Residual antibiotics in decontaminated human cardiovascular tissues intended for transplantation and risk of falsely negative microbiological analyses.

PubMed

Buzzi, Marina; Guarino, Anna; Gatto, Claudio; Manara, Sabrina; Dainese, Luca; Polvani, Gianluca; Tóthová, Jana D'Amato

2014-01-01

We investigated the presence of antibiotics in cryopreserved cardiovascular tissues and cryopreservation media, after tissue decontamination with antibiotic cocktails, and the impact of antibiotic residues on standard tissue bank microbiological analyses. Sixteen cardiovascular tissues were decontaminated with bank-prepared cocktails and cryopreserved by two different tissue banks according to their standard operating procedures. Before and after decontamination, samples underwent microbiological analysis by standard tissue bank methods. Cryopreserved samples were tested again with and without the removal of antibiotic residues using a RESEP tube, after thawing. Presence of antibiotics in tissue homogenates and processing liquids was determined by a modified agar diffusion test. All cryopreserved tissue homogenates and cryopreservation media induced important inhibition zones on both Staphylococcus aureus- and Pseudomonas aeruginosa-seeded plates, immediately after thawing and at the end of the sterility test. The RESEP tube treatment markedly reduced or totally eliminated the antimicrobial activity of tested tissues and media. Based on standard tissue bank analysis, 50% of tissues were found positive for bacteria and/or fungi, before decontamination and 2 out of 16 tested samples (13%) still contained microorganisms after decontamination. After thawing, none of the 16 cryopreserved samples resulted positive with direct inoculum method. When the same samples were tested after removal of antibiotic residues, 8 out of 16 (50%) were contaminated. Antibiotic residues present in tissue allografts and processing liquids after decontamination may mask microbial contamination during microbiological analysis performed with standard tissue bank methods, thus resulting in false negatives.

Residual Antibiotics in Decontaminated Human Cardiovascular Tissues Intended for Transplantation and Risk of Falsely Negative Microbiological Analyses

PubMed Central

Gatto, Claudio; Manara, Sabrina; Dainese, Luca; Polvani, Gianluca; Tóthová, Jana D'Amato

2014-01-01

We investigated the presence of antibiotics in cryopreserved cardiovascular tissues and cryopreservation media, after tissue decontamination with antibiotic cocktails, and the impact of antibiotic residues on standard tissue bank microbiological analyses. Sixteen cardiovascular tissues were decontaminated with bank-prepared cocktails and cryopreserved by two different tissue banks according to their standard operating procedures. Before and after decontamination, samples underwent microbiological analysis by standard tissue bank methods. Cryopreserved samples were tested again with and without the removal of antibiotic residues using a RESEP tube, after thawing. Presence of antibiotics in tissue homogenates and processing liquids was determined by a modified agar diffusion test. All cryopreserved tissue homogenates and cryopreservation media induced important inhibition zones on both Staphylococcus aureus- and Pseudomonas aeruginosa-seeded plates, immediately after thawing and at the end of the sterility test. The RESEP tube treatment markedly reduced or totally eliminated the antimicrobial activity of tested tissues and media. Based on standard tissue bank analysis, 50% of tissues were found positive for bacteria and/or fungi, before decontamination and 2 out of 16 tested samples (13%) still contained microorganisms after decontamination. After thawing, none of the 16 cryopreserved samples resulted positive with direct inoculum method. When the same samples were tested after removal of antibiotic residues, 8 out of 16 (50%) were contaminated. Antibiotic residues present in tissue allografts and processing liquids after decontamination may mask microbial contamination during microbiological analysis performed with standard tissue bank methods, thus resulting in false negatives. PMID:25397402

Residues and potential ecological risks of veterinary antibiotics in manures and composts associated with protected vegetable farming.

PubMed

Zhang, Haibo; Luo, Yongming; Wu, Longhua; Huang, Yujuan; Christie, Peter

2015-04-01

Veterinary antibiotics (VAs) are emerging contaminants and enter into soil principally by agricultural application of organic fertilizer. A total of 33 solid animal manures and 17 compost samples from protected vegetable farms in nine areas of China were analyzed for the antibiotic classes of tetracyclines, fluoroquinolones, sulfonamides, and macrolides (17 substances in total). Oxytetracycline was found as a dominant compound in the samples, and its highest concentration reached 416.8 mg kg(-1) in a chicken manure sample from Shouguang, Shandong Province. Among the samples, animal manures (especially pig manure) contained higher VA residues than composts. However, fluoroquinolones exhibited higher persistence in the compost samples than other antibiotic classes. This is particularly the case in the rice husk compost, which contained the highest level of ofloxacin and ciprofloxacin (1334.5 and 1717.4 μg kg(-1) on average, respectively). The veterinary antibiotic profile in the risk husk compost had a good relationship with that in the corresponding manures. The refined commercial compost had the lowest VA residues among the compost samples in general. This implied that composting process might be important to reduce the antibiotic residue. High residue of antibiotics in soil was assumed to be a hazard to ecosystem. This is especially noticeable under current application rates (150 t ha(-1) a(-1)) in protected vegetable farming because over half of the samples exhibited a risk quotient (RQ) >1 for one or more antibiotics.

The effectiveness of sewage treatment processes to remove faecal pathogens and antibiotic residues

PubMed Central

Hendricks, Rahzia; Pool, Edmund John

2012-01-01

Pathogens and antibiotics enter the aquatic environment via sewage effluents and may pose a health risk to wild life and humans. The aim of this study was to determine the levels of faecal bacteria, and selected antibiotic residues in raw wastewater and treated sewage effluents from three different sewage treatment plants in the Western Cape, South Africa. Sewage treatment plant 1 and 2 use older technologies, while sewage treatment plant 3 has been upgraded and membrane technologies were incorporated in the treatment processes. Coliforms and Escherichia coli (E. coli) were used as bioindicators for faecal bacteria. A chromogenic test was used to screen for coliforms and E. coli. Fluoroquinolones and sulfamethoxazole are commonly used antibiotics and were selected to monitor the efficiency of sewage treatment processes for antibiotic removal. Enzyme Linked Immunosorbent Assays (ELISAs) were used to quantitate antibiotic residues in raw and treated sewage. Raw intake water at all treatment plants contained total coliforms and E. coli. High removal of E. coli by treatment processes was evident for treatment plant 2 and 3 only. Fluoroquinolones and sulfamethoxazole were detected in raw wastewater from all sewage treatment plants. Treatment processes at plant 1 did not reduce the fluoroquinolone concentration in treated sewage effluents. Treatment processes at plant 2 and 3 reduced the fluoroquinolone concentration by 21% and 31%, respectively. Treatment processes at plant 1 did not reduce the sulfamethoxazole concentration in treated sewage effluents. Treatment processes at plant 2 and 3 reduced sulfamethoxazole by 34% and 56%, respectively. This study showed that bacteria and antibiotic residues are still discharged into the environment. Further research needs to be undertaken to improve sewage treatment technologies, thereby producing a better quality treated sewage effluent. PMID:22242882

Antibiotic Residues in Milk from Three Popular Kenyan Milk Vending Machines.

