarities between individual practitioners were analyzed. Results Urban and rural practices did not significantly differ in regard to the volume of antimicrobials prescribed. However, significant differences were found between individual physicians. Total consumption was 17.73 defined daily doses per 1000 inhabitants per day or 6456.85 defined daily doses per 1000 inhabitants per year. The 10 most frequently used antimicrobials (93.70% of the total quantity) were amoxicillin, co-amoxiclav, co-trimoxazole, cephalexin, norfloxacin, penicillin V, azithromycin, cefuroxime, doxycycline, and nitrofurantoin. Sore throat was the most frequent reason for prescribing antibiotics. Conclusion Prescription of medicines in Osijek-Baranja county was characterized by high consumption of broad-spectrum penicillins, combined penicillins, combined sulfonamides and long-acting macrolides (azithromycin), together with disproportionately low use of doxycycline and erythromycin. The use of combined sulfonamides and azithromycin in this part of Croatia was among the highest in Europe. Great differences between prescribers in regard to indication-based prescribing have been found, and future studies should examine the factors behind these heterogeneous practices. PMID:21162165

Trends in antibiotic utilization in eight Latin American countries, 1997-2007.

PubMed

Wirtz, Veronika J; Dreser, Anahí; Gonzales, Ralph

2010-03-01

To describe the trends in antibiotic utilization in eight Latin American countries between 1997-2007 We analyzed retail sales data of oral and injectable antibiotics (World Health Organization (WHO) Anatomic Therapeutic Chemical (ATC) code J01) between 1997 and 2007 for Argentina, Brazil, Chile, Colombia, Mexico, Peru, Uruguay, and Venezuela. Antibiotics were aggregated and utilization was calculated for all antibiotics (J01); for macrolides, lincosamindes, and streptogramins (J01 F); and for quinolones (J01 M). The kilogram sales of each antibiotic were converted into defined daily dose per 1 000 inhabitants per day (DID) according to the WHO ATC classification system. We calculated the absolute change in DID and relative change expressed in percent of DID variation, using 1997 as a reference Total antibiotic utilization has increased in Peru, Venezuela, Uruguay, and Brazil, with the largest relative increases observed in Peru (5.58 DID, +70.6%) and Venezuela (4.81 DID, +43.0%). For Mexico (-2.43 DID; -15.5%) and Colombia (-4.10; -33.7%), utilization decreased. Argentina and Chile showed major reductions in antibiotic utilization during the middle of this period. In all countries, quinolone use increased, particularly sharply in Venezuela (1.86 DID, +282%). The increase in macrolide, lincosaminde, and streptogramin use was greatest in Peru (0.76 DID, +82.1%), followed by Brazil, Argentina, and Chile Analyzing antibiotic utilization in Latin America presents a series of challenges. Creating policy-relevant evidence based on antimicrobial consumption patterns is needed in order to foster policies aimed at improving appropriate use of antibiotics in the region.

Simultaneous Gram and viability staining on activated sludge exposed to erythromycin: 3D CLSM time-lapse imaging of bacterial disintegration.

PubMed

Louvet, Jean-Noël; Attik, Ghania; Dumas, Dominique; Potier, Olivier; Pons, Marie-Noëlle

2011-11-01

The effect of erythromycin on activated sludge bacteria according to their Gram type was investigated with 3-dimensional Confocal Laser Scanning Microscopy (CLSM) time-lapse imaging. The fluorescent stains SYTOX Green and Texas Red-X conjugate of wheat germ agglutinin stained dying bacteria and Gram(+) bacteria respectively. Time-lapse imaging allowed an understanding of the staining mechanism and the measurement of the death rate. In presence of erythromycin (10mg/L), Gram(+) bacteria had a higher mortality rate than the Gram(-) bacteria. This result suggests that antibiotic in wastewater could change the activated sludge bacteria composition, according to their Gram type by selecting the bacteria which are the least sensitive to the antibiotics. However bacterial death was followed by bacterial disintegration leading to a decrease in the fluorescence. Results suggested that the viability indicators based on membrane integrity should be used with a correct sampling method, which can give the initial quantity of living bacteria. Copyright © 2011 Elsevier GmbH. All rights reserved.

The transport of antibiotic resistance genes and residues in groundwater near swine production facilities

NASA Astrophysics Data System (ADS)

Lin, Y. F.; Yannarell, A. C.; Mackie, R. I.; Krapac, I. G.; Chee-Sanford, J. S.; Koike, S.

2008-12-01

The use of antibiotics at concentrated animal feeding operations (CAFOs) for disease prevention, disease treatment, and growth promotion can contribute to the spread of antibiotic compounds, their breakdown products, and antibiotic resistant bacteria and/or the genes that confer resistance. In addition, constitutive use of antibiotics at sub-therapeutic levels can select for antibiotic resistance among the bacteria that inhabit animal intestinal tracts, onsite manure treatment facilities, and any environments receiving significant inputs of manure (e.g. through waste lagoon leakage or fertilizer amendments to farm soils). If the antibiotic resistant organisms persist in these new environments, or if they participate in genetic exchanges with the native microflora, then CAFOs may constitute a significant reservoir for the spread of antibiotic resistance to the environment at large. Our results have demonstrated that leakage from waste treatment lagoons can influence the presence and persistence of tetracycline resistance genes in the shallow aquifer adjacent to swine CAFOs, and molecular phylogeny allowed us to distinguish "native" tetracycline resistance genes in control groundwater wells from manure-associated genes introduced from the lagoon. We have also been able to detect the presence of erythromycin resistance genes in CAFO surface and groundwater even though erythromycin is strictly reserved for use in humans and thus is not utilized at any of these sites. Ongoing research, including modeling of particle transport in groundwater, will help to determine the potential spatial and temporal extent of CAFO-derived antibiotic resistance.

Multiplex PCR To Identify Macrolide Resistance Determinants in Mannheimia haemolytica and Pasteurella multocida

PubMed Central

Rose, Simon; Desmolaize, Benoit; Jaju, Puneet; Wilhelm, Cornelia; Warrass, Ralf

2012-01-01

The bacterial pathogens Mannheimia haemolytica and Pasteurella multocida are major etiological agents in respiratory tract infections of cattle. Although these infections can generally be successfully treated with veterinary macrolide antibiotics, a few recent isolates have shown resistance to these drugs. Macrolide resistance in members of the family Pasteurellaceae is conferred by combinations of at least three genes: erm(42), which encodes a monomethyltransferase and confers a type I MLSB (macrolide, lincosamide, and streptogramin B) phenotype; msr(E), which encodes a macrolide efflux pump; and mph(E), which encodes a macrolide-inactivating phosphotransferase. Here, we describe a multiplex PCR assay that detects the presence of erm(42), msr(E), and mph(E) and differentiates between these genes. In addition, the assay distinguishes P. multocida from M. haemolytica by amplifying distinctive fragments of the 23S rRNA (rrl) genes. One rrl fragment acts as a general indicator of gammaproteobacterial species and confirms whether the PCR assay has functioned as intended on strains that are negative for erm(42), msr(E), and mph(E). The multiplex system has been tested on more than 40 selected isolates of P. multocida and M. haemolytica and correlated with MICs for the veterinary macrolides tulathromycin and tilmicosin, and the newer compounds gamithromycin and tildipirosin. The multiplex PCR system gives a rapid and robustly accurate determination of macrolide resistance genotypes and bacterial genus, matching results from microbiological methods and whole-genome sequencing. PMID:22564832

NOVEL ANTIBIOTIC RESISTANCE DETERMINANTS FROM AGRICULTURAL SOIL EXPOSED TO ANTIBIOTICS WIDELY USED IN HUMAN MEDICINE AND ANIMAL FARMING.

PubMed

Lau, Calvin Ho-Fung; van Engelen, Kalene; Gordon, Stephen; Renaud, Justin; Topp, Edward

2017-06-16

Antibiotic resistance has emerged globally as one of the biggest threats to human and animal health. Although the excessive use of antibiotics is recognized for accelerating the selection for resistance, there is a growing body of evidence suggesting that natural environments are "hotspots" for the development of both ancient and contemporary resistance mechanisms. Given that pharmaceuticals can be entrained onto agricultural land through anthropogenic activities, this could be a potential driver for the emergence and dissemination of resistance in soil bacteria. Using functional metagenomics, we interrogated the "resistome" of bacterial communities found in a collection of Canadian agricultural soil, some of which had been receiving antibiotics widely used in human medicine (macrolides) or food animal production (sulfamethazine, chlortetracycline and tylosin) for up to 16 years. Of the 34 new antibiotic resistance genes (ARGs) recovered, the majority were predicted to encode for (multi)drug efflux systems, while a few share little to no homology with established resistance determinants. We characterized several novel gene products, including putative enzymes that can confer high-level resistance against aminoglycosides, sulfonamides, and broad range of beta-lactams, with respect to their resistance mechanisms and clinical significance. By coupling high-resolution proteomics analysis with functional metagenomics, we discovered an unusual peptide, PPP AZI 4 , encoded within an alternative open-reading frame not predicted by bioinformatics tools. Expression of the proline-rich PPP AZI 4 can promote resistance against different macrolides but not other ribosomal-targeting antibiotics, implicating a new macrolide-specific resistance mechanism that could be fundamentally linked to the evolutionary design of this peptide. IMPORTANCE Antibiotic resistance is a clinical phenomenon with an evolutionary link to the microbial pangenome. Genes and protogenes encoding for specialized and potential resistance mechanisms are abundant in natural environments, but understanding of their identity and genomic context remain limited. Our discovery of several previously-unknown antibiotic resistance genes from uncultured soil microorganisms indicates that soil is a significant reservoir of resistance determinants, which, once acquired and "re-purposed" by pathogenic bacteria, can have serious impacts on therapeutic outcomes. This study provides valuable insights into the diversity and identity of resistance within the soil microbiome. The finding of a novel peptide-mediated resistance mechanism involving an unpredicted gene product also highlights the usefulness of integrating proteomics analysis into metagenomics-driven gene discovery. © Crown copyright 2017.

Vaginal dysbiosis increases risk of preterm fetal membrane rupture, neonatal sepsis and is exacerbated by erythromycin.

PubMed

Brown, Richard G; Marchesi, Julian R; Lee, Yun S; Smith, Ann; Lehne, Benjamin; Kindinger, Lindsay M; Terzidou, Vasso; Holmes, Elaine; Nicholson, Jeremy K; Bennett, Phillip R; MacIntyre, David A

2018-01-24

Preterm prelabour rupture of the fetal membranes (PPROM) precedes 30% of preterm births and is a risk factor for early onset neonatal sepsis. As PPROM is strongly associated with ascending vaginal infection, prophylactic antibiotics are widely used. The evolution of vaginal microbiota compositions associated with PPROM and the impact of antibiotics on bacterial compositions are unknown. We prospectively assessed vaginal microbiota prior to and following PPROM using MiSeq-based sequencing of 16S rRNA gene amplicons and examined the impact of erythromycin prophylaxis on bacterial load and community structures. In contrast to pregnancies delivering at term, vaginal dysbiosis characterised by Lactobacillus spp. depletion was present prior to the rupture of fetal membranes in approximately a third of cases (0% vs. 27%, P = 0.026) and persisted following membrane rupture (31%, P = 0.005). Vaginal dysbiosis was exacerbated by erythromycin treatment (47%, P = 0.00009) particularly in women initially colonised by Lactobacillus spp. Lactobacillus depletion and increased relative abundance of Sneathia spp. were associated with subsequent funisitis and early onset neonatal sepsis. Our data show that vaginal microbiota composition is a risk factor for subsequent PPROM and is associated with adverse short-term maternal and neonatal outcomes. This highlights vaginal microbiota as a potentially modifiable antenatal risk factor for PPROM and suggests that routine use of erythromycin for PPROM be re-examined.

Antibiotic and heavy metal resistance in enterococci from coastal marine sediment.

PubMed

Vignaroli, Carla; Pasquaroli, Sonia; Citterio, Barbara; Di Cesare, Andrea; Mangiaterra, Gianmarco; Fattorini, Daniele; Biavasco, Francesca

2018-06-01

Sediment samples from three coastal sites - two beach resorts (Beach 1 and Beach 2 sites) and an area lying between an oil refinery and a river estuary (Estuarine site) - were analyzed for antibiotic- and heavy metal (HM)-resistant enterococci. A total of 123 enterococci, 36 E. faecium, 34 E. casseliflavus, 33 E. hirae, 5 E. faecalis, 3 E. durans, 3 E. gallinarum, and 9 Enterococcus spp, were recovered. Strains resistant to erythromycin, tetracycline and quinupristin/dalfopristin (Q/D) were recovered from all sites, whereas multidrug-resistant isolates were recovered only from "Beach 2" (14%) and "Estuarine" (3.7%). As regards HM resistance, the strains showed a high frequency (68%) of cadmium and/or copper resistance and uniform susceptibility to mercury. The prevalence of cadmium-resistant strains was significantly higher among erythromycin-resistant than among erythromycin-susceptible strains. A significant association between cadmium or copper resistance and Q/D resistance was also observed at "Estuarine" site. The levels of the two HMs in sediment from all sites were fairly low, ranging from 0.070 to 0.126 μg/g, for cadmium and from 1.00 to 7.64 μg/g for copper. Mercury was always undetectable. These findings are consistent with reports that low HM concentrations may contribute to co-selection of antibiotic-resistant bacterial strains, including enterococci. Copyright © 2018 Elsevier Ltd. All rights reserved.

Changes in Enterococcal Populations and Related Antibiotic Resistance along a Medical Center-Wastewater Treatment Plant-River Continuum

PubMed Central

Oberlé, Kenny; Galopin, Sébastien; Cattoir, Vincent; Budzinski, Hélène; Petit, Fabienne

2013-01-01

To determine if hospital effluent input has an ecological impact on downstream aquatic environment, antibiotic resistance in Enterococcus spp. along a medical center-retirement home-wastewater treatment plant-river continuum in France was determined using a culture-based method. Data on antibiotic consumption among hospitalized and general populations and levels of water contamination by antibiotics were collected. All isolated enterococci were genotypically identified to the species level, tested for in vitro antibiotic susceptibility, and typed by multilocus sequence typing. The erm(B) and mef(A) (macrolide resistance) and tet(M) (tetracycline resistance) genes were detected by PCR. Along the continuum, from 89 to 98% of enterococci, according to the sampled site, were identified as Enterococcus faecium. All E. faecium isolates from hospital and retirement home effluents were multiply resistant to antibiotics, contained erm(B) and mef(A) genes, and belonged to hospital-adapted clonal complex 17 (CC17). Even though this species remained dominant in the downstream continuum, the relative proportion of CC17 isolates progressively decreased in favor of other subpopulations of E. faecium that were more diverse, less resistant to antibiotics, and devoid of the classical macrolide resistance genes and that belonged to various sequence types. Antibiotic concentrations in waters were far below the MICs for susceptible isolates. CC17 E. faecium was probably selected in the gastrointestinal tract of patients under the pressure of administered antibiotics and then excreted together with the resistance genes in waters to progressively decrease along the continuum. PMID:23377946

Reduction in outpatient antibiotic sales for pre-school children: interrupted time series analysis of weekly antibiotic sales data in Sweden 1992-2002.

PubMed

Högberg, Liselotte; Oke, Thimothy; Geli, Patricia; Lundborg, Cecilia Stålsby; Cars, Otto; Ekdahl, Karl

2005-07-01

The aim of this study was to use detailed weekly data on outpatient antibiotic sales for pre-school children in Sweden to test for the significance of trends during 1992-2002. We also report on the special features found in weekly antibiotic data, and how the interrupted time series (ITS) design can adjust for this. Weekly data on the total number of dispensed outpatient antibiotic prescriptions to pre-school children were studied, as well as the individual subgroups commonly used to treat respiratory tract infections in children: narrow-spectrum penicillins, broad-spectrum penicillins and macrolides. In parallel, monthly data of paracetamol sales of paediatric dosages were analysed to reflect trends in symptomatic treatment. An ITS model controlling for seasonality and autocorrelation was used to examine the datasets for significant level and trend shifts. A significant increase in mean and change in level could be found in the total antibiotic data in 1997, also reflected in broad-spectrum penicillin data where a similar trend break occurred in 1996. For macrolides, a trend break with a decrease in mean was noted in 1996, but no trend breaks were found in narrow-spectrum penicillin data. In contrast to the general decreasing trends in antibiotic sales, the yearly over-the-counter sales of paracetamol in paediatric preparations increased during the same period, with no identified trend breaks. The overall decrease in antibiotic sales and increase in paediatric paracetamol sales might suggest that symptomatic treatment in the home has increased, as antibiotics are less commonly prescribed.

Trends and patterns of antibiotic consumption in Shanghai municipality, China: a 6 year surveillance with sales records, 2009-14.

PubMed

Lin, Hai; Dyar, Oliver James; Rosales-Klintz, Senia; Zhang, Jianzhong; Tomson, Göran; Hao, Mo; Stålsby Lundborg, Cecilia

2016-06-01

The objective of this study was to identify the trends and patterns of total antibiotic use in Shanghai from 2009 to 2014. Sales records were collected from a minimum of 160 hospitals and 241 primary healthcare settings and used as a proxy for consumption. Antibiotic sales expressed in DDD per 1000 inhabitants per day (DID) were calculated. We compared patterns of antibiotic use in the Shanghai municipality, populated by 24 million inhabitants, with European countries using indicators from the European Surveillance of Antimicrobial Consumption (ESAC). Total antibiotic use was highest at 25.9 DID in 2010, fell to 17.8 DID in 2012 and remained stable thereafter. The majority of this reduction occurred over 6 months in 2011. In 2014, two-thirds of the antibiotic sales were to hospitals (serving both inpatients and outpatients) and one-third to primary healthcare institutions. Cephalosporins accounted for 50.2% of total DID, followed by macrolides (18.2%), quinolones (16.0%) and penicillins (7.3%). A fifth of all antibiotics were used in parenteral form. We have successfully used aggregated sales data to monitor antibiotic usage across a large urban population over a 6 year period. A rapid, substantial and sustained reduction in antibiotic usage across the entire health system occurred. This coincided with several interventions across hierarchies in the health sector, including a national campaign. The patterns of antibiotic use indicate persistent preferences for cephalosporins, macrolides, quinolones and parenteral preparations. Further efforts are needed to investigate and improve the quality of antibiotic use. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Temporal relationship between antibiotic use and respiratory virus activities in the Republic of Korea: a time-series analysis.

PubMed

Ryu, Sukhyun; Kim, Sojung; Kim, Bryan I; Klein, Eili Y; Yoon, Young Kyung; Chun, Byung Chul

2018-01-01

Inappropriate use of antibiotics increases resistance and reduces their effectiveness. Despite evidence-based guidelines, antibiotics are still commonly used to treat infections likely caused by respiratory viruses. In this study, we examined the temporal relationships between antibiotic usage and respiratory infections in the Republic of Korea. The number of monthly antibiotic prescriptions and the incidence of acute respiratory tract infections between 2010 and 2015 at all primary care clinics were obtained from the Korean Health Insurance Review and Assessment Service. The monthly detection rates of respiratory viruses, including adenovirus, respiratory syncytial virus, influenza virus, human coronavirus, and human rhinovirus, were collected from Korea Centers for Disease Control and Prevention. Cross-correlation analysis was conducted to quantify the temporal relationship between antibiotic use and respiratory virus activities as well as respiratory infections in primary clinics. The monthly use of different classes of antibiotic, including penicillins, other beta-lactam antibacterials, macrolides and quinolones, was significantly correlated with influenza virus activity. These correlations peaked at the 0-month lag with cross-correlation coefficients of 0.45 ( p  < 0.01), 0.46 ( p  < 0.01), 0.40 ( p  < 0.01), and 0.35 (< 0.01), respectively. Furthermore, a significant correlation was found between acute bronchitis and antibiotics, including penicillin (0.73, p  < 0.01), macrolides (0.74, p  < 0.01), and quinolones (0.45, p  < 0.01), at the 0-month lag. Our findings suggest that there is a significant temporal relationship between influenza virus activity and antibiotic use in primary clinics. This relationship indicates that interventions aimed at reducing influenza cases in addition to effort to discourage the prescription of antibiotics by physicians may help to decrease unnecessary antibiotic consumption.

Decline in extractable antibiotics in manure-based composts during composting.

PubMed

Kim, K-R; Owens, G; Ok, Y S; Park, W-K; Lee, D B; Kwon, S-I

2012-01-01

A wide variety of antibiotics have been detected in natural water samples and this is of potential concern because of the adverse environmental effects of such antibiotic residues. One of the main sources of antibiotics effluence to the surrounding environment is livestock manures which often contain elevated concentrations of veterinary antibiotics (VAs) which survive digestion in the animal stomach following application in animal husbandry practices. In Korea, livestock manures are normally used for compost production indicating that there is potential for antibiotic release to the environment through compost application to agricultural lands. Therefore, reduction of the amount of VAs in composts is crucial. The purpose of this study was to understand the influence of the composting process and the components of the compost on the levels of three common classes of antibiotics (tetracyclines, sulfonamides, and macrolides). Composted materials at different stages of composting were collected from compost manufacturing plants and the variation in antibiotic concentrations was determined. Three different antibiotics, chlortetracycline (CTC), sulfamethazine (SMZ), and tylosin (TYL) at three different concentrations (2, 10, and 20mgkg(-1)) were also applied to a mixture of pig manure and sawdust and the mixtures incubated using a laboratory scale composting apparatus to monitor the changes in antibiotic concentrations during composting together with the physicochemical properties of the composts. During composting, in both field and lab-scale investigations, the concentrations of all three different antibiotics declined below the relevant Korean guideline values (0.8mgkg(-1) for tetracyclines, 0.2mgkg(-1) for sulfonamides and 1.0mgkg(-1) for macrolides). The decline of tetracycline and sulfonamide concentrations was highly dependent on the presence of sawdust while there was no influence of sawdust on TYL decline. Copyright © 2011 Elsevier Ltd. All rights reserved.

Use of microbial cultures and antibiotics in the prevention of infection-associated preterm birth.

PubMed

Klein, Laura L; Gibbs, Ronald S

2004-06-01

The purpose of this study was to summarize recent evidence regarding infection-associated preterm birth and to make appropriate recommendations. Antepartum treatment of lower genital tract infection or bacterial colonization has been found to reduce the incidence of preterm birth in the case of asymptomatic bacteriuria and bacterial vaginosis in selected patients but has been proved to be ineffective for vaginal colonization with organisms such as Ureaplasma urealyticum and group B streptococcus. This is a clinical opinion based on a review of recent data related to 1) the association between lower genital tract infection and preterm birth and 2) antibiotic trials to prevent preterm birth. Antepartum treatment of lower genital tract infection or bacterial colonization has been found to reduce the incidence of preterm birth in the case of asymptomatic bacteriuria and bacterial vaginosis in selected patients, but has been proven to be ineffective for vaginal colonization with organisms such as Ureaplasma urealyticum and group B streptococcus. Large well-designed trials have shown that the routine administration of antibiotics to women with preterm labor and intact membranes is not beneficial; however, antibiotic regimens including macrolides are recommended for preterm premature rupture of the membranes. Large well-designed trials have shown that the routine administration of antibiotics to women with preterm labor and intact membranes is not beneficial; however, antibiotic regimens that include macrolides are recommended for preterm premature rupture of the membranes.

Antibiotics for the treatment of rheumatoid arthritis

PubMed Central

Ogrendik, Mesut

2014-01-01

Antibiotic treatment for rheumatoid arthritis (RA) commenced in the 1930s with the use of sulfasalazine. Later, tetracyclines were successfully used for the treatment of RA. In double-blind and randomized studies, levofloxacin and macrolide antibiotics (including clarithromycin and roxithromycin) were also shown to be effective in the treatment of RA. There have been several reports in the literature indicating that periodontal pathogens are a possible cause of RA. Oral bacteria are one possible cause of RA. In this review, we aimed to investigate the effects of different antibiotics in RA treatment. PMID:24403843

Impact of Intermittent Preventive Treatment in Pregnancy with Azithromycin-Containing Regimens on Maternal Nasopharyngeal Carriage and Antibiotic Sensitivity of Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus: a Cross-Sectional Survey at Delivery

PubMed Central

Unger, Holger W.; Aho, Celestine; Ome-Kaius, Maria; Wangnapi, Regina A.; Umbers, Alexandra J.; Jack, Wanda; Lafana, Alice; Michael, Audrey; Hanieh, Sarah; Siba, Peter; Mueller, Ivo; Greenhill, Andrew R.

2015-01-01

Sulfadoxine-pyrimethamine (SP) plus azithromycin (AZ) (SPAZ) has the potential for intermittent preventive treatment of malaria in pregnancy (IPTp), but its use could increase circulation of antibiotic-resistant bacteria associated with severe pediatric infections. We evaluated the effect of monthly SPAZ-IPTp compared to a single course of SP plus chloroquine (SPCQ) on maternal nasopharyngeal carriage and antibiotic susceptibility of Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus at delivery among 854 women participating in a randomized controlled trial in Papua New Guinea. Serotyping was performed, and antibiotic susceptibility was evaluated by disk diffusion and Etest. Potential risk factors for carriage were examined. Nasopharyngeal carriage at delivery of S. pneumoniae (SPAZ, 7.2% [30/418], versus SPCQ, 19.3% [84/436]; P < 0.001) and H. influenzae (2.9% [12/418] versus 6.0% [26/436], P = 0.028), but not S. aureus, was significantly reduced among women who had received SPAZ-IPTp. The number of macrolide-resistant pneumococcal isolates was small but increased in the SPAZ group (13.3% [4/30], versus SPCQ, 2.2% [2/91]; P = 0.033). The proportions of isolates with serotypes covered by the 13-valent pneumococcal conjugate vaccine were similar (SPAZ, 10.3% [3/29], versus SPCQ, 17.6% [16/91]; P = 0.352). Although macrolide-resistant isolates were rare, they were more commonly detected in women who had received SPAZ-IPTp, despite the significant reduction of maternal carriage of S. pneumoniae and H. influenzae observed in this group. Future studies on SPAZ-IPTp should evaluate carriage and persistence of macrolide-resistant S. pneumoniae and other pathogenic bacteria in both mothers and infants and assess the clinical significance of their circulation. PMID:25673788

Chemoenzymatic Total Synthesis and Structural Diversification of Tylactone-Based Macrolide Antibiotics through Late-Stage Polyketide Assembly, Tailoring, and C-H Functionalization.

PubMed

Lowell, Andrew N; DeMars, Matthew D; Slocum, Samuel T; Yu, Fengan; Anand, Krithika; Chemler, Joseph A; Korakavi, Nisha; Priessnitz, Jennifer K; Park, Sung Ryeol; Koch, Aaron A; Schultz, Pamela J; Sherman, David H

2017-06-14

Polyketide synthases (PKSs) represent a powerful catalytic platform capable of effecting multiple carbon-carbon bond forming reactions and oxidation state adjustments. We explored the functionality of two terminal PKS modules that produce the 16-membered tylosin macrocycle, using them as biocatalysts in the chemoenzymatic synthesis of tylactone and its subsequent elaboration to complete the first total synthesis of the juvenimicin, M-4365, and rosamicin classes of macrolide antibiotics via late-stage diversification. Synthetic chemistry was employed to generate the tylactone hexaketide chain elongation intermediate that was accepted by the juvenimicin (Juv) ketosynthase of the penultimate JuvEIV PKS module. The hexaketide is processed through two complete modules (JuvEIV and JuvEV) in vitro, which catalyze elongation and functionalization of two ketide units followed by cyclization of the resulting octaketide into tylactone. After macrolactonization, a combination of in vivo glycosylation, selective in vitro cytochrome P450-mediated oxidation, and chemical oxidation was used to complete the scalable construction of a series of macrolide natural products in as few as 15 linear steps (21 total) with an overall yield of 4.6%.

Phenotypic and Genotypic Antimicrobial Resistance Profiles of Campylobacter jejuni Isolated from Cattle, Sheep, and Free-Range Poultry Faeces

PubMed Central

Oporto, Beatriz; Juste, Ramón A.; Hurtado, Ana

2009-01-01

Minimum inhibitory concentrations (MIC) of 13 antimicrobial agents were determined by broth microdilution for 72 Campylobacter jejuni strains from livestock. Twenty-three (31.9%) isolates were fully susceptible; all isolates were susceptible to erythromycin, chloramphenicol, streptomycin, gentamicin, sulfamethoxazole, and meropenem, and all but one to kanamycin. Resistance to quinolones was highest (52.8%), reaching similar values among poultry, dairy cattle, and sheep, but lower in beef cattle. Resistance to tetracyclines (48.6%) was mainly associated to dairy cattle and β-lactams (26.4%) to poultry. Multidrug resistance was mainly detected in dairy cattle (28.6%) and poultry (21.0%), whereas beef cattle had the highest percentage of fully susceptible isolates. Two real-time PCR assays to detect point mutations associated to quinolone (C257T in the gyrA gene) and macrolide (A2075G in the 23S rRNA genes) resistance were developed and validated on these strains. The analysis of a further set of 88 isolates by real-time PCR confirmed the absence of macrolide resistance and demonstrated the reproducibility and processability of the assay. PMID:20224816

Lactobacillus rhamnosus GG Intake Modifies Preschool Children's Intestinal Microbiota, Alleviates Penicillin-Associated Changes, and Reduces Antibiotic Use.

PubMed

Korpela, Katri; Salonen, Anne; Virta, Lauri J; Kumpu, Minna; Kekkonen, Riina A; de Vos, Willem M

2016-01-01

Antibiotic use is considered among the most severe causes of disturbance to children's developing intestinal microbiota, and frequently causes adverse gastrointestinal effects ranging from mild and transient diarrhoea to life-threatening infections. Probiotics are commonly advocated to help in preventing antibiotic-associated gastrointestinal symptoms. However, it is currently unknown whether probiotics alleviate the antibiotic-associated changes in children's microbiota. Furthermore, it is not known how long-term probiotic consumption influences the developing microbiota of children. We analysed the influence of long-term Lactobacillus rhamnosus GG intake on preschool children's antibiotic use, and antibiotic-associated gastrointestinal complaints in a double blind, randomized placebo-controlled trial with 231 children aged 2-7. In addition, we analysed the effect of L. rhanmosus GG on the intestinal microbiota in a subset of 88 children. The results show that long-term L. rhamnosus GG supplementation has an influence on the composition of the intestinal microbiota in children, causing an increase in the abundance of Prevotella, Lactococcus, and Ruminococcus, and a decrease in Escherichia. The treatment appeared to prevent some of the changes in the microbiota associated with penicillin use, but not those associated with macrolide use. The treatment, however, did reduce the frequency of gastrointestinal complaints after a macrolide course. Finally, the treatment appeared to prevent certain bacterial infections for up to 3 years after the trial, as indicated by reduced antibiotic use. ClinicalTrials.gov NCT01014676.

Lactobacillus rhamnosus GG Intake Modifies Preschool Children’s Intestinal Microbiota, Alleviates Penicillin-Associated Changes, and Reduces Antibiotic Use

PubMed Central

Korpela, Katri; Salonen, Anne; Virta, Lauri J.; Kumpu, Minna; Kekkonen, Riina A.; de Vos, Willem M.

2016-01-01

Antibiotic use is considered among the most severe causes of disturbance to children’s developing intestinal microbiota, and frequently causes adverse gastrointestinal effects ranging from mild and transient diarrhoea to life-threatening infections. Probiotics are commonly advocated to help in preventing antibiotic-associated gastrointestinal symptoms. However, it is currently unknown whether probiotics alleviate the antibiotic-associated changes in children’s microbiota. Furthermore, it is not known how long-term probiotic consumption influences the developing microbiota of children. We analysed the influence of long-term Lactobacillus rhamnosus GG intake on preschool children’s antibiotic use, and antibiotic-associated gastrointestinal complaints in a double blind, randomized placebo-controlled trial with 231 children aged 2–7. In addition, we analysed the effect of L. rhanmosus GG on the intestinal microbiota in a subset of 88 children. The results show that long-term L. rhamnosus GG supplementation has an influence on the composition of the intestinal microbiota in children, causing an increase in the abundance of Prevotella, Lactococcus, and Ruminococcus, and a decrease in Escherichia. The treatment appeared to prevent some of the changes in the microbiota associated with penicillin use, but not those associated with macrolide use. The treatment, however, did reduce the frequency of gastrointestinal complaints after a macrolide course. Finally, the treatment appeared to prevent certain bacterial infections for up to 3 years after the trial, as indicated by reduced antibiotic use. Trial Registration: ClinicalTrials.gov NCT01014676 PMID:27111772

Public health consequences of macrolide use in food animals: a deterministic risk assessment.

PubMed

Hurd, H Scott; Doores, Stephanie; Hayes, Dermot; Mathew, Alan; Maurer, John; Silley, Peter; Singer, Randall S; Jones, Ronald N

2004-05-01

The potential impact on human health from antibiotic-resistant bacteria selected by use of antibiotics in food animals has resulted in many reports and recommended actions. The U.S. Food and Drug Administration Center for Veterinary Medicine has issued Guidance Document 152, which advises veterinary drug sponsors of one potential process for conducting a qualitative risk assessment of drug use in food animals. Using this guideline, we developed a deterministic model to assess the risk from two macrolide antibiotics, tylosin and tilmicosin. The scope of modeling included all label claim uses of both macrolides in poultry, swine, and beef cattle. The Guidance Document was followed to define the hazard, which is illness (i) caused by foodborne bacteria with a resistance determinant, (ii) attributed to a specified animal-derived meat commodity, and (iii) treated with a human use drug of the same class. Risk was defined as the probability of this hazard combined with the consequence of treatment failure due to resistant Campylobacter spp. or Enterococcus faecium. A binomial event model was applied to estimate the annual risk for the U.S. general population. Parameters were derived from industry drug use surveys, scientific literature, medical guidelines, and government documents. This unique farm-to-patient risk assessment demonstrated that use of tylosin and tilmicosin in food animals presents a very low risk of human treatment failure, with an approximate annual probability of less than 1 in 10 million Campylobacter-derived and approximately 1 in 3 billion E. faecium-derived risk.

Broad-spectrum antibiotics for preterm, prelabour rupture of fetal membranes: the ORACLE I randomised trial. ORACLE Collaborative Group.

PubMed

Kenyon, S L; Taylor, D J; Tarnow-Mordi, W

2001-03-31

Preterm, prelabour rupture of the fetal membranes (pPROM) is the commonest antecedent of preterm birth, and can lead to death, neonatal disease, and long-term disability. Previous small trials of antibiotics for pPROM suggested some health benefits for the neonate, but the results were inconclusive. We did a randomised multicentre trial to try to resolve this issue. 4826 women with pPROM were randomly assigned 250 mg erythromycin (n=1197), 325 mg co-amoxiclav (250 mg amoxicillin plus 125 mg clavulanic acid; n=1212), both (n=1192), or placebo (n=1225) four times daily for 10 days or until delivery. The primary outcome measure was a composite of neonatal death, chronic lung disease, or major cerebral abnormality on ultrasonography before discharge from hospital. Analysis was by intention to treat. Two women were lost to follow-up, and there were 15 protocol violations. Among all 2415 infants born to women allocated erythromycin only or placebo, fewer had the primary composite outcome in the erythromycin group (151 of 1190 [12.7%] vs 186 of 1225 [15.2%], p=0.08) than in the placebo group. Among the 2260 singletons in this comparison, significantly fewer had the composite primary outcome in the erythromycin group (125 of 1111 [11.2%] vs 166 of 1149 [14.4%], p=0.02). Co-amoxiclav only and co-amoxiclav plus erythromycin had no benefit over placebo with regard to this outcome in all infants or in singletons only. Use of erythromycin was also associated with prolongation of pregnancy, reductions in neonatal treatment with surfactant, decreases in oxygen dependence at 28 days of age and older, fewer major cerebral abnormalities on ultrasonography before discharge, and fewer positive blood cultures. Although co-amoxiclav only and co-amoxiclav plus erythromycin were associated with prolongation of pregnancy, they were also associated with a significantly higher rate of neonatal necrotising enterocolitis. Erythromycin for women with pPROM is associated with a range of health benefits for the neonate, and thus a probable reduction in childhood disability. However, co-amoxiclav cannot be routinely recommended for pPROM because of its association with neonatal necrotising enterocolitis. A follow-up study of childhood development and disability after pPROM is planned.