PubMed

Kosgey, Amos; Shitandi, Anakalo; Marion, Jason W

2018-05-01

Milk vending machines (MVMs) are growing in popularity in Kenya and worldwide. Milk vending machines dispense varying quantities of locally sourced, pasteurized milk. The Kenya Dairy Board has a regulatory framework, but surveillance is weak because of several factors. Milk vending machines' milk is not routinely screened for antibiotics, thereby increasing potential for antibiotic misuse. To investigate, a total of 80 milk samples from four commercial providers ( N = 25), street vendors ( N = 21), and three MVMs ( N = 34) were collected and screened in Eldoret, Kenya. Antibiotic residue surveillance occurred during December 2016 and January 2017 using Idexx SNAP ® tests for tetracyclines, sulfamethazine, beta-lactams, and gentamicin. Overall, 24% of MVM samples and 24% of street vendor samples were presumably positive for at least one antibiotic. No commercial samples were positive. Research into cost-effective screening methods and increased monitoring by food safety agencies are needed to uphold hazard analysis and critical control point for improving antibiotic stewardship throughout the Kenyan private dairy industry.

Microbiological quality and antibiotic residues in informally marketed raw cow milk within the coastal savannah zone of Ghana.

PubMed

Addo, K K; Mensah, G I; Aning, K G; Nartey, N; Nipah, G K; Bonsu, C; Akyeh, M L; Smits, H L

2011-02-01

To investigate the microbiological quality and the presence of antibiotic residues in raw cow milk and in some indigenous milk products produced and marketed by the informal sector in the coastal savannah zone of Ghana. Milk samples were aseptically collected from 224 kraals and samples of 26 indigenous milk products were purchased from processors and retailers. Total plate counts, total coliform counts and the presence of Escherichia coli and E. coli O157:H7 were determined in all 250 samples. Milk samples were also tested for antibiotic residues. Total plate counts exceeded 10⁵ CFU/ml in 45.2% of the samples while coliforms exceeded 10³ CFU/ml in 66.0% and E. coli was detected in 11.2%. E. coli was present in raw cow milk but not in the indigenous products and all E. coli isolates were negative for E. coli O157:H7. Antibiotic residues were detected in 3.1% of the raw cow milk samples. Bulk milk contains unacceptable levels of hygiene indicators and antibiotic residues and is a potential source of milk-borne infections. The detection of E. coli and antibiotic residues raises public health concerns about the safety of fresh unpasteurized cow milk in the coastal savannah zone of Ghana and calls for improved farm hygiene, the need for milk pasteurization and the sensible use of antibiotics in the milk industry. © 2010 Blackwell Publishing Ltd.

Monitoring Antibiotic Use and Residue in Freshwater Aquaculture for Domestic Use in Vietnam.

PubMed

Pham, Dang Kim; Chu, Jacqueline; Do, Nga Thuy; Brose, François; Degand, Guy; Delahaut, Philippe; De Pauw, Edwin; Douny, Caroline; Nguyen, Kinh Van; Vu, Ton Dinh; Scippo, Marie-Louise; Wertheim, Heiman F L

2015-09-01

Vietnam is an important producer of aquaculture products, and aquatic products are essential to the Vietnamese diet. However, Vietnam also has very little enforced regulation pertaining to antibiotic usage in domestic aquaculture, which raises concerns for antibiotic resistance in pathogenic bacteria. In this study, analysis was conducted on the presence of antibiotic residues in domestically sold fish and shrimp raised in freshwater farms in Vietnam, and an assessment of farmers' knowledge of proper antibiotics usage was performed. The results indicated that a quarter of tested aquaculture products were antibiotic screening test positive, and there is a general lack of knowledge about the purpose and proper usage of antibiotics by aquaculture producers. Farmers' decision-making processes about antimicrobial use are influenced by biased sources of information, such as drug manufacturers and sellers, and by financial incentives.

Effect of cooking and cold storage on biologically active antibiotic residues in meat.

PubMed Central

O'Brien, J. J.; Campbell, N.; Conaghan, T.

1981-01-01

An investigation was undertaken to see if cooking or cold storage would destroy or decrease the level of biologically active antibiotic in tissues from animals given therapeutic doses of antibiotic on three occasions prior to slaughter. The effects of cooking and cold storage on the biological activity of the residues of ampicillin, chloramphenicol, oxytetracycline, streptomycin and sulphadimidine were varied; in some instances the effects were minimal, in others nil. PMID:7310129

Antibiotic residues in milk and eggs of commercial and local farms at Chittagong, Bangladesh.

PubMed

Chowdhury, Suchayan; Hassan, Mohammad Mahmudul; Alam, Mahabub; Sattar, Sarmina; Bari, Md Saiful; Saifuddin, A K M; Hoque, Md Ahasanul

2015-04-01

The study was conducted to detection and determination of concentration or level of antibiotic residues in milk and egg of local and commercial farms at Chittagong during December 2011 to June 2012. A total of 400 (200 milk and 200 egg) samples were collected from local and commercial dairy cows and local scavenging and commercial poultry farms, respectively. Microbial inhibition test and thin layer chromatography were used for screening and ultra-high performance liquid chromatography was used to estimate the concentrations of antibiotic residues in samples. Tetracycline, amoxicillin, and ciprofloxacin residues were significantly (p ≤ 0.05) higher in commercial farms than local. The boiling insignificantly (p>0.05) reduced residues level in milk and egg. The average concentrations of amoxicillin residue in local milk, commercial milk, local egg, and commercial egg were 9.84 µg/ml, 56.16 µg/ml, 10.46 µg/g and 48.82 µg/g, respectively, in raw samples and were reduced to 9.81 µg/ml, 55.54 µg/ml, 10.29 µg/g, and 48.38 µg/g, respectively, after boiling. Proper maintaining of the withdrawal period and development of active surveillance system are highly recommended for public health security.

Abusive use of antibiotics in poultry farming in Cameroon and the public health implications.

PubMed

Guetiya Wadoum, R E; Zambou, N F; Anyangwe, F F; Njimou, J R; Coman, M M; Verdenelli, M C; Cecchini, C; Silvi, S; Orpianesi, C; Cresci, A; Colizzi, V

2016-08-01

The types and methods of use of antibiotics in poultry farms in Cameroon, residual levels and potential microbial resistance were determined. A questionnaire-based survey identified the different antibiotics used and high-performance liquid chromatography (HPLC) was used to determine residual levels of antibiotics. Pathogens were isolated, identified by use of commercial API kits and minimum inhibition concentration (MIC) was determined. Oxytetracyclin, tylocip and TCN (oxytetracycline, chloramphenicol and neomycin) were the most frequently used antibiotics. Antibiotics screened by HPLC were chloramphenicol, tetracycline and vancomycin. All of them except vancomycin were detected, and the concentration of these antibiotics was higher than the maximum residual limits (MRL) set by regulatory authorities. No residues of various antibiotics were found in egg albumen or yolk. The concentration of tetracycline was significantly higher in liver (150 ± 30 µg/g) than in other tissues. Foodborne pathogens, including Salmonella spp., Staphylococcus spp., Listeria spp., Clostridium spp. and Escherichia spp., were identified. Most of the pathogens were resistant to these various antibiotics tested. These findings imply the need for better management of antibiotic use to control sources of food contamination and reduce health risks associated with the presence of residues and the development of resistant pathogens by further legislation and enforcement of regulations on food hygiene and use of antibiotics.

Adaption of the microbial community to continuous exposures of multiple residual antibiotics in sediments from a salt-water aquacultural farm.

PubMed

Xi, Xiuping; Wang, Min; Chen, Yongshan; Yu, Shen; Hong, Youwei; Ma, Jun; Wu, Qian; Lin, Qiaoyin; Xu, Xiangrong

2015-06-15

Residual antibiotics from aquacultural farming may alter microbial community structure in aquatic environments in ways that may adversely or positively impact microbially-mediated ecological functions. This study investigated 26 ponds (26 composited samples) used to produce fish, razor clam and shrimp (farming and drying) and 2 channels (10 samples) in a saltwater aquacultural farm in southern China to characterize microbial community structure (represented by phospholipid fatty acids) in surface sediments (0-10 cm) with long-term exposure to residual antibiotics. 11 out of 14 widely-used antibiotics were quantifiable at μg kg(-1) levels in sediments but their concentrations did not statistically differ among ponds and channels, except norfloxacin in drying shrimp ponds and thiamphenicol in razor clam ponds. Concentrations of protozoan PLFAs were significantly increased in sediments from razor clam ponds while other microbial groups were similar among ponds and channels. Both canonical-correlation and stepwise-multiple-regression analyses on microbial community and residual antibiotics suggested that roxithromycin residuals were significantly related to shifts in microbial community structure in sediments. This study provided field evidence that multiple residual antibiotics at low environmental levels from aquacultural farming do not produce fundamental shifts in microbial community structure. Copyright © 2015 Elsevier B.V. All rights reserved.

Potential of phytoceuticals to affect antibiotic residue detection tests in cow milk in a randomised trial

PubMed Central

Mullen, Keena AE; Beasley, Erin; Rizzo, Julio Q; Washburn, Steven P; Baynes, Ronald E; Mason, Sharon E

2017-01-01

Mastitis is a costly disease for dairy farmers. Some dairy farmers use herbal products, or phytoceuticals, to treat mastitis. Phytoceuticals have not been approved for this use by the United States Food and Drug Administration, and have not been tested to determine how they impact antibiotic residue detection testing. The current study tested the potential for phytoceuticals to cause positive results on two milk antibiotic residue screening tests, the Delvotest P and Charm SL Beta-lactam test, or to interfere with the detection of antibiotics by these tests. The three phytoceuticals tested were labelled for intramammary, topical or intravulvar administration. Testing was performed in vitro using the products diluted in milk obtained from healthy organic dairy cows. Phytoceuticals were tested at concentrations ranging from 1.5 per cent to 100 per cent. Concentration levels were replicated at least twice on each milk antibiotic residue screening test. The Delvotest P is based on detection of bacterial inhibitors and no positive results were obtained for any product at concentrations less than 50 per cent. The Charm SL Beta-lactam test uses a receptor for the detection of beta-lactam antibiotics and no concentration of phytoceuticals caused an interference with these tests. Based on dilution of the products in bovine milk at physiologically achievable levels, phytoceutical products tested at levels expected after treatment do not cause positive test results for the Delvotest P nor do they interfere with the Charm SL Beta-lactam test in detection of various antibiotics. PMID:28890791

Seasonal Variations in Water-Quality, Antibiotic Residues, Resistant Bacteria and Antibiotic Resistance Genes of Escherichia coli Isolates from Water and Sediments of the Kshipra River in Central India.

PubMed

Diwan, Vishal; Hanna, Nada; Purohit, Manju; Chandran, Salesh; Riggi, Emilia; Parashar, Vivek; Tamhankar, Ashok J; Stålsby Lundborg, Cecilia

2018-06-17

To characterize the seasonal variation, over one year, in water-quality, antibiotic residue levels, antibiotic resistance genes and antibiotic resistance in Escherichia coli isolates from water and sediment of the Kshipra River in Central India. Water and sediment samples were collected from seven selected points from the Kshipra River in the Indian city of Ujjain in the summer, rainy season, autumn and winter seasons in 2014. Water quality parameters (physical, chemical and microbiological) were analyzed using standard methods. High-performance liquid chromatography⁻tandem mass spectrometry was used to determine the concentrations of antibiotic residues. In river water and sediment samples, antibiotic resistance and multidrug resistance patterns of isolated E. coli to 17 antibiotics were tested and genes coding for resistance and phylogenetic groups were detected using multiplex polymerase chain reaction. One-way analysis of variance (ANOVA) and Fisher tests were applied to determine seasonal variation. In river water, seasonal variation was significantly associated with various water quality parameters, presence of sulfamethoxazole residues, bacteria resistant to ampicillin, cefepime, meropenem, amikacin, gentamicin, tigecycline, multidrug resistance and CTX-M-1 gene. The majority of the Extended Spectrum Beta-Lactamase (ESBL)-producing E. coli isolates from river water and sediment in all different seasons belonged to phylogenetic group A or B1. Antibiotic pollution, resistance and resistance genes in the Kshipra River showed significant seasonal variation. Guidelines and regulatory standards are needed to control environmental dissemination of these “pollutants” in this holy river.

Development of a new screening method for the detection of antibiotic residues in muscle tissues using liquid chromatography and high resolution mass spectrometry with a LC-LTQ-Orbitrap instrument.

PubMed

Hurtaud-Pessel, D; Jagadeshwar-Reddy, T; Verdon, E

2011-10-01

A liquid chromatography-high resolution mass spectrometry (LC-HRMS) method was developed for screening meat for a wide range of antibiotics used in veterinary medicine. Full-scan mode under high resolution mass spectral conditions using an LTQ-Orbitrap mass spectrometer with resolving power 60,000 full width at half maximum (FWHM) was applied for analysis of the samples. Samples were prepared using two extraction protocols prior to LC-HRMS analysis. The scope of the method focuses on screening the following main families of antibacterial veterinary drugs: penicillins, cephalosporins, sulfonamides, macrolides, tetracyclines, aminoglucosides and quinolones. Compounds were successfully identified in spiked samples from their accurate mass and LC retention times from the acquired full-scan chromatogram. Automated data processing using ToxId software allowed rapid treatment of the data. Analyses of muscle tissues from real samples collected from antibiotic-treated animals was carried out using the above methodology and antibiotic residues were identified unambiguously. Further analysis of the data for real samples allowed the identification of the targeted antibiotic residues but also non-targeted compounds, such as some of their metabolites.

Strategies for the screening of antibiotic residues in eggs: comparison of the validation of the classical microbiological method with an immunobiosensor method.

PubMed

Gaudin, Valérie; Rault, Annie; Hedou, Celine; Soumet, Christophe; Verdon, Eric

2017-09-01

Efficient screening methods are needed to control antibiotic residues in eggs. A microbiological kit (Explorer® 2.0 test (Zeu Inmunotech, Spain)) and an immunobiosensor kit (Microarray II (AM® II) on Evidence Investigator™ system (Randox, UK)) have been evaluated and validated for screening of antibiotic residues in eggs, according to the European decision EC/2002/657 and to the European guideline for the validation of screening methods. The e-reader™ system, a new automatic incubator/reading system, was coupled to the Explorer 2.0 test. The AM II kit can detect residues of six different families of antibiotics in different matrices including eggs. For both tests, a different liquid/liquid extraction of eggs had to be developed. Specificities of the Explorer 2.0 and AM II kit were equal to 8% and 0% respectively. The detection capabilities were determined for 19 antibiotics, with representatives from different families, for Explorer 2.0 and 12 antibiotics for the AM II kit. For the nine antibiotics having a maximum residue limit (MRL) in eggs, the detection capabilities CCβ of Explorer 2.0 were below the MRL for four antibiotics, equal to the MRL for two antibiotics and between 1 and 1.5 MRLs for the three remaining antibiotics (tetracyclines). For the antibiotics from other families, the detection capabilities were low for beta-lactams and sulfonamides and satisfactory for dihydrostreptomycin (DHS) and fluoroquinolones, which are usually difficult to detect with microbiological tests. The CCβ values of the AM II kit were much lower than the respective MRLs for three detected antibiotics (tetracycline, oxytetracycline, tylosin). Concerning the nine other antibiotics, the detection capabilities determined were low. The highest CCβ was obtained for streptomycin (100 µg kg -1 ).