The order of administration of macrolides and beta-lactams may impact the outcomes of hospitalized patients with community-acquired pneumonia: results from the community-acquired pneumonia organization.

PubMed

Peyrani, Paula; Wiemken, Timothy L; Metersky, Mark L; Arnold, Forest W; Mattingly, William A; Feldman, Charles; Cavallazzi, Rodrigo; Fernandez-Botran, Rafael; Bordon, Jose; Ramirez, Julio A

2018-01-01

The beneficial effect of macrolides for the treatment of community-acquired pneumonia (CAP) in combination with beta-lactams may be due to their anti-inflammatory activity. In patients with pneumococcal meningitis, the use of steroids improves outcomes only if they are administered before beta-lactams. The objective of this study was to compare outcomes in hospitalized patients with CAP when macrolides were administered before, simultaneously with, or after beta-lactams. Secondary data analysis of the Community-Acquired Pneumonia Organization (CAPO) International Cohort Study database. Study groups were defined based on the sequence of administration of macrolides and beta-lactams. The study outcomes were time to clinical stability (TCS), length of stay (LOS) and in-hospital mortality. Accelerated failure time models were used to evaluate the adjusted impact of sequential antibiotic administration and time-to-event outcomes, while a logistic regression model was used to evaluate their adjusted impact on mortality. A total of 99 patients were included in the macrolide before group and 305 in the macrolide after group. Administration of a macrolide before a beta-lactam compared to after a beta-lactam reduced TCS (3 vs. 4 days, p = .011), LOS (6 vs. 7 days, p = .002) and mortality (3 vs. 7.2%, p = .228). The administration of macrolides before beta-lactams was associated with a statistically significant decrease in TCS and LOS and a non-statistically significant decrease in mortality. The beneficial effect of macrolides in hospitalized patient with CAP may occur only if administered before beta-lactams.

Antimicrobial susceptibility and molecular characterization of macrolide resistance of Mycoplasma bovis isolates from multiple provinces in China

PubMed Central

KONG, Ling-Cong; GAO, Duo; JIA, Bo-Yan; WANG, Zi; GAO, Yun-Hang; PEI, Zhi-Hua; LIU, Shu-Ming; XIN, Jiu-Qing; MA, Hong-Xia

2015-01-01

Mycoplasma bovis has spread widely throughout the world via animal movement and has become an important pathogen of bovine respiratory disease. However, the minimum inhibitory concentrations of antimicrobials for Mycoplasma bovis have not been studied in China. The objective of this study was to determine the prevalence and antibiotic resistance of Mycoplasma bovis isolated from young cattle with respiratory infection in China. Mycoplasma bovis was detected in 32/45 bovine respiratory infection outbreaks at beef farms in 8 provinces in China. The isolates were susceptible or had medium sensitivity to ciprofloxacin, enrofloxacin and doxycycline, but were frequently resistant to macrolides (13/32, 41%). An A2058G (Escherichia coli Numbering) mutation located in the rrnA operon in domain V of 23S rRNA was observed in strains that were resistant to macrolides. This single mutations at the rrnA operon in domain V of 23S rRNA may play an important role in the resistance of Mycoplasma bovis strains to macrolides. PMID:26346744

Impairment of innate immune killing mechanisms by bacteriostatic antibiotics.

PubMed

Kristian, Sascha A; Timmer, Anjuli M; Liu, George Y; Lauth, Xavier; Sal-Man, Neta; Rosenfeld, Yosef; Shai, Yechiel; Gallo, Richard L; Nizet, Victor

2007-04-01

Antibiotics are designed to support host defense in controlling infection. Here we describe a paradoxical inhibitory effect of bacteriostatic antibiotics on key mediators of mammalian innate immunity. When growth of species including Escherichia coli and Staphylococcus aureus is suppressed by chloramphenicol or erythromycin, the susceptibility of the bacteria to cathelicidin antimicrobial peptides or serum complement was markedly diminished. Survival of the bacteria in human whole blood, human wound fluid, or a mouse wound infection model was in turn increased after antibiotic-induced bacteriostasis. These findings provide a further rationale against the indiscriminate use of antibiotics.

Genetic Basis and Clonal Population Structure of Antibiotic Resistance in Campylobacter jejuni Isolated From Broiler Carcasses in Belgium.

PubMed

Elhadidy, Mohamed; Miller, William G; Arguello, Hector; Álvarez-Ordóñez, Avelino; Duarte, Alexandra; Dierick, Katelijne; Botteldoorn, Nadine

2018-01-01

Human campylobacteriosis is the leading food-borne zoonosis in industrialized countries. This study characterized the clonal population structure, antimicrobial resistance profiles and occurrence of antimicrobial resistance determinants of a set of Campylobacter jejuni strains isolated from broiler carcasses in Belgium. Minimum inhibitory concentrations (MICs) against five commonly-used antibiotics (ciprofloxacin, nalidixic acid, tetracycline, gentamicin, and erythromycin) were determined for 204 C. jejuni isolates. More than half of the isolates were resistant to ciprofloxacin or nalidixic acid. In contrast, a lower percentage of screened isolates were resistant to gentamicin or erythromycin. C. jejuni isolates resistant to ciprofloxacin and/or nalidixic acid were screened for the substitution T86I in the quinolone resistance determining region (QRDR) of the gyrA gene, while C. jejuni isolates resistant to tetracycline were screened for the presence of the tet(O) gene. These resistance determinants were observed in most but not all resistant isolates. Regarding resistance to erythromycin, different mutations occurred in diverse genetic loci, including mutations in the 23S rRNA gene, the rplD and rplV ribosomal genes, and the intergenic region between cmeR and cmeABC . Interestingly, and contrary to previous reports, the A2075G transition mutation in the 23S rRNA gene was only found in one strain displaying a high level of resistance to erythromycin. Ultimately, molecular typing by multilocus sequence typing revealed that two sequence types (ST-824 and ST-2274) were associated to quinolones resistance by the presence of mutations in the gene gyrA ( p = 0.01). In addition, ST-2274 was linked to the CIP-NAL-TET-AMR multidrug resistant phenotype. In contrast, clonal complex CC-45 was linked to increased susceptibility to the tested antibiotics. The results obtained in this study provide better understanding of the phenotypic and the molecular basis of antibiotic resistance in C. jejuni , unraveling some the mechanisms which confer antimicrobial resistance and particular clones associated to the carriage and spread of resistance genes.

Erythromycin and penicillin resistance mechanisms among viridans group streptococci isolated from blood cultures of adult patients with underlying diseases.

PubMed

Ergin, Alper; Eser, Özgen Köseoğlu; Hasçelik, Gülşen

2011-04-01

The aim of the study was to evaluate the species distribution, antimicrobial susceptibility and erythromycin-penicillin resistance mechanisms of viridans streptococci (VGS) isolates from blood cultures of adult patients with underlying diseases. Fifty VGS blood culture isolates were screened for their antibiotic susceptibilities against penicillin G, erythromycin and tetracycline by E-test. Clindamycin, cefotaxime, chloramphenicol, levofloxacin, linezolid and vancomycin susceptibility were performed by broth microdilution method. Erythromycin and penicillin resistance genotypes, ermB and mefA/E, pbp1a, pbp2b and pbp2x are amplified using PCR method. The clinical isolates included Streptococcus mitis (n. 19), S.oralis (n. 13), S.sanguinis, S.parasanguinis (n. 6, each), S.salivarius, S.vestibularis (n. 2, each), S.constellatus, S.sobrinus (n. 1, each). The percentage resistance against erythromycin and penicillin was 36% and 30%, respectively. The genotypic carriage rate of erythromycin resistance genes were: 56% ermB, 28% mefE, 8% ermB+mefE. Penicillin-resistant isolates carried pbp2b (33.3%) and pbp2x (20%) genes. Twenty-four VGS isolates were recovered from patients with cancer. S.mitis and S.oralis predominated among patients with cancer who had erythromycin and penicillin resistance isolates. The importance of classical antimicrobial agents like penicillin and erythromycin warrants the continuous surveillance of invasive VGS isolates and can guide better treatment options especially in patients with underlying diseases.

Diversity and dynamics of antibiotic-resistant bacteria in cheese as determined by PCR denaturing gradient gel electrophoresis.

PubMed

Flórez, Ana Belén; Mayo, Baltasar

2015-12-02

This work reports the composition and succession of tetracycline- and erythromycin-resistant bacterial communities in a model cheese, monitored by polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE). Bacterial 16S rRNA genes were examined using this technique to detect structural changes in the cheese microbiota over manufacturing and ripening. Total bacterial genomic DNA, used as a template, was extracted from cultivable bacteria grown without and with tetracycline or erythromycin (both at 25 μg ml(-1)) on a non-selective medium used for enumeration of total and viable cells (Plate Count agar with Milk; PCA-M), and from those grown on selective and/or differential agar media used for counting various bacterial groups; i.e., lactic acid bacteria (de Man, Rogosa and Sharpe agar; MRSA), micrococci and staphylococci (Baird-Parker agar; BPA), and enterobacteria (Violet Red Bile Glucose agar; VRBGA). Large numbers of tetracycline- and erythromycin-resistant bacteria were detected in cheese samples at all stages of ripening. Counts of antibiotic-resistant bacteria varied widely depending on the microbial group and the point of sampling. In general, resistant bacteria were 0.5-1.0 Log10 units fewer in number than the corresponding susceptible bacteria. The PCR-DGGE profiles obtained with DNA isolated from the plates for total bacteria and the different bacterial groups suggested Escherichia coli, Lactococcus lactis, Enterococcus faecalis and Staphylococcus spp. as the microbial types resistant to both antibiotics tested. This study shows the suitability of the PCR-DGGE technique for rapidly identifying and tracking antibiotic resistant populations in cheese and, by extension, in other foods. Copyright © 2015 Elsevier B.V. All rights reserved.

Influence of subinhibitory antibiotic concentration on Streptococcus pyogenes adherence and biofilm production.

PubMed

Šmitran, Aleksandra; Vuković, Dragana; Opavski, Nataša; Gajić, Ina; Marinković, Jelena; Božić, Ljiljana; Živanović, Irena; Kekić, Dušan; Popović, Sunčica; Ranin, Lazar

2018-06-01

In this study, the focus was on the effects of sub-MICs of the antibiotics on adherence, hydrophobicity, and biofilm formation by two groups of Streptococcus pyogenes strains, which were responsible for different clinical cases. The aim of this study was to explore the effects of sub-MICs of penicillin, ceftriaxone, erythromycin, and clindamycin on adherence, surface hydrophobicity, and biofilm biomass in two selected collections of group A streptococcus (GAS): strains isolated from carriers (CA) and strains isolated from patients with tonsillopharyngitis (TPh). Isolates were tested for hydrophobicity to xylene, adherence, and biofilm production in uncoated microtiter plates before and after treatment with 1/2 and 1/4 MICs of antibiotics. Penicillin reduced adherence and biofilm production in TPh strains, whereas ceftriaxone diminished adherence and biofilm formation in CA group. On the contrary, clindamycin enhanced adherence and biofilm production in both groups of strains. Erythromycin did not significantly alter adherence, but triggered biofilm production in both groups of isolates. Hydrophobicity of both groups of strains was significantly reduced after exposure to all antibiotics. Beta-lactams displayed anti-biofilm activity; penicillin diminished both adherence and biofilm production in TPh strains, whereas ceftriaxone reduced it in strains isolated from CA.

Synergy between antibiotics and natural agents results in increased antimicrobial activity against Staphylococcus epidermidis.

PubMed

Abidi, Syed Hani; Ahmed, Khalid; Sherwani, Sikander Khan; Kazmi, Shahana Urooj

2015-09-27

Staphylococcus epidermidis is one of the most frequent causes of biofilm-associated infections on indwelling medical devices. With the emergence of methicillin-resistant S. epidermidis (MRSE), there is an urgent need to discover novel active agents against a range of Gram-positive pathogens. We screened the clinical isolates of S. epidermidis for susceptibility/resistance against commonly prescribed antibiotics. Furthermore, we tested some natural agents alone and in combination with antibiotics to find possible synergistic antimicrobial effects. S. epidermidis clinical isolates were screened for susceptibility/resistance against vancomycin, erythromycin, tetracycline, chloramphenicol, ampicillin, ofloxacin, cephalexin, and gentamicin using the Kirby-Bauer disk diffusion method. The antimicrobial potential of Camellia sinensis, Juglans regia, and Hippophae rhamnoides alone and in combination with antibiotics were examined using the disk diffusion method, where the antimicrobial potential activity was measured in terms of formation of zones of inhibition. Most S. epidermidis isolates were found to be resistant to one or more antibiotics. Gentamycin and ofloxacin were found to be the most effective antibiotics against S. epidermidis isolates. Extracts of Hippophae rhamnoides, Juglans regia, and Camellia sinensis were found to be equally effective against S. epidermidis isolates. In combination with antibiotics, these extracts exhibited appreciable synergistic activity; the highest synergistic activity was observed with erythromycin and cephalexin. In the case of cephalexin, a reversion in resistance was observed. The plant extracts used in the study exhibited additive and synergistic antibacterial activity against S. epidermidis, hence providing an effective alternative to deal with the problem of multidrug resistance.

Meta-analysis of antibiotics and the risk of community-associated Clostridium difficile infection.

PubMed

Brown, Kevin A; Khanafer, Nagham; Daneman, Nick; Fisman, David N

2013-05-01

The rising incidence of Clostridium difficile infection (CDI) could be reduced by lowering exposure to high-risk antibiotics. The objective of this study was to determine the association between antibiotic class and the risk of CDI in the community setting. The EMBASE and PubMed databases were queried without restriction to time period or language. Comparative observational studies and randomized controlled trials (RCTs) considering the impact of exposure to antibiotics on CDI risk among nonhospitalized populations were considered. We estimated pooled odds ratios (OR) for antibiotic classes using random-effect meta-analysis. Our search criteria identified 465 articles, of which 7 met inclusion criteria; all were observational studies. Five studies considered antibiotic risk relative to no antibiotic exposure: clindamycin (OR = 16.80; 95% confidence interval [95% CI], 7.48 to 37.76), fluoroquinolones (OR = 5.50; 95% CI, 4.26 to 7.11), and cephalosporins, monobactams, and carbapenems (CMCs) (OR = 5.68; 95% CI, 2.12 to 15.23) had the largest effects, while macrolides (OR = 2.65; 95% CI, 1.92 to 3.64), sulfonamides and trimethoprim (OR = 1.81; 95% CI, 1.34 to 2.43), and penicillins (OR = 2.71; 95% CI, 1.75 to 4.21) had lower associations with CDI. We noted no effect of tetracyclines on CDI risk (OR = 0.92; 95% CI, 0.61 to 1.40). In the community setting, there is substantial variation in the risk of CDI associated with different antimicrobial classes. Avoidance of high-risk antibiotics (such as clindamycin, CMCs, and fluoroquinolones) in favor of lower-risk antibiotics (such as penicillins, macrolides, and tetracyclines) may help reduce the incidence of CDI.

Trends in broad-spectrum antibiotic prescribing for children with acute otitis media in the United States, 1998–2004

PubMed Central

Coco, Andrew S; Horst, Michael A; Gambler, Angela S

2009-01-01

Background Overuse of broad-spectrum antibiotics is associated with antibiotic resistance. Acute otitis media (AOM) is responsible for a large proportion of antibiotics prescribed for US children. Rates of broad-spectrum antibiotic prescribing for AOM are unknown. Methods Analysis of the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, 1998 to 2004 (N = 6,878). Setting is office-based physicians, hospital outpatient departments, and emergency departments. Patients are children aged 12 years and younger prescribed antibiotics for acute otitis media. Main outcome measure is percentage of broad-spectrum antibiotics, defined as amoxicillin/clavulanate, macrolides, cephalosporins and quinolones. Results Broad-spectrum prescribing for acute otitis media increased from 34% of visits in 1998 to 45% of visits in 2004 (P < .001 for trend). The trend was primarily attributable to an increase in prescribing of amoxicillin/clavulanate (8% to 15%; P < .001 for trend) and macrolides (9% to 15%; P < .001 for trend). Prescribing remained stable for amoxicillin and cephalosporins while decreasing for narrow-spectrum agents (12% to 3%; P < .001 for trend) over the study period. Independent predictors of broad-spectrum antibiotic prescribing were ear pain, non-white race, public and other insurance (compared to private), hospital outpatient department setting, emergency department setting, and West region (compared to South and Midwest regions), each of which was associated with lower rates of broad-spectrum prescribing. Age and fever were not associated with prescribing choice. Conclusion Prescribing of broad-spectrum antibiotics for acute otitis media has steadily increased from 1998 to 2004. Associations with non-clinical factors suggest potential for improvement in prescribing practice. PMID:19552819

Application of silver ion in the separation of macrolide antibiotic components by high-speed counter-current chromatography.

PubMed

Wen, Yaoming; Wang, Jiaoyan; Chen, Xiuming; Le, Zhanxian; Chen, Yuxiang; Zheng, Wei

2009-05-29

Three macrolide antibiotic components - ascomycin, tacrolimus and dihydrotacrolimus - were separated and purified by silver ion high-speed counter-current chromatography (HSCCC). The solvent system consisted of n-hexane-tert-butyl methyl ether-methanol-water (1:3:6:5, v/v) and silver nitrate (0.10mol/l). The silver ion acted as a pi-complexing agent with tacrolimus because of its extra side double bond compared with ascomycin and dihydrotacrolimus. This complexation modified the partition coefficient values and the separation factors of the three components. As a result, ascomycin, tacrolimus and dihydrotacrolimus were purified from 150mg extracted crude sample with purities of 97.6%, 98.7% and 96.5%, respectively, and yields over 80% (including their tautomers). These results cannot be achieved with the same solvent system but without the addition of silver ion.

Antibiotic sensitivity pattern from pregnant women with urinary tract infection in Bangalore, India.

PubMed

Sibi, G; Kumari, Pinki; Kabungulundabungi, Neema

2014-09-01

To determine the antibacterial profile of pregnant women with urinaty tract infections and analyze the antibiotic sensitivity pattern for the effective treatment. A total of 395 urine samples from pregnant women with different gestational age were processed for the isolation of uropathogens and tested against eight groups of antibiotics namely penicillins, cephalosporins, fluoroquinolones, aminoglycosides, macrolides, lincosamides, glycopeptides and sulfonamides. A positive culture percentage of 46.6% was obtained with the highest urinary tract infection in third trimester gestational age. Among the uropathogens isolated, 85.6% were Gram negative and 14.4% were Gram positive with Escherichia coli as the predominant bacteria (43.9%) followed by Klebsiella oxytoca (19.4%) and Klebsiella pneumoniae (13.3%). Antibiotic sensitivity assay revealed that amikacin had the highest overall sensitivity (n=136; 76.7%) and the subsequent highest sensitivity was observed with ciprofloxacin (n=132; 73.3%), clindamycin (n=124; 68.9%), cefotaxime (n=117; 65%) and nalidixic acid (n=115; 63.9%). The findings revealed that uropathogens were more resistant to penicillins, macrolides and glycopeptides which restrict their use in treating urinaty tract infections during pregnancy. In conclusion, common causative bacteria and their antibiotic sensitivity pattern are to be determined along with their safety to mother and fetus for the effective treatment of urinary tract infections during pregnancy. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

3D assembly based on 2D structure of Cellulose Nanofibril/Graphene Oxide Hybrid Aerogel for Adsorptive Removal of Antibiotics in Water

PubMed Central

Yao, Qiufang; Fan, Bitao; Xiong, Ye; Jin, Chunde; Sun, Qingfeng; Sheng, Chengmin

2017-01-01

Cellulose nanofibril/graphene oxide hybrid (CNF/GO) aerogel was fabricated via a one-step ultrasonication method for adsorptive removal of 21 kinds of antibiotics in water. The as-prepared CNF/GO aerogel possesses interconnected 3D network microstructure, in which GO nanosheets with 2D structure were intimately grown along CNF through hydrogen bonds. The aerogel exhibited superior adsorption capacity toward the antibiotics. The removal percentages (R%) of the antibiotics were more than 69% and the sequence of six categories antibiotics according to the adsorption efficiency was as follows: Tetracyclines > Quinolones > Sulfonamides > Chloramphenicols > β-Lactams > Macrolides. The adsorption mechanism was proposed to be electrostatic attraction, p-π interaction, π-π interaction and hydrogen bonds. In detail, the adsorption capacities of CNF/GO aerogel were 418.7 mg·g−1 for chloramphenicol, 291.8 mg·g−1 for macrolides, 128.3 mg·g−1 for quinolones, 230.7 mg·g−1 for β-Lactams, 227.3 mg·g−1 for sulfonamides, and 454.6 mg·g−1 for tetracyclines calculated by the Langmuir isotherm models. Furthermore, the regenerated aerogels still could be repeatedly used after ten cycles without obvious degradation of adsorption performance. PMID:28368045

Mutations Associated with Decreased Susceptibility to Seven Antimicrobial Families in Field and Laboratory-Derived Mycoplasma bovis Strains.

PubMed

Sulyok, Kinga M; Kreizinger, Zsuzsa; Wehmann, Enikő; Lysnyansky, Inna; Bányai, Krisztián; Marton, Szilvia; Jerzsele, Ákos; Rónai, Zsuzsanna; Turcsányi, Ibolya; Makrai, László; Jánosi, Szilárd; Nagy, Sára Ágnes; Gyuranecz, Miklós

2017-02-01

The molecular mechanisms of resistance to fluoroquinolones, tetracyclines, an aminocyclitol, macrolides, a lincosamide, a phenicol, and pleuromutilins were investigated in Mycoplasma bovis For the identification of mutations responsible for the high MICs of certain antibiotics, whole-genome sequencing of 35 M. bovis field isolates and 36 laboratory-derived antibiotic-resistant mutants was performed. In vitro resistant mutants were selected by serial passages of M. bovis in broth medium containing subinhibitory concentrations of the antibiotics. Mutations associated with high fluoroquinolones MICs were found at positions 244 to 260 and at positions 232 to 250 (according to Escherichia coli numbering) of the quinolone resistance-determining regions of the gyrA and parC genes, respectively. Alterations related to elevated tetracycline MICs were described at positions 962 to 967, 1058, 1195, 1196, and 1199 of genes encoding the 16S rRNA and forming the primary tetracycline binding site. Single transversion at position 1192 of the rrs1 gene resulted in a spectinomycin MIC of 256 μg/ml. Mutations responsible for high macrolide, lincomycin, florfenicol, and pleuromutilin antibiotic MICs were identified in genes encoding 23S rRNA. Understanding antibiotic resistance mechanisms is an important tool for future developments of genetic-based diagnostic assays for the rapid detection of resistant M. bovis strains. Copyright © 2017 American Society for Microbiology.

[Urinary pneumococcal or Legionella antigen detection tests and low-spectrum antibiotic therapy for community-acquired pneumonia].

PubMed

Roger, P-M; Risso, K; Hyvernat, H; Landraud, L; Vassallo, M; Dellamonica, J; de Salvador, F; Cua, E; Bernardin, G

2010-06-01

We performed urinary antigen tests for pneumococcus and Legionella for patients with community-acquired pneumonia (CAP), to prescribe a documented antibiotic therapy. We report the efficiency of low-spectrum antibiotic treatment, illustrating the inappropriateness of bacteriological respiratory sampling. Patients with CAP were enrolled from three different units; the pneumonia severity index was used to assess the disease. Respiratory samples were also listed. Low-spectrum antibiotic therapy was amoxicillin for pneumococcal infection, and macrolides or non-anti-pneumococcal fluoroquinolone for legionellosis. Six hundred and seventy-five CAP were diagnosed during the study period,, 150 with positive urinary antigen tests (23%), among which 108 pneumococcal infections (73%), 40 legionellosis (26%), and two mixed infections. The pneumonia severity index was 106+/-38. Amoxicillin was prescribed in 108 cases, fluoroquinolone in 24 cases, macrolide in 18 cases. The outcome was favourable for 138 patients (92%). Eighty three respiratory samples allowed identification of a bacterium for 58 patients (39%), among which 24 strains were not in the antibiotic spectrum: Haemophilus influenzae and Pseudmomonas aeruginosa in six cases, Staphylococcus aureus in five cases, Klebsiella pneumoniae in two cases, and another Gram negative bacillus in five cases. These strains were resistant in vitro to the prescribed treatment in 19/24 cases (79%). One out of 12 patients who died had a respiratory sample positive for Enterobacter spp strain resistant to the ongoing antibiotic treatment. The low-spectrum antibiotic therapy based on urinary antigen tests is efficient, and demonstrates respiratory tract colonisation with bacteriological strains usually considered as pathogenic.

Antimicrobial Susceptibility of Bacillus Strains Isolated from Primary Starters for African Traditional Bread Production and Characterization of the Bacitracin Operon and Bacitracin Biosynthesis

PubMed Central

Sørensen, Kim I.; Thorsen, Line; Stuer-Lauridsen, Birgitte; Abdelgadir, Warda S.; Nielsen, Dennis S.; Derkx, Patrick M. F.; Jespersen, Lene

2012-01-01

Bacillus spp. are widely used as feed additives and probiotics. However, there is limited information on their resistance to various antibiotics, and there is a growing concern over the transfer of antibiotic resistance genes. The MIC for 8 antibiotics was determined for 85 Bacillus species strains, Bacillus subtilis subsp. subtilis (n = 29), Bacillus licheniformis (n = 38), and Bacillus sonorensis (n = 18), all of which were isolated from starters for Sudanese bread production. All the strains were sensitive to tetracycline (8.0 mg/liter), vancomycin (4.0 mg/liter), and gentamicin (4.0 mg/liter) but resistant to streptomycin. Sensitivity to clindamycin, chloramphenicol, and kanamycin was species specific. The erythromycin resistance genes ermD and ermK were detected by PCR in all of the erythromycin-resistant (MIC, ≥16.0 mg/liter) B. licheniformis strains and one erythromycin-sensitive (MIC, 4.0 mg/liter) B. licheniformis strain. Several amino acid changes were present in the translated ermD and ermK nucleotide sequences of the erythromycin-sensitive strain, which could indicate ErmD and ErmK protein functionalities different from those of the resistance strains. The ermD and ermK genes were localized on an 11.4-kbp plasmid. All of the B. sonorensis strains harbored the bacitracin synthetase gene, bacA, and the transporter gene bcrA, which correlated with their observed resistance to bacitracin. Bacitracin was produced by all the investigated species strains (28%), as determined by ultra-high-definition quadrupole time-of-flight liquid chromatography-mass spectrometry (UHD-QTOF LC/MS). The present study has revealed species-specific variations in the antimicrobial susceptibilities of Bacillus spp. and provides new information on MIC values, as well as the occurrence of resistance genes in Bacillus spp., including the newly described species B. sonorensis. PMID:22941078

Childhood outcomes after prescription of antibiotics to pregnant women with preterm rupture of the membranes: 7-year follow-up of the ORACLE I trial.

PubMed

Kenyon, S; Pike, K; Jones, D R; Brocklehurst, P; Marlow, N; Salt, A; Taylor, D J

2008-10-11

The ORACLE I trial compared the use of erythromycin and/or amoxicillin-clavulanate (co-amoxiclav) with that of placebo for women with preterm rupture of the membranes without overt signs of clinical infection, by use of a factorial randomised design. The aim of the present study--the ORACLE Children Study I--was to determine the long-term effects on children of these interventions. We assessed children at age 7 years born to the 4148 women who had completed the ORACLE I trial and who were eligible for follow-up with a structured parental questionnaire to assess the child's health status. Functional impairment was defined as the presence of any level of functional impairment (severe, moderate, or mild) derived from the mark III Multi-Attribute Health Status classification system. Educational outcomes were assessed with national curriculum test results for children resident in England. Outcome was determined for 3298 (75%) eligible children. There was no difference in the proportion of children with any functional impairment after prescription of erythromycin, with or without co-amoxiclav, compared with those born to mothers who received no erythromycin (594 [38.3%] of 1551 children vs 655 [40.4%] of 1620; odds ratio 0.91, 95% CI 0.79-1.05) or after prescription of co-amoxiclav, with or without erythromycin, compared with those born to mothers who received no co-amoxiclav (645 [40.6%] of 1587 vs 604 [38.1%] of 1584; 1.11, 0.96-1.28). Neither antibiotic had a significant effect on the overall level of behavioural difficulties experienced, on specific medical conditions, or on the proportions of children achieving each level in reading, writing, or mathematics at key stage one. The prescription of antibiotics for women with preterm rupture of the membranes seems to have little effect on the health of children at 7 years of age. UK Medical Research Council.

Antimicrobial susceptibility of Bacillus strains isolated from primary starters for African traditional bread production and characterization of the bacitracin operon and bacitracin biosynthesis.

PubMed

Adimpong, David B; Sørensen, Kim I; Thorsen, Line; Stuer-Lauridsen, Birgitte; Abdelgadir, Warda S; Nielsen, Dennis S; Derkx, Patrick M F; Jespersen, Lene

2012-11-01

Bacillus spp. are widely used as feed additives and probiotics. However, there is limited information on their resistance to various antibiotics, and there is a growing concern over the transfer of antibiotic resistance genes. The MIC for 8 antibiotics was determined for 85 Bacillus species strains, Bacillus subtilis subsp. subtilis (n = 29), Bacillus licheniformis (n = 38), and Bacillus sonorensis (n = 18), all of which were isolated from starters for Sudanese bread production. All the strains were sensitive to tetracycline (8.0 mg/liter), vancomycin (4.0 mg/liter), and gentamicin (4.0 mg/liter) but resistant to streptomycin. Sensitivity to clindamycin, chloramphenicol, and kanamycin was species specific. The erythromycin resistance genes ermD and ermK were detected by PCR in all of the erythromycin-resistant (MIC, ≥16.0 mg/liter) B. licheniformis strains and one erythromycin-sensitive (MIC, 4.0 mg/liter) B. licheniformis strain. Several amino acid changes were present in the translated ermD and ermK nucleotide sequences of the erythromycin-sensitive strain, which could indicate ErmD and ErmK protein functionalities different from those of the resistance strains. The ermD and ermK genes were localized on an 11.4-kbp plasmid. All of the B. sonorensis strains harbored the bacitracin synthetase gene, bacA, and the transporter gene bcrA, which correlated with their observed resistance to bacitracin. Bacitracin was produced by all the investigated species strains (28%), as determined by ultra-high-definition quadrupole time-of-flight liquid chromatography-mass spectrometry (UHD-QTOF LC/MS). The present study has revealed species-specific variations in the antimicrobial susceptibilities of Bacillus spp. and provides new information on MIC values, as well as the occurrence of resistance genes in Bacillus spp., including the newly described species B. sonorensis.

Macrolide resistance in Legionella pneumophila: the role of LpeAB efflux pump.

PubMed

Massip, Clémence; Descours, Ghislaine; Ginevra, Christophe; Doublet, Patricia; Jarraud, Sophie; Gilbert, Christophe

2017-05-01

A previous study on 12 in vitro -selected azithromycin-resistant Legionella pneumophila lineages showed that ribosomal mutations were major macrolide resistance determinants. In addition to these mechanisms that have been well described in many species, mutations upstream of lpeAB operon, homologous to acrAB in Escherichia coli , were identified in two lineages. In this study, we investigated the role of LpeAB and of these mutations in macrolide resistance of L. pneumophila . The role of LpeAB was studied by testing the antibiotic susceptibility of WT, deleted and complemented L. pneumophila Paris strains. Translational fusion experiments using GFP as a reporter were conducted to investigate the consequences of the mutations observed in the upstream sequence of lpeAB operon. We demonstrated the involvement of LpeAB in an efflux pump responsible for a macrolide-specific reduced susceptibility of L. pneumophila Paris strain. Mutations in the upstream sequence of lpeAB operon were associated with an increased protein expression. Increased expression was also observed under sub-inhibitory macrolide concentrations in strains with both mutated and WT promoting regions. LpeAB are components of an efflux pump, which is a macrolide resistance determinant in L. pneumophila Paris strain. Mutations observed in the upstream sequence of lpeAB operon in resistant lineages led to an overexpression of this efflux pump. Sub-inhibitory concentrations of macrolides themselves participated in upregulating this efflux and could constitute a first step in the acquisition of a high macrolide resistance level. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Community-Acquired Pneumonia in Adults: Diagnosis and Management.

PubMed

Kaysin, Alexander; Viera, Anthony J

2016-11-01

Community-acquired pneumonia is a leading cause of death. Risk factors include older age and medical comorbidities. Diagnosis is suggested by a history of cough, dyspnea, pleuritic pain, or acute functional or cognitive decline, with abnormal vital signs (e.g., fever, tachycardia) and lung examination findings. Diagnosis should be confirmed by chest radiography or ultrasonography. Validated prediction scores for pneumonia severity can guide the decision between outpatient and inpatient therapy. Using procalcitonin as a biomarker for severe infection may further assist with risk stratification. Most outpatients with community-acquired pneumonia do not require microbiologic testing of sputum or blood and can be treated empirically with a macrolide, doxycycline, or a respiratory fluoroquinolone. Patients requiring hospitalization should be treated with a fluoroquinolone or a combination of beta-lactam plus macrolide antibiotics. Patients with severe infection requiring admission to the intensive care unit require dual antibiotic therapy including a third-generation cephalosporin plus a macrolide alone or in combination with a fluoroquinolone. Treatment options for patients with risk factors for Pseudomonas species include administration of an antipseudomonal antibiotic and an aminoglycoside, plus azithromycin or a fluoroquinolone. Patients with risk factors for methicillin-resistant Staphylococcus aureus should be given vancomycin or linezolid, or ceftaroline in resistant cases. Administration of corticosteroids within 36 hours of hospital admission for patients with severe community-acquired pneumonia decreases the risk of adult respiratory distress syndrome and length of treatment. The 23-valent pneumococcal polysaccharide and 13-valent pneumococcal conjugate vaccinations are both recommended for adults 65 years and older to decrease the risk of invasive pneumococcal disease, including pneumonia.

Impact of antibiotic therapy in severe community-acquired pneumonia: Data from the Infauci study.

PubMed

Pereira, J M; Gonçalves-Pereira, J; Ribeiro, O; Baptista, J P; Froes, F; Paiva, J A

2018-02-01

Antibiotic therapy (AT) is the cornerstone of the management of severe community-acquired pneumonia (CAP). However, the best treatment strategy is far from being established. To evaluate the impact of different aspects of AT on the outcome of critically ill patients with CAP, we performed a post hoc analysis of all CAP patients enrolled in a prospective, observational, multicentre study. Of the 502 patients included, 76% received combination therapy, mainly a β-lactam with a macrolide (80%). AT was inappropriate in 16% of all microbiologically documented CAP (n=177). Hospital and 6months mortality were 34% and 35%. In adjusted multivariate logistic regression analysis, combination AT with a macrolide was independently associated with a reduction in hospital (OR 0.17, 95%CI 0.06-0.51) and 6months (OR 0.21, 95%CI 0.07-0.57) mortality. Prolonged AT (>7days) was associated with a longer ICU (14 vs. 7days; p<0.001) and hospital length of stay (LOS) (25 vs. 17days; p<0.001). Combination AT with a macrolide may be the most suitable AT strategy to improve both short and long term outcome of severe CAP patients. AT >7days had no survival benefit and was associated with a longer LOS. Copyright © 2017 Elsevier Inc. All rights reserved.

Determination of Ten Macrolide Drugs in Environmental Water Using Molecularly Imprinted Solid-Phase Extraction Coupled with Liquid Chromatography-Tandem Mass Spectrometry.

PubMed

Song, Xuqin; Zhou, Tong; Li, Jiufeng; Zhang, Meiyu; Xie, Jingmeng; He, Limin

2018-05-14

With the extensive application of antibiotics in livestock, their contamination of the aquatic environment has received more attention. Molecularly imprinted polymer (MIP), as an eco-friendly and durable solid-phase extraction material, has shown great potential for the separation and enrichment of antibiotics in water. This study aims at developing a practical and economical method based on molecularly imprinted solid phase extraction (MISPE) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for simultaneously detecting ten macrolide drugs in different sources of water samples. The MIP was synthesized by bulk polymerization using tylosin as the template and methacrylic acid as the functional monomer. The MIP exhibited a favorable load-bearing capacity for water (>90 mL), which is more than triple that of non-molecularly imprinted polymers (NIP). The mean recoveries of macrolides at four spiked concentration levels (limit of quantification, 40, 100, and 400 ng/L) were 62.6⁻100.9%, with intra-day and inter-day relative standard deviations below 12.6%. The limit of detection and limit of quantification were 1.0⁻15.0 ng/L and 3.0⁻40.0 ng/L, respectively. Finally, the proposed method was successfully applied to the analysis of real water samples.

Bacteria evade immune recognition via TLR13 and binding of their 23S rRNA by MLS antibiotics by the same mechanisms

PubMed Central

Hochrein, Hubertus; Kirschning, Carsten J.

2013-01-01

The immune system recognizes pathogens and other danger by means of pattern recognition receptors. Recently, we have demonstrated that the orphan Toll-like receptor 13 (TLR13) senses a defined sequence of the bacterial rRNA and that bacteria use specific mechanisms to evade macrolide lincosamide streptogramin (MLS) antibiotics detection via TLR13. PMID:23802068

DNA Microarray for Detection of Macrolide Resistance Genes

PubMed Central

Cassone, Marco; D'Andrea, Marco M.; Iannelli, Francesco; Oggioni, Marco R.; Rossolini, Gian Maria; Pozzi, Gianni

2006-01-01

A DNA microarray was developed to detect bacterial genes conferring resistance to macrolides and related antibiotics. A database containing 65 nonredundant genes selected from publicly available DNA sequences was constructed and used to design 100 oligonucleotide probes that could specifically detect and discriminate all 65 genes. Probes were spotted on a glass slide, and the array was reacted with DNA templates extracted from 20 reference strains of eight different bacterial species (Streptococcus pneumoniae, Streptococcus pyogenes, Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Staphylococcus haemolyticus, Escherichia coli, and Bacteroides fragilis) known to harbor 29 different macrolide resistance genes. Hybridization results showed that probes reacted with, and only with, the expected DNA templates and allowed discovery of three unexpected genes, including msr(SA) in B. fragilis, an efflux gene that has not yet been described for gram-negative bacteria. PMID:16723563

Antibiotic Sensitivity of Micrococcus radiodurans

PubMed Central

Hawiger, J.; Jeljaszewicz, J.

1967-01-01

A wild-type strain of Micrococcus radiodurans and its nonpigmented mutant W1 were tested for sensitivity to 10 antibiotics selected from the standpoint of their mechanism of action. Representatives of groups of antibiotics inhibiting deoxyribonucleic acid (DNA) synthesis, DNA-dependent ribonucleic acid synthesis, protein synthesis, and cell wall synthesis were selected. M. radiodurans and its mutant exhibited full susceptibility to all antibiotics tested (mitomycin C, actinomycin D, chloramphenicol, dihydrostreptomycin, erythromycin, neomycin, kanamycin, benzylpenicillin, bacitracin, and vancomycin), the degree of susceptibility being of the same order as that of a standard strain of Staphylococcus aureus 209 P, with the exception of dihydrostreptomycin. PMID:4166078

Correlation between genetic features of the mef(A)-msr(D) locus and erythromycin resistance in Streptococcus pyogenes.

PubMed

Vitali, Luca Agostino; Di Luca, Maria Chiara; Prenna, Manuela; Petrelli, Dezemona

2016-01-01

We investigated the correlation between the genetic variation within mef(A)-msr(D) determinants of efflux-mediated erythromycin resistance in Streptococcus pyogenes and the level of erythromycin resistance. Twenty-eight mef(A)-positive strains were selected according to erythromycin MIC (4-32 μg/mL), and their mef(A)-msr(D) regions were sequenced. Strains were classified according to the bacteriophage carrying mef(A)-msr(D). A new Φm46.1 genetic variant was found in 8 strains out of 28 and named VP_00501.1. Degree of allelic variation was higher in mef(A) than in msr(D). Hotspots for recombination were mapped within the locus that could have shaped the apparent mosaic structure of the region. There was a general correlation between mef(A)-msr(D) sequence and erythromycin resistance level. However, lysogenic conversion of susceptible strains by mef(A)-msr(D)-carrying Φm46.1 indicated that key determinants may not all reside within the mef(A)-msr(D) locus and that horizontal gene transfer could contribute to changes in the level of antibiotic resistance in S. pyogenes. Copyright © 2016 Elsevier Inc. All rights reserved.

Cellular accumulation of the new ketolide RU 64004 by human neutrophils: comparison with that of azithromycin and roxithromycin.

PubMed Central

Vazifeh, D; Abdelghaffar, H; Labro, M T

1997-01-01

We analyzed the uptake of RU 64004 by human neutrophils (polymorphonuclear leukocytes [PMNs]) relative to those of azithromycin and roxithromycin. RU 64004 was strongly and rapidly accumulated by PMNs, with a cellular concentration/extracellular concentration ratio (C/E) of greater than 200 in the first 5 min, and this was followed by a plateau at 120 to 180 min, with a C/E of 461 +/- 14.8 (10 experiments) at 180 min. RU 64004 uptake was moderately sensitive to external pH, and activation energy was also moderate (63 +/- 3.8 kJ/mol). RU 64004 was mainly located in PMN granules (about 70%) and egressed slowly from loaded cells, owing to avid reuptake. The possibility that PMN uptake of RU 64004 and other macrolides occurs through a carrier-mediated system was suggested by three key results. First, there existed a strong interindividual variability in uptake kinetics, suggesting variability in the numbers or activity of a transport protein. Second, macrolide uptake displayed saturation kinetics characteristic of that of a carrier-mediated transport system: RU 64004 had the highest Vmax value (3,846 ng/2.5 x 10(6) PMNs/5 min) and the lowest Km value (about 28 microM), indicating a high affinity for the transporter. Third, as observed previously with other erythromycin A derivatives, Ni2+ (a blocker of the Na+/Ca2+ exchanger which mediates Ca2+ influx in resting neutrophils) impaired RU 64004 uptake by PMNs, with a 50% inhibitory concentration of about 3.5 mM. In addition, we found that an active process is also involved in macrolide efflux, because verapamil significantly potentiated the release of all three macrolides tested. This effect of verapamil does not seem to be related to an inhibition of Ca2+ influx, because neither EGTA [ethylene glycol-bis (beta-aminoethyl ether)-N,N',N'-tetraacetic acid] nor Ni2+ modified macrolide efflux. The nature and characteristics of the entry- and efflux-mediating carrier systems are under investigation. PMID:9333032

Role of rifampin-based combination therapy for severe community-acquired Legionella pneumophila pneumonia.

PubMed

Varner, Terra R; Bookstaver, P Brandon; Rudisill, Celeste N; Albrecht, Helmut

2011-07-01

To review the literature concerning the role of rifampin in the combination treatment of Legionella pneumophila pneumonia. A search of MEDLINE and Ovid databases was conducted (January 1970-May 2011) using the search terms Legionella pneumophila, pneumonia, Legionnaires' disease, rifampin or rifampicin, macrolide, fluoroquinolone, erythromycin, clarithromycin, levofloxacin, ciprofloxacin, and moxifloxacin In vivo studies published in English that compared antimicrobial therapies including rifampin for the treatment of Legionella pneumonia, as well as in vitro studies including an assessment of rifampin bioactivity, were included. Macrolides and fluoroquinolones have been effective as monotherapy in the treatment of L. pneumophila pneumonia. This review includes evidence summaries from 4 bioactivity evaluations, 6 clinical studies, and 6 reported cases of combination rifampin use. Combined with supporting evidence, the role of combination rifampin therapy is further delineated. Interpretation of the data is limited by the potential for selection bias and lack of consistent comparators. Rifampin therapy should be considered only for patients with severe disease or significant comorbid conditions (eg, uncontrolled diabetes, smoking, or obstructive lung disease) including immunocompromised hosts and those refractory to conventional monotherapy regimens. Caution for significant adverse drug events and drug-drug interactions should be taken with the addition of rifampin.

Pneumococcal antimicrobial resistance: therapeutic strategy and management in community-acquired pneumonia.

PubMed

Aspa, Javier; Rajas, Olga; de Castro, Felipe Rodríguez

2008-02-01

Streptococcus pneumoniae has been consistently shown to represent the most frequent causative agent of community-acquired pneumonia (CAP) and pneumococcal antibiotic resistance towards different families of antibiotics continues to be a much-debated issue. Microbial resistance causes a great deal of confusion in choosing an empirical treatment for pneumonia and this makes it necessary to know which factors actually determine the real impact of antimicrobial resistance on the outcome of pneumococcal infections. Several different aspects have to be taken into account when analyzing this matter, such as the study design, the condition of the patient at the time of diagnosis, the choice of the initial antimicrobial regimen (combination or monotherapy) and the pharmacokinetic/pharmacodynamic variables of the chosen antibiotic. It is generally accepted that in the treatment of beta-lactam-resistant pneumococcal infections, the use of standard antipneumococcal beta-lactam agents is unlikely to impact negatively on the outcome of CAP when appropriate agents are given in sufficient doses. As a general rule, for infections with penicillin-sensitive strains, penicillin or an aminopenicillin in a standard dosage will be effective; in the cases of strains with intermediate resistance, beta-lactam agents are still considered appropriate treatment although higher dosages are recommended; finally, infections with isolates of high-level penicillin resistance should be treated with alternative agents such as the third-generation cephalosporins or the new antipneumococcal fluoroquinolones. In areas of high prevalence of high-level macrolide resistance, empirical monotherapy with a macrolide is not optimal for the treatment of hospitalised patients with moderate or moderately-severe CAP. Fluoroquinolones are considered to be excellent antibiotics in the treatment of pneumococcal CAP in adults, but their general recommendation has been withheld due to fears of a widespread development of resistance. Most international guidelines recommend combination therapy (beta-lactam plus a macrolide) for the treatment of hospitalised patients with CAP.

Molecular characterization of antibiotic resistance in enterococci recovered from seagulls (Larus cachinnans) representing an environmental health problem.

PubMed

Radhouani, Hajer; Igrejas, Gilberto; Pinto, Luís; Gonçalves, Alexandre; Coelho, Céline; Rodrigues, Jorge; Poeta, Patrícia

2011-08-01

Antimicrobial resistance and the mechanisms implicated were studied in 54 enterococci recovered from 57 seagull fecal samples. Almost 78% of the recovered enterococci showed resistance against one or more antibiotics and these isolates were identified to the species level. E. faecium was the most prevalent species (52.4%). High percentages of erythromycin and tetracycline resistances were found among our isolates (95.2%), and lower percentages were identified to other antibiotics. Most of the tetracycline-resistant strains carried the tet(M) and/or tet(L) genes. Genes associated with Tn916/Tn1545 and/or Tn5397 transposons were detected in 45% of tetracycline-resistant isolates. The erm(B) gene was detected in 65% of erythromycin-resistant isolates. The vat(D) and vat(E) genes were present in 5.9% and 11.8% of quinupristin/dalfopristin-resistant isolates, respectively. The ant(6)-Ia gene was identified in 57.1% of streptomycin-resistant isolates. All nine kanamycin-resistant isolates carried the aph(3)'-IIIa gene. The cat(A) gene was found in two chloramphenicol-resistant isolates. Seagulls should be considered a risk species for spreading in the environment antimicrobial resistant enterococci and can serve as a sentinel for antibiotic pressure from the surrounding farm and urban setting.

In vitro evaluation of the antibiotic lock technique (ALT) for the treatment of catheter-related infections caused by staphylococci.

PubMed

Lee, Ji-Young; Ko, Kwan Soo; Peck, Kyong Ran; Oh, Won Sup; Song, Jae-Hoon

2006-06-01

To investigate appropriate antimicrobial agents, the optimal concentration and treatment duration for the antibiotic lock technique (ALT) to treat catheter-related infections caused by Staphylococcus epidermidis and Staphylococcus aureus. We evaluated the bacterial killing activity of vancomycin, teicoplanin, ciprofloxacin, rifampicin, cefazolin, gentamicin, nafcillin and erythromycin against biofilms formed by two strains of S. aureus and two strains of S. epidermidis. The effectiveness of the antibiotic lock was assayed after exposure to antibiotics (1, 5 and 10 mg/mL) for 1, 3, 5, 7, 10 or 14 days using an in vitro model of biofilms on polyurethane film. The biofilms were completely sterile after exposure to vancomycin (5 mg/mL) for 5 days and teicoplanin (5 and 10 mg/mL) for 7 days. Ciprofloxacin and rifampicin (both 5 mg/mL) achieved eradication of the biofilms of both staphylococcal species more rapidly than vancomycin or teicoplanin. Significant biofilm eradication was not achieved with cefazolin, nafcillin, gentamicin and erythromycin at any of the time exposures examined. The data suggest that 5 mg/mL vancomycin, ciprofloxacin or rifampicin can eradicate S. epidermidis and S. aureus biofilms within 5 days. These findings warrant prospective clinical trials for the evaluation of the clinical efficacy of ALT for less than 10 days.

Antibiotics and antibiotic resistance genes in global lakes: A review and meta-analysis.

PubMed

Yang, Yuyi; Song, Wenjuan; Lin, Hui; Wang, Weibo; Du, Linna; Xing, Wei

2018-04-10

Lakes are an important source of freshwater, containing nearly 90% of the liquid surface fresh water worldwide. Long retention times in lakes mean pollutants from discharges slowly circulate around the lakes and may lead to high ecological risk for ecosystem and human health. In recent decades, antibiotics and antibiotic resistance genes (ARGs) have been regarded as emerging pollutants. The occurrence and distribution of antibiotics and ARGs in global freshwater lakes are summarized to show the pollution level of antibiotics and ARGs and to identify some of the potential risks to ecosystem and human health. Fifty-seven antibiotics were reported at least once in the studied lakes. Our meta-analysis shows that sulfamethoxazole, sulfamerazine, sulfameter, tetracycline, oxytetracycline, erythromycin, and roxithromycin were found at high concentrations in both lake water and lake sediment. There is no significant difference in the concentration of sulfonamides in lake water from China and that from other countries worldwide; however, there was a significant difference in quinolones. Erythromycin had the lowest predicted hazardous concentration for 5% of the species (HC 5 ) and the highest ecological risk in lakes. There was no significant difference in the concentration of sulfonamide resistance genes (sul1 and sul2) in lake water and river water. There is surprisingly limited research on the role of aquatic biota in propagation of ARGs in freshwater lakes. As an environment that is susceptible to cumulative build-up of pollutants, lakes provide an important environment to study the fate of antibiotics and transport of ARGs with a broad range of niches including bacterial community, aquatic plants and animals. Copyright © 2018 Elsevier Ltd. All rights reserved.

Assessing the concentrations and risks of toxicity from the antibiotics ciprofloxacin, sulfamethoxazole, trimethoprim and erythromycin in European rivers.

PubMed

Johnson, Andrew C; Keller, Virginie; Dumont, Egon; Sumpter, John P

2015-04-01

This study evaluated the potential concentrations of four antibiotics: ciprofloxacin (CIP), sulfamethoxazole (SUF), trimethoprim (TRI) and erythromycin (ERY) throughout the rivers of Europe. This involved reviewing national consumption rates together with assessing excretion and sewage treatment removal rates. From this information, it was possible to construct best, expected and worst case scenarios for the discharge of these antibiotics into rivers. Consumption data showed surprising variations, up to 200-fold in the popularity of different antibiotics across different European nations. Using the water resources model GWAVA which has a spatial resolution of approximately 6×9 km, river water concentrations throughout Europe were predicted based on 31-year climate data. The modelled antibiotic concentrations were within the range of measurements reported previously in European effluents and rivers. With the expected scenario, the predicted annual-average antibiotic concentrations ranged between 0 and 10 ng/L for 90% by length of surface waters. In the worst case scenario concentrations could reach between 0.1 and 1 μg/L at the most exposed locations. As both predicted and observed sewage effluent concentrations were below reported effect levels for the most sensitive aquatic wildlife, no direct toxicity in rivers is expected. Predicted river concentrations for CIP and ERY were closest to effect levels in wildlife, followed by SUF which was 2-3 orders of magnitude lower. TRI appeared to be of the least concern with around 6 orders of magnitude difference between predicted and effect levels. However, mixture toxicity may elevate this risk and antibiotic levels of 0.1-1 μg/L in hotspots may contribute to local environmental antibiotic resistance in microorganisms. Copyright © 2014 Elsevier B.V. All rights reserved.

Antibiotics for URTI and UTI -- prescribing in Malaysian primary care settings.

PubMed

Teng, Cheong Lieng; Tong, Seng Fah; Khoo, Ee Ming; Lee, Verna; Zailinawati, Abu Hassan; Mimi, Omar; Chen, Wei Seng; Nordin, Salleh

2011-05-01

Overprescription of antibiotics is a continuing problem in primary care. This study aims to assess the antibiotic prescribing rates and antibiotic choices for upper respiratory tract infections (URTI) and urinary tract infections (UTI) in Malaysian primary care. Antibiotic prescribing data for URTI and UTI was extracted from a morbidity survey of randomly selected primary care clinics in Malaysia. Analysis was performed of 1,163 URTI and 105 UTI encounters. Antibiotic prescribing rates for URTI and UTI were 33.8% and 57.1% respectively. Antibiotic prescribing rates were higher in private clinics compared to public clinics for URTI, but not for UTI. In URTI encounters, the majority of antibiotics prescribed were penicillins and macrolides, but penicillin V was notably underused. In UTI encounters, the antibiotics prescribed were predominantly penicillins or cotrimoxazole. Greater effort is needed to bring about evidence based antibiotic prescribing in Malaysian primary care, especially for URTIs in private clinics.

[Clinical characteristics of whooping cough in neonates and antimicrobial resistance of the pathogenic bacteria].

PubMed

Luo, Jie; Wang, Hui-Xin; Yuan, Lin; Gu, Song; Jiang, Min; Ding, Yi-Jun; Guo, Dan; Yao, Kai-Hu; Wang, Ya-Juan

2014-10-01

To study the clinical characteristics of whooping cough in neonates and the antimicrobial resistance of the bacterial isolates. Clinical information of 7 neonates with whooping cough confirmed by bacterial culture was collected. The antimirobial resistance of the isolates was tested using E-test and disk diffusion methods. The children′s mothers or other family members had cough for more than 10 days in 6 neonates, in which four neonates contacted with 3 or more family members with cough. All the neonates had rhinobyon and slight cough at the beginning of the disease. Five cases presented typical spasmodic cough after 4-7 days of the onset. Five cases displayed cyanosis, four cases occurred apnea, three cases suffered breath holding, and only two cases had fever. Nares flaring and three depression signs were found in the physical examination. No bacteriostatic ring around the erythromycin disks were found for five bacterial isolates. The minimal inhibitory concentration (MIC) for erythromycin, azithromycin, clarithromycin and clindamycin were all >256 mg/L against the five isolates. Whooping cough should be considered for neonates with respiratory symptoms and a history of close contact with respiratory infection patients. Macrolide-resistant Bordetella pertussis is common in children with whooping cough.

Nepem-211 ion exchange conductive membrane immobilized tris(2,2´-bipyridyl) ruthenium(II) electrogenerated chemiluminescence flow sensor for high-performance liquid chromatography and its application.

PubMed

Li, Yongbo; Zhang, Zhujun

2013-01-01

We developed a sensitive and robust electrogenerated chemiluminescence (ECL) flow sensor based on Ru(bpy)3(2+) immobilized with a Nepem-211 perfluorinated ion exchange conductance membrane, which has robustness and stability under a wide range of chemical and physical conditions, good electrical conductivity, isotropy and a high exchange capacity for immobilization of Ru(bpy)3(2+). The flow sensor has been used as a post-column detector in high-performance liquid chromatography for determination of erythromycin and clarithromycin in honey and pork, and tricyclic antidepressant drugs in human urine. Under optimal conditions, the linear ranges were 0.03-26 ng/μL and 0.01-1 ng/μL for macrolides and tricyclic antidepressant drugs, respectively. The detection limits were 0.02, 0.01, 0.01, 0.06 and 0.003 ng/μL for erythromycin, clarithromycin, doxepin, amitriptyline and clomipramine, respectively. There is no post-column reagent addition. In addition to the conservation expensive reagents, the experimental setup was simplified. The flow sensor was used for 2 years with high sensitivity and stability. Copyright © 2013 John Wiley & Sons, Ltd.

Activity of telithromycin (HMR 3647) against anaerobic bacteria compared to those of eight other agents by time-kill methodology.

PubMed

Credito, K L; Ednie, L M; Jacobs, M R; Appelbaum, P C

1999-08-01

Time-kill studies examined the activities of telithromycin (HMR 3647), erythromycin A, azithromycin, clarithromycin, roxithromycin, clindamycin, pristinamycin, amoxicillin-clavulanate, and metronidazole against 11 gram-positive and gram-negative anaerobic bacteria. Time-kill studies were carried out with the addition of Oxyrase in order to prevent the introduction of CO(2). Macrolide-azalide-ketolide MICs were 0.004 to 32.0 microg/ml. Of the latter group, telithromycin had the lowest MICs, especially against non-Bacteroides fragilis group strains, followed by azithromycin, clarithromycin, erythromycin A, and roxithromycin. Clindamycin was active (MIC /=99.9% killing) against 6 strains, with 99% killing of 9 strains and 90% killing of 10 strains. After 24 h at twice the MIC, 90, 99, and 99.9% killing of nine, six, and three strains, respectively, occurred. Lower rates of killing were seen at earlier times. Similar kill kinetics relative to the MIC were seen with other macrolides. After 48 h at the MIC, clindamycin was bactericidal against 8 strains, with 99 and 90% killing of 9 and 10 strains, respectively. After 24 h, 90% killing of 10 strains occurred at the MIC. The kinetics of clindamycin were similar to those of pristinamycin. After 48 h at the MIC, amoxicillin-clavulanate showed 99.9% killing of seven strains, with 99% killing of eight strains and 90% killing of nine strains. At four times the MIC, metronidazole was bactericidal against 8 of 10 strains tested after 48 h and against all 10 strains after 24 h; after 12 h, 99% killing of all 10 strains occurred.

Structure-activity relations of successful pharmacologic chaperones for rescue of naturally occurring and manufactured mutants of the gonadotropin-releasing hormone receptor.

PubMed

Janovick, Jo Ann; Goulet, Mark; Bush, Eugene; Greer, Jonathan; Wettlaufer, David G; Conn, P Michael

2003-05-01

We expressed a test system of wild-type (WT) rat (r) and human (h) gonadotropin-releasing hormone (GnRH) receptors (GnRHRs), including naturally occurring (13) and manufactured (five) "loss-of-function" mutants of the GnRHR. These were used to assess the ability of different GnRH peptidomimetics to rescue defective GnRHR mutants and determine their effect on the level of membrane expression of the WT receptors. Among the manufactured mutants were the shortest rGnRHR C-terminal truncation mutant that resulted in receptor loss-of-function (des(325-327)-rGnRHR), two nonfunctional deletion mutants (des(237-241)-rGnRHR and des(260-265)-rGnRHR), two nonfunctional Cys mutants (C(229)A-rGnRHR and C(278)A-rGnRHR); the naturally occurring mutants included all 13 full-length GnRHR point mutations reported to date that result in full or partial human hypogonadotropic hypogonadism. The 10 peptidomimetics assessed as potential rescue molecules ("pharmacoperones") are from three differing chemical pedigrees (indoles, quinolones, and erythromycin-derived macrolides) and were originally developed as GnRH peptidomimetic antagonists. These structures were selected for this study because of their predicted ability to permeate the cell membrane and interact with a defined affinity with the GnRH receptor. All peptidomimetics studied with an IC(50) value (for hGnRHR)

Statin therapy in patients with community-acquired pneumonia.

PubMed

Grudzinska, Frances S; Dosanjh, Davinder Ps; Parekh, Dhruv; Dancer, Rachel Ca; Patel, Jaimin; Nightingale, Peter; Walton, Georgia M; Sapey, Elizabeth; Thickett, David R

2017-10-01

Community-acquired pneumonia (CAP) is the leading cause of death from infection in developed countries. There is evidence of an association between improved survival from infection and statin use. The possible beneficial effects of statins are complicated by the common use of macrolide antibiotics for pneumonia, with current guidance suggesting that concurrent macrolide and statin use is contraindicated.We conducted an observational study of statin use in patients with CAP. Of 2,067 patients with CAP, 30.4% were on statin therapy at admission. Statin users were more likely to survive the admission (p<0.001). In addition, we conducted a survey of doctors and found that knowledge regarding concurrent macrolide and statin use was lacking.These data suggest a potential role of statins in the management of CAP. Further research using high-dose statins is required to assess their safe use in subjects with mild to moderate infections. © Royal College of Physicians 2017. All rights reserved.

ICESag37, a Novel Integrative and Conjugative Element Carrying Antimicrobial Resistance Genes and Potential Virulence Factors in Streptococcus agalactiae.

PubMed

Zhou, Kaixin; Xie, Lianyan; Han, Lizhong; Guo, Xiaokui; Wang, Yong; Sun, Jingyong

2017-01-01

ICE Sag37 , a novel integrative and conjugative element carrying multidrug resistance and potential virulence factors, was characterized in a clinical isolate of Streptococcus agalactiae . Two clinical strains of S. agalactiae , Sag37 and Sag158, were isolated from blood samples of new-borns with bacteremia. Sag37 was highly resistant to erythromycin and tetracycline, and susceptible to levofloxacin and penicillin, while Sag158 was resistant to tetracycline and levofloxacin, and susceptible to erythromycin. Transfer experiments were performed and selection was carried out with suitable antibiotic concentrations. Through mating experiments, the erythromycin resistance gene was found to be transferable from Sag37 to Sag158. Sma I-PFGE revealed a new Sma I fragment, confirming the transfer of the fragment containing the erythromycin resistance gene. Whole genome sequencing and sequence analysis revealed a mobile element, ICE Sag37 , which was characterized using several molecular methods and in silico analyses. ICE Sag37 was excised to generate a covalent circular intermediate, which was transferable to S. agalactiae . Inverse PCR was performed to detect the circular form. A serine family integrase mediated its chromosomal integration into rumA , which is a known hotspot for the integration of streptococcal ICEs. The integration site was confirmed using PCR. ICE Sag37 carried genes for resistance to multiple antibiotics, including erythromycin [ erm(B) ], tetracycline [ tet(O) ], and aminoglycosides [ aadE, aphA , and ant(6) ]. Potential virulence factors, including a two-component signal transduction system ( nisK/nisR ), were also observed in ICE Sag37 . S1-PFGE analysis ruled out the existence of plasmids. ICE Sag37 is the first ICE Sa2603 family-like element identified in S. agalactiae carrying both resistance and potential virulence determinants. It might act as a vehicle for the dissemination of multidrug resistance and pathogenicity among S. agalactiae .

Pharmaceuticals in Surface Waters and Potential Transfer to Irrigated Food Crops

EPA Science Inventory

A number of pharmaceuticals have been detected in surface waters across the United States. The objective of this study was to evaluate the presence of selected pharmaceuticals (macrolidic antibiotics and pseudoephedrine) and illicit drugs (methamphetamine, Ecstasy) in surface wat...

PHARMACEUTICALS IN WASTE STREAMS AND SURFACE WATERS OF THE COLORADO RIVER BASIN

EPA Science Inventory

A number of pharmaceuticals have been detected in surface waters across the United States. The objective of this study was to evaluate the presence of selected pharmaceuticals (macrolidic antibiotics and pseudoephedrine) and illicit drugs (methamphetamine and Ecstasy) in surface ...

Initial antibiotic selection and patient outcomes: observations from the National Pneumonia Project.

PubMed

Bratzler, Dale W; Ma, Allen; Nsa, Wato

2008-12-01

Guidelines for empirical treatment of hospitalized patients with pneumonia provide specific recommendations for antibiotic selection that are primarily based on findings from observational studies. We conducted a retrospective study of 27,330 community-dwelling, immunocompetent Medicare patients (age, >65 years) with pneumonia who were hospitalized in 1998-1999 and 2000-2001. Associations between initial antimicrobial regimens and risk-adjusted mortality were assessed, accounting for differences in patient characteristics, comorbidities, illness severity, geographic location, and processes of care. Treatment with nonpseudomonal third-generation cephalosporin monotherapy constituted the reference group for comparisons. For patients not in the intensive care unit, initial treatment with fluoroquinolone monotherapy was associated with reduced in-hospital mortality, 14-day mortality, and 30-day mortality rates (adjusted odds ratio [AOR] for 30-day mortality, 0.7; 95% confidence interval [CI], 0.6-0.9; P = .001). The combination of a cephalosporin plus a macrolide was associated with reduced 14-day and 30-day mortality rates (AOR for 30-day mortality, 0.7; 95% CI, 0.6-0.9; P < .001). For intensive care unit patients, the combination of a cephalosporin and a macrolide was associated with reduced in-hospital mortality (AOR, 0.6; 95% CI, 0.3-0.9; P = .018). Initial antimicrobial treatment with the combination of a second- or third-generation cephalosporin and a macrolide or initial treatment with a fluoroquinolone was associated with a reduced 30-day mortality rate, compared with treatment with third-generation cephalosporin monotherapy, among non-intensive care unit patients. Although our results are consistent with other observational studies, controversy continues to exist about the use of nonexperimental cohort studies to demonstrate associations between processes of care, such as antibiotic selection, and patient outcomes.

SACE_5599, a putative regulatory protein, is involved in morphological differentiation and erythromycin production in Saccharopolyspora erythraea.

PubMed

Kirm, Benjamin; Magdevska, Vasilka; Tome, Miha; Horvat, Marinka; Karničar, Katarina; Petek, Marko; Vidmar, Robert; Baebler, Spela; Jamnik, Polona; Fujs, Štefan; Horvat, Jaka; Fonovič, Marko; Turk, Boris; Gruden, Kristina; Petković, Hrvoje; Kosec, Gregor

2013-12-17

Erythromycin is a medically important antibiotic, biosynthesized by the actinomycete Saccharopolyspora erythraea. Genes encoding erythromycin biosynthesis are organized in a gene cluster, spanning over 60 kbp of DNA. Most often, gene clusters encoding biosynthesis of secondary metabolites contain regulatory genes. In contrast, the erythromycin gene cluster does not contain regulatory genes and regulation of its biosynthesis has therefore remained poorly understood, which has for a long time limited genetic engineering approaches for erythromycin yield improvement. We used a comparative proteomic approach to screen for potential regulatory proteins involved in erythromycin biosynthesis. We have identified a putative regulatory protein SACE_5599 which shows significantly higher levels of expression in an erythromycin high-producing strain, compared to the wild type S. erythraea strain. SACE_5599 is a member of an uncharacterized family of putative regulatory genes, located in several actinomycete biosynthetic gene clusters. Importantly, increased expression of SACE_5599 was observed in the complex fermentation medium and at controlled bioprocess conditions, simulating a high-yield industrial fermentation process in the bioreactor. Inactivation of SACE_5599 in the high-producing strain significantly reduced erythromycin yield, in addition to drastically decreasing sporulation intensity of the SACE_5599-inactivated strains when cultivated on ABSM4 agar medium. In contrast, constitutive overexpression of SACE_5599 in the wild type NRRL23338 strain resulted in an increase of erythromycin yield by 32%. Similar yield increase was also observed when we overexpressed the bldD gene, a previously identified regulator of erythromycin biosynthesis, thereby for the first time revealing its potential for improving erythromycin biosynthesis. SACE_5599 is the second putative regulatory gene to be identified in S. erythraea which has positive influence on erythromycin yield. Like bldD, SACE_5599 is involved in morphological development of S. erythraea, suggesting a very close relationship between secondary metabolite biosynthesis and morphological differentiation in this organism. While the mode of action of SACE_5599 remains to be elucidated, the manipulation of this gene clearly shows potential for improvement of erythromycin production in S. erythraea in industrial setting. We have also demonstrated the applicability of the comparative proteomics approach for identifying new regulatory elements involved in biosynthesis of secondary metabolites in industrial conditions.

SACE_5599, a putative regulatory protein, is involved in morphological differentiation and erythromycin production in Saccharopolyspora erythraea

PubMed Central

2013-01-01

Background Erythromycin is a medically important antibiotic, biosynthesized by the actinomycete Saccharopolyspora erythraea. Genes encoding erythromycin biosynthesis are organized in a gene cluster, spanning over 60 kbp of DNA. Most often, gene clusters encoding biosynthesis of secondary metabolites contain regulatory genes. In contrast, the erythromycin gene cluster does not contain regulatory genes and regulation of its biosynthesis has therefore remained poorly understood, which has for a long time limited genetic engineering approaches for erythromycin yield improvement. Results We used a comparative proteomic approach to screen for potential regulatory proteins involved in erythromycin biosynthesis. We have identified a putative regulatory protein SACE_5599 which shows significantly higher levels of expression in an erythromycin high-producing strain, compared to the wild type S. erythraea strain. SACE_5599 is a member of an uncharacterized family of putative regulatory genes, located in several actinomycete biosynthetic gene clusters. Importantly, increased expression of SACE_5599 was observed in the complex fermentation medium and at controlled bioprocess conditions, simulating a high-yield industrial fermentation process in the bioreactor. Inactivation of SACE_5599 in the high-producing strain significantly reduced erythromycin yield, in addition to drastically decreasing sporulation intensity of the SACE_5599-inactivated strains when cultivated on ABSM4 agar medium. In contrast, constitutive overexpression of SACE_5599 in the wild type NRRL23338 strain resulted in an increase of erythromycin yield by 32%. Similar yield increase was also observed when we overexpressed the bldD gene, a previously identified regulator of erythromycin biosynthesis, thereby for the first time revealing its potential for improving erythromycin biosynthesis. Conclusions SACE_5599 is the second putative regulatory gene to be identified in S. erythraea which has positive influence on erythromycin yield. Like bldD, SACE_5599 is involved in morphological development of S. erythraea, suggesting a very close relationship between secondary metabolite biosynthesis and morphological differentiation in this organism. While the mode of action of SACE_5599 remains to be elucidated, the manipulation of this gene clearly shows potential for improvement of erythromycin production in S. erythraea in industrial setting. We have also demonstrated the applicability of the comparative proteomics approach for identifying new regulatory elements involved in biosynthesis of secondary metabolites in industrial conditions. PMID:24341557

Streptococcus agalactiae Causing Neonatal Infections in Portugal (2005-2015): Diversification and Emergence of a CC17/PI-2b Multidrug Resistant Sublineage.

PubMed

Martins, Elisabete R; Pedroso-Roussado, Cristiano; Melo-Cristino, José; Ramirez, Mário

2017-01-01

The molecular characterization of 218 GBS isolates recovered from neonatal invasive infections in Portugal in 2005-2015 revealed the existence of a small number of genetically distinct lineages that were present over a significant time-span. Serotypes III and Ia were dominant in the population, together accounting for >80% of the isolates. Clonal complex 17 included 50% of all isolates, highlighting the importance of the hypervirulent genetic lineage represented by serotype III ST17/ rib /PI-1+PI-2b. Serotype Ia was represented mainly by ST23, previously reported as dominant among invasive disease in non-pregnant adults in Portugal, but also by ST24, showing an increased frequency among late-onset disease. Overall erythromycin resistance was 16%, increasing during the study period ( p < 0.001). Macrolide resistance was overrepresented among CC1 and CC19 isolates ( p < 0.001 and p = 0.008, respectively). While representatives of the hypervirulent CC17 lineage were mostly susceptible to macrolides, we identified for the first time in Europe a recently emerging sublineage characterized by the loss of PI-1 (CC17/PI-2b), simultaneously resistant to macrolides, lincosamides, and tetracycline, also exhibiting high-level resistance to streptomycin and kanamycin. The stability and dominance of CC17 among neonatal invasive infections in the past decades indicates that it is extremely well adapted to its niche; however emerging resistance in this genetic background may have significant implications for the prevention and management of GBS disease.

Outcome of the Vaginal Infections and Prematurity Study: results of a clinical trial of erythromycin among pregnant women colonized with group B streptococci.