Antibiotic residues in milk samples obtained from cows after treatment for papillomatous digital dermatitis.

PubMed

Britt, J S; Carson, M C; von Bredow, J D; Condon, R J

1999-09-15

To determine whether there would be detectable antibiotic residues in milk obtained from dairy cattle with papillomatous digital dermatitis (PDD) after topical treatment with oxytetracycline. Randomized controlled clinical trial. 28 lactating Holstein cows with PDD. Cows were assigned to 2 treatment groups. Treatment 1 (n = 16) consisted of spraying of PDD lesions with 15 ml of a solution containing 100 mg of oxytetracycline/ml; lesions were sprayed twice daily for 7 days, using a garden sprayer. Treatment 2 (n = 12) consisted of a one-time application of a bandage that consisted of cotton soaked with 20 ml of a solution containing 100 mg of oxytetracycline/ml. Milk samples were obtained before and after treatment and assayed for tetracycline content by use of high-performance liquid chromatography and a commercially available tetracycline screening test. None of the cows in either treatment group had violative residues of oxytetracycline in milk samples. Producers treating lactating cows that have PDD, via topical application of oxytetracycline solution at the concentrations reported in this study, have a low risk of causing violative antibiotic residues in milk.

The relationship between blood and muscle samples to monitor for residues of the antibiotic enrofloxacin in chickens

USDA-ARS?s Scientific Manuscript database

Use of antibiotics in food animals has generated concern as the presence of these residues in food may contribute to increased microbial resistance in humans. Fluoroquinolone antibiotics are thus now no longer allowed by the U.S. Food and Drug Administration for use in poultry and monitoring of the...

Screening of quinolone antibiotic residues in chicken meat and beef sold in the markets of Ankara, Turkey.

PubMed

Er, Buket; Onurdag, Fatma Kaynak; Demirhan, Burak; Ozgacar, Selda Özgen; Oktem, Aysel Bayhan; Abbasoglu, Ufuk

2013-08-01

This study aimed to find the effects of quinolone antibiotics in chicken and beef used in Ankara, Turkey. Total number of 127 chicken and 104 beef meat samples were collected randomly from local markets for analysis. Extraction and determination of quinolones were made by ELISA procedure. One hundred eighteen of 231 (51.1%) examined chicken meat and beef samples were found to contain quinolone antibiotic residue. Among the chicken meat and beef samples, 58 (45.7%) of chicken meat samples and 60 (57.7%) of beef meat samples were positive for quinolones, respectively. The mean levels (±SE) of quinolones were found to be 30.81 ± 0.45 µg/kg and 6.64 ± 1.11 µg/kg in chicken and beef samples, respectively. This study indicated that some chicken and beef meat sold in Ankara contains residues of quinolone antibiotics.

Antibiotics and antibiotic-resistant bacteria in waters associated with a hospital in Ujjain, India

PubMed Central

2010-01-01

Background Concerns have been raised about the public health implications of the presence of antibiotic residues in the aquatic environment and their effect on the development of bacterial resistance. While there is information on antibiotic residue levels in hospital effluent from some other countries, information on antibiotic residue levels in effluent from Indian hospitals is not available. Also, concurrent studies on antibiotic prescription quantity in a hospital and antibiotic residue levels and resistant bacteria in the effluent of the same hospital are few. Therefore, we quantified antibiotic residues in waters associated with a hospital in India and assessed their association, if any, with quantities of antibiotic prescribed in the hospital and the susceptibility of Escherichia coli found in the hospital effluent. Methods This cross-sectional study was conducted in a teaching hospital outside the city of Ujjain in India. Seven antibiotics - amoxicillin, ceftriaxone, amikacin, ofloxacin, ciprofloxacin, norfloxacin and levofloxacin - were selected. Prescribed quantities were obtained from hospital records. The samples of the hospital associated water were analysed for the above mentioned antibiotics using well developed and validated liquid chromatography/tandem mass spectrometry technique after selectively isolating the analytes from the matrix using solid phase extraction. Escherichia coli isolates from these waters were tested for antibiotic susceptibility, by standard Kirby Bauer disc diffusion method using Clinical and Laboratory Standard Institute breakpoints. Results Ciprofloxacin was the highest prescribed antibiotic in the hospital and its residue levels in the hospital wastewater were also the highest. In samples of the municipal water supply and the groundwater, no antibiotics were detected. There was a positive correlation between the quantity of antibiotics prescribed in the hospital and antibiotic residue levels in the hospital wastewater

Evaluation of certification in the Milk and Dairy Beef Quality Assurance Program and associated factors on the risk of having violative antibiotic residues in milk from dairy farms in Michigan.

PubMed

Gibbons-Burgener, S N; Kaneene, J B; Lloyd, J W; Erskine, R J

1999-10-01

To determine whether certification in a Milk and Dairy Beef Quality Assurance Program (MDBQAP) was associated with a reduced risk of having antibiotic residues in milk and to define specific management factors that may have predisposed dairy farms to having violative antibiotic residues in milk. 124 dairy farms in Michigan that had > 1 violative residue in milk during 1993 and 248 randomly selected control farms in Michigan that did not have violative residues in milk during 1993. A pretested structured questionnaire was mailed to case and control farms. A conditional multivariate logistic regression model was developed to determine risk factors associated with having a violative antibiotic residue in milk. Certification in the MDBQAP did not significantly reduce the risk of having a violative antibiotic residue. Annual treatment of > 10% of a herd for metritis was associated with a reduced risk of having a violative residue. Evidence suggested that a routine request for a milk processor to perform residue testing was associated with a decreased risk of having had a violative antibiotic residue, but routine on-farm residue testing was associated with an increased risk of having had a residue. MDBQAP certification was associated, although not significantly, with a reduced risk of having violative antibiotic residues in milk. Risk factors significantly associated with violative antibiotic residues are addressed by various critical control points in the MDBQAP and may be indicators for strengths and weaknesses of MDBQAP.

Portable surface plasmon resonance immunosensor for the detection of fluoroquinolone antibiotic residues in milk.

PubMed

Fernández, Fátima; Pinacho, Daniel G; Sánchez-Baeza, Francisco; Marco, M Pilar

2011-05-11

An inexpensive and portable surface plasmon resonance (SPR) sensor, SPReeta Evaluation Kit SPR3, has been used to develop a biosensor for the determination of fluoroquinolone antibiotics (FQs) and to demonstrate its performance analyzing FQ residues in milk samples. The SPReeta three-channel gold chips were activated with a mixed self-assembled monolayer (m-SAM) and functionalized with a FQ haptenized protein. Binding of the antibody produced a concentration-dependent increase of the SPR signal as a result of the change in the refraction index. Similarly, the presence of the FQ produced a dose-dependent decrease of the response, which allowed a good limit of detection (LOD) to be obtained (1.0 ± 0.4 μg L(-1) for enrofloxacin in buffer). The response was reproducible in all three channels, on different injections and days, and also between chips. Milk samples could be analyzed after a simple sample treatment involving fat removal by centrifugation and dilution with water. Under these conditions calibration curves were obtained showing that FQ residues can be analyzed in milk samples with an IC(50) value of 26.4 ± 7.2 μg L(-1) and a LOD of 2.0 ± 0.2 μg L(-1) (for enrofloxacin), far below the European Union regulations for this antibiotic family in this matrix. Finally, the paper also demonstrates that the biosensor is able to selectively detect the presence of FQs in milk samples, even in the presence of other antibiotics. Enrofloxacin, ciprofloxacin, and norfloxacin residues were detected in blind samples supplied by Nestlé Co.