PubMed

Klebanoff, M A; Regan, J A; Rao, A V; Nugent, R P; Blackwelder, W C; Eschenbach, D A; Pastorek, J G; Williams, S; Gibbs, R S; Carey, J C

1995-05-01

Our purpose was to determine whether erythromycin treatment of pregnant women colonized with group B streptococci would reduce the occurrence of low birth weight (< 2500 gm) and preterm (< 37 completed weeks) birth. In a double-blind clinical trial, 938 carriers of group B streptococci were randomized to receive erythromycin base (333 mg three times a day) or matching placebo beginning during the third trimester and before 30 weeks and continuing for 10 weeks or until 35 weeks 6 days of pregnancy. Pregnancy outcomes were available for 97% of randomized women; 14% of subjects withdrew from the trial. Birth weight < 2500 gm occurred in 8.6% of the erythromycin and 6.1% of the placebo recipients (relative risk 1.4, 0.9 to 2.2, p = 0.16). Preterm delivery occurred in 11.4% of women randomized to erythromycin and in 12.3% randomized to placebo (relative risk 0.9, 95% confidence limits 0.6 to 1.3, p = 0.65). Greater benefit of erythromycin in reducing these outcomes was not observed among women reporting the best compliance. In this study of pregnant women colonized with group B streptococci treatment with erythromycin was not shown to be effective at prolonging gestation or reducing low birth weight. Greater than anticipated complicating factors, including spontaneous clearance of the organism, use of nontrial antibiotics, and density of colonization, may have resulted in population sizes too small to detect a benefit of treatment. Future studies should take these factors into account in determining sample sizes.

Development of an Analytical Method to Extract and Detect Pharmaceuticals in Plant Matrices

EPA Science Inventory

It has been shown that human-use macrolide antibiotics (azithromycin, clindamycin, and roxithromycin) are environmentally available in wastewaters, source waters, and biosolids. Since some water authorities use the treated wastewater effluent for non-potable water reuse such as f...

MRC ORACLE Children Study. Long term outcomes following prescription of antibiotics to pregnant women with either spontaneous preterm labour or preterm rupture of the membranes.

PubMed

Kenyon, Sara; Brocklehurst, Peter; Jones, David; Marlow, Neil; Salt, Alison; Taylor, David

2008-04-24

The Medical Research Council (MRC) ORACLE trial evaluated the use of co-amoxiclav 375 mg and/or erythromycin 250 mg in women presenting with preterm rupture of membranes (PROM) ORACLE I or in spontaneous preterm labour (SPL) ORACLE II using a factorial design. The results showed that for women with a singleton baby with PROM the prescription of erythromycin is associated with improvements in short term neonatal outcomes, although co-amoxiclav is associated with prolongation of pregnancy, a significantly higher rate of neonatal necrotising enterocolitis was found in these babies. Prescription of erythromycin is now established practice for women with PROM. For women with SPL antibiotics demonstrated no improvements in short term neonatal outcomes and are not recommended treatment. There is evidence that both these conditions are associated with subclinical infection so perinatal antibiotic administration may reduce the risk of later disabilities, including cerebral palsy, although the risk may be increased through exposure to inflammatory cytokines, so assessment of longer term functional and educational outcomes is appropriate. The MRC ORACLE Children's Study will follow up UK children at age 7 years born to 4809 women with PROM and the 4266 women with SPL enrolled in the earlier ORACLE trials. We will use a parental questionnaire including validated tools to assess disability and behaviour. We will collect the frequency of specific medical conditions: cerebral palsy, epilepsy, respiratory illness including asthma, diabetes, admission to hospital in last year and other diseases, as reported by parents. National standard test results will be collected to assess educational attainment at Key Stage 1 for children in England. This study is designed to investigate whether or not peripartum antibiotics improve health and disability for children at 7 years of age. The ORACLE Trial and Children Study is registered in the Current Controlled Trials registry. ISCRTN 52995660.

MRC ORACLE Children Study. Long term outcomes following prescription of antibiotics to pregnant women with either spontaneous preterm labour or preterm rupture of the membranes

PubMed Central

Kenyon, Sara; Brocklehurst, Peter; Jones, David; Marlow, Neil; Salt, Alison; Taylor, David

2008-01-01

Background The Medical Research Council (MRC) ORACLE trial evaluated the use of co-amoxiclav 375 mg and/or erythromycin 250 mg in women presenting with preterm rupture of membranes (PROM) ORACLE I or in spontaneous preterm labour (SPL) ORACLE II using a factorial design. The results showed that for women with a singleton baby with PROM the prescription of erythromycin is associated with improvements in short term neonatal outcomes, although co-amoxiclav is associated with prolongation of pregnancy, a significantly higher rate of neonatal necrotising enterocolitis was found in these babies. Prescription of erythromycin is now established practice for women with PROM. For women with SPL antibiotics demonstrated no improvements in short term neonatal outcomes and are not recommended treatment. There is evidence that both these conditions are associated with subclinical infection so perinatal antibiotic administration may reduce the risk of later disabilities, including cerebral palsy, although the risk may be increased through exposure to inflammatory cytokines, so assessment of longer term functional and educational outcomes is appropriate. Methods The MRC ORACLE Children's Study will follow up UK children at age 7 years born to 4809 women with PROM and the 4266 women with SPL enrolled in the earlier ORACLE trials. We will use a parental questionnaire including validated tools to assess disability and behaviour. We will collect the frequency of specific medical conditions: cerebral palsy, epilepsy, respiratory illness including asthma, diabetes, admission to hospital in last year and other diseases, as reported by parents. National standard test results will be collected to assess educational attainment at Key Stage 1 for children in England. Discussion This study is designed to investigate whether or not peripartum antibiotics improve health and disability for children at 7 years of age. Trial registration The ORACLE Trial and Children Study is registered in the Current Controlled Trials registry. ISCRTN 52995660 PMID:18435833

Polysensitivity in delayed cutaneous adverse drug reactions to macrolides, clindamycin, and pristinamycin: clinical history and patch testing.

PubMed

El Khoury, M; Assier, H; Gener, G; Paul, M; Haddad, C; Chosidow, O; Wolkenstein, P; Ingen-Housz-Oro, S

2018-05-10

Although they have different biochemical structures, macrolides, lincosamides (including clindamycin) and streptogramins (including pristinamycin) share a similar mechanism of action on Gram-positive bacteria and are grouped into the MLS family. 1 Cross-allergies induced by drugs of similar mechanism of action but different chemical structure (polysensitivity) are poorly described. Our objectives were to investigate the possibility of polysensitivity among MLS antibiotics, and to compare the value of patch tests (PTs) in MLS-induced delayed-cutaneous adverse drug reactions (D-CADRs). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Intra- and Inter-Pandemic Variations of Antiviral, Antibiotics and Decongestants in Wastewater Treatment Plants and Receiving Rivers

PubMed Central

Singer, Andrew C.; Järhult, Josef D.; Grabic, Roman; Khan, Ghazanfar A.; Lindberg, Richard H.; Fedorova, Ganna; Fick, Jerker; Bowes, Michael J.; Olsen, Björn; Söderström, Hanna

2014-01-01

The concentration of eleven antibiotics (trimethoprim, oxytetracycline, ciprofloxacin, azithromycin, cefotaxime, doxycycline, sulfamethoxazole, erythromycin, clarithromycin, ofloxacin, norfloxacin), three decongestants (naphazoline, oxymetazoline, xylometazoline) and the antiviral drug oseltamivir’s active metabolite, oseltamivir carboxylate (OC), were measured weekly at 21 locations within the River Thames catchment in England during the month of November 2009, the autumnal peak of the influenza A[H1N1]pdm09 pandemic. The aim was to quantify the pharmaceutical response to the pandemic and compare this to drug use during the late pandemic (March 2010) and the inter-pandemic periods (May 2011). A large and small wastewater treatment plant (WWTP) were sampled in November 2009 to understand the differential fate of the analytes in the two WWTPs prior to their entry in the receiving river and to estimate drug users using a wastewater epidemiology approach. Mean hourly OC concentrations in the small and large WWTP’s influent were 208 and 350 ng/L (max, 2070 and 550 ng/L, respectively). Erythromycin was the most concentrated antibiotic measured in Benson and Oxford WWTPs influent (max = 6,870 and 2,930 ng/L, respectively). Napthazoline and oxymetazoline were the most frequently detected and concentrated decongestant in the Benson WWTP influent (1650 and 67 ng/L) and effluent (696 and 307 ng/L), respectively, but were below detection in the Oxford WWTP. OC was found in 73% of November 2009’s weekly river samples (max = 193 ng/L), but only in 5% and 0% of the late- and inter-pandemic river samples, respectively. The mean river concentration of each antibiotic during the pandemic largely fell between 17–74 ng/L, with clarithromycin (max = 292 ng/L) and erythromycin (max = 448 ng/L) yielding the highest single measure. In general, the concentration and frequency of detecting antibiotics in the river increased during the pandemic. OC was uniquely well-suited for the wastewater epidemiology approach owing to its nature as a prodrug, recalcitrance and temporally- and spatially-resolved prescription statistics. PMID:25254643

Diversity of Antibiotic Resistance Genes in Enterococcus Strains Isolated from Ready-to-Eat Meat Products.

PubMed

Chajęcka-Wierzchowska, Wioleta; Zadernowska, Anna; Łaniewska-Trokenheim, Łucja

2016-10-25

The objective of the study was to answer the question of whether the ready-to-eat meat products can pose indirect hazard for consumer health serving as reservoir of Enterococcus strains harboring tetracyclines, aminoglycosides, and macrolides resistance genes. A total of 390 samples of ready-to-eat meat products were investigated. Enterococcus strains were found in 74.1% of the samples. A total of 302 strains were classified as: Enterococcus faecalis (48.7%), Enterococcus faecium (39.7%), Enterococcus casseliflavus (4.3%), Enterococcus durans (3.0%), Enterococcus hirae (2.6%), and other Enterococcus spp. (1.7%). A high percentage of isolates were resistant to streptomycin high level (45%) followed by erythromycin (42.7%), fosfomycin (27.2%), rifampicin (19.2%), tetracycline (36.4%), tigecycline (19.9%). The ant(6')-Ia gene was the most frequently found gene (79.6%). Among the other genes that encode aminoglycosides-modifying enzymes, the highest portion of the strains had the aac(6')-Ie-aph(2'')-Ia (18.5%) and aph(3'')-IIIa (16.6%), but resistance of isolates from food is also an effect of the presence of aph(2'')-Ib, aph(2'')-Ic, aph(2'')-Id genes. Resistance to tetracyclines was associated with the presence of tetM (43.7%), tetL (32.1%), tetK (14.6%), tetW (0.7%), and tetO (0.3%) genes. The ermB and ermA genes were found in 33.8% and 18.9% of isolates, respectively. Nearly half of the isolates contained a conjugative transposon of the Tn916/Tn1545 family. Enterococci are widely present in retail ready-to-eat meat products. Many isolated strains (including such species as E. casseliflavus, E. durans, E. hirae, and Enterococcus gallinarum) are antibiotic resistant and carry transferable resistance genes. © 2016 Institute of Food Technologists®.

Synthesis of silver nanoparticles using Dioscorea bulbifera tuber extract and evaluation of its synergistic potential in combination with antimicrobial agents

PubMed Central

Ghosh, Sougata; Patil, Sumersing; Ahire, Mehul; Kitture, Rohini; Kale, Sangeeta; Pardesi, Karishma; Cameotra, Swaranjit S; Bellare, Jayesh; Dhavale, Dilip D; Jabgunde, Amit; Chopade, Balu A

2012-01-01

Background Development of an environmentally benign process for the synthesis of silver nanomaterials is an important aspect of current nanotechnology research. Among the 600 species of the genus Dioscorea, Dioscorea bulbifera has profound therapeutic applications due to its unique phytochemistry. In this paper, we report on the rapid synthesis of silver nanoparticles by reduction of aqueous Ag+ ions using D. bulbifera tuber extract. Methods and results Phytochemical analysis revealed that D. bulbifera tuber extract is rich in flavonoid, phenolics, reducing sugars, starch, diosgenin, ascorbic acid, and citric acid. The biosynthesis process was quite fast, and silver nanoparticles were formed within 5 hours. Ultraviolet-visible absorption spectroscopy, transmission electron microscopy, high-resolution transmission electron microscopy, energy dispersive spectroscopy, and x-ray diffraction confirmed reduction of the Ag+ ions. Varied morphology of the bioreduced silver nanoparticles included spheres, triangles, and hexagons. Optimization studies revealed that the maximum rate of synthesis could be achieved with 0.7 mM AgNO3 solution at 50°C in 5 hours. The resulting silver nanoparticles were found to possess potent antibacterial activity against both Gram-negative and Gram-positive bacteria. Beta-lactam (piperacillin) and macrolide (eryth-romycin) antibiotics showed a 3.6-fold and 3-fold increase, respectively, in combination with silver nanoparticles selectively against multidrug-resistant Acinetobacter baumannii. Notable synergy was seen between silver nanoparticles and chloramphenicol or vancomycin against Pseudomonas aeruginosa, and was supported by a 4.9-fold and 4.2-fold increase in zone diameter, respectively. Similarly, we found a maximum 11.8-fold increase in zone diameter of streptomycin when combined with silver nanoparticles against E. coli, providing strong evidence for the synergistic action of a combination of antibiotics and silver nanoparticles. Conclusion This is the first report on the synthesis of silver nanoparticles using D. bulbifera tuber extract followed by an estimation of its synergistic potential for enhancement of the antibacterial activity of broad spectrum antimicrobial agents. PMID:22334779

Synthesis of silver nanoparticles using Dioscorea bulbifera tuber extract and evaluation of its synergistic potential in combination with antimicrobial agents.

PubMed

Ghosh, Sougata; Patil, Sumersing; Ahire, Mehul; Kitture, Rohini; Kale, Sangeeta; Pardesi, Karishma; Cameotra, Swaranjit S; Bellare, Jayesh; Dhavale, Dilip D; Jabgunde, Amit; Chopade, Balu A

2012-01-01

Development of an environmentally benign process for the synthesis of silver nanomaterials is an important aspect of current nanotechnology research. Among the 600 species of the genus Dioscorea, Dioscorea bulbifera has profound therapeutic applications due to its unique phytochemistry. In this paper, we report on the rapid synthesis of silver nanoparticles by reduction of aqueous Ag(+) ions using D. bulbifera tuber extract. Phytochemical analysis revealed that D. bulbifera tuber extract is rich in flavonoid, phenolics, reducing sugars, starch, diosgenin, ascorbic acid, and citric acid. The biosynthesis process was quite fast, and silver nanoparticles were formed within 5 hours. Ultraviolet-visible absorption spectroscopy, transmission electron microscopy, high-resolution transmission electron microscopy, energy dispersive spectroscopy, and x-ray diffraction confirmed reduction of the Ag(+) ions. Varied morphology of the bioreduced silver nanoparticles included spheres, triangles, and hexagons. Optimization studies revealed that the maximum rate of synthesis could be achieved with 0.7 mM AgNO(3) solution at 50°C in 5 hours. The resulting silver nanoparticles were found to possess potent antibacterial activity against both Gram-negative and Gram-positive bacteria. Beta-lactam (piperacillin) and macrolide (eryth-romycin) antibiotics showed a 3.6-fold and 3-fold increase, respectively, in combination with silver nanoparticles selectively against multidrug-resistant Acinetobacter baumannii. Notable synergy was seen between silver nanoparticles and chloramphenicol or vancomycin against Pseudomonas aeruginosa, and was supported by a 4.9-fold and 4.2-fold increase in zone diameter, respectively. Similarly, we found a maximum 11.8-fold increase in zone diameter of streptomycin when combined with silver nanoparticles against E. coli, providing strong evidence for the synergistic action of a combination of antibiotics and silver nanoparticles. This is the first report on the synthesis of silver nanoparticles using D. bulbifera tuber extract followed by an estimation of its synergistic potential for enhancement of the antibacterial activity of broad spectrum antimicrobial agents.

Stepwise impact of urban wastewater treatment on the bacterial community structure, antibiotic contents, and prevalence of antimicrobial resistance.

PubMed

Wang, Mingyu; Shen, Weitao; Yan, Lei; Wang, Xin-Hua; Xu, Hai

2017-12-01

Bacteria, antibiotics, and antibiotic resistance determinants are key biological pollutants in aquatic systems, which may lead to bacterial infections or prevent the cure of bacterial infections. In this study, we investigated how the wastewater treatment processes in wastewater treatment plants (WWTPs) affect these pollutants. We found that the addition of oxygen, polyaluminum chloride (PAC), and polyacrylamide (PAM), as well as ultraviolet (UV) disinfection could significantly alter the bacterial communities in the water samples. An overall shift from Gram-negative bacteria to Gram-positive bacteria was observed throughout the wastewater treatment steps, but the overall bacterial biomass was not reduced in the WWTP samples. The antibiotic contents were reduced by the WWTP, but the size of the reduction and the step when antibiotic degradation occurred differed among antibiotics. Ciprofloxacin, sulfamethoxazole and erythromycin could be removed completely by the WWTP, whereas cephalexin could not. The removal of ciprofloxacin, cephalexin, and erythromycin occurred in the anaerobic digester, whereas the removal of sulfamethoxazole occurred after the addition of PAC and PAM, and UV disinfection. Antimicrobial resistance determinants were highly prevalent in all of the samples analyzed, except for those targeting vancomycin and colistin. However, wastewater treatment was ineffective at removing antimicrobial resistance determinants from wastewater. There were strong correlations between intI1, floR, sul1, and ermB, thereby suggesting the importance of integrons for the spread of these antimicrobial resistance genes. In general, this study comprised a stepwise analysis of the impact of WWTPs on three biological pollutants: bacteria, antibiotics, and antimicrobial resistance determinants, where our results suggest that the design of WWTPs needs to be improved to address the threats due to these pollutants. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antimicrobial susceptibility monitoring of mastitis pathogens isolated from acute cases of clinical mastitis in dairy cows across Europe: VetPath results.

PubMed

Thomas, Valérie; de Jong, Anno; Moyaert, Hilde; Simjee, Shabbir; El Garch, Farid; Morrissey, Ian; Marion, Hervé; Vallé, Michel

2015-07-01

VetPath is an ongoing pan-European antimicrobial susceptibility monitoring programme collecting pathogens from diseased cattle, pigs and poultry not recently treated with antibiotics. Non-replicate milk samples were collected from cows with acute clinical mastitis in eight countries. Escherichia coli, Staphylococcus aureus and Streptococcus uberis were isolated by standardised methods. Antimicrobial susceptibility was determined in a central laboratory by CLSI broth microdilution methodology; results were interpreted using clinical breakpoints where available. Among E. coli (n=280), resistance to tetracycline (14.3%) and cefapirin (11.1%) were most common. Resistance to other β-lactam antibiotics was absent (ceftiofur) or very low (cefalexin, amoxicillin/clavulanic acid). The MIC90 of enrofloxacin and marbofloxacin was 0.03 and 0.06μg/mL, respectively, with 0.7% of strains displaying a deviating high MIC. Staphylococcus aureus (n=250) were susceptible to most antibiotics tested, although 36.0% were resistant to penicillin G. For other β-lactam antibiotics where a CLSI breakpoint was available, no resistance was detected. Tetracycline resistance was low (5.2%). Streptococcus uberis (n=282) were susceptible to all β-lactam antibiotics, although 29.8% were intermediately susceptible to penicillin G; 18.8% of strains were resistant to erythromycin and 28.7% to tetracycline. This European study shows that bacteria associated with acute clinical mastitis are susceptible to most antibiotics with the exception of penicillin G against S. aureus, and erythromycin and tetracycline against S. uberis. The results of this study should serve as a reference baseline. This work also highlights the urgent need to set additional clinical breakpoints for antibiotics frequently used to treat mastitis. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

[Severe legionellosis after abuse of anti-inflammatory drugs--diagnostic and intensive care aspects based on a case report].

PubMed

Bein, T; Ehret, W; Metz, C; Hobbhahn, J; Taeger, K

1995-06-01

Legionella infections are getting increasingly important as causes of severe pneumonias or of acute respiratory insufficiency. Consumptive or immunosuppressive underlying diseases such as diabetes mellitus, cardiac insufficiency, alcohol-induced liver damage, malignant tumours or drug-induced immunosuppression after organ transplantation, are among the risk factors. Diagnosis is based on direct identification of the pathogen from body secretions by means of direct immunofluorescence. The serological immunoresponse often takes place long after outbreak of the disease or fails entirely to appear and is therefore only suitable for retrospective confirmation. Therapy of choice is an intravenous administration of erythromycin. There are now increasing pointers to the efficiency of fluoroquinolone antibiotics, such as ciprofloxacin. We report on the course of a severe case of legionnaire's disease with multiple organ failure occurring in a patient after bone marrow depression induced by anti-inflammatory drugs. Treatment erythromycin resulted in a marked cholestasis, so that antibiotic treatment was changed to ciprofloxacin. This therapy as well as the supportive intensive-care treatment eventually led to the patient's complete recovery. Based on the case report, fundamental aspects of diagnostics, antibiotic treatment, intensive-care treatment and prognosis of severe cases of legionellosis are discussed.

SULFAMETHOXAZOLE-TRIMETHOPRIM TREATMENT OF GUINEA PIGS INFECTED WITH 'LEGIONELLA PNEUMPOPHILA'

EPA Science Inventory

Legionnaires' disease is a bacterial pneumonia caused by Legionella pneumophila. Many antibiotics inhibit the growth of L. pneumophila in vitro, but only erythromycin and rifampin have been clinically effective. Parallel results have been observed in guinea pigs infected ip with ...

Are Sewage Treatment Plants Promoting Antibiotic Resistance?

EPA Science Inventory

1. Introduction 1.1. How bacteria exhibit resistance 1.1.1. Resistance to -lactams 1.1.2. Resistance to sulphonamides and trimethoprim 1.1.3. Resistance to macrolides 1.1.4. Resistance to fluoroquinolones 1.1.5. Resistance to tetracyclines 1.1.6. Resistance to nitroimidaz...

Emergence of antibiotic-resistant non-vaccine serotype pneumococci in nasopharyngeal carriage in children after the use of extended-valency pneumococcal conjugate vaccines in Korea.

PubMed

Choe, Young June; Lee, Hoan Jong; Lee, Hyunju; Oh, Chi Eun; Cho, Eun Young; Choi, Jae Hong; Kang, Hyun Mi; Yoon, In Ae; Jung, Hyun Joo; Choi, Eun Hwa

2016-09-14

This study was performed to assess the serotype distribution and antibiotic nonsusceptibility of pneumococcal carriage isolates from children in Korea following the introduction of extended-valency pneumococcal conjugate vaccines (PCVs). From April to June 2014, nasopharyngeal swabs were collected from children who were attending daycare centers in Korea. The collection was conducted in accordance with the World Health Organization Pneumococcal Carriage Working Group standards. Isolates were identified based on colony morphology, the presence of alpha-hemolysis, and inhibition by optochin test. Serotype was determined by Quellung reaction and sequencing analysis (for serogroup 6). The E-test was performed to determine antibiotic susceptibility. A total of 267 pneumococcal isolates were collected from 734 children. Non-PCV13 serotypes accounted for 88.3% and 23A (12.6%), 15B (10.4%), and 15C (9.5%) were most common. Younger age was associated with higher carriage (65.6% vs. 31.2%, P<0.001), while completion of PCV vaccination was associated with lower carriage caused by PCV13 serotypes (7.4% vs. 20.8%, P=0.007). Overall, nonsusceptibility rates were 86.0% to penicillin and 90.5% to erythromycin, with a multidrug resistance rate of 81.5%. Among penicillin-nonsusceptible isolates, those caused by PCV13 serotypes were 11% and non-PCV13 serotypes were 89%. Frequent non-PCV13 serotypes (23A, 15B, and 15C) were all nonsusceptible to both penicillin and erythromycin except one. High rates of carriage caused by non-PCV13 serotypes such as 23A, 15B, and 15C that show nonsusceptibilities to penicillin and erythromycin were noted following the introduction of extended-valency PCVs in Korea. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genetic diversity and clonal characteristics of ciprofloxacin-resistant Campylobacter jejuni isolated from Chilean patients with gastroenteritis.

PubMed

Collado, Luis; Muñoz, Nataly; Porte, Lorena; Ochoa, Sofía; Varela, Carmen; Muñoz, Ivo

2018-03-01

Campylobacter jejuni is a major cause of acute gastroenteritis worldwide. However, it has also been associated with other diseases such as bacteremia and with several post-infection sequelae. Although campylobacteriosis is usually a self-limited infection, antibiotics are indicated for severe and chronic conditions. Unfortunately, several industrialised nations have reported a substantial increase in antibiotic resistance of C. jejuni. However, there is still a lack of knowledge about the epidemiology of resistance developed by this pathogen in the developing world. For this reason, our objective was to determine the resistance of clinical C. jejuni strains to ciprofloxacin and erythromycin in Chile and their associated genotypes. Fifty C. jejuni isolates recovered from fecal samples of people with acute gastroenteritis, in central and southern Chile between 2006 and 2015, were analysed. Resistance to erythromycin and ciprofloxacin was assessed by disk diffusion and agar dilution methods. Furthermore, these strains were genotyped by Multilocus Sequence Typing (MLST). Only one of the isolates was resistant to erythromycin. However, 48% of them were resistant to ciprofloxacin. The minimal inhibitory concentration of these ciprofloxacin-resistant isolates was in the range between 4 and 32 μg/ml. Moreover, MLST analyses showed that most ciprofloxacin-resistant strains were grouped into three dominant clonal complexes (ST-21, ST-48 and ST-353), while the unique strain resistant to both antibiotics belonged to the ST-45 complex. Our results evidence a high ciprofloxacin resistance and suggest that there is a dissemination of resistant clonal lineages responsible for cases of campylobacteriosis in Chile. Further studies should elucidate the origin of these resistant genotypes. Copyright © 2018 Elsevier B.V. All rights reserved.

Characterization of in vivo-acquired resistance to macrolides of Mycoplasma gallisepticum strains isolated from poultry

PubMed Central

2011-01-01

The macrolide class of antibiotics, including tylosin and tilmicosin, is widely used in the veterinary field for prophylaxis and treatment of mycoplasmosis. In vitro susceptibility testing of 50 strains of M. gallisepticum isolated in Israel during the period 1997-2010 revealed that acquired resistance to tylosin as well as to tilmicosin was present in 50% of them. Moreover, 72% (13/18) of the strains isolated from clinical samples since 2006 showed acquired resistance to enrofloxacin, tylosin and tilmicosin. Molecular typing of the field isolates, performed by gene-target sequencing (GTS), detected 13 molecular types (I-XIII). Type II was the predominant type prior to 2006 whereas type X, first detected in 2008, is currently prevalent. All ten type X strains were resistant to both fluoroquinolones and macrolides, suggesting selective pressure leading to clonal dissemination of resistance. However, this was not a unique event since resistant strains with other GTS molecular types were also found. Concurrently, the molecular basis for macrolide resistance in M. gallisepticum was identified. Our results revealed a clear-cut correlation between single point mutations A2058G or A2059G in domain V of the gene encoding 23S rRNA (rrnA, MGA_01) and acquired macrolide resistance in M. gallisepticum. Indeed, all isolates with MIC ≥ 0.63 μg/mL to tylosin and with MIC ≥ 1.25 μg/mL to tilmicosin possess one of these mutations, suggesting an essential role in decreased susceptibility of M. gallisepticum to 16-membered macrolides. PMID:21810258

Negative environmental impacts of antibiotic-contaminated effluents from pharmaceutical industries.

PubMed

Bielen, Ana; Šimatović, Ana; Kosić-Vukšić, Josipa; Senta, Ivan; Ahel, Marijan; Babić, Sanja; Jurina, Tamara; González Plaza, Juan José; Milaković, Milena; Udiković-Kolić, Nikolina

2017-12-01

Effluents from pharmaceutical industries are recognized as significant contributors to aquatic pollution with antibiotics. Although such pollution has been mostly reported in Asia, knowledge on industrial discharges in other regions of the world, including Europe, and on the effects associated with such exposures is still limited. Thus, we performed chemical, microbiological and ecotoxicological analyses of effluents from two Croatian pharmaceutical industries during four seasons. In treated effluents of the company synthesizing macrolide antibiotic azithromycin (AZI), the total concentration of AZI and two macrolide by-products from its synthesis was 1-3 orders of magnitude higher in winter and springtime (up to 10.5 mg/L) than during the other two seasons (up to 638 μg/L). Accordingly, the highest total concentrations (up to 30 μg/L) in the recipient river were measured in winter and spring. Effluents from second company formulating veterinary antibiotics contained fluoroquinolones, trimethoprim, sulfonamides and tetracyclines ranging from low μg/L to approx. 200 μg/L. Low concentrations of these antibiotics, from below the limit of quantification to approx. few μg/L, have also been measured in the recipient stream. High frequency of culturable bacteria resistant to AZI (up to 83%) or sulfamethazine (up to 90%) and oxytetracycline (up to 50%) were also found in studied effluents. Finally, we demonstrated that toxicity to algae and water fleas often exceeded the permitted values. Most highly contaminated effluents induced multiple abnormalities in zebrafish embryos. In conclusion, using a wide array of analyses we have demonstrated that discharges from pharmaceutical industries can pose a significant ecological and public health concern due to their toxicity to aquatic organisms and risks for promoting development and spread of antibiotic resistance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Folliculitis decalvans--a retrospective study in a tertiary referred centre, over five years.

PubMed

Chandrawansa, P H; Giam, Y C

2003-02-01

Folliculitis decalvans is a rare condition affecting mainly the scalp leading to scarring alopecia. Aetiology of the condition is still unknown, abnormal host response to Staphylococcus aureus has been postulated. We present a retrospective analysis of six cases of folliculitis decalvans presented to National Skin Centre (NSC), Singapore for the past five years, 1995-2000. The mean age of presentation was 39 years and ages ranged from 17 to 62 years. There were five male patients and one female patient. Duration of symptoms at presentation varied from six months to seven years. Occipital and vertex areas of the scalp were the only regions involved. Staphylococcus aureus was isolated in three patients; in one patient culture yielded negative results and no culture was done in the other two patients. All our patients were treated with several separate courses of systemic antibiotics which include doxycycline, erythromycin, minocycline, co-trimoxazole, cloxacillin, erythromycin, rifampicin and clindamycin. In addition one patient was treated with fucidic acid and zinc sulphate. The disease ran a protracted course with temporary improvement while on antibiotic and flare up of disease when antibiotics were stopped. The effectiveness of early treatment with rifampicin has been highlighted in some case reports in the past. We did use rifampicin in one of our patients. Our concern over emergence of antibiotic resistance, if used widely, may not permit us to use rifampicin on a wide scale.

Antimicrobial resistant coliform bacteria in the Gomti river water and determination of their tolerance level.

PubMed

Akhter, Asma; Imran, Mohd; Akhter, Firoz

2014-01-01

The distribution of resistance to ampicillin, chloramphenicol, sulfonamides, tetracycline, and streptomycin among coliform in the Gomti river water samples was investigated. The coliform populations were isolated on Mac Conky and eosin methylene blue (EMB) agar plates supplemented with antibiotics. The incidence of resistance among the coliform population varied considerably in different drug and water sampling sites. Coliform bacteria showed lower drug resistant viable count in sampling site-III (receiving treated wastewater) as compared to more polluted site-I and site-II. Viable count of coliform population obtained on both medium was recorded higher against erythromycin from sampling site-III. Lower viable count of coliforms was recorded against tetracycline in site-II and III. Similar resistance pattern was obtained in the frequency of E. coli and Enterobacter species from all the three sampling sites. Percentage of antibiotic resistant E. coli was observed higher than Enterobacter spp among the total coliforms against all antibiotics tested without Erythromycin and penicillin in site-I and II respectively. Isolates of E. coli and Enterobacter spp. showed their tolerance level (MIC) in the range of 2-100 against the antibiotics tested. Maximum number of isolates of both genus exhibited their MICs at lower concentration range 2-5µg/ml against ciprofloxacin, tetracyclin and amoxycillin. EMB - Eosin methylene blue, IMViC tests - Indole, Methyl Red, Voges Proskauer and Citrate Utilization Tests, MIC - Minimum inhibitory concentration.

Antimicrobial resistant coliform bacteria in the Gomti river water and determination of their tolerance level

PubMed Central

Akhter, Asma; Imran, Mohd; Akhter, Firoz

2014-01-01

The distribution of resistance to ampicillin, chloramphenicol, sulfonamides, tetracycline, and streptomycin among coliform in the Gomti river water samples was investigated. The coliform populations were isolated on Mac Conky and eosin methylene blue (EMB) agar plates supplemented with antibiotics. The incidence of resistance among the coliform population varied considerably in different drug and water sampling sites. Coliform bacteria showed lower drug resistant viable count in sampling site-III (receiving treated wastewater) as compared to more polluted site-I and site-II. Viable count of coliform population obtained on both medium was recorded higher against erythromycin from sampling site-III. Lower viable count of coliforms was recorded against tetracycline in site-II and III. Similar resistance pattern was obtained in the frequency of E. coli and Enterobacter species from all the three sampling sites. Percentage of antibiotic resistant E. coli was observed higher than Enterobacter spp among the total coliforms against all antibiotics tested without Erythromycin and penicillin in site-I and II respectively. Isolates of E. coli and Enterobacter spp. showed their tolerance level (MIC) in the range of 2-100 against the antibiotics tested. Maximum number of isolates of both genus exhibited their MICs at lower concentration range 2-5µg/ml against ciprofloxacin, tetracyclin and amoxycillin. Abbreviations EMB - Eosin methylene blue, IMViC tests - Indole, Methyl Red, Voges Proskauer and Citrate Utilization Tests, MIC - Minimum inhibitory concentration. PMID:24966515

Biotransformation and recovery of the isoflavones genistein and daidzein from industrial antibiotic fermentations

PubMed Central

Weber, J. Mark; Reeves, Andrew R.; Seshadri, Ramya; Cernota, William H.; Gonzalez, Melissa C.; Gray, Danielle L.; Wesley, Roy K.

2013-01-01

The objective of this study was to follow the metabolic fate of isoflavone glucosides from the soybean meal in a model industrial fermentation to determine if commercially useful isoflavones could be harvested as coproducts from the spent broth at the end of the fermentation. The isoflavone aglycones, genistein and daidzein, together make up 0.1 - 0.2% of the soybean meal by weight but serve no known function in the manufacturing process. After feeding genistein to washed cells of the erythromycin-producing organism, Saccharopolyspora erythraea, the first biotransformation product (Gbp1) was determined by x-ray crystallography to be genistein-7-O-α-rhamnoside (rhamnosylgenistein). Subsequent feeding of rhamnosylgenistein to growing cells of S. erythraea led to the production of a second biotransformation product, Gbp2. Chromatographic evidence suggested that Gbp2 accumulated in the spent broth of the erythromycin fermentation. When the spent broth was hydrolyzed with acid or industrial enzyme preparations the isoflavone biotransformation products were returned back to their parental forms, genistein and daidzein, which were then recovered as coproducts. Desirable features of this method are that it does not require modification of the erythromycin manufacturing process or genetic engineering of the producing organism to be put into practice. A preliminary investigation of five additional antibiotic fermentations of industrial importance were also found to have isoflavone coproduct potential. PMID:23604533

Antibiotic resistance assessment in S. aureus strains isolated from raw sheep's milk cheese.

PubMed

Spanu, V; Virdis, S; Scarano, C; Cossu, F; De Santis, E P L; Cosseddu, A M

2010-06-01

In vitro activities of 16 antibiotics were tested against 36 Staphylococcus aureus (SA) strains isolated from raw sheep's milk cheese from six dairies. The minimum inhibitory concentration (MIC) was determined using a broth microdilution method (CLSI). All 36 isolates were analyzed for the presence of the accessory gene regulator gene, agr (I-IV), and genes encoding resistance to methicillin (mecA), erythromycin (ermA), penicillin (blaZ), and vancomycin (vanA-B). The isolates were also analyzed for similarities in pulsed-field gel electrophoresis (PFGE) patterns. SA strains showed resistance to ampicillin (36.1%), penicillin (33.3%), tetracycline (11.1%), and cloxacillin (2.8%) but were susceptible (>or=94.4%) to 12 out of 16 tested antimicrobials. The overall susceptibility of the strains to oxacillin, vancomycin, and erythromycin was confirmed by the absence of the mecA, vanA-B, and ermA genes. The PFGE results showed that 32 strains belonged to 10 different clusters (P1-P10) while four strains were untypeable.

Mutation in a locus linked to penB-nmp causes suppression of the Mtr phenotype of Neisseria gonorrhoeae.

PubMed Central

Shinners, E N; Catlin, B W

1988-01-01

The chromosomal locus mtr, which encodes low-level resistance to multiple antibacterial agents in Neisseria gonorrhoeae, is subject to phenotypic suppression by env mutations that increase the permeability of the envelope. We have identified a new locus, mom (for modifier of Mtr), which is located on the chromosome very close to penB and nmp, loci known to be linked to each other and to spc. Phenotypic suppression of Mtr was recognized by reductions of resistance to benzylpenicillin and also to oxacillin and the hydrophobic agents novobiocin and erythromycin. The resistance to each of these antibiotics returned to the Mtr levels in mom+ transformants isolated by selection for increased resistance to either novobiocin or erythromycin; the accompanying change of the outer membrane protein I seroreactions confirmed the proximity of nmp and mom. Thus, some mutant gonococci display wild-type antibiotic susceptibilities but can express multiple resistance following a mom+ mutation that releases the suppressed Mtr phenotype. PMID:3142343

Ancient Resistome.

PubMed

Olaitan, Abiola Olumuyiwa; Rolain, Jean-Marc

2016-08-01

Antibiotic resistance is an ancient biological mechanism in bacteria, although its proliferation in our contemporary world has been amplified through antimicrobial therapy. Recent studies conducted on ancient environmental and human samples have uncovered numerous antibiotic-resistant bacteria and resistance genes. The resistance genes that have been reported from the analysis of ancient bacterial DNA include genes coding for several classes of antibiotics, such as glycopeptides, β-lactams, tetracyclines, and macrolides. The investigation of the resistome of ancient bacteria is a recent and emerging field of research, and technological advancements such as next-generation sequencing will further contribute to its growth. It is hoped that the knowledge gained from this research will help us to better understand the evolution of antibiotic resistance genes and will also be used in drug design as a proactive measure against antibiotic resistance.

The distribution and partitioning of common antibiotics in water and sediment of the Pearl River Estuary, South China.

PubMed

Liang, Ximei; Chen, Baowei; Nie, Xiangping; Shi, Zhen; Huang, Xiaoping; Li, Xiangdong

2013-09-01

Antibiotics released into the aquatic environment play an important role in the spread of antibiotic resistance. In the Pearl River Estuary (PRE) and the coastal zone, the concentrations of antibiotics decreased from the Pearl River to the estuary, suggesting that antibiotics primarily originated from river tributaries and terrigenous sources. Within the PRE area, the concentrations of antibiotics in water were higher in the west coast than the east side, reflecting the high density of anthropogenic activities and hydraulic conditions along the west riverbank. Seasonal variations were also observed for most of detected antibiotics in water. The pseudo-partitioning coefficient of norfloxacin had a good correlation with the TOC content of sediments, as did erythromycin-H2O with the pH of water. The results suggest that environmental conditions can significantly affect the distribution of antibiotics between water and sediment. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Analysis of antibiotic susceptibility of foodborne Listeria monocytogenes in China].

PubMed

Yang, Yang; Fu, Ping; Guo, Yunchang; Liu, Xiurmei

2008-03-01

To study the antibiotic susceptibility of foodborne Listeria monocytogenes in China. The susceptibilities of 476 strains of foodborne Listeria monocytogenes to antibiotics were determined in Broth Microdilution Susceptibility Testing in Clinical and Laboratory Standards Institute. The antibiotics of gentamicin, ampicillin, penicillin, tetracycline, doxycycline, imipenem, erythromycin, ciprofloxacin, levofloxacin, cephalothin, rifampin, vancomycin, chloramphenicol, Trimethoprim-sulfamethoxazole, ampicillin-sulbactam were used. The rates of antibiotic resistance in 467 is olates were 4.5%. Tetracycline resistance was most prevalent, accouting for 4.07% . The foods that the rates of antibiotic resistance were highest were vegetable (10%). Among 14 provinces, Jilin, Hubei and Hebei were the third top, the rate of which were 19.6% and 9.1% and 8%, respectively. It was suggested that antibiotic resistance exists in foodborne Listeria monocytogenes to a certain extent in China. It should pay more attention to the use of drugs in prevention and clinic treatment to reduce the antibiotic resistant strains.

Contamination Profiles and Mass Loadings of Macrolide Antibiotics and Illicit Drugs from a Small Urban Wastewater Treatment Plant

EPA Science Inventory

Information is limited regarding sources, distribution, environmental behavior, and fate of prescribed and illicit drugs. Wastewater treatment plant (WWTP) effluents can be one of the sources of pharmaceutical and personal care products (PPCP) into streams, rivers and lakes. The ...

Seasonal variation of macrolide resistance gene abundances in the South Fork Iowa River Watershed

USDA-ARS?s Scientific Manuscript database

The Midwestern United States is dominated by agricultural production with high concentrations of swine, leading to application of swine manure onto lands with artificial subsurface drainage. Previous reports have indicated elevated levels of antibiotic resistance genes (ARGs) in surface water and gr...

Evaluation of a Microbiological Multi-Residue System on the detection of antibacterial substances in ewe milk.

PubMed

Althaus, Rafael; Berruga, Maria Isabel; Montero, Ana; Roca, Marta; Molina, Maria Pilar

2009-01-19

To protect both, public health and the dairy industry, from the presence of antibiotic residues in milk, control programmes have been established, which include the needed screening tests. This work focuses on the application of a Microbiological Multi-Residue System in ewe milk, a method based on the use of six different plates, each seeded with one of the following bacteria: Geobacillus stearothermophilus var. calidolactis (beta-lactams), Bacillus subtilis at pH 8.0 (aminoglycosides), Kocuria rhizophila (macrolides), Escherichia coli (quinolones), B. cereus (tetracyclines) and B. subtilis at pH 7.0 (sulphonamides), respectively. Twenty-three antimicrobial substances were analysed and a logistic regression was established for each substance assayed to relate the antibiotic concentration and the zone of microbial growth inhibition. Great linearity in the response was observed (regression coefficients of over 0.97). This fact suggests the possibility of establishing a decision level of antibiotic concentrations near to the Maximum Residue Limits (MRL). Zones of inhibition were suggested as proposed action levels for the different antimicrobial groups (diameters of inhibition of 18 mm for the aminoglycoside, beta-lactam and sulphonamide plates; 19 mm for the tetracycline plate, 21 mm for the macrolide plate, and 24 mm for the quinolone plate). Specificity and cross-reactivity were also assayed.

The suppository form of antibiotic administration: pharmacokinetics and clinical application.

PubMed

Bergogne-Bérézin, E; Bryskier, A

1999-02-01

The rectal route of antibiotic administration might be used effectively when other routes of administration are inadequate or unsuitable. With the use of various adjuvants, the rectal route can provide satisfactory pharmacokinetics and acceptable local tolerance. Experiments in animals have demonstrated the influence of the pharmaceutical formulation of suppositories on the rectal absorption and systemic distribution of beta-lactams and aminoglycosides. In healthy volunteers and in children under treatment, similar adjuvants--mainly glyceride mixtures or non-ionic surface agents--have increased the rectal absorption of aminopenicillins, cephalosporins and macrolides. Other antibiotics, including metronidazole and cotrimoxazole, have been investigated in respect of their potential rectal administration.

Community-Acquired Legionella pneumophila Pneumonia

PubMed Central

Viasus, Diego; Di Yacovo, Silvana; Garcia-Vidal, Carolina; Verdaguer, Ricard; Manresa, Frederic; Dorca, Jordi; Gudiol, Francesc; Carratalà, Jordi

2013-01-01

Abstract Legionella pneumophila has been increasingly recognized as a cause of community-acquired pneumonia (CAP) and an important public health problem worldwide. We conducted the present study to assess trends in epidemiology, diagnosis, clinical features, treatment, and outcomes of sporadic community-acquired L. pneumophila pneumonia requiring hospitalization at a university hospital over a 15-year period (1995–2010). Among 3934 nonimmunosuppressed hospitalized patients with CAP, 214 (5.4%) had L. pneumophila pneumonia (16 cases were categorized as travel-associated pneumonia, and 21 were part of small clusters). Since the introduction of the urinary antigen test, the diagnosis of L. pneumophila using this method remained stable over the years (p = 0.42); however, diagnosis by means of seroconversion and culture decreased (p < 0.001 and p = 0.001, respectively). The median age of patients with L. pneumophila pneumonia was 58.2 years (SD 13.8), and 76.4% were male. At least 1 comorbid condition was present in 119 (55.6%) patients with L. pneumophila pneumonia, mainly chronic heart disease, diabetes mellitus, and chronic pulmonary disease. The frequency of older patients (aged >65 yr) and comorbidities among patients with L. pneumophila pneumonia increased over the years (p = 0.06 and p = 0.02, respectively). In addition, 100 (46.9%) patients were classified into high-risk classes according to the Pneumonia Severity Index (groups IV–V). Twenty-four (11.2%) patients with L. pneumophila pneumonia received inappropriate empirical antibiotic therapy at hospital admission. Compared with patients who received appropriate empirical antibiotic, patients who received inappropriate therapy more frequently had acute onset of illness (p = 0.004), pleuritic chest pain (p = 0.03), and pleural effusion (p = 0.05). The number of patients who received macrolides decreased over the study period (p < 0.001), whereas the number of patients who received levofloxacin increased (p < 0.001). No significant difference was found in the outcomes between patients who received erythromycin and clarithromycin. However, compared with macrolide use during hospital admission, levofloxacin therapy was associated with a trend toward a shorter time to reach clinical stability (median, 3 vs. 5 d; p = 0.09) and a shorter length of hospital stay (median, 7 vs. 10 d; p < 0.001). Regarding outcomes, 38 (17.8%) patients required intensive care unit (ICU) admission, and the inhospital case-fatality rate was 6.1% (13 of 214 patients). The frequency of ICU admission (p = 0.34) and the need for mechanical ventilation (p = 0.57) remained stable over the study period, but the inhospital case-fatality rate decreased (p = 0.04). In the logistic regression analysis, independent factors associated with severe disease (ICU admission and death) were current/former smoker (odds ratio [OR], 2.96; 95% confidence interval [CI], 1.01–8.62), macrolide use (OR, 2.40; 95% CI, 1.03–5.56), initial inappropriate therapy (OR, 2.97; 95% CI, 1.01–8.74), and high-risk Pneumonia Severity Index classes (OR, 9.1; 95% CI, 3.52–23.4). In conclusion, L. pneumophila is a relatively frequent causative pathogen among hospitalized patients with CAP and is associated with high morbidity. The annual number of L. pneumophila cases remained stable over the study period. In recent years, there have been significant changes in diagnosis and treatment, and the inhospital case-fatality rate of L. pneumophila pneumonia has decreased. PMID:23266795

Community-acquired Legionella pneumophila pneumonia: a single-center experience with 214 hospitalized sporadic cases over 15 years.

PubMed

Viasus, Diego; Di Yacovo, Silvana; Garcia-Vidal, Carolina; Verdaguer, Ricard; Manresa, Frederic; Dorca, Jordi; Gudiol, Francesc; Carratalà, Jordi

2013-01-01

Legionella pneumophila has been increasingly recognized as a cause of community-acquired pneumonia (CAP) and an important public health problem worldwide. We conducted the present study to assess trends in epidemiology, diagnosis, clinical features, treatment, and outcomes of sporadic community-acquired L. pneumophila pneumonia requiring hospitalization at a university hospital over a 15-year period (1995-2010). Among 3934 nonimmunosuppressed hospitalized patients with CAP, 214 (5.4%) had L. pneumophila pneumonia (16 cases were categorized as travel-associated pneumonia, and 21 were part of small clusters). Since the introduction of the urinary antigen test, the diagnosis of L. pneumophila using this method remained stable over the years (p = 0.42); however, diagnosis by means of seroconversion and culture decreased (p < 0.001 and p = 0.001, respectively). The median age of patients with L. pneumophila pneumonia was 58.2 years (SD 13.8), and 76.4% were male. At least 1 comorbid condition was present in 119 (55.6%) patients with L. pneumophila pneumonia, mainly chronic heart disease, diabetes mellitus, and chronic pulmonary disease. The frequency of older patients (aged >65 yr) and comorbidities among patients with L. pneumophila pneumonia increased over the years (p = 0.06 and p = 0.02, respectively). In addition, 100 (46.9%) patients were classified into high-risk classes according to the Pneumonia Severity Index (groups IV-V). Twenty-four (11.2%) patients with L. pneumophila pneumonia received inappropriate empirical antibiotic therapy at hospital admission. Compared with patients who received appropriate empirical antibiotic, patients who received inappropriate therapy more frequently had acute onset of illness (p = 0.004), pleuritic chest pain (p = 0.03), and pleural effusion (p = 0.05). The number of patients who received macrolides decreased over the study period (p < 0.001), whereas the number of patients who received levofloxacin increased (p < 0.001). No significant difference was found in the outcomes between patients who received erythromycin and clarithromycin. However, compared with macrolide use during hospital admission, levofloxacin therapy was associated with a trend toward a shorter time to reach clinical stability (median, 3 vs. 5 d; p = 0.09) and a shorter length of hospital stay (median, 7 vs. 10 d; p < 0.001). Regarding outcomes, 38 (17.8%) patients required intensive care unit (ICU) admission, and the inhospital case-fatality rate was 6.1% (13 of 214 patients). The frequency of ICU admission (p = 0.34) and the need for mechanical ventilation (p = 0.57) remained stable over the study period, but the inhospital case-fatality rate decreased (p = 0.04). In the logistic regression analysis, independent factors associated with severe disease (ICU admission and death) were current/former smoker (odds ratio [OR], 2.96; 95% confidence interval [CI], 1.01-8.62), macrolide use (OR, 2.40; 95% CI, 1.03-5.56), initial inappropriate therapy (OR, 2.97; 95% CI, 1.01-8.74), and high-risk Pneumonia Severity Index classes (OR, 9.1; 95% CI, 3.52-23.4). In conclusion, L. pneumophila is a relatively frequent causative pathogen among hospitalized patients with CAP and is associated with high morbidity. The annual number of L. pneumophila cases remained stable over the study period. In recent years, there have been significant changes in diagnosis and treatment, and the inhospital case-fatality rate of L. pneumophila pneumonia has decreased.

Experimental pleurodesis induced by antibiotics (macrolides or quinolones).

PubMed

Teixeira, Lisete R; Vargas, Francisco S; Acencio, Milena M P; Bumlai, Renan U M; Antonangelo, Leila; Marchi, Evaldo

2006-12-01

Chemical pleurodesis is a therapeutic tool for the treatment of recurrent pleural effusions, mainly those of neoplastic etiology. In the past, tetracycline was the sclerosant agent of choice in clinical practice, but presently, there is no consensus about an ideal agent. The aim of this study was to evaluate the effectiveness of macrolides (azithromycin and clarithromycin) or quinolones (levofloxacin and gatifloxacin) in inducing experimental pleurodesis in rabbits. Forty New Zealand rabbits randomized into groups of 10 received (at a total volume of 2 mL for each animal) 1 of the 4 drugs by intrapleural injection. After 28 days, the animals were euthanized and the pleural cavity was evaluated macroscopically and microscopically. The intensity of the macroscopic adhesions was mild in all groups. On microscopic analysis, minimal pleural fibrosis and inflammation were observed in all animals. The macrolides (azithromycin or clarithromycin) and the quinolones (levofloxacin or gatifloxacin) when injected into the normal pleural space of rabbits are not effective in promoting pleurodesis. Additional research is required to identify sclerosing agents capable of inducing pleurodesis.

Co-selection of antibiotic resistance via copper shock loading on bacteria from a drinking water bio-filter.

PubMed

Zhang, Menglu; Chen, Lihua; Ye, Chengsong; Yu, Xin

2018-02-01

Heavy metal contamination of source water frequently occurred in developing countries as a result of accidents. To address the problems, most of the previous studies have focused on engineering countermeasures. In this study, we investigated the effects of heavy metals, particularly copper, on the development of antibiotic resistance by establishing a copper shock loading test. Results revealed that co-selection occurred rapidly within 6 h. Copper, at the levels of 10 and 100 mg/L, significantly increased bacterial resistance to the antibiotics tested, including rifampin, erythromycin, kanamycin, and a few others. A total of 117 antimicrobial-resistance genes were detected from 12 types of genes, and the relative abundance of most genes (particularly mobile genetic elements intⅠand transposons) was markedly enriched by at least one fold. Furthermore, the copper shock loading altered the bacterial community. Numerous heavy metal and antibiotic resistant strains were screened out and enriched. These strains are expected to enhance the overall level of resistance. More noticeably, the majority of the co-selected antibiotic resistance could sustain for at least 20 h in the absence of copper and antimicrobial drugs. Resistance to vancomycin, erythromycin and lincomycin even could remain for 7 days. The prominent selection pressure by the copper shock loading implies that a real accident most likely poses similar impacts on the water environment. An accidental release of heavy metals would not only cause harm to the ecological environment, but also contribute to the development of bacterial antibiotic resistance. Broader concerns should be raised about the biological risks caused by sudden releases of pollutants by accidents. Copyright © 2017. Published by Elsevier Ltd.

Prevalence of methicillin resistance and macrolide-lincosamide-streptogramin B resistance in Staphylococcus haemolyticus among clinical strains at a tertiary-care hospital in Thailand.

PubMed

Teeraputon, S; Santanirand, P; Wongchai, T; Songjang, W; Lapsomthob, N; Jaikrasun, D; Toonkaew, S; Tophon, P

2017-09-01

Staphylococcus spp. is a major cause of nosocomial infection and sepsis. However, increasing drug resistance is becoming a challenge to microbiologists. The purpose of this study was to identify and determine antimicrobial resistance phenotypes and drug resistance genes of clinical coagulase-negative staphylococci (CoNS) isolates at Mae Sot Hospital in Tak province, Thailand. A total of 229 CoNS isolates were collected from clinical specimens during two periods in 2014 and in 2015. Staphylococcus haemolyticus was the most prevalent species (37.55%), followed by S. epidermidis (21.83%), S. saprophyticus (11.79%) and S. hominis (11.35%) respectively. The remaining 17.48% of the organisms comprised S. capitis, S. arlettae, S. cohnii, S. equorum, S. xylosus, S. warneri, S. sciuri, S. pettenkoferi, S. kloosii and S. lugdunensis. Methicillin-resistant CoNS (MRCoNS), containing the mec A gene, were detected in 145 of 229 isolates, mostly found in S. haemolyticus and S. epidermidis. In addition, the differentiation of their macrolide-lincosamide-streptogramin B (MLS B ) resistance phenotypes was determined by the D-test and corresponding resistance genes. Among 125 erythromycin-resistant CoNS, the prevalence of constitutive type of MLS B , inducible clindamycin resistance and macrolide-streptogramin B resistance phenotypes were 72, 13.60 and 14.40% respectively. These phenotypes were expressed in 80% of MRCoNS strains. In addition, the erm C gene (79.20%) was found to be more prevalent than the erm A gene (22.40%), especially among MRCoNS. These results indicate that CoNS may play an important role in spreading of drug resistance genes. More attention to these organisms in surveillance and monitoring programs is needed.

Antimicrobial resistance genes in Actinobacillus pleuropneumoniae, Haemophilus parasuis and Pasteurella multocida isolated from Australian pigs.

PubMed

Dayao, Dae; Gibson, J S; Blackall, P J; Turni, C

2016-07-01

To identify genes associated with the observed antimicrobial resistance in Actinobacillus pleuropneumoniae, Haemophilus parasuis and Pasteurella multocida isolated from Australian pigs. Isolates with known phenotypic resistance to β-lactams, macrolides and tetracycline were screened for the presence of antimicrobial resistance genes. A total of 68 A. pleuropneumoniae, 62 H. parasuis and 20 P. multocida isolates exhibiting phenotypic antimicrobial resistance (A. pleuropneumoniae and P. multocida) or elevated minimal inhibitory concentrations (MICs) (H. parasuis) to any of the following antimicrobial agents - ampicillin, erythromycin, penicillin, tetracycline, tilmicosin and tulathromycin - were screened for a total of 19 associated antimicrobial resistance genes (ARGs) by PCR. The gene bla ROB-1 was found in all ampicillin- and penicillin-resistant isolates, but none harboured the bla TEM-1 gene. The tetB gene was found in 76% (74/97) of tetracycline-resistant isolates, 49/53 A. pleuropneumoniae, 17/30 H. parasuis and 8/14 P. multocida. One A. pleuropneumoniae isolate harboured the tetH gene, but none of the 97 isolates had tetA, tetC, tetD, tetE, tetL, tetM or tetO. A total of 92 isolates were screened for the presence of macrolide resistance genes. None was found to have ermA, ermB, ermC, erm42, mphE, mefA, msrA or msrE. The current study has provided a genetic explanation for the resistance or elevated MIC of the majority of isolates of Australian porcine respiratory pathogens to ampicillin, penicillin and tetracycline. However, the macrolide resistance observed by phenotypic testing remains genetically unexplained and further studies are required. © 2016 Australian Veterinary Association.

Six-Year Retrospective Review of Hospital Data on Antimicrobial Resistance Profile of Staphylococcus aureus Isolated from Skin Infections from a Single Institution in Greece.

PubMed

Stefanaki, Christina; Ieronymaki, Alexandra; Matoula, Theoni; Caroni, Chrysseis; Polythodoraki, Evaggelia; Chryssou, Stella-Eugenia; Kontochristopoulos, George; Antoniou, Christina

2017-12-20

Objective: To determine the prevalence of resistant strains of Staphylococcus aureus ( S. aureus ) isolated from Skin and soft tissue infections (SSTI) to various antibiotics. Material and Methods: All culture-positive results for S. aureus from swabs taken from patients presenting at one Greek hospital with a skin infection between the years 2010-2015 were examined retrospectively. Bacterial cultures, identification of S. aureus and antimicrobial susceptibility testing were performed using the disk diffusion method according to Clinical and Laboratory Standards Institute (CLSI) guidelines and European Committee on Antimicrobial testing (EUCAST) breakpoints. EUCAST breakpoints were applied if no CLSI were available. Results: Of 2069 S. aureus isolates identified, 1845 (88%) were resistant to one or more antibiotics. The highest resistance was observed for benzylpenicillin (71.9%), followed by erythromycin (34.3%). Resistant strains to cefoxitin defined as MRSA (methicillin-resistant S. aureus ) represented 21% of total isolates. Interestingly, resistance to fusidic acid was 22.9% and to mupirocin as high as 12.7%. Low rates were observed for minocycline, rifampicin and trimethoprim/sulfamethoxazole (SXT). Resistance to antibiotics remained relatively stable throughout the six-year period, with the exception of cefoxitin, fusidic acid and SXT. A high percentage of MRSA strains were resistant to erythromycin (60%), fusidic acid (46%), clindamycin (38%) and tetracycline (35.5%). Conclusions: Special attention is required in prescribing appropriate antibiotic therapeutic regimens, particularly for MRSA. These data on the susceptibility of S. aureus may be useful for guiding antibiotic treatment.

Pitted keratolysis, erythromycin, and hyperhidrosis.

PubMed

Pranteda, Guglielmo; Carlesimo, Marta; Pranteda, Giulia; Abruzzese, Claudia; Grimaldi, Miriam; De Micco, Sabrina; Muscianese, Marta; Bottoni, Ugo

2014-01-01

Pitted keratolysis (PK) is a plantar skin disorder mainly caused by coryneform bacteria. A common treatment consists of the topical use of erythromycin. Hyperhidrosis is considered a predisposing factor for bacterial proliferation and, consequently, for the onset of PK. The aim of this study was to evaluate the relationship between PK erythromycin and hyperhidrosis. All patients with PK seen in Sant'Andrea Hospital, between January 2009 and December 2011, were collected. PK was clinically and microscopically diagnosed. All patients underwent only topical treatment with erythromycin 3% gel twice daily. At the beginning of the study and after 5 and 10 days of treatment, a clinical evaluation and a gravimetric measurement of plantar sweating were assessed. A total of 97 patients were diagnosed as PK and were included in the study. Gravimetric measurements showed that in 94 of 97 examined patients (96.90%) at the time of the diagnosis, there was a bilateral excessive sweating occurring specifically in the areas affected by PK. After 10 days of antibiotic therapy, hyperhidrosis regressed together with the clinical manifestations. According to these data, we hypothesize that hyperhidrosis is due to an eccrine sweat gland hyperfunction, probably secondary to bacterial infection. © 2013 Wiley Periodicals, Inc.

Antibiotic susceptibility of enterococci isolated from traditional fermented meat products.

PubMed

Barbosa, J; Ferreira, V; Teixeira, P

2009-08-01

Antibiotic susceptibility was evaluated for 182 Enterococcus spp. isolated from Alheira, Chouriça de Vinhais and Salpicão de Vinhais, fermented meat products produced in the North of Portugal. Previously, a choice was made from a group of 1060 isolates, using phenotypic and genotypic tests. From these, 76 were previously identified as Enterococcus faecalis, 44 as Enterococcus faecium, one as Enterococcus casseliflavus and 61 as Enteroccocus spp. In order to encompass several of the known chemical and functional classes of antibiotics, resistance to ampicillin, penicillin G, ciprofloxacin, chloramphenicol, erythromycin, nitrofurantoin, rifampicin, tetracycline and vancomycin was evaluated. All the isolates were sensitive to antibiotics of clinical importance, such as penicillins and vancomycin. Some differences in Minimal Inhibitory Concentrations (MICs) of antibiotics, could be associated with the enterococcal species.

Determination of josamycin residues in porcine tissues using high-performance liquid chromatography with pre-column derivatization and spectrofluorimetric detection.

PubMed

Leroy, P; Decolin, D; Nicolas, A; Archimbault, P

1994-12-01

A simple, selective and sensitive high-performance liquid chromatographic (HPLC) method has been developed for the measurement of josamycin residues in four porcine tissues (i.e., muscle, liver, kidney and fat). The sample preparation consisted of a homogenization step in an acetonitrile-10 mmol l-1 phosphate buffer mixture, pH 6.0 (35 + 65), centrifugation and a liquid-liquid extractive clean-up of the resulting supernatant with isooctane. Pre-column derivatization of josamycin was performed using cyclohexa-1,3-dione in ammonium acetate buffer, pH 5.0 (90 degrees C for 2 h). The derivative was chromatographed in an isocratic reversed-phase HPLC system. A LiChrospher RP 18 end-capped (5 microns) column was eluted with an acetonitrile-methanol-10 mmol l-1 phosphate buffer mixture, pH 6.0 (45 + 5 + 50). The capacity factor of the josamycin derivative was 17.5. Detection was achieved using spectrofluorimetry (lambda ex = 375 nm; lambda em = 450 nm). The structure of the derivative was assessed by using mass spectrometry. Full selectivity was obtained in the HPLC system versus other macrolide antibiotics (tylosin, spiramycin and erythromycin), aldehydes (formaldehyde, acetaldehyde and benzaldehyde) and endogenous compounds. Linearity and repeatability were tested. Correlation coefficients, for calibration curves in the range of 0.1-3.2 micrograms g-1, were greater than 0.999 for all tissues and the relative standard deviation (S(r)) was 4.9% (1.6 micrograms g-1; n = 6); recovery was higher than 88%.

Emergency Medical Response Capability Analysis

DTIC Science & Technology

1982-07-01

Analgesics, non-narcotic Anesthesia aooaratus Antibiotics and anti-bacterials Basin, qash, solution Antidiabetic Agents (Oral) Blade, surgical Knife...for replace- Holder, suture needle nent therapy Inhaler, anesthesia , Yankauer (atner fask) Local anesthetics Intravenous injection sets Lubricant...Medium-Spectrum Erythromycin Kanamycin Clindamycin Narrow-Spectrum Penicillins Oxacillin Methicillin Streptomycin Gentamicin Other Amphotericin B Nystatin

[A case of legionnaire's disease in Germany (author's transl)].

PubMed

Missalek, W; Helmecke, G

1979-12-07

Severe bronchopneumonia in a 66-year-old patient failed to respond to sensitivity-tested antibiotics, with only erythromycin providing improvement. The indirect immunofluorescence test for legionnaire's disease gave a highly significant titre rise (eightfold). Legionnaire's disease should be considered in the differential diagnosis of treatment-resistant bronchopneumonia.

Comparing HPLC-ESI-ITMS and UPLC-ESI-OA-TOF-MS in Characterizing Macrolide Antibiotics and Illicit Drugs in Complex Environmental Matrices

EPA Science Inventory

Among the challenges of characterizing emerging contaminants in complex environmental matrices (e.g., biosolids, sewage, or wastewater) are the co-eluting interferences. For example, surfactants, fats, and humic acids, can be preferentially ionized instead of the analyte(s) of in...

Production and characterization of monoclonal antibodies against the antibiotic tilmicosin.

PubMed

Beier, Ross C; Creemer, Lawrence C; Ziprin, Richard L; Nisbet, David J

2005-12-14

Monoclonal antibodies (Mabs) were developed that specifically bind tilmicosin. Keyhole limpet hemocyanin (KLH) and bovine serum albumin (BSA) conjugates were used for the immunogen and plate coating antigen, respectively. The conjugates were synthesized by different methods, resulting in different linkages. Six hybridoma cell lines were isolated that produced Mabs that competed with tilmicosin, and have IgG1 isotype. The Til-1 and Til-5 Mabs had IC50 values for tilmicosin of 9.6 and 6.4 ng/well (48 and 32 ng/mL), respectively, and limits of detection at IC20 of 1.84 and 0.89 ng/well (9.2 and 4.45 ng/mL), respectively. The Mabs demonstrated high cross-reactivity to the macrolides containing 3,5-dimethylpiperidine at C20 and the amino sugar at C5. No cross-reactivity was observed for tylosin and other macrolides that did not contain 3,5-dimethylpiperidine. A competitive enzyme-linked immunosorbent assay (ELISA) was developed for the antibiotic tilmicosin by use of the developed Mabs. These Mabs may be excellent candidates for the determination and immunolocalization of tilmicosin.

Microbiological assay for the analysis of certain macrolides in pharmaceutical dosage forms.

PubMed

Mahmoudi, A; Fourar, R E-A; Boukhechem, M S; Zarkout, S

2015-08-01

Clarithromycin (CLA) and roxithromycin (ROX) are macrolide antibiotics with an expanded spectrum of activity that are commercially available as tablets. A microbiological assay, applying the cylinder-plate method and using a strain of Micrococcus luteus ATCC 9341 as test organism, has been used and validated for the quantification of two macrolide drugs; CLA and ROX in pure and pharmaceutical formulations. The validation of the proposed method was carried out for linearity, precision, accuracy and specificity. The linear dynamic ranges were from 0.1 to 0.5μg/mL for both compounds. Logarithmic calibration curve was obtained for each macrolide (r>0.989) with statistically equal slopes varying from 3.275 to 4.038, and a percentage relative standard deviation in the range of 0.24-0.92%. Moreover, the method was applied successfully for the assay of the studied drugs in pharmaceutical tablet dosage forms. Recovery from standard addition experiments in commercial products was 94.71-96.91% regarding clarithromycin and 93.94-98.12% regarding roxithromycin, with a precision (%RSD) 1.32-2.11%. Accordingly, this microbiological assay can be used for routine quality control analysis of titled drugs in tablet formulations. Copyright © 2015 Elsevier B.V. All rights reserved.

Antibiotic susceptibility in Streptococcus pneumoniae, Haemophilus influenzae and Streptococcus pyogenes in Pakistan: a review of results from the Survey of Antibiotic Resistance (SOAR) 2002-15.

PubMed

Zafar, A; Hasan, R; Nizamuddin, S; Mahmood, N; Mukhtar, S; Ali, F; Morrissey, I; Barker, K; Torumkuney, D

2016-05-01

To investigate changes in the antibiotic susceptibility of Streptococcus pneumoniae, Haemophilus influenzae and Streptococcus pyogenes from the Survey of Antibiotic Resistance (SOAR) in community-acquired respiratory tract infections (CA-RTIs) between 2002 and 2015 in Pakistan. This is a review based on previously published studies from 2002-03, 2004-06 and 2007-09 and also new data from 2014-15. Susceptibility was determined by Etest(®) or disc diffusion according to CLSI and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. A total of 706 isolates from CA-RTIs comprising 381 S. pneumoniae, 230 H. influenzae and 95 S. pyogenes were collected between 2002 and 2015 and tested against a range of antibiotics. Antibiotic resistance in S. pneumoniae rose steeply from 2002 to 2009, with isolates non-susceptible to penicillin and macrolides increasing from 10% to 34.1% and from 13%-14% to 29.7%, respectively. Susceptibility to amoxicillin/clavulanic acid (and by inference amoxicillin) remained between 99.4% and 100% from 2002 to 2015. Over the years, the prevalence of susceptibility to cefuroxime was 98%-100% among S. pneumoniae. Resistance in S. pneumoniae to some older antibiotics between 2007 and 2009 was high (86.8% for trimethoprim/sulfamethoxazole and 57.2% for tetracycline). Between 2002 and 2015, ampicillin resistance (β-lactamase-positive strains) among H. influenzae has remained low (between 2.6% and 3.2%) and almost unchanged over the years (H. influenzae was not tested during 2004-06). For S. pyogenes isolates, macrolide resistance reached 22%; however, susceptibility to penicillin, amoxicillin/clavulanic acid and cefuroxime remained stable at 100%. In S. pneumoniae from Pakistan, there has been a clear reduction in susceptibility to key antibiotics since 2002, but not to amoxicillin/clavulanic acid (amoxicillin) or cefuroxime. However, susceptibility in H. influenzae has remained stable. Local antibiotic susceptibility/resistance data are essential to support informed prescribing for CA-RTIs and other infections. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Occurrence of antibiotic compounds in source water and finished drinking water from the upper Scioto River Basin, Ohio, 2005-6

USGS Publications Warehouse

Finnegan, Dennis P.; Simonson, Laura A.; Meyer, Michael T.

2010-01-01

The occurrence of antibiotics in surface water and groundwater in urban basins has become a topic of increasing interest in recent years. Little is known about the occurrence, fate, or transport of these compounds and the possible health effects in humans and aquatic life. The U.S. Geological Survey, in cooperation with the City of Columbus, Division of Power and Water, did a study to provide a synoptic view of the occurrence of antibiotics in source and finished waters in the upper Scioto River Basin. Water samples were collected seasonally-winter (December 2005), spring (May 2006), summer (August 2006) and fall (October 2006)-at five surface-water sites, one groundwater site, and three water-treatment plants (WTPs). Within the upper Scioto River Basin, sampling at each WTP involved two sampling sites: a source-water intake site and a finished-water site. One or more antibiotics were detected at 11 of the 12 sampling sites. Of the 49 targeted antibiotic compounds, 12 (24 percent) were detected at least one time for a total of 61 detections overall. These compounds were azithromycin, tylosin, erythromycin-H2O, erythromycin, roxithromycin, ciprofloxacin, ofloxacin, sulfamethazine, sulfamethoxazole, iso-chlorotetracycline, lincomycin, and trimethoprim. Detection results were at low levels, with an overall median of 0.014 (u or mu)g/L. Hap Cremean WTP had the fewest detections, with two source-water detections of sulfamethoxazole and azithromycin and no detections in the finished water. Of the total of 61 detections, 31 were in the winter sample run. Sulfamethoxazale and azithromycin detections represent 41 percent of all antibiotic detections. Azithromycin was detected only in the winter sample. Some antibiotics, such as those in the quinoline and tetracycline families, dissipate more quickly in warm water, which may explain why they were detected in the cool months (winter, spring, and fall) and not in the summer. Antibiotic data collected during this study were compared to antibiotic data collected in previous national, regional, and local studies. Many of the same antibiotic compounds detected in the upper Scioto River Basin also were detected in those investigations.

Antimicrobial susceptibility, tetracycline and erythromycin resistance genes, and multilocus sequence typing of Streptococcus suis isolates from diseased pigs in China.