Multiclass methods for the analysis of antibiotic residues in milk by liquid chromatography coupled to mass spectrometry: A review.

PubMed

Rossi, Rosanna; Saluti, Giorgio; Moretti, Simone; Diamanti, Irene; Giusepponi, Danilo; Galarini, Roberta

2018-02-01

Milk is an important and beneficial food from a nutritional point of view, being an indispensable source of high quality proteins. Furthermore, it is a raw material for many dairy products, such as yoghurt, cheese, cream etc. Before reaching consumers, milk goes through production, processing and circulation. Each step involves potentially unsafe factors, such as chemical contamination that can affect milk quality. Antibiotics are widely used in veterinary medicine for dry cow therapy and mastitis treatment in lactating cows, which can cause the presence of antimicrobial residues in milk. In order to ensure consumers' safety, milk is analyzed to make sure that the fixed Maximum Residue Limits (MRLs) for antibiotics are not exceeded. Multiclass methods can monitor more drug classes through a single analysis, so they are faster, less time-consuming and cheaper than traditional methods (single-class); this aspect is particularly important for milk, which is a highly perishable food. Nevertheless, multiclass methods for veterinary drug residues in foodstuffs are real analytical challenges. This article reviews the major multiclass methods published for the determination of antibiotic residues in milk by liquid chromatography coupled to mass spectrometry, with a special focus on sample preparation approaches.

Risks of antibiotic residues in milk following intramammary and intramuscular treatments in dairy sheep.

PubMed

Pengov, A; Kirbis, A

2009-04-01

Very few drugs on the market are approved for use in lactating ewes. Veterinarians in the European Union are allowed to prescribe drugs in an off-label manner but are then obligated to assure that residues do not enter the food chain. In case of mastitis treatment in dairy ewes antibiotic preparations designed and authorized for the bovine mammary gland are usually used. Due to inter-species differences, available bovine data cannot be accurately extrapolated for use in the dairy ewe. The objective of the study was therefore to determine appropriate withdrawal periods for ewe's milk following mastitis treatment with two commercial lactating cow products. For the detection of all components standard agar plate diffusion techniques were used. Regardless of the therapy regime and the product used, residues of antibiotics in milk were detected up to 192h after the last infusion. These results indicate that the required withholding periods for ewe's milk are considerably longer than recommended on the label for bovine milk.

Residues of 2-hydroxy-3-phenylpyrazine, a degradation product of some β-lactam antibiotics, in environmental water in Vietnam.

PubMed

Sy, Nguyen Van; Harada, Kazuo; Asayama, Megumi; Warisaya, Minae; Dung, Le Hong; Sumimura, Yoshinori; Diep, Khong Thi; Ha, Le Viet; Thang, Nguyen Nam; Hoa, Tran Thi Tuyet; Phu, Tran Minh; Khai, Pham Ngoc; Phuong, Nguyen Thanh; Tuyen, Le Danh; Yamamoto, Yoshimasa; Hirata, Kazumasa

2017-04-01

Antibiotic-resistant bacteria have become a serious problem worldwide, caused in part by the excessive use and discharge of antibiotics into the environment. Ampicillin (ABPC) is a widely used antibiotic. However, this chemical rapidly decomposes in water containing divalent cations like Ca 2+ and Mg 2+ , thus, detection of ABPC in environmental water is difficult. This study was carried out to evaluate the presence of 2-hydroxy-3-phenylpyrazine (HPP), one of the degradation products of ABPC and β-lactam antibiotics with an ABPC substructure, in environmental water. An analytical method for HPP monitoring in environmental water was developed using liquid chromatography/tandem mass spectrometry. The analyte was extracted from water samples and enriched using a solid-phase extraction cartridge. The quantification limit was 1 ng L -1 . The HPP recovery rates from spiked water samples of 25 and 125 ng L -1 were 84.1 and 86.1%, respectively. The method was then used to determine HPP residue levels in 98 environmental water samples from rivers, household ponds, and aquacultural ponds in Vietnam. HPP residues were detected in 60 samples. The HPP detection rates in rivers and household ponds were 42 and 79%, respectively. HPP was not detected in aquacultural ponds. HPP residue concentrations in the samples ranged from 1.3 to 413.3 ng L -1 . The residue levels in rivers flowing through city centres were higher than levels in other sampling locations. The findings of this study suggest that HPP is a promising marker for assessing the discharge of ABPC and β-lactam antibiotics with an ABPC substructure into the environment around sampling sites. Copyright © 2017 Elsevier Ltd. All rights reserved.

Performances of antibiotic screening tests in determining the persistence of penicillin residues in ewe's milk.

PubMed

Berruga, M I; Yamaki, M; Althaus, R L; Molina, M P; Molina, A

2003-11-01

Milk collected at 12-h intervals throughout 6 days from three groups of Manchega ewes (n = 12 per group), treated intramuscularly with beta-lactams (benzyl penicillin procaine, ampicillin, and amoxicillin, respectively), was evaluated for antibiotic residue persistence with four microbial inhibitor tests (BRT MRL, CH ATK P&S, Delvotest SP, and Eclipse 100ov) and one enzymatic test (Penzym 100). Antibiotic depletion time was established using a logistic regression model. A clear effect (P < 0.0001) of milking order on the response of all tests was observed with the three antibiotics, but no significant effects were found for milk yield. Except with Eclipse 100ov, positive tests were observed after the recommended withdrawal period of benzyl penicillin procaine (five milkings) from 2% (Delvotest SP) to 11% (CH ATK P&S). There were almost no positive responses beyond the withdrawal period (six milkings) of ampicillin, except for the Penzym 100 test (7%). Residues of amoxicillin were found to persist beyond the six milkings established as the withdrawal period, from 2.8% (Eclipse 100ov) to 72.4% (CH ATK P&S) of positive cases. Higher frequencies of doubtful cases were found with BRT MRL and Delvotest SP assays with the three beta-lactams. Positive and doubtful results could be obtained when milk samples from individual ewes were analyzed using BRT MRL, CH ATK P&S, Delvotest SP, and Penzym 100 tests, even if farmers follow the antibiotic withdrawal periods.

Evaluation of Antibiotic Residues in Pasteurized and Raw Milk Distributed in the South of Khorasan-e Razavi Province, Iran.