PubMed

Chen, Lei; Song, Yajing; Wei, Zigong; He, Hongkui; Zhang, Anding; Jin, Meilin

2013-01-01

Streptococcus suis (S. suis) is an emerging zoonotic pathogen causing significant economic losses in the swine industry. Here, we investigated the antimicrobial susceptibility, associated antibiotic-resistant determinants and sequence type (ST) of S. suis isolates from diseased pigs in China from 2008 to 2010. Serotype 2 was the most frequently observed strain (n=95) among the 106 S. suis strains collected, followed by serotypes 3 (n=3), 5 (n=3), 4 (n=2), 7 (n=1), 11 (n=1) and 28 (n=1). Multilocus sequence typing analysis revealed that ST1 (n=21) and ST7 (n=74) were the predominant STs, and serotype 2 was found to be significantly correlated with ST7 (P=0.017, Fisher's exact test) and CC1 (P=0.024, Fisher's exact test). The antimicrobial susceptibility results indicated that the antibiotic resistance rate was highest for tetracycline (99.1%), followed by azithromycin (68.9%), erythromycin (67.9%), clindamycin (67.9%), trimethoprim/sulfamethoxazole (16%), levofloxacin (2.8%), chloramphenicol (1.9%), cefaclor (0.9%) and ceftriaxone (0.9%). Antibiotic-resistant genes tet(M), tet(O), tet(O/W/32/O), tet(O/32/O), tet(S), tet(W), tet(L), tet(40), erm(B), mef(A/E) and msr(D) could be detected, and several tandem organizations of antibiotic resistance genes were also found in this study. In conclusion, S. suis strains isolated from diseased pigs in China were less diverse and multi-drug resistant.

Results from the Survey of Antibiotic Resistance (SOAR) 2011-13 in Ukraine.

PubMed

Feshchenko, Y; Dzyublik, A; Pertseva, T; Bratus, E; Dzyublik, Y; Gladka, G; Morrissey, I; Torumkuney, D

2016-05-01

To determine the antibiotic susceptibility of respiratory isolates of Streptococcus pneumoniae and Haemophilus influenzae collected in 2011-13 from Ukraine. MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. A total of 134 isolates of S. pneumoniae and 67 of H. influenzae were collected from eight sites in Ukraine. Overall, 87.3% of S. pneumoniae were penicillin susceptible by CLSI oral breakpoints and 99.3% by CLSI iv breakpoints. Susceptibility to amoxicillin/clavulanic acid (amoxicillin), ceftriaxone and levofloxacin was 100% by CLSI and PK/PD breakpoints. Cephalosporin and macrolide susceptibility was ≥95.5% and 88.1%, respectively using CLSI breakpoints. Trimethoprim/sulfamethoxazole was essentially inactive against pneumococci. Of the 67 H. influenzae tested, 4.5% were β-lactamase positive and all H. influenzae were fully susceptible to amoxicillin/clavulanic acid, ceftriaxone, ciprofloxacin, cefixime and levofloxacin (all breakpoints). Cefuroxime susceptibility was 100% by CLSI but 73.1% by EUCAST and PK/PD breakpoints. A discrepancy was found in macrolide susceptibility between CLSI (∼100% susceptible), EUCAST (22%-43% susceptible) and PK/PD (0%-22% susceptible) breakpoints. Trimethoprim/sulfamethoxazole was poorly active (59.7% susceptible). Generally, antibiotic resistance was low in respiratory pathogens from Ukraine. However, only amoxicillin/clavulanic acid (amoxicillin), ceftriaxone and levofloxacin were fully active against both species. Trimethoprim/sulfamethoxazole was the least active, particularly against S. pneumoniae. Some susceptibility differences were apparent between CLSI, EUCAST and PK/PD breakpoints, especially with macrolides against H. influenzae. These data suggest that further efforts are required to harmonize these international breakpoints. Future studies are warranted to monitor continued low resistance levels in Ukraine compared with other parts of Eastern Europe. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Antibiotic Susceptibility Profiles of Dairy Leuconostoc, Analysis of the Genetic Basis of Atypical Resistances and Transfer of Genes In Vitro and in a Food Matrix

PubMed Central

Delgado, Susana; Alegría, Ángel; Salvetti, Elisa; Felis, Giovanna E.; Mayo, Baltasar; Torriani, Sandra

2016-01-01

In spite of a global concern on the transfer of antibiotic resistances (AR) via the food chain, limited information exists on this issue in species of Leuconostoc and Weissella, adjunct cultures used as aroma producers in fermented foods. In this work, the minimum inhibitory concentration was determined for 16 antibiotics in 34 strains of dairy origin, belonging to Leuconostoc mesenteroides (18), Leuconostoc citreum (11), Leuconostoc lactis (2), Weissella hellenica (2), and Leuconostoc carnosum (1). Atypical resistances were found for kanamycin (17 strains), tetracycline and chloramphenicol (two strains each), and erythromycin, clindamycin, virginiamycin, ciprofloxacin, and rifampicin (one strain each). Surprisingly, L. mesenteroides subsp. mesenteroides LbE16, showed resistance to four antibiotics, kanamycin, streptomycin, tetracycline and virginiamycin. PCR analysis identified tet(S) as responsible for tetracycline resistance in LbE16, but no gene was detected in a second tetracycline-resistant strain, L. mesenteroides subsp. cremoris LbT16. In Leuconostoc mesenteroides subsp. dextranicum LbE15, erythromycin and clindamycin resistant, an erm(B) gene was amplified. Hybridization experiments proved erm(B) and tet(S) to be associated to a plasmid of ≈35 kbp and to the chromosome of LbE15 and LbE16, respectively. The complete genome sequence of LbE15 and LbE16 was used to get further insights on the makeup and genetic organization of AR genes. Genome analysis confirmed the presence and location of erm(B) and tet(S), but genes providing tetracycline resistance in LbT16 were again not identified. In the genome of the multi-resistant strain LbE16, genes that might be involved in aminoglycoside (aadE, aphA-3, sat4) and virginiamycin [vat(E)] resistance were further found. The erm(B) gene but not tet(S) was transferred from Leuconostoc to Enterococcus faecalis both under laboratory conditions and in cheese. This study contributes to the characterization of AR in the Leuconostoc-Weissella group, provides evidence of the genetic basis of atypical resistances, and demonstrates the inter-species transfer of erythromycin resistance. PMID:26726815

New insights into the structural and functional involvement of the gate loop in AcrB export activity.

PubMed

Ababou, Abdessamad

2018-02-01

AcrB is a major multidrug exporter in Escherichia coli and other Gram-negative bacteria. Its gate loop, located between the proximal and the distal pockets, have been reported to play important role in the export of many antibiotics. This loop location, rigidity and interactions with substrates have led recent reports to suggest that AcrB export mechanism operates in a sequential manner. First the substrate binds the proximal pocket in the access monomer, then it moves to bind the distal pocket in the binding monomer and subsequently it is extruded in the extrusion monomer. Recently, we have demonstrated that the gate loop is not required for the binding of Erythromycin but the integrity of this loop is important for an efficient export of this substrate. However, here we show that the antibiotic susceptibilities of the same AcrB gate loop mutants for Doxorubicin were unaffected, suggesting that this loop is not required for its export, and we demonstrate that this substrate may use principally the tunnel-1, located between transmembranes 8 and 9, more often than previously reported. To further explain our findings, here we address the gate loop mutations effects on AcrB solution energetics (fold, stability, molecular dynamics) and on the in vivo efflux of Erythromycin and Doxorubicin. Finally, we discuss the efflux and the discrepancy between the structural and the functional experiments for Erythromycin in these gate loop mutants. Copyright © 2017 Elsevier B.V. All rights reserved.

COMPARISON BETWEEN AUTOMATED SYSTEM AND PCR-BASED METHOD FOR IDENTIFICATION AND ANTIMICROBIAL SUSCEPTIBILITY PROFILE OF CLINICAL Enterococcus spp

PubMed Central

Furlaneto-Maia, Luciana; Rocha, Kátia Real; Siqueira, Vera Lúcia Dias; Furlaneto, Márcia Cristina

2014-01-01

Enterococci are increasingly responsible for nosocomial infections worldwide. This study was undertaken to compare the identification and susceptibility profile using an automated MicrosScan system, PCR-based assay and disk diffusion assay of Enterococcus spp. We evaluated 30 clinical isolates of Enterococcus spp. Isolates were identified by MicrosScan system and PCR-based assay. The detection of antibiotic resistance genes (vancomycin, gentamicin, tetracycline and erythromycin) was also determined by PCR. Antimicrobial susceptibilities to vancomycin (30 µg), gentamicin (120 µg), tetracycline (30 µg) and erythromycin (15 µg) were tested by the automated system and disk diffusion method, and were interpreted according to the criteria recommended in CLSI guidelines. Concerning Enterococcus identification the general agreement between data obtained by the PCR method and by the automatic system was 90.0% (27/30). For all isolates of E. faecium and E. faecalis we observed 100% agreement. Resistance frequencies were higher in E. faecium than E. faecalis. The resistance rates obtained were higher for erythromycin (86.7%), vancomycin (80.0%), tetracycline (43.35) and gentamicin (33.3%). The correlation between disk diffusion and automation revealed an agreement for the majority of the antibiotics with category agreement rates of > 80%. The PCR-based assay, the van(A) gene was detected in 100% of vancomycin resistant enterococci. This assay is simple to conduct and reliable in the identification of clinically relevant enterococci. The data obtained reinforced the need for an improvement of the automated system to identify some enterococci. PMID:24626409

Systemic and topical antibiotics for chronic rhinosinusitis.

PubMed

Head, Karen; Chong, Lee Yee; Piromchai, Patorn; Hopkins, Claire; Philpott, Carl; Schilder, Anne G M; Burton, Martin J

2016-04-26

This review is one of six looking at the primary medical management options for patients with chronic rhinosinusitis.Chronic rhinosinusitis is common and is characterised by inflammation of the lining of the nose and paranasal sinuses leading to nasal blockage, nasal discharge, facial pressure/pain and loss of sense of smell. The condition can occur with or without nasal polyps. Systemic and topical antibiotics are used with the aim of eliminating infection in the short term (and some to reduce inflammation in the long term), in order to normalise nasal mucus and improve symptoms. To assess the effects of systemic and topical antibiotics in people with chronic rhinosinusitis. The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; CENTRAL (2015, Issue 8); MEDLINE; EMBASE; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 29 September 2015. Randomised controlled trials (RCTs) with a follow-up period of at least three months comparing systemic or topical antibiotic treatment to (a) placebo or (b) no treatment or (c) other pharmacological interventions. We used the standard methodological procedures expected by Cochrane. Our primary outcomes were disease-specific health-related quality of life (HRQL), patient-reported disease severity and the commonest adverse event - gastrointestinal disturbance. Secondary outcomes included general HRQL, endoscopic nasal polyp score, computerised tomography (CT) scan score and the adverse events of suspected allergic reaction (rash or skin irritation) and anaphylaxis or other very serious reactions. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics. We included five RCTs (293 participants), all of which compared systemic antibiotics with placebo or another pharmacological intervention.The varying study characteristics made comparison difficult. Four studies recruited only adults and one only children. Three used macrolide, one tetracycline and one a cephalosporin-type antibiotic. Three recruited only patients with chronic rhinosinusitis without nasal polyps, one recruited patients with chronic rhinosinusitis with nasal polyps and one had a mixed population. Three followed up patients for 10 to 12 weeks after treatment had finished. Systemic antibiotics versus placebo Three studies compared antibiotics with placebo (176 participants).One study (64 participants, without polyps) reported disease-specific HRQL using the SNOT-20 (0 to 5, 0 = best quality of life). At the end of treatment (three months) the SNOT-20 score was lower in the group receiving macrolide antibiotics than the placebo group (mean difference (MD) -0.54 points, 95% confidence interval (CI) -0.98 to -0.10), corresponding to a moderate effect size favouring antibiotics (moderate quality evidence). Three months after treatment, it is uncertain if there was a difference between groups.One study (33 participants, with polyps) provided information on gastrointestinal disturbances and suspected allergic reaction (rash or skin irritation) after a short course of tetracycline antibiotic compared with placebo. We are very uncertain if antibiotics were associated with an increase in gastrointestinal disturbances (risk ratio (RR) 1.36, 95% CI 0.22 to 8.50) or skin irritation (RR 6.67, 95% CI 0.34 to 128.86) (very low quality evidence). Systemic antibiotics plus saline irrigation and intranasal corticosteroids versus placebo plus saline irrigation and intranasal corticosteroids One study (60 participants, some with and some without polyps) compared a three-month course of macrolide antibiotic with placebo; all participants also used saline irrigation and 70% used intranasal corticosteroids. Disease-specific HRQL was reported using SNOT-22 (0 to 110, 0 = best quality of life). Data were difficult to interpret (highly skewed and baseline imbalances) and it is unclear if there was an important difference at any time point (low quality evidence). To assess patient-reported disease severity participants rated the effect of treatment on a five-point scale (-2 for "desperately worse" to 2 for "cured") at the end of treatment (three months). For improvement in symptoms there was no difference between the antibiotics and placebo groups; the RR was 1.50 (95% CI 0.81 to 2.79; very low quality evidence), although there were also slightly more people who felt worse after treatment in the antibiotics group. There was no demonstrable difference in the rate of gastrointestinal disturbances between the groups (RR 1.07, 95% CI 0.16 to 7.10). General HRQL was measured using the SF-36. The authors stated that there was no difference between groups at the end of treatment (12 weeks) or two weeks later. Systemic antibiotics versus intranasal corticosteroids One study (43 participants, without polyps) compared a three-month course of macrolide antibiotic with intranasal corticosteroids. Patient-reported disease severity was assessed using a composite symptom score (0 to 40; 0 = no symptoms). It is very uncertain if there was a difference as patient-reported disease severity was similar between groups (MD -0.32, 95% CI -2.11 to 1.47; low quality evidence). Systemic antibiotics versus oral corticosteroids One study (28 participants, with polyps) compared a short course of tetracycline antibiotic (unclear duration, ˜20 days) with a 20-day course of oral corticosteroids. We were unable to extract data on any of the primary efficacy outcomes. It is uncertain if there was a difference ingastrointestinal disturbances (RR 1.00, 95% CI 0.16 to 6.14) or skin irritation (RR 2.00, 95% CI 0.20 to 19.62) as the results for these outcomes were similar between groups (very low quality evidence). We found very little evidence that systemic antibiotics are effective in patients with chronic rhinosinusitis. We did find moderate quality evidence of a modest improvement in disease-specific quality of life in adults with chronic rhinosinusitis without polyps receiving three months of a macrolide antibiotic. The size of improvement was moderate (0.5 points on a five-point scale) and only seen at the end of the three-month treatment; by three months later no difference was found.Despite a general understanding that antibiotics can be associated with adverse effects, including gastrointestinal disturbances, the results in this review were very uncertain because the studies were small and few events were reported.No RCTs of topical antibiotics met the inclusion criteria.More research in this area, particularly evaluating longer-term outcomes and adverse effects, is required.

Magnitude of antibiotic use.

PubMed

Finkel, M J

1978-11-01

Trends in antibiotic prescribing can be examined by a review of data from dispensed prescriptions and from antibiotic certification records of the Food and Drug Administration (FDA). Prescription data on selected oral antibiotics and anti-infectives were obtained from IMS America's National Prescription Audit. Data compiled between 1965 and 1977 show increasing use until 1973--with a plateau thereafter--for antibiotics judged by physicians to be relatively "safe," namely, the erythromycins, ampicillin and other penicillins, and the cephalosporins. Tetracycline use, although rising until 1973, declined somewhat thereafter, perhaps because of increasing concern with dental staining in children. Sulfonamide use has declined steadily since 1965, presumably for safety reasons. Used of clindamycin was nearing a level similar to that of cephalosporin use until 1975, when its risk of precipitating severe colitis, including pseudomembranous colitis, became well-known. The FDA's antibiotic certification records show that the volume of injectable cephalosporins and gentamicin administered has increased steadily and as of 1977 was still rising.

Treatment strategies for Legionella infection.

PubMed

Pedro-Botet, M Luisa; Yu, Victor L

2009-05-01

Given the nonspecific clinical manifestations of Legionnaires' disease and the high mortality of untreated Legionnaires' disease, we recommend routine use of Legionella testing, especially the Legionella urinary antigen test, for all patients with community-acquired pneumonia. This includes patients with ambulatory pneumonia and hospitalized children. Legionella cultures should be more widely available, especially in hospitals where the drinking water is colonized with Legionella. Azithromycin or levofloxacin can be considered as first-line therapy. Other antibiotics including tetracyclines, tigecycline, other fluoroquinolones and other macrolides (especially clarithromycin) are also effective. The clinical response of quinolones may be somewhat more favorable compared to macrolides, but the outcome is similar. If the Legionnaires' disease is hospital-acquired, culturing of the hospital drinking water for Legionella is indicated.

Activity of Telithromycin (HMR 3647) against Anaerobic Bacteria Compared to Those of Eight Other Agents by Time-Kill Methodology†

PubMed Central

Credito, Kim L.; Ednie, Lois M.; Jacobs, Michael R.; Appelbaum, Peter C.

1999-01-01

Time-kill studies examined the activities of telithromycin (HMR 3647), erythromycin A, azithromycin, clarithromycin, roxithromycin, clindamycin, pristinamycin, amoxicillin-clavulanate, and metronidazole against 11 gram-positive and gram-negative anaerobic bacteria. Time-kill studies were carried out with the addition of Oxyrase in order to prevent the introduction of CO2. Macrolide-azalide-ketolide MICs were 0.004 to 32.0 μg/ml. Of the latter group, telithromycin had the lowest MICs, especially against non-Bacteroides fragilis group strains, followed by azithromycin, clarithromycin, erythromycin A, and roxithromycin. Clindamycin was active (MIC ≤ 2.0 μg/ml) against all anaerobes except Peptostreptococcus magnus and Bacteroides thetaiotaomicron, while pristinamycin MICs were 0.06 to 4.0 μg/ml. Amoxicillin-clavulanate had MICs of ≤1.0 μg/ml, while metronidazole was active (MICs, 0.03 to 2.0 μg/ml) against all except Propionibacterium acnes. After 48 h at twice the MIC, telithromycin was bactericidal (≥99.9% killing) against 6 strains, with 99% killing of 9 strains and 90% killing of 10 strains. After 24 h at twice the MIC, 90, 99, and 99.9% killing of nine, six, and three strains, respectively, occurred. Lower rates of killing were seen at earlier times. Similar kill kinetics relative to the MIC were seen with other macrolides. After 48 h at the MIC, clindamycin was bactericidal against 8 strains, with 99 and 90% killing of 9 and 10 strains, respectively. After 24 h, 90% killing of 10 strains occurred at the MIC. The kinetics of clindamycin were similar to those of pristinamycin. After 48 h at the MIC, amoxicillin-clavulanate showed 99.9% killing of seven strains, with 99% killing of eight strains and 90% killing of nine strains. At four times the MIC, metronidazole was bactericidal against 8 of 10 strains tested after 48 h and against all 10 strains after 24 h; after 12 h, 99% killing of all 10 strains occurred. PMID:10428930

Susceptibilities of Haemophilus influenzae and Moraxella catarrhalis to ABT-773 compared to their susceptibilities to 11 other agents.

PubMed

Credito, K L; Lin, G; Pankuch, G A; Bajaksouzian, S; Jacobs, M R; Appelbaum, P C

2001-01-01

The activity of the ketolide ABT-773 against Haemophilus and Moraxella was compared to those of 11 other agents. Against 210 Haemophilus influenzae strains (39.0% beta-lactamase positive), microbroth dilution tests showed that azithromycin and ABT-773 had the lowest MICs (0.5 to 4.0 and 1.0 to 8.0 microg/ml, respectively), followed by clarithromycin and roxithromycin (4.0 to >32.0 microg/ml). Of the beta-lactams, ceftriaxone had the lowest MICs (32.0 microg/ml). Against 50 Moraxella catarrhalis strains, all of the compounds except amoxicillin and cefprozil were active. Time-kill studies against 10 H. influenzae strains showed that ABT-773, at two times the MIC, was bactericidal against 9 of 10 strains, with 99% killing of all strains at the MIC after 24 h; at 12 h, ABT-773 gave 90% killing of all strains at two times the MIC. At 3 and 6 h, killing by ABT-773 was slower, with 99.9% killing of four strains at two times the MIC after 6 h. Similar results were found for azithromycin, with slightly slower killing by erythromycin, clarithromycin, and roxithromycin, especially at earlier times. beta-Lactams were bactericidal against 8 to 10 strains at two times the MIC after 24 h, with slower killing at earlier time periods. Most compounds gave good killing of five M. catarrhalis strains, with beta-lactams killing more rapidly than other drugs. ABT-773 and azithromycin gave the longest postantibiotic effects (PAEs) of the ketolide-macrolide-azalide group tested (4.4 to >8.0 h), followed by clarithromycin, erythromycin, and roxithromycin. beta-Lactam PAEs were similar and shorter than those of the ketolide-macrolide-azalide group for all strains tested.

Combinatorial approaches with selected phytochemicals to increase antibiotic efficacy against Staphylococcus aureus biofilms.

PubMed

Abreu, Ana Cristina; Saavedra, Maria José; Simões, Lúcia C; Simões, Manuel

2016-10-01

Combinations of selected phytochemicals (reserpine, pyrrolidine, quinine, morin and quercetin) with antibiotics (ciprofloxacin, tetracycline and erythromycin) were tested on the prevention and control of Staphylococcus aureus biofilms. The phytochemicals were also studied for their ability to avoid antibiotic adaptation and to inhibit antibiotic efflux pumps. Morin, pyrrolidine and quercetin at subinhibitory concentrations had significant effects in biofilm prevention and/or control when applied alone and combined with antibiotics. Synergism between antibiotics and phytochemicals was found especially against biofilms of NorA overexpressing strain S. aureus SA1199B. This strain when growing with subinhibitory concentrations of ciprofloxacin developed increased tolerance to this antibiotic. However, this was successfully reversed by quinine and morin. In addition, reserpine and quercetin showed significant efflux pump inhibition. The overall results demonstrate the role of phytochemicals in co-therapies to promote more efficient treatments and decrease antimicrobial resistance to antibiotics, with substantial effects against S. aureus in both planktonic and biofilm states.

A Gene Homologous to rRNA Methylase Genes Confers Erythromycin and Clindamycin Resistance in Bifidobacterium breve.

PubMed

Martínez, Noelia; Luque, Roberto; Milani, Christian; Ventura, Marco; Bañuelos, Oscar; Margolles, Abelardo

2018-05-15

Bifidobacteria are mutualistic intestinal bacteria, and their presence in the human gut has been associated with health-promoting activities. The presence of antibiotic resistance genes in this genus is controversial, since, although bifidobacteria are nonpathogenic microorganisms, they could serve as reservoirs of resistance determinants for intestinal pathogens. However, until now, few antibiotic resistance determinants have been functionally characterized in this genus. In this work, we show that Bifidobacterium breve CECT7263 displays atypical resistance to erythromycin and clindamycin. In order to delimit the genomic region responsible for the observed resistance phenotype, a library of genomic DNA was constructed and a fragment of 5.8 kb containing a gene homologous to rRNA methylase genes was able to confer erythromycin resistance in Escherichia coli This genomic region seems to be very uncommon, and homologs of the gene have been detected in only one strain of Bifidobacterium longum and two other strains of B. breve In this context, analysis of shotgun metagenomics data sets revealed that the gene is also uncommon in the microbiomes of adults and infants. The structural gene and its upstream region were cloned into a B. breve -sensitive strain, which became resistant after acquiring the genetic material. In vitro conjugation experiments did not allow us to detect gene transfer to other recipients. Nevertheless, prediction of genes potentially acquired through horizontal gene transfer events revealed that the gene is located in a putative genomic island. IMPORTANCE Bifidobacterium breve is a very common human intestinal bacterium. Often described as a pioneer microorganism in the establishment of early-life intestinal microbiota, its presence has been associated with several beneficial effects for the host, including immune stimulation and protection against infections. Therefore, some strains of this species are considered probiotics. In relation to this, because probiotic bacteria are used for human and animal consumption, one of the safety concerns over these bacteria is the presence of antibiotic resistance genes, since the human gut is a densely populated habitat that could favor the transfer of genetic material to potential pathogens. In this study, we analyzed the genetic basis responsible for the erythromycin and clindamycin resistance phenotype of B. breve CECT7263. We were able to identify and characterize a novel gene homologous to rRNA methylase genes which confers erythromycin and clindamycin resistance. This gene seems to be very uncommon in other bifidobacteria and in the gut microbiomes of both adults and infants. Even though conjugation experiments showed the absence of transferability under in vitro conditions, it has been predicted to be located in a putative genomic island recently acquired by specific bifidobacterial strains. Copyright © 2018 American Society for Microbiology.

Association of socioeconomic status with the use of chronic therapies and healthcare utilization in children with cystic fibrosis.

PubMed

Schechter, Michael S; McColley, Susanna A; Silva, Stefanie; Haselkorn, Tmirah; Konstan, Michael W; Wagener, Jeffrey S

2009-11-01

To determine whether previously reported socioeconomic status (SES)-related disparities in cystic fibrosis (CF) health outcomes vary by the indicator used (median household income by zip code [MIZ], maternal educational attainment [MEA], and state insurance coverage [MA]), and whether these disparities can be explained by differences in medical treatment. A cross-sectional analysis of data on patients age <18 years from the Epidemiologic Study of Cystic Fibrosis (ESCF). Disease severity showed a similar inverse correlation with all 3 SES measures. The number of stable clinic visits was unrelated to SES. Patients with MA had more sick outpatient visits and more courses of intravenous (IV) antibiotics for pulmonary exacerbations, and were more likely to be prescribed all chronic therapies. Low-MIZ patients had slightly fewer sick visits and more courses of IV antibiotics, and were more likely to receive oral nutrition supplements but less likely to receive macrolide prescriptions. Low-MEA patients were less likely to receive IV antibiotics at home, more likely to receive oral nutrition supplements, but less likely to receive macrolide prescriptions. CF health outcomes are correlated with the SES spectrum, but these disparities are not explained by differential use of health services or prescription of chronic therapy. Future investigations should focus on the possible impact of environmental exposures and differences in disease self-management.

In vitro activity of tylvalosin against Spanish field strains of Mycoplasma hyopneumoniae.

PubMed

Tavío, M M; Poveda, C; Assunção, P; Ramírez, A S; Poveda, J B

2014-11-29

Mycoplasma hyopneumoniae is involved in the porcine enzootic pneumonia and respiratory disease complex; therefore, the search for new treatment options that contribute to the control of this organism is relevant. The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations of tylvalosin and 19 other antimicrobial agents against 20 Spanish field isolates of M. hyopneumoniae were determined using the broth microdilution method, with the type strain (J) as a control strain. Tylvalosin had MIC50 and MIC90 values of 0.016 and 0.06 µg/ml, respectively, and was the second-most effective of the assayed antibiotics, after valnemulin. Tiamulin, tylosin and lincomycin were also among the antibiotics with the lowest MIC50 and MIC90 values against the 20 field isolates (0.06-0.25 µg/ml). However, resistance to tylosin and spiramycin, which like tylvalosin, are 16-membered macrolides, was observed. The MIC50 and MIC90 values for ciprofloxacin and enrofloxacin ranged from 0.125 to 1 µg/ml; the corresponding values ranged from 2 to 4 µg/ml for oxytetracyline, which was the most active tetracycline. Furthermore, tylvalosin and valnemulin exhibited the highest bactericidal activities. In conclusion, the macrolide tylvalosin and the pleuromutilin valnemulin exhibited the highest in vitro antimicrobial activities against M. hyopneumoniae field isolates in comparison with the other tested antibiotics. British Veterinary Association.

An antibiotic recipe for an arrhythmic disaster.

PubMed

McCutcheon, Keir; Manga, Pravin

2015-01-01

We describe the case of a patient who developed torsade de pointes during temporary pacemaker insertion after administration of intravenous erythromycin. The case highlights the dangers of administering drugs that prolong the QT interval in patients with complete atrioventricular block, and we discuss the underlying pathophysiological recipe that can lead to a potential arrhythmic disaster.

Short communication: In vitro antimicrobial susceptibility of Mycoplasma bovis isolates identified in milk from dairy cattle in Belgium, Germany, and Italy.

PubMed

Barberio, A; Flaminio, B; De Vliegher, S; Supré, K; Kromker, V; Garbarino, C; Arrigoni, N; Zanardi, G; Bertocchi, L; Gobbo, F; Catania, S; Moroni, P

2016-08-01

The objective of this study was to assess the in vitro antimicrobial susceptibility of 73 isolates of Mycoplasma bovis isolated from milk of dairy cattle herds of Belgium, Germany, and Italy. Minimal inhibitory concentration (MIC) values were determined by the microbroth dilution method for the following antimicrobials: erythromycin, spiramycin, tilmicosin, tylosin, lincomycin, enrofloxacin, doxycycline, oxytetracycline, florfenicol, and tiamulin. Macrolides, florfenicol, oxytetracycline, and enrofloxacin, were chosen because they represent antimicrobials families commonly used in several countries for treatment of M. bovis, and their MIC values in cattle population are reported in several studies, allowing a comparison with previous data. Doxycycline and tiamulin were selected to assess the susceptibility of M. bovis to new antimicrobials, because they are not registered in the European Union for the treatment of dairy cattle. Among the agents of the different antimicrobial classes, the macrolides showed the highest concentration to inhibit 90% of isolates (MIC90), all above the highest concentration tested: >8μg/mL for erythromycin, >16μg/mL for spiramycin, and >32μg/mL for tilmicosin and tylosin. Also the MIC90 of lincomycin was above the highest concentration tested (>32μg/mL), but the distribution of the MIC values was almost perfectly bimodal: 41 isolates had a MIC ≤0.5μg/mL and 30 isolates >32μg/mL. Oxytetracycline had a 2-fold higher concentration to inhibit 50% of isolates (2 vs. 0.5μg/mL) and 1-fold higher MIC90 (4 vs. 2μg/mL) than doxycycline. Enrofloxacin and florfenicol had both a MIC90 of 2μg/mL, whereas tiamulin had a MIC90 of 0.5μg/mL. Significant differences on the MIC values were found among the 3 countries for several antimicrobials: compared with Germany, Belgium and Italy showed significantly higher MIC for lincomycin, spiramycin, and tylosin, and lower for oxytetracycline and florfenicol. The Belgian isolates showed the lowest MIC for enrofloxacin compared with Germany and Italy. The MIC results obtained in our study suggest the presence of a high level of resistance of M. bovis isolates originating from milk to macrolides in all countries involved in this study. On the contrary, a low level of resistance was found against the antimicrobials that are not used in cattle, such as tiamulin and doxycycline, highlighting a possible link between antimicrobial treatments and development of resistance in the studied M. bovis population. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Serotype distribution and antimicrobial susceptibility of group B streptococci in pregnant women: results from a Swiss tertiary centre.

PubMed

Fröhlicher, Simone; Reichen-Fahrni, Gabriela; Müller, Martin; Surbek, Daniel; Droz, Sara; Spellerberg, Barbara; Sendi, Parham

2014-03-20

To evaluate the rates of penicillin, clindamycin and erythromycin resistance and the serotype distribution among isolates of group B streptococcus (GBS) obtained from pregnant women at the University Hospital of Bern in Switzerland. We prospectively collected screening samples for GBS colonisation at the University Women's Hospital Bern, Switzerland, between March 2009 and August 2010. We included 364 GBS isolates collected from vaginal, cervical or vaginal-perianal swabs at any gestation time. The minimal inhibitory concentrations for penicillin, clindamycin and erythromycin were established using Etest with 24 hours of incubation, and inducible clindamycin resistance was tested with double disk diffusion tests. Serotyping was done with a rapid latex agglutination test or, if not conclusive, with polymerase chain-reaction (PCR) testing. We looked for significant associations between resistance patterns, age groups, serotype and ethnicity. All isolates were susceptible to penicillin. Resistance rates were 14.5% for erythromycin and 8.2% for clindamycin. Of 364 isolates, 5.8% were susceptible to clindamycin but not to erythromycin, although demonstrating inducible clindamycin resistance. Hence, the final reported clindamycin resistance rate was 14%. Serotype III was the most frequent serotype (29%), followed by V (25%) and Ia (19%). Serotype V was associated with erythromycin resistance (p = 0.0007). In comparison with all other ethnicities, patients from Asia showed a higher proportion of erythromycin and clindamycin resistance (p = 0.018). No significant association between resistance patterns and age groups was found. In pregnant women with GBS colonisation, penicillin is the antibiotic of choice for intrapartum prophylaxis to prevent neonatal early-onset GBS sepsis. In women with penicillin allergy and at high risk for anaphylactic reaction, clindamycin may be an alternative. The resistance rate for clindamycin at our institution was 14%; therefore, susceptibility must be tested before administration.

Effects of chlorophyll-derived efflux pump inhibitor pheophorbide a and pyropheophorbide a on growth and macrolide antibiotic resistance of indicator and anaerobic swine manure bacteria

USDA-ARS?s Scientific Manuscript database

Natural plant compounds, such as the chlorophyll a catabolites pheophorbide a (php) and pyropheophorbide a (pyp), are potentially active in the gastrointestinal tracts and wastes of livestock as antimicrobial resistance-modifying agents through inhibition of bacterial efflux pumps. To investigate w...

Pipeline of Known Chemical Classes of Antibiotics

PubMed Central

d’Urso de Souza Mendes, Cristina; de Souza Antunes, Adelaide Maria

2013-01-01

Many approaches are used to discover new antibiotic compounds, one of the most widespread being the chemical modification of known antibiotics. This type of discovery has been so important in the development of new antibiotics that most antibiotics used today belong to the same chemical classes as antibiotics discovered in the 1950s and 1960s. Even though the discovery of new classes of antibiotics is urgently needed, the chemical modification of antibiotics in known classes is still widely used to discover new antibiotics, resulting in a great number of compounds in the discovery and clinical pipeline that belong to existing classes. In this scenario, the present article presents an overview of the R&D pipeline of new antibiotics in known classes of antibiotics, from discovery to clinical trial, in order to map out the technological trends in this type of antibiotic R&D, aiming to identify the chemical classes attracting most interest, their spectrum of activity, and the new subclasses under development. The result of the study shows that the new antibiotics in the pipeline belong to the following chemical classes: quinolones, aminoglycosides, macrolides, oxazolidinones, tetracyclines, pleuromutilins, beta-lactams, lipoglycopeptides, polymyxins and cyclic lipopeptides. PMID:27029317

Molecular Characteristics of Erythromycin-Resistant Streptococcus pyogenes Strains Isolated from Children Patients in Tunis, Tunisia.

PubMed

Ksia, Sonia; Smaoui, Hanen; Hraoui, Manel; Bouafsoun, Aida; Boutiba-Ben Boubaker, Ihem; Kechrid, Amel

2017-07-01

The aims of our study were to characterize phenotypically and genotypically erythromycin-resistant Streptococcus pyogenes or group A streptococci (ERGAS) isolates, to evaluate macrolide resistance and to analyze the association between emm types and virulence factors. Included in this study were all ERGAS strains isolated from 2000 to 2013 at the Children's hospital of Tunis. Antimicrobial susceptibility was performed according to the CA-SFM guidelines. Macrolide resistance genes were revealed by polymerase chain reaction (PCR) method. Virulence factor genes (pyrogenic exotoxin genes and superantigen gene) were detected by PCR, and the emm types were defined by the sequencing of the variable 5' end of the emm gene. Among the 289 GAS isolates collected, 15 (5.2%) were resistant to erythromycin; 7 of the strains were assigned to the cMLS B phenotype (46.6%); 5 harbored ermB gene alone (33.3%); and 2 strains coharbored ermB and mefA (13.3%). The remaining (53.4%) were assigned to the M phenotype and harbored the mefA gene. The frequency of detection of each toxin gene among ERGAS was 13.4% for speA (2 strains), 53.4% for speC (8 strains), and 13.4% for ssa (2 strains). Emm types 1, 58, 11, and 78 were the most frequent among ERGAS strains. The distribution of the cMLS B and M phenotypes changed over the period of investigation with a decrement of cMLS B phenotype and ermB gene that predominated between 2000 and 2006 and an increase of M phenotype and mefA gene between 2007 and 2013, but this difference was nonstatistically significant because of the low number of resistant strains. Emm types 1, 58, and 4 were only present among strains assigned to the M phenotype. However strains assigned to the cMLS B phenotype were associated to emm11, emm22, emm28, emm78, or emm76. There was diversity in emm distribution in ERGAS between the two study periods. There was diversity in emm distribution among ERGAS particularly in 2000-2006. Indeed, from 2000 to 2006, the 6 ERGAS belonged to 5 different emm types (22, 28, 76, 11, and 4), while between 2007 and 2013, seven among the nine ERGAS belonged to only 2 emm types 58 and 1. The speA gene was present only among emm1 isolates, and the ssa gene was associated with emm4 and emm78 types. All emm78, emm28, and emm11 strains harbored speC gene. Our study revealed a low frequency of ERGAS and few emm types were associated with these strains.

Occurrence, seasonal variation and risk assessment of antibiotics in the reservoirs in North China.

PubMed

Li, Nan; Zhang, Xinbo; Wu, Wei; Zhao, Xinhua

2014-09-01

The occurrence and seasonal variability of five groups (tetracycline, quinolone, chloramphenicol, macrolide and sulfonamide) of antibiotics were investigated in the surface water of four reservoirs. The dissolved concentrations of 29 antibiotics were in the ngL(-1) level. Trace levels of all target antibiotics were analyzed using solid-phase extraction followed by liquid chromatography electrospray tandem mass spectrometry. All of the antibiotics were detected at all sampling sites, indicating widespread occurrence of antibiotics in the study area. The detection of florfenicol, josamycin, kitasamycin, spiramycin and sulfameter is the first report of these compounds in reservoir samples. The results showed an association between the presence of some antibiotics at Panjiakou reservoir and cage culture of fish. Twenty-three types of antibiotics showed significant seasonal variations (p<0.001) due to human activities and flow conditions. A risk assessment showed that all antibiotics detected could cause very low risk to algae, daphnid and fish. Further health risk need to be investigated because these reservoirs are drinking water sources. Copyright © 2014 Elsevier Ltd. All rights reserved.

Characterisation of a collection of Streptococcus pneumoniae isolates from patients suffering from acute exacerbations of chronic bronchitis: in vitro susceptibility to antibiotics and biofilm formation in relation to antibiotic efflux and serotypes/serogroups.

PubMed

Vandevelde, Nathalie M; Tulkens, Paul M; Diaz Iglesias, Yvan; Verhaegen, Jan; Rodriguez-Villalobos, Hector; Philippart, Ivan; Cadrobbi, Julie; Coppens, Nathalie; Boel, An; Van Vaerenbergh, Kristien; Francart, Hugo; Vanhoof, Raymond; Liistro, Giuseppe; Jordens, Paul; d'Odemont, Jean-Paul; Valcke, Yvan; Verschuren, Franck; Van Bambeke, Françoise

2014-09-01

The correlation between Streptococcus pneumoniae serotypes, biofilm production, antibiotic susceptibility and drug efflux in isolates from patients suffering from acute exacerbations of chronic bronchitis (AECB) remains largely unexplored. Using 101 isolates collected from AECB patients for whom partial (n=51) or full (n=50) medical details were available, we determined serotypes (ST)/serogroups (SG) (Quellung reaction), antibiotic susceptibility patterns [MIC (microdilution) using EUCAST and CLSI criteria] and ability to produce biofilm in vitro (10-day model; crystal violet staining). The majority of patients were 55-75 years old and <5% were vaccinated against S. pneumoniae. Moreover, 54% showed high severity scores (GOLD 3-4), and comorbidities were frequent including hypertension (60%), cancer (24%) and diabetes (20%). Alcohol and/or tobacco dependence was >30%. Isolates of SG6-11-15-23, known for large biofilm production and causing chronic infections, were the most prevalent (>15% each), but other isolates also produced biofilm (SG9-18-22-27 and ST8-20 being most productive), except SG7, SG29 and ST5 (<2% of isolates each). Resistance (EUCAST breakpoints) was 8-13% for amoxicillin and cefuroxime, 35-39% for macrolides, 2-8% for fluoroquinolones and 2% for telithromycin. ST19A isolates showed resistance to all antibiotics, ST14 to all except moxifloxacin, and SG9 and SG19 to all except telithromycin, moxifloxacin and ceftriaxone (SG19 only). Solithromycin and telithromycin MICs were similar. No correlation was observed between biofilm production and MIC or efflux (macrolides, fluoroquinolones). S. pneumoniae serotyping may improve AECB treatment by avoiding antibiotics with predictable low activity, but it is not predictive of biofilm production. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Pharmacodynamic Evaluation of the Intracellular Activities of Antibiotics against Staphylococcus aureus in a Model of THP-1 Macrophages

PubMed Central

Barcia-Macay, Maritza; Seral, Cristina; Mingeot-Leclercq, Marie-Paule; Tulkens, Paul M.; Van Bambeke, Françoise

2006-01-01

The pharmacodynamic properties governing the activities of antibiotics against intracellular Staphylococcus aureus are still largely undetermined. Sixteen antibiotics of seven different pharmacological classes (azithromycin and telithromycin [macrolides]; gentamicin [an aminoglycoside]; linezolid [an oxazolidinone]; penicillin V, nafcillin, ampicillin, and oxacillin [β-lactams]; teicoplanin, vancomycin, and oritavancin [glycopeptides]; rifampin [an ansamycin]; and ciprofloxacin, levofloxacin, garenoxacin, and moxifloxacin [quinolones]) have been examined for their activities against S. aureus (ATCC 25923) in human THP-1 macrophages (intracellular) versus that in culture medium (extracellular) by using a 0- to 24-h exposure time and a wide range of extracellular concentrations (including the range of the MIC to the maximum concentration in serum [Cmax; total drug] of humans). All molecules except the macrolides caused a net reduction in bacterial counts that was time and concentration/MIC ratio dependent (four molecules tested in detail [gentamicin, oxacillin, moxifloxacin, and oritavancin] showed typical sigmoidal dose-response curves at 24 h). Maximal intracellular activities remained consistently lower than extracellular activities, irrespective of the level of drug accumulation and of the pharmacological class. Relative potencies (50% effective concentration or at a fixed extracellular concentration/MIC ratio) were also decreased, but to different extents. At an extracellular concentration corresponding to their Cmaxs (total drug) in humans, only oxacillin, levofloxacin, garenoxacin, moxifloxacin, and oritavancin had truly intracellular bactericidal effects (2-log decrease or more, as defined by the Clinical and Laboratory Standards Institute guidelines). The intracellular activities of antibiotics against S. aureus (i) are critically dependent upon their extracellular concentrations and the duration of cell exposure (within the 0- to 24-h time frame) to antibiotics and (ii) are always lower than those that can be observed extracellularly. This model may help in rationalizing the choice of antibiotic for the treatment of S. aureus intracellular infections. PMID:16495241

Antibacterial activities of gemifloxacin, levofloxacin, gatifloxacin, moxifloxacin and erythromycin against intracellular Legionella pneumophila and Legionella micdadei in human monocytes.

PubMed

Baltch, Aldona L; Bopp, Lawrence H; Smith, Raymond P; Michelsen, Phyllis B; Ritz, William J

2005-07-01

The antibacterial activity of a new fluoroquinolone, gemifloxacin, was tested against intracellular Legionella pneumophila and Legionella micdadei and was compared with the activities of levofloxacin, gatifloxacin, moxifloxacin and erythromycin. For intracellular assays, bacteria were used to infect human monocyte-derived macrophages prepared from heparinized blood of healthy volunteers. Antibiotics were added following phagocytosis. Numbers of viable bacteria were determined at 0, 24, 48, 72 and 96 h. The intracellular antibacterial activity of gemifloxacin was concentration- and time-dependent. All of the quinolones had similar activities against L. pneumophila and L. micdadei at 10 x MIC, but there were minor differences: at 24 h moxifloxacin was significantly more active than the other quinolones against L. pneumophila, while gemifloxacin was more active against L. micdadei (P < 0.01). All of the quinolones were markedly more active than erythromycin (P < 0.01). The antibacterial effect of gemifloxacin against L. pneumophila following drug removal at 24 h persisted for 72 h at 20 x MIC but not at 10 x MIC, while for L. micdadei the antibacterial effect persisted for 24 h at 10 x MIC. All of the quinolones had similar activities against intracellular L. pneumophila and L. micdadei and were markedly more effective than erythromycin.

MacA, a periplasmic membrane fusion protein of the macrolide transporter MacAB-TolC, binds lipopolysaccharide core specifically and with high affinity.

PubMed

Lu, Shuo; Zgurskaya, Helen I

2013-11-01

The Escherichia coli MacAB-TolC transporter has been implicated in efflux of macrolide antibiotics and secretion of enterotoxin STII. In this study, we found that purified MacA, a periplasmic membrane fusion protein, contains one tightly bound rough core lipopolysaccharide (R-LPS) molecule per MacA molecule. R-LPS was bound specifically to MacA protein with affinity exceeding that of polymyxin B. Sequence analyses showed that MacA contains two high-density clusters of positively charged amino acid residues located in the cytoplasmic N-terminal domain and the periplasmic C-terminal domain. Substitutions in the C-terminal cluster reducing the positive-charge density completely abolished binding of R-LPS. At the same time, these substitutions significantly reduced the functionality of MacA in the protection of E. coli against macrolides in vivo and in the in vitro MacB ATPase stimulation assays. Taken together, our results suggest that R-LPS or a similar glycolipid is a physiological substrate of MacAB-TolC.

MacA, a Periplasmic Membrane Fusion Protein of the Macrolide Transporter MacAB-TolC, Binds Lipopolysaccharide Core Specifically and with High Affinity

PubMed Central

Lu, Shuo

2013-01-01

The Escherichia coli MacAB-TolC transporter has been implicated in efflux of macrolide antibiotics and secretion of enterotoxin STII. In this study, we found that purified MacA, a periplasmic membrane fusion protein, contains one tightly bound rough core lipopolysaccharide (R-LPS) molecule per MacA molecule. R-LPS was bound specifically to MacA protein with affinity exceeding that of polymyxin B. Sequence analyses showed that MacA contains two high-density clusters of positively charged amino acid residues located in the cytoplasmic N-terminal domain and the periplasmic C-terminal domain. Substitutions in the C-terminal cluster reducing the positive-charge density completely abolished binding of R-LPS. At the same time, these substitutions significantly reduced the functionality of MacA in the protection of E. coli against macrolides in vivo and in the in vitro MacB ATPase stimulation assays. Taken together, our results suggest that R-LPS or a similar glycolipid is a physiological substrate of MacAB-TolC. PMID:23974027

Global antibiotic resistance in Streptococcus pneumoniae.

PubMed

Adam, Dieter

2002-07-01

The last two decades of the 20th century were marked by an increasing resistance rate among several bacteria. Threat of resistance is present in Staphylococcus spp., Enterococcus spp., Pseudomonas spp. and Enterobacteriaceae, which are the major pathogens in nosocomial infections. In the community, too, increasing resistance can be observed and is attributed mainly (but not exclusively) to Streptococcus pneumoniae and Haemophilus influenzae. To scrutinize this trend, resistance surveillance in the community was established about 10 years ago. One of the multinational, longitudinal surveillance programmes in place is the Alexander Project, which was established in 1992 to monitor the susceptibility of the major community-acquired lower respiratory tract pathogens to a range of antibacterial drugs. The Alexander Project has revealed a tendency towards increasing resistance of S. pneumoniae to penicillin and macrolide therapy. Within Europe, the prevalence of penicillin resistance among S. pneumoniae isolates is particularly high in France and Spain. Macrolide resistance in S. pneumoniae is also a growing problem in European countries such as France, Spain, Belgium and Italy, where the extent of macrolide resistance in S. pneumoniae now exceeds that of penicillin resistance.

Impact of antibiotics on conjugational resistance gene transfer in Staphylococcus aureus in sewage.

PubMed

Ohlsen, Knut; Ternes, Thomas; Werner, Guido; Wallner, Ursula; Löffler, Dirk; Ziebuhr, Wilma; Witte, Wolfgang; Hacker, Jörg

2003-08-01

The growing rate of microbial pathogens becoming resistant to standard antibiotics is an important threat to public health. In order to assess the role of antibiotics in the environment on the spread of resistance factors, the impact of subinhibitory concentrations of antibiotics in sewage on gene transfer was investigated using conjugative gentamicin resistance (aacA-aphD) plasmids of Staphylococcus aureus. Furthermore, the concentration of antibiotics in hospital sewage was measured by high-performance liquid chromatography (HPLC)-electrospray tandem mass spectrometry. Several antibiotics were found to be present in sewage, e.g. ciprofloxacin up to 0.051 mgl(-1) and erythromycin up to 0.027 mgl(-1). Resistance plasmid transfer occurred both on solidified (dewatered) sewage and in liquid sewage in a bioreactor with a frequency of 1.1x10(-5)-5.0x10(-8). However, low-level concentrations of antibiotics measured in sewage are below concentrations that can increase plasmid transfer frequencies of gentamicin resistance plasmids of staphylococci.

[Impact of regulatory measures in the trends of community consumption of antibiotics in Chile].

PubMed

Bavestrello, Luis; Cabello, Angela; Casanova, Dunny

2002-11-01

The indiscriminate use of antibiotics increases the appearance of bacterial resistance and forces the use of more expensive alternatives. The Chilean Ministry of Health is regulating the consumption of antibiotics since September 1999. These regulatory measures restricted the sale of antibiotics only when these were prescribed by an MD or an DS. To study the impact of these regulatory measures on antibiotics sales in pharmacies. A retrospective analysis of antibiotics sales in pharmacies from 1996 to 2000. The information was obtained from the International Marketing System (IMS Health), an auditing system of pharmacy sales. The consumption unit used was the Defined Daily Dose per 1000 inhabitants/day (DDD). There was an important reduction in DDD, after the introduction of regulatory measures, for amoxicillin, ampicillin, erythromycin, trimethoprim/sulpha, chroramphenicol, cloxacillin and phenoxymethylpenicillin. There was also a important fall in sales, expressed in dollars. The regulatory measures of the Ministry of Health, had an immediate and great impact on antibiotics sales in Chile.

Principles of Antibiotic Management of Community-Acquired Pneumonia.

PubMed

Bender, Michael T; Niederman, Michael S

2016-12-01

Community-acquired pneumonia (CAP) encompasses a broad spectrum of disease severity and may require outpatient, inpatient, or intensive care management. Successful treatment hinges on expedient delivery of appropriate antibiotic therapy tailored to both the likely offending pathogens and the severity of disease. This review summarizes key principles in starting treatment and provides recommended empiric therapy regimens for each site of care. In addition, we discuss the antimicrobial and anti-inflammatory role macrolides play in CAP, as well as specific information for managing individual CAP pathogens such as community-acquired methicillin-resistant Staphylococcus aureus and drug-resistant Streptococcus pneumoniae . We also examine several novel antibiotics being developed for CAP and review the evidence guiding duration of therapy and current best practices for the transition of hospitalized patients from intravenous antibiotics to oral therapy. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Shattering a myth - Whooping cough susceptible to antibiotics.

PubMed

Syed, Muhammad Ali; Jamil, Bushra; Bokhari, Habib

2016-05-01

Bordetella parapertussis is the causative agent of a milder form of pertussis or whooping cough. Little is reported about the antibiotic resistance patterns and mechanism of drug resistance of Bordetella parapertussis. The objective of this study has been to investigate antimicrobial resistance, distribution of integrons and presence of gene cassettes to quinolones (qnr) and sulfonamides (sul) among B. parapertussis strains' isolated from Pakistan. Thirty-five (35) samples were collected from various hospitals of Pakistan from children (median age 3 years) with pertussis-like symptoms, all were tested and confirmed to be B. Parapertussis. Resistance profile of Ampicillin, Cephalexin, Sulphamethoxazole, Chloramphenicol, Ofloxacin, Nalidixic acid, Gentamycin and Erythromycin were investigated through all samples. Majority of the isolates were found to be resistant to the afore-mentioned antibiotics except erythromycin. All isolates were resistant to quinolones phenotypically, but qnr genes were detected in only 25.7% (9/35) of isolates. On the other hand, 71.4% (25/35) isolates were resistant to sulfonamides phenotypically. From these 71% strains showing phenotypical resistance, 96% (24/25) were found to possess sul genes. Only two isolates were carrying class 1 integrons, which also harbored sul gene and qnr gene cassettes. It can be safely concluded that the phenotypic resistance patterns seemed mostly independent of presence of integrons. However, interestingly both integrons harboring strains were resistant to quinolones and sulfonamides and also possessed qnr and sul genes.

The ORACLE Children Study: educational outcomes at 11 years of age following antenatal prescription of erythromycin or co-amoxiclav

PubMed Central

Marlow, Neil; Bower, Hannah; Jones, David; Brocklehurst, Peter; Kenyon, Sara; Pike, Katie; Taylor, David; Salt, Alison

2017-01-01

Background Antibiotics used for women in spontaneous preterm labour without overt infection, in contrast to those with preterm rupture of membranes, are associated with altered functional outcomes in their children. Methods From the National Pupil Database, we used Key Stage 2 scores, national test scores in school year 6 at 11 years of age, to explore the hypothesis that erythromycin and co-amoxiclav were associated with poorer educational outcomes within the ORACLE Children Study. Results Anonymised scores for 97% of surviving children born to mothers recruited to ORACLE and resident in England were analysed against treatment group adjusting for key available socio-demographic potential confounders. No association with crude or with adjusted scores for English, mathematics or science was observed by maternal antibiotic group in either women with preterm rupture of membranes or spontaneous preterm labour with intact membranes. While the proportion receiving special educational needs was similar in each group (range 31.6–34.4%), it was higher than the national rate of 19%. Conclusions Despite evidence that antibiotics are associated with increased functional impairment at 7 years, educational test scores and special needs at 11 years of age show no differences between trial groups. Trial registration number ISCRT Number 52995660 (original ORACLE trial number). PMID:27515985

Prescribing patterns for upper respiratory tract infections: a prescription-review of primary care practice in Kedah, Malaysia, and the implications.

PubMed

Rezal, Rabiatul Salmi; Hassali, Mohamed Azmi; Alrasheedy, Alian A; Saleem, Fahad; Yusof, Faridah Aryani Md; Kamal, Mardhiyah; Mohd Din, Rosminah; Godman, Brian

2015-01-01

It is necessary to ascertain current prescribing of antibiotics for upper respiratory tract infections (URTIs) to address potential overuse. A retrospective analysis was conducted of all prescriptions for URTIs among 10 public primary healthcare centers in Kedah, Malaysia, from 1 January to 31 March 2014. A total of 123,524 prescriptions were screened and analyzed. Of these, 7129 prescriptions were for URTI, with 31.8% (n = 2269) containing antibiotics. Macrolides were the most commonly prescribed antibiotic, constituting 61% (n = 1403) of total antibiotics prescribed. There was a statistically significant association between different prescribers and diagnoses (p = 0.001) and a weak positive trend suggesting family medicine specialists are more competent in antibiotic prescribing, followed by medical officers and assistant medical officers (τ = 0.122). Prescribing practices of some prescribers were inconsistent with current guidelines encouraging resistance development. National antimicrobial stewardship programs and further educational initiatives are ongoing in Malaysia to improve antibiotic use.

The structure of ribosome-lankacidin complex reveals ribosomal sites for synergistic antibiotics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Auerbach, Tamar; Mermershtain, Inbal; Davidovich, Chen

2010-04-26

Crystallographic analysis revealed that the 17-member polyketide antibiotic lankacidin produced by Streptomyces rochei binds at the peptidyl transferase center of the eubacterial large ribosomal subunit. Biochemical and functional studies verified this finding and showed interference with peptide bond formation. Chemical probing indicated that the macrolide lankamycin, a second antibiotic produced by the same species, binds at a neighboring site, at the ribosome exit tunnel. These two antibiotics can bind to the ribosome simultaneously and display synergy in inhibiting bacterial growth. The binding site of lankacidin and lankamycin partially overlap with the binding site of another pair of synergistic antibiotics, themore » streptogramins. Thus, at least two pairs of structurally dissimilar compounds have been selected in the course of evolution to act synergistically by targeting neighboring sites in the ribosome. These results underscore the importance of the corresponding ribosomal sites for development of clinically relevant synergistic antibiotics and demonstrate the utility of structural analysis for providing new directions for drug discovery.« less

Validation approach for a fast and simple targeted screening method for 75 antibiotics in meat and aquaculture products using LC-MS/MS.

PubMed

Dubreil, Estelle; Gautier, Sophie; Fourmond, Marie-Pierre; Bessiral, Mélaine; Gaugain, Murielle; Verdon, Eric; Pessel, Dominique

2017-04-01

An approach is described to validate a fast and simple targeted screening method for antibiotic analysis in meat and aquaculture products by LC-MS/MS. The strategy of validation was applied for a panel of 75 antibiotics belonging to different families, i.e., penicillins, cephalosporins, sulfonamides, macrolides, quinolones and phenicols. The samples were extracted once with acetonitrile, concentrated by evaporation and injected into the LC-MS/MS system. The approach chosen for the validation was based on the Community Reference Laboratory (CRL) guidelines for the validation of screening qualitative methods. The aim of the validation was to prove sufficient sensitivity of the method to detect all the targeted antibiotics at the level of interest, generally the maximum residue limit (MRL). A robustness study was also performed to test the influence of different factors. The validation showed that the method is valid to detect and identify 73 antibiotics of the 75 antibiotics studied in meat and aquaculture products at the validation levels.

Evidence on Possible Mycoplasma Etiology of Aster Yellows Disease II. Suppression of Aster Yellows in Insect Vectors

PubMed Central

Whitcomb, R. F.; Davis, R. E.

1970-01-01

Chlortetracycline or chloramphenicol (but not kanamycin, penicillin, or erythromycin), when administered in hydroponic solution to diseased aster, reduced the availability of the aster yellows (AY) agent to nymphs of Macrosteles fascifrons (Stål). Insects exposed to healthy plants whose roots were immersed in chlortetracycline were able to acquire AY agent from diseased plants the day after removal from the antibiotic-treated plants, but the latent period of the ensuing disease in the insects was prolonged. Chlortetracycline or tylosin tartrate blocked AY infection in nymphs injected with a mixture of antibiotic and the AY agent, but polymyxin, neomycin, vancomycin, penicillin, carbomycin, or chloramphenicol did not. All tetracyclines tested, methacycline, oxytetracycline, and chlortetracycline, produced a dramatic reduction in the ability of infected vectors to transmit AY agent. Tylosin tartrate also reduced transmission when injected into AY-transmitting vectors, but carbomycin, spectinomycin, cycloserine, penicillin, erythromycin, or kanamycin had no such effect. During the first 10 days after injection of tylosin tartrate or oxytetracycline into transmitting vectors, ability of the insects to transmit AY decayed rapidly. Transmission by insects injected with buffer alone, after decreasing the first day after injection, gradually returned to its normal level in less than 1 week. By 2 to 3 weeks after injection with tylosin or oxytetracycline, ability to transmit AY was regained by vectors. The results suggest that tetracycline antibiotics and tylosin tartrate inhibit multiplication of AY agent in the insect. The spectrum of antibiotic activity in the insect is consistent with the hypothesis that AY and other plant yellows diseases are caused by mycoplasma-like organisms. PMID:16557821

Antibiotic resistances of intestinal lactobacilli isolated from wild boars.

PubMed

Klose, Viviana; Bayer, Katharina; Kern, Corinna; Goelß, Florian; Fibi, Silvia; Wegl, Gertrude

2014-01-10

Acquired antibiotic resistances have been reported in lactobacilli of various animal and food sources, but there are no data from wild boar. The objective was a preliminary examination of the antibiotic resistance prevalence of intrinsically vancomycin-resistant lactobacilli isolated from wild boar intestines and analysis of the genetic determinants implicated. Out of three wild boars, 121 lactobacilli were recovered and grouped according to their whole cell protein patterns. Initial phenotypic screening revealed that all were susceptible to erythromycin (2 μg/ml), but 30 were resistant to tetracycline (32 μg/ml). Based on Randomly Amplified Polymorphic DNA-PCR clustering, 64 strains were selected as representative genotypes for identification and minimum inhibitory concentration (MIC) determination. Partial 16S rRNA gene sequencing identified four species: (i) L. mucosae (n=57), (ii) L. reuteri (n=47), (iii) L. fermentum (n=12), and (iv) L. murinus (n=5). Most heterofermentative strains displayed low MICs for ampicillin (AMP), chloramphenicol (CHL), streptomycin (STR), kanamycin (KAN), gentamicin (GEN), erythromycin (ERY), quinupristin/dalfopristin (Q/D), and clindamycin (CLI). Atypical MICs were found mainly in L. mucosae and L. reuteri for TET, KAN, STR, AMP and CHL, but except the TET MICs of L. mucosae mostly at low level. L. murinus strains revealed atypical MICs for aminoglycosides, and/or CHL, AMP, CLI. PCR screening detected tet(W) in 12 and tet(M) in one of heterofermentative strains, as well as the aph(3')-III kanamycin gene in L. murinus. This is the first report showing acquired antibiotic resistance determinants in intestinal lactobacilli of wild boar origin. Copyright © 2013 Elsevier B.V. All rights reserved.

Epoch-making milestones in antibiotic exploratory researches in Japan.

PubMed

Hotta, Kunimoto

2017-01-01

Professor Satoshi Ōmura was awarded the 2015 Nobel Prize in Physiology or Medicine. He is the third to win the award for research on antibiotic, following Fleming' (UK, 1945, discovery of penicillin) and Waksman (USA, 1952, discovery of streptomycin), and the second person after Waksman to receive the award for research on actinomycetes. By focusing his research on macrolides stemming from leucomycin research rather than β-lactams like penicillin or aminoglycosides like streptomycin, Prof. Ōmura realized many scientific achievements. These efforts finally led to the discovery of avermectin and its semi-synthetic derivative, ivermectin, considered a monumental contribution to the human race. In this manuscript, I will outline the chronicles of the epoch-making antibiotic exploratory researches preceding Prof. Ōmura.

Infective endocarditis caused by multidrug-resistant Streptococcus mitis in a combined immunocompromised patient: an autopsy case report.

PubMed

Matsui, Natsuko; Ito, Makoto; Kuramae, Hitoshi; Inukai, Tomomi; Sakai, Akiyoshi; Okugawa, Masaru

2013-04-01

An autopsy case of infective endocarditis caused by multidrug-resistant Streptococcus mitis was described in a patient with a combination of factors that compromised immune status, including autoimmune hemolytic anemia, post-splenectomy state, prolonged steroid treatment, and IgA deficiency. The isolated S. mitis strain from blood culture was broadly resistant to penicillin, cephalosporins, carbapenem, macrolides, and fluoroquinolone. Recurrent episodes of bacterial infections and therapeutic use of several antibiotics may underlie the development of multidrug resistance for S. mitis. Because clinically isolated S. mitis strains from chronically immunocompromised patients have become resistant to a wide spectrum of antibiotics, appropriate antibiotic regimens should be selected when treating invasive S. mitis infections in these compromised patients.

Antibiotic sensitivity and resistance in Ornithobacterium rhinotracheale strains from Belgian broiler chickens.

PubMed

Devriese, L A; De Herdt, P; Haesebrouck, F

2001-06-01

Establishing the antibiotic sensitivity of the avian respiratory pathogen Ornithobacterium rhinotracheale is difficult because of the organism's complex growth requirements and the unusually frequent occurrence of resistance. The minimal inhibitory concentrations of 10 antibiotics were determined for 45 strains of O. rhinotracheale from Belgian broiler chickens collected from 45 farms between 1995 and 1998. They were compared with the type strain, which was isolated from a turkey, and a strain isolated from a rook. All the broiler strains were resistant to lincomycin and to the beta-lactams ampicillin and ceftiofur. Less than 10% of the strains were sensitive to the macrolides tylosin and spiramycin, tilmicosin and flumequine. A few strains were sensitive to enrofloxacin and doxycycline. All strains were sensitive to tiamulin.

Bronchiectasis in the Last Five Years: New Developments

PubMed Central

Khoo, Jun Keng; Venning, Victoria; Wong, Conroy; Jayaram, Lata

2016-01-01

Bronchiectasis, a chronic lung disease characterised by cough and purulent sputum, recurrent infections, and airway damage, is associated with considerable morbidity and mortality. To date, treatment options have been limited to physiotherapy to clear sputum and antibiotics to treat acute infections. Over the last decade, there has been significant progress in understanding the epidemiology, pathophysiology, and microbiology of this disorder. Over the last five years, methods of assessing severity have been developed, the role of macrolide antibiotic therapy in reducing exacerbations cemented, and inhaled antibiotic therapies show promise in the treatment of chronic Pseudomonas aeruginosa infection. Novel therapies are currently undergoing Phase 1 and 2 trials. This review aims to address the major developments within the field of bronchiectasis over this time. PMID:27941638

Molecular epidemiological characteristics of Streptococcus pyogenes strains involved in an outbreak of scarlet fever in China, 2011.

PubMed

You, Yuan Hai; Song, Yan Yan; Yan, Xiao Mei; Wang, Hai Bin; Zhang, Meng Han; Tao, Xiao Xia; Li, Lei Lei; Zhang, Yu Xin; Jiang, Xi Hong; Zhang, Bing Hua; Zhou, Hao; Xiao, Di; Jin, Lian Mei; Feng, Zi Jian; Luo, Feng Ji; Zhang, Jian Zhong

2013-11-01

To investigate molecular characterization of streptococcus pyogenes isolates involved in an outbreak of scarlet fever in China in 2011. Seventy-four Streptococcal pyogenes involved in an outbreak of scarlet fever were isolated from pediatric patients in the areas with high incidence in China from May to August of 2011. Emm genotyping, pulsed-field gel electrophoresis (PFGE), superantigen (SAg) genes and antimicrobial susceptibility profiling were analyzed for these isolates. A total of 4 different emm types were identified. Emm12 was the most prevalent type which contained four predominating PFGE patterns corresponding to four different virulence and superantigen profiles. Emm12 (79.7%) and emm1 (14.9%) accounted for approximately 94% of all the isolates. The speA gene was all negative in emm12 isolates and positive in emm1 isolates. All strains were resistant to erythromycin, and 89.4% of them were resistant to erythromycin, tracycline, and clindamycin simultaneously. Several highly diversified clones with a high macrolide resistance rate comprise a predominant proportion of circulating strains, though no new emm type was found in this outbreak. The data provide a baseline for further surveillance of scarlet fever, which may contribute to the explanation of the outbreak and development of a GAS vaccine in China. Copyright © 2013 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Antibiotic resistance profile of bacterial isolates from animal farming aquatic environments and meats in a peri-urban community in Daejeon, Korea.

PubMed

Rho, Hyunjin; Shin, Bongjin; Lee, Okbok; Choi, Yu-Hyun; Rho, Jaerang; Lee, Jiyoung

2012-05-01

The increasing usage of antibiotics in the animal farming industry is an emerging worldwide problem contributing to the development of antibiotic resistance. The purpose of this work was to investigate the prevalence and antibiotic resistance profile of bacterial isolates collected from animal farming aquatic environments and meats in a peri-urban community in Daejeon, Korea. In an antibacterial susceptibility test, the bacterial isolates showed a high incidence of resistance (∼26.04%) to cefazolin, tetracycline, gentamycin, norfloxacin, erythromycin and vancomycin. The results from a test for multiple antibiotic resistance indicated that the isolates were displaying an approximately 5-fold increase in the incidence of multiple antibiotic resistance to combinations of two different antibiotics compared to combinations of three or more antibiotics. Most of the isolates showed multi-antibiotic resistance, and the resistance patterns were similar among the sampling groups. Sequencing data analysis of 16S rRNA showed that most of the resistant isolates appeared to be dominated by the classes Betaproteobacteria and Gammaproteobacteria, including the genera Delftia, Burkholderia, Escherichia, Enterobacter, Acinetobacter, Shigella and Pseudomonas.

Borrelidins C-E: New Antibacterial Macrolides from a Saltern-Derived Halophilic Nocardiopsis sp.

PubMed

Kim, Jungwoo; Shin, Daniel; Kim, Seong-Hwan; Park, Wanki; Shin, Yoonho; Kim, Won Kyung; Lee, Sang Kook; Oh, Ki-Bong; Shin, Jongheon; Oh, Dong-Chan

2017-06-06

Chemical investigation of a halophilic actinomycete strain belonging to the genus Nocardiopsis inhabiting a hypersaline saltern led to the discovery of new 18-membered macrolides with nitrile functionality, borrelidins C-E ( 1 - 3 ), along with a previously reported borrelidin ( 4 ). The planar structures of borrelidins C-E, which are new members of the rare borrelidin class of antibiotics, were elucidated by NMR, mass, IR, and UV spectroscopic analyses. The configurations of borrelidines C-E were determined by the interpretation of ROESY NMR spectra, J-based configuration analysis, a modified Mosher's method, and CD spectroscopic analysis. Borrelidins C and D displayed inhibitory activity, particularly against the Gram-negative pathogen Salmonella enterica , and moderate cytotoxicity against the SNU638 and K562 carcinoma cell lines.

Turning the tide or riding the waves? Impacts of antibiotic stewardship and infection control on MRSA strain dynamics in a Scottish region over 16 years: non-linear time series analysis.

PubMed

Lawes, Timothy; López-Lozano, José-María; Nebot, César; Macartney, Gillian; Subbarao-Sharma, Rashmi; Dare, Ceri R J; Edwards, Giles F S; Gould, Ian M

2015-03-26

To explore temporal associations between planned antibiotic stewardship and infection control interventions and the molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA). Retrospective ecological study and time-series analysis integrating typing data from the Scottish MRSA reference laboratory. Regional hospital and primary care in a Scottish Health Board. General adult (N=1,051,993) or intensive care (18,235) admissions and primary care registrations (460,000 inhabitants) between January 1997 and December 2012. Hand-hygiene campaign; MRSA admission screening; antibiotic stewardship limiting use of macrolides and '4Cs' (cephalosporins, coamoxiclav, clindamycin and fluoroquinolones). Prevalence density of MRSA clonal complexes CC22, CC30 and CC5/Other in hospital (isolates/1000 occupied bed days, OBDs) and community (isolates/10,000 inhabitant-days). 67% of all clinical MRSA isolates (10,707/15,947) were typed. Regional MRSA population structure was dominated by hospital epidemic strains CC30, CC22 and CC45. Following declines in overall MRSA prevalence density, CC5 and other strains of community origin became increasingly important. Reductions in use of '4Cs' and macrolides anticipated declines in sublineages with higher levels of associated resistances. In multivariate time-series models (R(2)=0.63-0.94) introduction of the hand-hygiene campaign, reductions in mean length of stay (when >4 days) and bed occupancy (when >74 to 78%) predicted declines in CC22 and CC30, but not CC5/other strains. Lower importation pressures, expanded MRSA admission screening, and reductions in macrolide and third generation cephalosporin use (thresholds for association: 135-141, and 48-81 defined daily doses/1000 OBDs, respectively) were followed by declines in all clonal complexes. Strain-specific associations with fluoroquinolones and clindamycin reflected resistance phenotypes of clonal complexes. Infection control measures and changes in population antibiotic use were important predictors of MRSA strain dynamics in our region. Strategies to control MRSA should consider thresholds for effects and strain-specific impacts. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Investigation of the antibiotic resistance and biofilm-forming ability of Staphylococcus aureus from subclinical bovine mastitis cases.