PubMed

Moghadam, Mortez Mohammadzadeh; Amiri, Mostafa; Riabi, Hamed Ramezani Awal; Riabi, Hamid Ramezani Awal

2016-12-01

The presence of antibiotic residues in milk and other products livestock is a health problem which can endanger public health. Antibiotics are used widely in animal husbandry to treat diseases related to bacterial infections. Antimicrobial drugs have been in use for decades in industry. They are commonly used in livestock facilities to treat mastitis. This study aimed to investigate antibiotic residues in pasteurized milk distributed in schools, in milk collection centers, and in milk production factories in Gonabad city. This cross-sectional study was conducted on 251 samples of commercial pasteurized milk packet distributed in schools (code A), raw milk collection centers in Gonabad city (code B), and pasteurized milk production factories (code C) in Gonabad city. The Copan test kit of Denmark Christian Hansen Company was used to monitor antibiotic residues in milk. The data were analysed employing Chi-square test and one-way analysis of variance (ANOVA) to determine significant differences using SPSS software version 20. The significant level was considered at p<0.05. In total, 251 milk samples were collected out of which 143 (57%) were code A, 84 (33.5%) code B and 24 (9.6%) code C. Total number of 189 samples (75.2%) were negative and 62 (24.8%) were positive. From the three types of milk samples, 41 samples (28.7%) of the code A, 18 samples (21.4%) of the code B and 3 samples (12.5%) of the code C were positive. In general, from the milk samples most contaminated with antibiotics, 17 samples were positive in January and regarding code A, 13 samples were positive in the same month. There was not a significant difference among the three types of milk (p>0.05). The highest number of milk samples (n=7) contaminated with antibiotics were related to code B (38.5%). Most positive cases were related to code A in winter. Also, there was no significant difference among the three types of contaminated milk regarding the year and month (p=0.164 and p=0.917, respectively

Evaluation of Antibiotic Residues in Pasteurized and Raw Milk Distributed in the South of Khorasan-e Razavi Province, Iran

PubMed Central

Moghadam, Mortez Mohammadzadeh; Amiri, Mostafa; Riabi, Hamid Ramezani Awal

2016-01-01

Introduction The presence of antibiotic residues in milk and other products livestock is a health problem which can endanger public health. Antibiotics are used widely in animal husbandry to treat diseases related to bacterial infections. Antimicrobial drugs have been in use for decades in industry. They are commonly used in livestock facilities to treat mastitis. Aim This study aimed to investigate antibiotic residues in pasteurized milk distributed in schools, in milk collection centers, and in milk production factories in Gonabad city. Materials and Methods This cross-sectional study was conducted on 251 samples of commercial pasteurized milk packet distributed in schools (code A), raw milk collection centers in Gonabad city (code B), and pasteurized milk production factories (code C) in Gonabad city. The Copan test kit of Denmark Christian Hansen Company was used to monitor antibiotic residues in milk. The data were analysed employing Chi-square test and one-way analysis of variance (ANOVA) to determine significant differences using SPSS software version 20. The significant level was considered at p<0.05. Results In total, 251 milk samples were collected out of which 143 (57%) were code A, 84 (33.5%) code B and 24 (9.6%) code C. Total number of 189 samples (75.2%) were negative and 62 (24.8%) were positive. From the three types of milk samples, 41 samples (28.7%) of the code A, 18 samples (21.4%) of the code B and 3 samples (12.5%) of the code C were positive. In general, from the milk samples most contaminated with antibiotics, 17 samples were positive in January and regarding code A, 13 samples were positive in the same month. There was not a significant difference among the three types of milk (p>0.05). The highest number of milk samples (n=7) contaminated with antibiotics were related to code B (38.5%). Most positive cases were related to code A in winter. Also, there was no significant difference among the three types of contaminated milk regarding the

Electrochemical Quartz Crystal Nanobalance (EQCN) Based Biosensor for Sensitive Detection of Antibiotic Residues in Milk.

PubMed

Bhand, Sunil; Mishra, Geetesh K

2017-01-01

An electrochemical quartz crystal nanobalance (EQCN), which provides real-time analysis of dynamic surface events, is a valuable tool for analyzing biomolecular interactions. EQCN biosensors are based on mass-sensitive measurements that can detect small mass changes caused by chemical binding to small piezoelectric crystals. Among the various biosensors, the piezoelectric biosensor is considered one of the most sensitive analytical techniques, capable of detecting antigens at picogram levels. EQCN is an effective monitoring technique for regulation of the antibiotics below the maximum residual limit (MRL). The analysis of antibiotic residues requires high sensitivity, rapidity, reliability and cost effectiveness. For analytical purposes the general approach is to take advantage of the piezoelectric effect by immobilizing a biosensing layer on top of the piezoelectric crystal. The sensing layer usually comprises a biological material such as an antibody, enzymes, or aptamers having high specificity and selectivity for the target molecule to be detected. The biosensing layer is usually functionalized using surface chemistry modifications. When these bio-functionalized quartz crystals are exposed to a particular substance of interest (e.g., a substrate, inhibitor, antigen or protein), binding interaction occurs. This causes a frequency or mass change that can be used to determine the amount of material interacted or bound. EQCN biosensors can easily be automated by using a flow injection analysis (FIA) setup coupled through automated pumps and injection valves. Such FIA-EQCN biosensors have great potential for the detection of different analytes such as antibiotic residues in various matrices such as water, waste water, and milk.

Tet and sul antibiotic resistance genes in livestock lagoons of various operation type, configuration, and antibiotic occurrence

USGS Publications Warehouse

McKinney, C.W.; Loftin, K.A.; Meyer, M.T.; Davis, J.G.; Pruden, A.

2010-01-01

Although livestock operations are known to harbor elevated levels of antibiotic resistant bacteria, few studies have examined the potential of livestock waste lagoons to reduce antibiotic resistance genes (ARGs). The purpose of this study was to determine the prevalence and examine the behavior of tetracycline [tet(O) and tet(W)] and sulfonamide [sul(I) and su/(II)] ARGsin a broad cross-section of livestock lagoons within the same semiarid western watershed. ARGs were monitored for one year in the water and the settled solids of eight lagoon systems by quantitative polymerase chain reaction. In addition, antibiotic residues and various bulk water quality constituents were analyzed. It was found that the lagoons of the chicken layer operation had the lowest concentrations of both tet and sul ARGs and low total antibiotic concentrations, whereas su ARGs were highest in the swine lagoons, which generally corresponded to the highest total antibiotic concentrations. A marginal benefit of organic and small dairy operations also was observed compared to conventional and large dairies, respectively. In all lagoons, su ARGs were observed to be generally more recalcitrant than tet ARGs. Also, positive correlations of various bulk water quality constituents were identified with tet ARGs but not sul ARGs. Significant positive correlations were identified between several metals and tet ARGs, but Pearson's correlation coefficients were mostly lower than those determined between antibiotic residues and ARGs. This study represents a quantitative characterization of ARGs in lagoons across a variety of livestock operations and provides insight into potential options for managing antibiotic resistance emanating from agricultural activities. ?? 2010 American Chemical Society.

Ciprofloxacin residue and antibiotic-resistant biofilm bacteria in hospital effluent.

PubMed

Ory, Jérôme; Bricheux, Geneviève; Togola, Anne; Bonnet, Jean Louis; Donnadieu-Bernard, Florence; Nakusi, Laurence; Forestier, Christiane; Traore, Ousmane

2016-07-01

Discharge of antimicrobial residues and resistant bacteria in hospital effluents is supposed to have strong impacts on the spread of antibiotic resistant bacteria in the environment. This study aimed to characterize the effluents of the Gabriel Montpied teaching hospital, Clermont-Ferrand, France, by simultaneously measuring the concentration of ciprofloxacin and of biological indicators resistant to this molecule in biofilms formed in the hospital effluent and by comparing these data to ciprofloxacin consumption and resistant bacterial isolates of the hospital. Determination of the measured environmental concentration of ciprofloxacin by spot sampling and polar organic chemical integrative (POCIS) sampling over 2 weeks, and comparison with predicted environmental concentrations produced a hazard quotient >1, indicating a potential ecotoxicological risk. A negative impact was also observed with whole hospital effluent samples using the Tetrahymena pyriformis biological model. During the same period, biofilms were formed within the hospital effluent, and analysis of ciprofloxacin-resistant isolates indicated that Gamma-Proteobacteria were numerous, predominantly Aeromonadaceae (69.56%) and Enterobacteriaceae (22.61%). Among the 115 isolates collected, plasmid-mediated fluoroquinolone-resistant genes were detected, with mostly aac(6')-lb-cr and qnrS. In addition, 60% of the isolates were resistant to up to six antibiotics, including molecules mostly used in the hospital (aminosides and third-generation cephalosporins). In parallel, 1247 bacteria isolated from hospitalized patients and resistant to at least one of the fluoroquinolones were collected. Only 5 of the 14 species identified in the effluent biofilm were also found in the clinical isolates, but PFGE typing of the Gram-negative isolates found in both compartments showed there was no clonality among the strains. Altogether, these data confirm the role of hospital loads as sources of pollution for wastewater

[Evolution of the concept of residues in the products of animals raised with the use of antibiotics].

PubMed

Wal, J M

1979-01-01

The concept of residues of antibiotics used as feed additives or veterinary drugs in food producing animals is analysed, and implications on human public health are discussed. The examples of Tylosin and Penicillin are developed to illustrate the both notions of "high risk residue" and "toxicodisponibility" of residues. The "high risk residue" may be an active metabolite different by its chemical structure and by its pharmacological properties from the original drug administered. Slight modifications of the molecule, as the rupture of the beta lactam ring of the Penicillin, occuring in vivo, lead to a metabolite, e.g. penicilloyl group, that has lost all antibiotic activity but possesses allergenic potential. Toxicity of the residue, compared with that of the original drug, can then be modified or increased. On the other hand, such an active metabolite having a definite chemical structure, even if different from the original compound, can be present in the organism, either free or bound to serum or tissues proteins. Moreover, it is shown here, that in the case of a covalent binding of the drug or its metabolite (e.g. penicilloyl group) to serum albumin, the residues are mostly masked inside the tertiary structure of the albumin molecule, and are not accessible to antibodies. These different forms have then an effect upon the biodisponibility, the "toxicodisponibility", of the residues for the human consumer of animal products where they are present. These forms are only accessible with more and more specific and sensitive analytical methods which relates also the qualitative and quantitative notions of residue to the technological degree used for investigation, determination and identification. As to cooking techniques, they can lead to a thermodegradation of the residue or, on the opposite, to an unmasking of the residue present as a protein conjugate, e.g. penicilloyl-protein conjugate in milk.

Veterinary antibiotic resistance, residues, and ecological risks in environmental samples obtained from poultry farms, Egypt.

PubMed

Dahshan, Hesham; Abd-Elall, Amr Mohamed Mohamed; Megahed, Ayman Mohamed; Abd-El-Kader, Mahdy A; Nabawy, Ehab Elsayed

2015-02-01

In Egypt, poultry production constitutes one of the main sources of pollution with veterinary antibiotics (VAs) into the environment. About 80 % of meat production in Egypt is of poultry origin, and the potential environmental risks associated with the use of VAs in these farms have not yet been properly evaluated. Thus, the main purpose of this research was to evaluate the prevalence of antibiotic-resistant enteric key bacteria and the incidence of residual antibiotics in poultry farm environmental samples and to determine whether fertilizing soils with poultry litter from farms potentially brings ecological risks. From December 2011 to September 2012, a total of 225 litter, bird dropping, and water samples were collected from 75 randomly selected boiler poultry farms. A high prevalence of Escherichia coli (n = 179; 79.5 %) in contrast to the low prevalence of Salmonella spp. (n = 7; 3.1 %) was detected. Amongst E. coli isolates, serotypes O142:K86, O125:K70, O91:K, and O119:K69 were the most common. Meanwhile, Salmonella enterica serotypes emek and enteritidis were recovered. The antibiograms using the disc diffusion method revealed significantly more common resistant and multi-resistant isolates in broiler poultry farms. Residues of tetracycline and ciprofloxacin were detected at 2.125 and 1.401 mg kg(-1) mean levels, respectively, in environmental samples contaminated with E. coli-resistant strains by HPLC. The risk evaluations highlighted that tetracycline residues in poultry litter significantly display environmental risks with a hazard quotient value above 1 (1.64). Our study implies that ineffective implementation of veterinary laws which guide and guard against incorrect VA usage may potentially bring health and environmental risks.

Beta lactam antibiotics residues in cow's milk: comparison of efficacy of three screening tests used in Bosnia and Herzegovina.

PubMed

Fejzic, Nihad; Begagic, Muris; Šerić-Haračić, Sabina; Smajlovic, Muhamed

2014-08-27

Beta lactam antibiotics are widely used in therapy of cattle, particularly for the treatment of mastitis.  Over 95% of residue testing in dairies in Bosnia and Herzegovina is for Beta lactams. The aim of this paper is to compare the efficacy of three most common screening tests for Beta lactam residues in cow's milk in our country. The tests used in the study are SNAP β Lactam test (Idexx), Rosa Charm β Lactam test and Inhibition MRL test. Study samples included: standardized concentrations of penicillin solution (0, 2, 3, 4, 5 and 6 ppb). In addition we tested milk samples from three equal size study groups (not receiving any antibiotic therapy, treated with Beta lactams for mastitis and treated with Beta lactams for diseases other than mastitis). Sensitivity and specificity were determined for each test, using standard penicillin concentrations with threshold value set at concentration of 4 ppb (Maximum residue level - MLR). Additionally we determined proportions of presumably false negative and false positive results for each test using results of filed samples testing. Agreement of test results for each test pair was assessed through Kappa coefficients interpreted by Landis-Koch scale. Detection level of all tests was shown to be well below MRL. This alongside with effects of natural inhibitors in milk contributed to finding of positive results in untreated and treated animals after the withholding period. Screening tests for beta lactam residues are important tools for ensuring that milk for human consumption is free from antibiotics residues.

Residual antibiotics, antibiotic resistant superbugs and antibiotic resistance genes in surface water catchments: Public health impact

NASA Astrophysics Data System (ADS)

Anthony A, Adegoke; Adekunle C, Faleye; Thor A, Stenstrӧm

2018-06-01

Antibiotics are released to the surface water through different routes, like for example the wastewater treatment plants, from human and animal metabolic waste, agriculture run off, industrial antibiotic waste. The release of the antibiotics to the water catchment and/or the environments in sub-lethal concentrations for the microorganisms lead to the emergence of antibiotic resistance (AR) and selection for antibiotic resistance genes (ARGs). The bacteria utilize their quorum sensing to form biofilm within which ARGs are transferred from antibiotic resistant bacteria (ARB) to the susceptible strains, conferring resistance on them. This has contributed substantially to the growing trend of resistance from multiple antibiotic resistance to extended spectrum resistance, extreme resistance and recently to total antibiotic resistance. The antibiotics, ARB, ARGs are sometimes internalized into the crops irrigated with the surface water returning the bacteria to human in a difficult to control form. While quorum quenching strategy is being advocated during treatment of wastewater to disrupt biofilm as well as the spread of resistance, intermittent check for effectiveness of treatment of wastewater before release into receiving water bodies is hereby advocated. To achieve this, there is the need for better measurements, surveillance and follow-up and thereby the further needs to incorporate more integrative (multidisciplinary) approaches and state of the art tools, for appropriate detection and action. This presentation is to critically review the effect of antibiotic release, ARGs, ARB in water catchment on other water related applications in Southern African countries in relation to other part of the world.