PubMed

Aslantaş, Özkan; Demir, Cemil

2016-11-01

A total of 112 Staphylococcus aureus isolates obtained from subclinical bovine mastitis cases were examined for antibiotic susceptibility and biofilm-forming ability as well as genes responsible for antibiotic resistance, biofilm-forming ability, and adhesin. Antimicrobial susceptibility of the isolates were determined by disk diffusion method. Biofilm forming ability of the isolates were investigated by Congo red agar method, standard tube method, and microplate method. The genes responsible for antibiotic resistance, biofilm-forming ability, and adhesion were examined by PCR. Five isolates (4.5%) were identified as methicillin-resistant Staph. aureus by antibiotic susceptibility testing and confirmed by mecA detection. The resistance rates to penicillin, ampicillin, tetracycline, erythromycin, trimethoprim-sulfamethoxazole, enrofloxacin, and amoxicillin-clavulanic acid were 45.5, 39.3, 33, 26.8, 5.4, 0.9, and 0.9%, respectively. All isolates were susceptible against vancomycin and gentamicin. The blaZ (100%), tetK (67.6%), and ermA (70%) genes were the most common antibiotic-resistance genes. Using Congo red agar, microplate, and standard tube methods, 70.5, 67, and 62.5% of the isolates were found to be biofilm producers, respectively. The percentage rate of icaA, icaD, and bap genes in Staph. aureus isolates were 86.6, 86.6, and 13.4%, respectively. The adhesion molecules fnbA, can, and clfA were detected in 87 (77.7%), 98 (87.5%), and 75 (70%) isolates, respectively. The results indicated that Staph. aureus from sublinical bovine mastitis cases were mainly resistant to β-lactams and, to a lesser extent, to tetracycline and erythromycin. Also, biofilm- and adhesion-related genes, which are increasingly accepted as an important virulence factor in the pathogenesis of Staph. aureus infections, were detected at a high rate. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Activity of nadifloxacin (OPC-7251) and seven other antimicrobial agents against aerobic and anaerobic Gram-positive bacteria isolated from bacterial skin infections.

PubMed

Nenoff, P; Haustein, U-F; Hittel, N

2004-10-01

The in vitro activity of nadifloxacin (OPC-7251), a novel topical fluoroquinolone, was assessed and compared with those of ofloxacin, oxacillin, flucloxacillin, cefotiam, erythromycin, clindamycin, and gentamicin against 144 Gram-positive bacteria: 28 Staphylococcus aureus, 10 Streptococcus spp., 68 coagulase-negative staphylococci (CNS), 36 Propionibacterium acnes, and 2 Propionibacterium granulosum strains. All strains originated from bacterial-infected skin disease and were isolated from patients with impetigo, secondary infected wounds, folliculitis and sycosis vulgaris, and impetiginized dermatitis. In vitro susceptibility of all clinical isolates was tested by agar dilution procedure and minimum inhibitory concentrations (MICs) were determined. Nadifloxacin was active against all aerobic and anaerobic isolates. MIC(90) (MIC at which 90% of the isolates are inhibited) was 0.1 microg/ml for S. aureus, 0.78 microg/ml for both Streptococcus spp. and CNS, and 0.39 microg/ml for Propionibacterium spp. On the other hand, resistant strains with MICs exceeding 12.5 mug/ml were found in tests with the other antibiotics. For both CNS and Propionibacterium acnes, MIC(90) values > or =100 microg/ml were demonstrated for erythromycin. Ofloxacin, cefotiam, erythromycin, clindamycin and gentamicin exhibited MIC(90) values < or =1 microg/ml for some bacterial species tested. Both oxacillin and flucloxacillin were active against all investigated bacterial species with MIC(90) values < or =1 microg/ml. In summary, nadifloxacin, a topical fluoroquinolone, was found to be highly active against aerobic and anaerobic bacteria isolated from patients with infected skin disease, and seems to be a new alternative for topical antibiotic treatment in bacterial skin infections.

Trends in penicillin and macrolide resistance among pneumococci in the UK and the Republic of Ireland in relation to antibiotic sales to pharmacies and dispensing doctors.

PubMed

Livermore, David M; Reynolds, Rosy; Stephens, Peter; Duckworth, Georgia; Felmingham, David; Johnson, Alan P; Murchan, Stephen; Murphy, Olive; Gungabissoon, Usha; Waight, Pauline; Pebody, Richard; Shackcloth, Jemma; Warner, Marina; Williams, Laura; George, Robert C

2006-10-01

It is widely believed that reducing antimicrobial usage should reduce resistance, although observational evidence is mixed. Pneumococci make ideal subjects to test this belief as they are widely surveyed and lack an animal reservoir. Accordingly, susceptibility data for pneumococci in the UK and Ireland were retrieved from the Health Protection Agency's LabBase/CoSurv system and from the European Antimicrobial Resistance Surveillance System (EARSS) and British Society for Antimicrobial Chemotherapy (BSAC) databases. The BSAC surveillance examines respiratory pneumococci; the other systems focus upon invasive organisms only, with the LabBase/CoSurv system being the most comprehensive, capturing data on most bacteraemias in England and Wales. National pharmacy sales data were obtained from the IMS Health MIDAS database and were modelled to the resistance data by logistic and linear regression analysis. All systems except for the BSAC respiratory surveillance data indicated that penicillin resistance has fallen significantly since 1999 in the UK, whereas macrolide resistance has been essentially stable, or has risen slightly. The data for Ireland were based on smaller sample sizes but suggested a fall in penicillin non-susceptibility from 1999 to 2004, with conflicting evidence for macrolide resistance. The recent decreasing trend in penicillin resistance is in contrast to a rising trend in England and Wales until (at least) 1997 and strongly rising macrolide resistance from 1989 to 1993. UK pharmacy sales of macrolides and oral beta-lactams fell by ca. 30% in the late 1990s following increased concern about resistance, before stabilising or rising weakly; sales in Ireland were stable or rose slightly in the study period. We conclude that falling penicillin resistance in pneumococci followed reduced sales of oral beta-lactams to pharmacies in the UK, but a similar fall in macrolide sales was not associated with any fall in resistance. Stabilisation or decline in penicillin resistance has occurred in Ireland despite stable or increasing oral beta-lactam sales.

Outcomes of resistance-guided sequential treatment of Mycoplasma genitalium infections: a prospective evaluation.

PubMed

Read, T R H; Fairley, C K; Murray, G L; Jensen, J S; Danielewski, J; Worthington, K; Doyle, M; Mokany, E; Tan, L; Chow, E P F; Garland, S M; Bradshaw, C S

2018-06-05

Rising macrolide and quinolone resistance in Mycoplasma genitalium necessitate new treatment approaches. We evaluated outcomes of sequential antimicrobial therapy for M.genitalium guided by a macrolide-resistance assay. In mid-2016 Melbourne Sexual Health Centre switched from azithromycin to doxycycline (100mg twice daily,7 days) for non-gonococcal urethritis/cervicitis/proctitis. Cases were tested for M. genitalium and macrolide-resistance mutations (MRM) by polymerase chain reaction (PCR). Directly after doxycycline, MRM-negative infections received 2.5g azithromycin (1g then 500mg daily for 3 days), and MRM-positive infections received sitafloxacin (100mg twice daily, 7 days). Assessment of test-of-cure and reinfection risk, occurred 14-90 days after the second antibiotic. Those reporting condomless sex with incompletely treated partners were excluded. Of 244 evaluable M. genitalium infections (52 women, 68 heterosexual men, 124 men who have sex with men) diagnosed from 20 June 2016 to 15 May 2017, MRM were detected in 167 [68.4% (95%confidence interval(CI):62.2%, 74.2%)]. Treatment with doxycycline decreased bacterial load by a mean 2.60 log10 (n=56, p<0.0001). Microbiologic cure occurred in: 73/77 MRM-negative infections [94.8% (95%CI:87.2%, 98.6%)] and in 154/167 MRM-positive infections [92.2% (95%CI:87.1%, 95.8%)]. Selection of macrolide-resistance occurred in only 2 [2.6% (95%CI: 0.3%, 9.2%)] of 76 macrolide-susceptible infections. Proportions reporting no missed doses and no adverse events, respectively, were: doxycycline 89.9% and 86.6%, sitafloxacin 90.8% and 80.5%, azithromycin 100% and 91.4%. In the context of high levels of antimicrobial resistance, switching from azithromycin to doxycycline for presumptive treatment of M. genitalium, followed by resistance-guided therapy, cured ≥92% of infections, with infrequent selection of macrolide resistance.

Identification of significant transport processes for organic micropollutant classes during soil aquifer treatment (SAT) - a controlled field experiment

NASA Astrophysics Data System (ADS)

Nödler, Karsten; Licha, Tobias; Sauter, Martin

2010-05-01

Supplementing existing water resources with alternative sources of water is a challenge in semi-arid areas, as deterioration of water quality must be avoided. Soil aquifer treatment (SAT) can greatly improve the quality of the injected water by attenuation of organic pollutants via sorption and degradation processes. However, only little is known about the specific transport processes of organic micropollutants under artificial recharge conditions. Organic micropollutants such as pharmaceuticals and their metabolites exhibit a wide range of chemical properties and may undergo very different environmental processes resulting in specific reactions within specified environments. In the presented study fate and transport processes of 25 organic micropollutants (iodinated contrast media, antihypertensive agents, antibiotics, anticonvulsants, lipid regulators, anti-inflammatories, antihistamines and analgesics) were investigated under SAT conditions in a controlled field experiment. Secondary treated effluent (STE) containing the compounds of interest was introduced into the aquifer by an infiltration pond and shallow wells in the vicinity were used for water quality monitoring. By means of strategic sampling procedure and a specialized multi-residue analytical method based on high-performance liquid chromatography / tandem mass spectrometry (LC/MS-MS) 3 main transport processes were identified: 1. Transport of non-polar compounds according to their respective octanol-water distribution coefficient (Kow) 2. Cation exchange 3. Colloidal transport Identification of transport processes 2 & 3 was not expected to act as a transport controlling process. Results of the positively charged beta-blockers sotalol, atenolol and metoprolol gave clear evidence for cation exchange processes of the compounds with the aquifer material. Correlation of turbidity and concentrations of macrolide antibiotics (clarithromycin, erythromycin and roxithromycin) demonstrated the colloidal transport of the respective compounds. Concentrations of almost all micropollutants decreased with increasing soil passage. However, since compounds transported by processes 2 & 3 can be re-mobilized by changing water chemistry, the importance of a diligent characterisation of aquifer material and raw water is apparent for risk assessment. The experiments were conducted within the context of the project GABARDINE, funded by the European Commission.

Antibiotic Susceptibility and Sequence Type Distribution of Ureaplasma Species Isolated from Genital Samples in Switzerland.

PubMed

Schneider, Sarah C; Tinguely, Regula; Droz, Sara; Hilty, Markus; Donà, Valentina; Bodmer, Thomas; Endimiani, Andrea

2015-10-01

Antibiotic resistance in Ureaplasma urealyticum/Ureaplasma parvum and Mycoplasma hominis is an issue of increasing importance. However, data regarding the susceptibility and, more importantly, the clonality of these organisms are limited. We analyzed 140 genital samples obtained in Bern, Switzerland, in 2014. Identification and antimicrobial susceptibility tests were performed by using the Mycoplasma IST 2 kit and sequencing of 16S rRNA genes. MICs for ciprofloxacin and azithromycin were obtained in broth microdilution assays. Clonality was analyzed with PCR-based subtyping and multilocus sequence typing (MLST), whereas quinolone resistance and macrolide resistance were studied by sequencing gyrA, gyrB, parC, and parE genes, as well as 23S rRNA genes and genes encoding L4/L22 ribosomal proteins. A total of 103 samples were confirmed as positive for U. urealyticum/U. parvum, whereas 21 were positive for both U. urealyticum/U. parvum and M. hominis. According to the IST 2 kit, the rates of nonsusceptibility were highest for ciprofloxacin (19.4%) and ofloxacin (9.7%), whereas low rates were observed for clarithromycin (4.9%), erythromycin (1.9%), and azithromycin (1%). However, inconsistent results between microdilution and IST 2 kit assays were recorded. Various sequence types (STs) observed previously in China (ST1, ST2, ST4, ST9, ST22, and ST47), as well as eight novel lineages, were detected. Only some quinolone-resistant isolates had amino acid substitutions in ParC (Ser83Leu in U. parvum of serovar 6) and ParE (Val417Thr in U. parvum of serovar 1 and the novel Thr417Val substitution in U. urealyticum). Isolates with mutations in 23S rRNA or substitutions in L4/L22 were not detected. This is the first study analyzing the susceptibility of U. urealyticum/U. parvum isolates in Switzerland and the clonality outside China. Resistance rates were low compared to those in other countries. We hypothesize that some hyperepidemic STs spread worldwide via sexual intercourse. Large combined microbiological and clinical studies should address this important issue. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Antibiotic Susceptibility and Sequence Type Distribution of Ureaplasma Species Isolated from Genital Samples in Switzerland

PubMed Central

Schneider, Sarah C.; Tinguely, Regula; Droz, Sara; Hilty, Markus; Donà, Valentina; Bodmer, Thomas

2015-01-01

Antibiotic resistance in Ureaplasma urealyticum/Ureaplasma parvum and Mycoplasma hominis is an issue of increasing importance. However, data regarding the susceptibility and, more importantly, the clonality of these organisms are limited. We analyzed 140 genital samples obtained in Bern, Switzerland, in 2014. Identification and antimicrobial susceptibility tests were performed by using the Mycoplasma IST 2 kit and sequencing of 16S rRNA genes. MICs for ciprofloxacin and azithromycin were obtained in broth microdilution assays. Clonality was analyzed with PCR-based subtyping and multilocus sequence typing (MLST), whereas quinolone resistance and macrolide resistance were studied by sequencing gyrA, gyrB, parC, and parE genes, as well as 23S rRNA genes and genes encoding L4/L22 ribosomal proteins. A total of 103 samples were confirmed as positive for U. urealyticum/U. parvum, whereas 21 were positive for both U. urealyticum/U. parvum and M. hominis. According to the IST 2 kit, the rates of nonsusceptibility were highest for ciprofloxacin (19.4%) and ofloxacin (9.7%), whereas low rates were observed for clarithromycin (4.9%), erythromycin (1.9%), and azithromycin (1%). However, inconsistent results between microdilution and IST 2 kit assays were recorded. Various sequence types (STs) observed previously in China (ST1, ST2, ST4, ST9, ST22, and ST47), as well as eight novel lineages, were detected. Only some quinolone-resistant isolates had amino acid substitutions in ParC (Ser83Leu in U. parvum of serovar 6) and ParE (Val417Thr in U. parvum of serovar 1 and the novel Thr417Val substitution in U. urealyticum). Isolates with mutations in 23S rRNA or substitutions in L4/L22 were not detected. This is the first study analyzing the susceptibility of U. urealyticum/U. parvum isolates in Switzerland and the clonality outside China. Resistance rates were low compared to those in other countries. We hypothesize that some hyperepidemic STs spread worldwide via sexual intercourse. Large combined microbiological and clinical studies should address this important issue. PMID:26195516

Occurrence of 25 pharmaceuticals in Taihu Lake and their removal from two urban drinking water treatment plants and a constructed wetland.

PubMed

Hu, Xia-Lin; Bao, Yi-Fan; Hu, Jun-Jian; Liu, You-Yu; Yin, Da-Qiang

2017-06-01

Pharmaceuticals in drinking water sources have raised significant concerns due to their persistent input and potential human health risks. The seasonal occurrence of 25 pharmaceuticals including 23 antibiotics, paracetamol (PAR), and carbamazepine (CMZ) in Taihu Lake was investigated; meanwhile, the distribution and removal of these pharmaceuticals in two drinking water treatment plants (DWTPs) and a constructed wetland were evaluated. A high detection frequency (>70%) in the Taihu Lake was observed for nearly all the 25 pharmaceutics. Chlortetracycline (234.7 ng L -1 ), chloramphenicol (27.1 ng L -1 ), erythromycin (72.6 ng L -1 ), PAR (71.7 ng L -1 ), and CMZP (23.6 ng L -1 ) are compounds with both a high detection frequency (100%) and the highest concentrations, suggesting their wide use in the Taihu Basin. Higher concentrations of chloramphenicols, macrolides, PAR, and CMZP were observed in dry season than in wet season, probably due to the low flow conditions of the lake in winter and the properties of pharmaceuticals. The overall contamination levels of antibiotic pharmaceutics (0.2-74.9 ng L -1 ) in the Taihu Lake were lower than or comparable to those reported worldwide. However, for nonantibiotic pharmaceutics, PAR (45.0 ng L -1 ) and CMZP (14.5 ng L -1 ), significantly higher concentrations were observed in the Taihu Lake than at a global scale. High detection frequencies of 25 pharmaceuticals were observed in both the two DWTPs (100%) and the wetland (>60%) except for florfenicol and sulfapyridine. The removal efficacies of the studied pharmaceuticals in DWTP B with advanced treatment processes including ozonation and granular activated carbon filtration (16.7-100%) were superior to DWTP A with conventional treatment processes (2.9-100%), except for sulfonamides. Wetland C with the constructed root channel technology was efficient (24.2-100%) for removing most pharmaceuticals. This work suggests that the application of cost-effective technologies such as constructed wetlands should be considered as an efficient alternative for removing pharmaceuticals from water supply sources.

Occurrence, distribution and risks of antibiotics in urban surface water in Beijing, China.

PubMed

Li, Wenhui; Gao, Lihong; Shi, Yali; Liu, Jiemin; Cai, Yaqi

2015-09-01

The occurrence and distribution of 22 antibiotics, including eight fluoroquinolones, nine sulfonamides and five macrolides, were investigated in the urban surface waters in Beijing, China. A total of 360 surface water samples were collected from the main rivers and lakes in the urban area of Beijing monthly from July 2013 to June 2014 (except the frozen period). Laboratory analyses revealed that antibiotics were widely used and extensively distributed in the surface water of Beijing, and sulfonamides and fluoroquinolones were the predominant antibiotics with the average concentrations of 136 and 132 ng L(-1), respectively. A significant difference of antibiotic concentrations from different sampling sites was observed, and the southern and eastern regions of Beijing showed higher concentrations of antibiotics. Seasonal variation of the antibiotics in the urban surface water was also studied, and the highest level of antibiotics was found in November, which may be due to the low temperature and flow of the rivers during the period of cold weather. Risk assessment showed that several antibiotics might pose high ecological risks to aquatic organisms (algae and plants) in surface water, and more attention should be paid to the risk of antibiotics to the aquatic environment in Beijing.

Antimicrobial susceptibility and genetic relatedness of respiratory tract pathogens in weaner pigs over a 12-month period.

PubMed

Niemann, Lisa; Müller, Petra; Brauns, Jasmin; Nathaus, Rolf; Schäkel, Franziska; Kipschull, Kerstin; Höltig, Doris; Wendt, Michael; Schwarz, Stefan; Kadlec, Kristina

2018-06-01

The collaboration project VASIB aims at reducing the antibiotic consumption in pig production by integrating information from consulting expertise in clinical inspection, hygiene, epidemiology, microbiology and pharmacology. In this VASIB subproject, we investigated the antimicrobial susceptibility and relatedness of porcine respiratory tract pathogens. Bordetella bronchiseptica (n = 47), Pasteurella multocida (n = 18) and Streptococcus suis (n = 58) were obtained from weaner pigs at two farms. Antimicrobial susceptibility testing was performed by broth microdilution according to CLSI standards. Resistance genes were detected via specific PCR assays. Macrorestriction analysis was conducted to determine the relatedness of the isolates and to identify clones. The B. bronchiseptica isolates showed indistinguishable (farm 1) or two closely related XbaI-patterns (farm 2). Different SmaI-PFGE patterns of P. multocida isolates were obtained at three different time points. In contrast, PFGE analysis of S. suis indicated more than one fragment pattern per pig and time point. Isolates exhibiting indistinguishable PFGE patterns were considered to represent the same clone. This study showed that only two closely related B. bronchiseptica clones were present in both farms, which had low MICs to all antimicrobials, except to β-lactams. Different P. multocida clones were present at the three time points. They showed overall low MIC values, with two clones being resistant and one intermediate to tetracycline. S. suis clones were resistant to tetracycline (n = 19) and/or erythromycin/clindamycin (n = 16). They harboured the tetracycline resistance genes tet(O), tet(M) or tet(L) and/or the macrolide/lincosamide/streptogramin B resistance gene erm(B). Five penicillin-resistant S. suis clones were also detected. Copyright © 2018 Elsevier B.V. All rights reserved.

Occurrence and removal of organic micropollutants: An overview of the watch list of EU Decision 2015/495.

PubMed

Barbosa, Marta O; Moreira, Nuno F F; Ribeiro, Ana R; Pereira, Manuel F R; Silva, Adrián M T

2016-05-01

Although there are no legal discharge limits for micropollutants into the environment, some regulations have been published in the last few years. Recently, a watch list of substances for European Union-wide monitoring was reported in the Decision 2015/495/EU of 20 March 2015. Besides the substances previously recommended to be included by the Directive 39/2013/EU, namely two pharmaceuticals (diclofenac and the synthetic hormone 17-alpha-ethinylestradiol (EE2)) and a natural hormone (17-beta-estradiol (E2)), the first watch list of 10 substances/groups of substances also refers three macrolide antibiotics (azithromycin, clarithromycin and erythromycin), other natural hormone (estrone (E1)), some pesticides (methiocarb, oxadiazon, imidacloprid, thiacloprid, thiamethoxam, clothianidin, acetamiprid and triallate), a UV filter (2-ethylhexyl-4-methoxycinnamate) and an antioxidant (2,6-di-tert-butyl-4-methylphenol) commonly used as food additive. Since little is known about the removal of most of the substances included in the Decision 2015/495/EU, particularly regarding realistic concentrations in aqueous environmental samples, this review aims to: (i) overview the European policy in the water field; (ii) briefly describe the most commonly used conventional and advanced treatment processes to remove micropollutants; (iii) summarize the relevant data published in the last decade, regarding occurrence and removal in aqueous matrices of the 10 substances/groups of substances that were recently included in the first watch list for European Union monitoring (Decision 2015/495/EU); and (iv) highlight the lack of reports concerning some substances of the watch list, the study of un-spiked aquatic matrices and the assessment of transformation by-products. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chronic Lyme Disease and Co-infections: Differential Diagnosis

PubMed Central

Berghoff, Walter

2012-01-01

In Lyme disease concurrent infections frequently occur. The clinical and pathological impact of co-infections was first recognized in the 1990th, i.e. approximately ten years after the discovery of Lyme disease. Their pathological synergism can exacerbate Lyme disease or induce similar disease manifestations. Co-infecting agents can be transmitted together with Borrelia burgdorferi by tick bite resulting in multiple infections but a fraction of co-infections occur independently of tick bite. Clinically relevant co-infections are caused by Bartonella species, Yersinia enterocolitica, Chlamydophila pneumoniae, Chlamydia trachomatis, and Mycoplasma pneumoniae. In contrast to the USA, human granulocytic anaplasmosis (HGA) and babesiosis are not of major importance in Europe. Infections caused by these pathogens in patients not infected by Borrelia burgdorferi can result in clinical symptoms similar to those occurring in Lyme disease. This applies particularly to infections caused by Bartonella henselae, Yersinia enterocolitica, and Mycoplasma pneumoniae. Chlamydia trachomatis primarily causes polyarthritis. Chlamydophila pneumoniae not only causes arthritis but also affects the nervous system and the heart, which renders the differential diagnosis difficult. The diagnosis is even more complex when co-infections occur in association with Lyme disease. Treatment recommendations are based on individual expert opinions. In antibiotic therapy, the use of third generation cephalosporins should only be considered in cases of Lyme disease. The same applies to carbapenems, which however are used occasionally in infections caused by Yersinia enterocolitica. For the remaining infections predominantly tetracyclines and macrolides are used. Quinolones are for alternative treatment, particularly gemifloxacin. For Bartonella henselae, Chlamydia trachomatis, and Chlamydophila pneumoniae the combination with rifampicin is recommended. Erythromycin is the drug of choice for Campylobacter jejuni. PMID:23400696

Wild-type MIC distribution and epidemiological cut-off values in clinical Legionella pneumophila serogroup 1 isolates.

PubMed

Bruin, Jacob P; Ijzerman, Ed P F; den Boer, Jeroen W; Mouton, Johan W; Diederen, Bram M W

2012-01-01

The purpose of this study was to establish wild-type (WT) distributions and determine the epidemiological cut-off values (ECOFF) in clinical L. pneumophila serogroup 1 isolates for 10 antimicrobials commonly used for the treatment of Legionella infections using a method feasible in a routine clinical laboratory. MICs of 183 clinical L. pneumophila serogroup 1 isolates, collected as part of an outbreak detection program, were tested using E-test methodology on buffered charcoal yeast extract agar supplemented with α-ketoglutarate (BCYE-α). The MICs were read after 2 days of incubation at 35 °C with increased humidity and without CO(2). ECOFFs were determined according to EUCAST methodology and expressed as WT ≤ X mg/L. All antimicrobials showed a WT distribution, although the width varied from 2 two-fold dilutions to 8 dilutions, depending on antibiotic class. The ECOFFs determined were 1.0 mg/L for ciprofloxacin, 0.50 mg/L for levofloxacin, 1.0 mg/L for moxifloxacin, 1.0 mg/L for erythromycin, 1.0 mg/L for azithromycin, 0.50 mg/L for clarithromycin, 1.0 mg/L for cefotaxime, 0.032 mg/L for rifampicin, 16 mg/L for tigecycline, and 8 mg/L for doxycycline. All isolates were inhibited by low concentrations of the fluoroquinolones and macrolides tested, with somewhat higher MICs for the fluoroquinolones. Rifampicin was found to be the most active against L. pneumophila isolates in vitro. These data can be used as a reference for the detection of resistance in clinical L. pneumophila isolates and as a setting of clinical breakpoints. Copyright © 2012 Elsevier Inc. All rights reserved.

Identification of antibiotic resistant bacteria community and a GeoChip based study of resistome in urban watersheds.

PubMed

Low, Adrian; Ng, Charmaine; He, Jianzhong

2016-12-01

Urban watersheds from point sources are potential reservoirs of antibiotic resistance genes (ARGs). However, few studies have investigated urban watersheds of non-point sources. To understand the type of ARGs and bacteria that might carry such genes, we investigated two non-point source urban watersheds with different land-use profiles. Antibiotic resistance levels of two watersheds (R1, R3) were examined using heterotrophic plate counts (HPC) as a culturing method to obtain counts of bacteria resistant to seven antibiotics belonging to different classes (erythromycin, kanamycin, lincomycin, norfloxacin, sulfanilamide, tetracycline and trimethoprim). From the HPC study, 239 antibiotic resistant bacteria were characterized for resistance to more antibiotics. Furthermore, ARGs and antimicrobial biosynthesis genes were identified using GeoChip version 5.0 to elucidate the resistomes of surface waters in watersheds R1 and R3. The HPC study showed that water samples from R1 had significantly higher counts of bacteria resistant to erythromycin, kanamycin, norfloxacin, sulfanilamide, tetracycline and trimethoprim than those from R3 (Analysis of Similarity (ANOSIM), R = 0.557, p < 0.01). Of the seven antibiotics tested, lincomycin and trimethoprim resistant bacteria are greater in abundances. The 239 antibiotic resistant isolates represent a subset of resistant bacterial populations, including bacteria not previously known for resistance. Majority of the isolates had resistance to ampicillin, vancomycin, lincomycin and trimethoprim. GeoChip revealed similar ARGs in both watersheds, but with significantly higher intensities for tetX and β-lactamase B genes in R1 than R3. The genes with the highest average normalized intensities in R1 and R3 were tetracycline (tet) and fosfomycin (fosA) resistance genes, respectively. The higher abundance of tetX genes in R1 is congruent with the higher abundance of tetracycline resistant HPC observed in R1 samples. Strong correlations (r ≥ 0.8) of efflux pumps with antimicrobial biosynthesis genes suggest that natural production of antimicrobials may act as a selective pressure of transporter proteins in the absence of antibiotics from anthropogenic sources. In conclusion, distinct antibiotic resistant bacteria phylotypes and a variety of ARGs were present in the non-point sources urban watersheds of different land-use profiles, suggesting that ARG risk assessments and monitoring studies need to include these types of watersheds. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Multicenter Collaborative to Improve Care of Community Acquired Pneumonia in Hospitalized Children.

PubMed

Parikh, Kavita; Biondi, Eric; Nazif, Joanne; Wasif, Faiza; Williams, Derek J; Nichols, Elizabeth; Ralston, Shawn

2017-03-01

The Value in Inpatient Pediatrics Network sponsored the Improving Care in Community Acquired Pneumonia collaborative with the goal of increasing evidence-based management of children hospitalized with community acquired pneumonia (CAP). Project aims included: increasing use of narrow-spectrum antibiotics, decreasing use of macrolides, and decreasing concurrent treatment of pneumonia and asthma. Data were collected through chart review across emergency department (ED), inpatient, and discharge settings. Sites reviewed up to 20 charts in each of 6 3-month cycles. Analysis of means with 3-σ control limits was the primary method of assessment for change. The expert panel developed project measures, goals, and interventions. A change package of evidence-based tools to promote judicious use of antibiotics and raise awareness of asthma and pneumonia codiagnosis was disseminated through webinars. Peer coaching and periodic benchmarking were used to motivate change. Fifty-three hospitals enrolled and 48 (91%) completed the 1-year project (July 2014-June 2015). A total of 3802 charts were reviewed for the project; 1842 during baseline cycles and 1960 during postintervention cycles. The median before and after use of narrow-spectrum antibiotics in the collaborative increased by 67% in the ED, 43% in the inpatient setting, and 25% at discharge. Median before and after use of macrolides decreased by 22% in the ED and 27% in the inpatient setting. A decrease in asthma and CAP codiagnosis was noted, but the change was not sustained. Low-cost strategies, including collaborative sharing, peer benchmarking, and coaching, increased judicious use of antibiotics in a diverse range of hospitals for pediatric CAP. Copyright © 2017 by the American Academy of Pediatrics.

Large-area burns with pandrug-resistant Pseudomonas aeruginosa infection and respiratory failure.

PubMed

Ning, Fang-Gang; Zhao, Xiao-Zhuo; Bian, Jing; Zhang, Guo-An

2011-02-01

Infection due to pandrug-resistant Pseudomonas aeruginosa (PDRPA) has become a challenge in clinical practice. The aim of this research was to summarize the treatment of large-area burns (60% - 80%) with PDRPA infection and respiratory failure in our hospital over the last two years, and to explore a feasible treatment protocol for such patients. We retrospectively analyzed the treatment of five patients with large-area burns accompanied by PDRPA infection and respiratory failure transferred to our hospital from burn units in hospitals in other Chinese cities from January 2008 to February 2010. Before PDRPA infection occurred, all five patients had open wounds with large areas of granulation because of the failure of surgery and dissolving of scar tissue; they had also undergone long-term administration of carbapenems. This therapy included ventilatory support, rigorous repair of wounds, and combined antibiotic therapy targeted at drug-resistance mechanisms, including carbapenems, ciprofloxacin, macrolide antibiotics and β-lactamase inhibitors. Four patients recovered from burns and one died after therapy. First, compromised immunity caused by delayed healing of burn wounds in patients with large-area burns and long-term administration of carbapenems may be the important factors in the initiation and progression of PDRPA infection. Second, if targeted at drug-resistance mechanisms, combined antibiotic therapy using carbapenems, ciprofloxacin, macrolide antibiotics and β-lactamase inhibitors could effectively control PDRPA infection. Third, although patients with large-area burns suffered respiratory failure and had high risks from anesthesia and surgery, only aggressive skin grafting with ventilatory support could control the infection and save lives. Patients may not be able to tolerate a long surgical procedure, so the duration of surgery should be minimized, and the frequency of surgery increased.

Results from the Survey of Antibiotic Resistance (SOAR) 2014-16 in the Czech Republic.

PubMed

Torumkuney, D; Zemlickova, H; Maruscak, M; Morrissey, I

2018-04-01

To determine the antibiotic susceptibility of isolates of Streptococcus pneumoniae and Haemophilus influenzae collected in 2014-16 from patients with community-acquired respiratory infections in the Czech Republic. MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. S. pneumoniae isolates (n = 200) showed high rates of susceptibility (>95%) to amoxicillin, amoxicillin/clavulanic acid, penicillin [intravenous (iv) non-meningitis], ceftriaxone, cefuroxime and the fluoroquinolones using CLSI breakpoints. Susceptibility to cefaclor and trimethoprim/sulfamethoxazole was 94%-94.5%, to penicillin (oral) 91.5% and to the macrolides 89.5%. Susceptibility of H. influenzae (n = 197) to amoxicillin/clavulanic acid, ceftriaxone, cefuroxime, azithromycin and the fluoroquinolones was ≥98% by CLSI criteria. Rates of susceptibility to the remaining agents were ≥75% except for clarithromycin at 37.1%. Great variability was seen across breakpoints, especially for the macrolides, cefaclor and cefuroxime (oral), 98.0% of H. influenzae showing susceptibility to the latter by CLSI criteria, 69.5% by PK/PD and 1.5% by EUCAST standards. The β-lactamase rate was 13.7% with no β-lactamase-negative-ampicillin-resistant (BLNAR) isolates by CLSI criteria. Antibiotic resistance among the two major respiratory pathogens remained low in the Czech Republic. These findings support local clinicians in continuing the historically restrictive use of antibiotics in the Czech Republic, with selection of narrower-spectrum agents for the empirical therapy of community-acquired respiratory tract infections. This highlights one of the great benefits of continuous surveillance of antimicrobial resistance: knowledge of current local resistance patterns reduces the need to choose broad-spectrum agents that contribute to increasing resistance worldwide.

Enhanced Molecular Typing of Treponema pallidum subspecies pallidum Strains From 4 Italian Hospitals Shows Geographical Differences in Strain Type Heterogeneity, Widespread Resistance to Macrolides, and Lack of Mutations Associated With Doxycycline Resistance.

PubMed

Giacani, Lorenzo; Ciccarese, Giulia; Puga-Salazar, Christian; Dal Conte, Ivano; Colli, Laura; Cusini, Marco; Ramoni, Stefano; Delmonte, Sergio; DʼAntuono, Antonietta; Gaspari, Valeria; Drago, Francesco

2018-04-01

Although syphilis rates have been relatively high in Italy for more than 15 years, no data on the molecular types of Treponema pallidum subspecies pallidum circulating in this country are yet available. Likewise, no data on how widespread is resistance to macrolide or tetracycline antibiotics in these strains exist. Such data would, however, promote comprehensive studies on the molecular epidemiology of syphilis infections in Italy and inform future interventions aiming at syphilis control in this and other European countries. Swabs from oral, genital, cutaneous, or anal lesions were obtained from 60 syphilis patients attending dermatology clinics in Milan, Turin, Genoa, and Bologna. Molecular typing of T. pallidum DNA was performed to provide a snapshot of the genetic diversity of strains circulating in Northern Italy. Samples were also screened for mutations conferring resistance to macrolides and tetracyclines. T. pallidum DNA was detected in 88.3% (53/60) of the specimens analyzed. Complete and partial T. pallidum typing data were obtained for 77.3% (41/53) and 15.0% (8/53) of samples, respectively, whereas 4 samples could not be typed despite T. pallidum DNA being detected. The highest strain type heterogeneity was seen in samples from Bologna and Milan, followed by Genoa. Minimal diversity was detected in samples from Turin, despite the highest number of typeable samples collected there. Resistance to macrolides was detected in 94.3% (50/53) of the strains, but no known mutations associated with tetracycline resistance were found. Genetic diversity among T. pallidum strains circulating in Northern Italy varies significantly among geographical areas regardless of physical distance. Resistance to macrolides is widespread.

Antibiotic Resistant Salmonella and Vibrio Associated with Farmed Litopenaeus vannamei

PubMed Central

Banerjee, Sanjoy; Ooi, Mei Chen; Shariff, Mohamed; Khatoon, Helena

2012-01-01

Salmonella and Vibrio species were isolated and identified from Litopenaeus vannamei cultured in shrimp farms. Shrimp samples showed occurrence of 3.3% of Salmonella and 48.3% of Vibrio. The isolates were also screened for antibiotic resistance to oxolinic acid, sulphonamides, tetracycline, sulfamethoxazole/trimethoprim, norfloxacin, ampicillin, doxycycline hydrochloride, erythromycin, chloramphenicol, and nitrofurantoin. Salmonella enterica serovar Corvallis isolated from shrimp showed individual and multiple antibiotic resistance patterns. Five Vibrio species having individual and multiple antibiotic resistance were also identified. They were Vibrio cholerae (18.3%), V. mimicus (16.7%), V. parahaemolyticus (10%), V. vulnificus (6.7%), and V. alginolyticus (1.7%). Farm owners should be concerned about the presence of these pathogenic bacteria which also contributes to human health risk and should adopt best management practices for responsible aquaculture to ensure the quality of shrimp. PMID:22619583