Antibiotic residues in liquid manure from swine feedlot and their effects on nearby groundwater in regions of North China.

PubMed

Li, Xiaohua; Liu, Chong; Chen, Yongxing; Huang, Hongkun; Ren, Tianzhi

2018-04-01

A survey was conducted in regions of North China to better understand the effect of antibiotic residue pollution from swine feedlots to nearby groundwater environment. A total of nine experimental sites located in the regions of Beijing, Hebei, and Tianjin were selected to analyze the presence of residues of 11 most commonly used antibiotics, including tetracyclines (TCs), fluoroquinolones (FQNs), sulfonamides (SAs), macrolides, and fenicols, by using liquid chromatography spectrometry. The three most common antibiotics were TCs, FQNs, and SAs, with mean concentrations of 416.4, 228.8, and 442.4 μg L -1 in wastewater samples; 19.9, 11.8, and 0.3 μg L -1 in groundwater samples from swine feedlots; and 29.7, 14.0, and 0 μg L -1 in groundwater samples from villages. Ordination analysis revealed that the composition and distribution of antibiotics and antibiotic resistance genes (AGRs) were similar in groundwater samples from swine feedlots and villages. FQNs and TCs occurred along the path from wastewater to groundwater at high concentrations and showed correlations with ARGs, with a strong correlation between FQN resistance gene (qnrA) copy number. FQN concentration was also found (P < 0.01) in wastewater and groundwater in villages (P < 0.01). Therefore, antibiotics discharged from swine feedlots through wastewater could disseminate into surrounding groundwater environments together with ARG occurrence (i.e., qnrA, sulI, sulII, tetG, tetM, and tetO). Overall, this study suggests that the spread of veterinary antibiotics from swine feedlots to groundwater environments should be highly attended and controlled by restricting excess antibiotic usage or improving the technology of manure management.

Development of Novel Antibiotic Lysocin E Identified by Silkworm Infection Model.

PubMed

Hamamoto, Hiroshi; Sekimizu, Kazuhisa

2017-01-01

In this symposium, we reported the identification and mechanistic analysis of a novel antibiotic named lysocin E. Lysocin E was identified by screening for therapeutic effectiveness in a silkworm Staphylococcus aureus infection model. The advantages of the silkworm infection model for screening and purification of antibiotics from the culture supernatant of soil bacteria are: 1) low cost; 2) no ethical issues; 3) convenient for evaluation of the therapeutic effectiveness of antibiotics; and 4) pharmacokinetics similar to those of mammals. Lysocin E has remarkable features compared with known antibiotics such as a novel mechanism of action and target. Here, we summarize our reports presented in this symposium.

Residues of selected antibiotics in the South Moravian Rivers, Czech Republic.

PubMed

Jarova, Katerina; Vavrova, Milada; Koleckarova, Alice

2015-01-01

The aim of this study was to assess the contamination level of aquatic ecosystems of the Oslava and the Jihlava Rivers, and of the Nove Mlyny Water Reservoir, situated in the South Moravian Region (Czech Republic), by residues of selected veterinary pharmaceuticals. We isolated and determined 10 sulfonamide antibiotics in samples of surface water and bottom sediments using optimized analytical methods. A representative number of sampling sites in the entire basin of selected waters were chosen. Samples were collected particularly near the larger cities in order to assess their possible impact to the aquatic ecosystems. Extraction, pre-concentration and purification of samples were performed using optimized methods of solid phase extraction and pressurized solvent extraction. Final identification and quantification were carried out by high-performance liquid chromatography coupled with diode array detector. The concentration of sulfonamides in water samples were all under the limit of detection. Regarding sediment samples, sulfadimidine was found at most sampling sites; its highest values were recorded in the Jihlava River (up to 979.8 µg.kg(-1) dry matter). Other frequently detected sulfonamides were sulfamethoxazole and sulfamerazine. Most other sulfonamides were under the limit of detection or limit of quantification. Monitoring of antibiotic residues in the environment, especially in the aquatic ecosystem, is a current topic due to the growing worldwide use in both human and veterinary medicine. According to obtained results, we document the pollution of selected rivers and water reservoir by particular sulfonamides which basically reflects their application in veterinary medicine.

Identification of beta-lactam antibiotics in tissue samples containing unknown microbial inhibitors.

PubMed

Moats, W A; Romanowski, R D; Medina, M B

1998-01-01

Antibiotic residues in animal tissues can be detected by various screening tests based on microbial inhibition. In the 7-plate assay used by the U.S. Department of Agriculture's Food Safety and Inspection Service (FSIS), penicillinase is incorporated into all but one plate to distinguish beta-lactam antibiotics from other types. However, beta-lactams such as cloxacillin and the cephalosporins are resistant to degradation by penicillinase. They may not be identified as beta-lactams by this procedure, and thus, they may be identified as unidentified microbial inhibitors (UMIs). However, these penicillinase-resistant compounds can be degraded by other beta-lactamases. The present study describes an improved screening protocol to identify beta-lactam antibiotics classified as UMIs. A multiresidue liquid chromatographic procedure based on a method for determining beta-lactams in milk was also used to identify and quantitate residues. The 2 methods were tested with 24 tissue FSIS samples classified as containing UMIs. Of these, 3 contained penicillin G, including one at a violative level, and 5 contained a metabolite of ceftiofur. The others were negative for beta-lactam antibiotics.

The relationship between blood and muscle samples to monitor for residues of the antibiotic enrofloxacin in chickens.

PubMed

Reyes-Herrera, I; Schneider, M J; Blore, P J; Donoghue, D J

2011-02-01

In 2005, the US Food and Drug Administration withdrew approval for use of enrofloxacin in poultry, thus effectively imposing zero tolerance for residues of this antibiotic in poultry. Conventional residue monitoring for most antibiotics, including enrofloxacin, involves removing poultry carcasses from the processing line and collecting muscle tissues for analysis. Because of the loss of valuable edible products and the difficulties and expense of sampling all the carcasses, only a small portion of carcasses are tested for violative residues. Unlike muscle tissue, blood is readily available from all birds at the beginning of processing and may be used to screen for illegal residues in all poultry carcasses. It is unknown, however, if enrofloxacin concentrations in blood are predictive of muscle concentrations. In an effort to evaluate this relationship, 156 broiler chickens, 5 wk of age, were dosed with either 25 or 50 µg/mL of enrofloxacin for 3 or 7 d, respectively, in the drinking water. Blood and muscle samples were collected at 0, 1, 3, 6, 12, and 24 h (n = 6 birds/group) during the first dosing day, every 48 h during the dosing period, and every 12 h during the withdrawal period for up to 60 h after withdrawal. Enrofloxacin residues were determined in all blood and tissue samples during the dosing periods and in most of the withdrawal period for both doses. These results support the potential to use blood to screen for illegal enrofloxacin residues in edible poultry tissues in an effort to protect the human food supply.

Multi-residue method for the determination of antibiotics and some of their metabolites in seafood.

PubMed

Serra-Compte, Albert; Álvarez-Muñoz, Diana; Rodríguez-Mozaz, Sara; Barceló, Damià

2017-06-01

The presence of antibiotics in seafood for human consumption may pose a risk for consumers. A methodology for the analysis of antibiotics in seafood based on QuEChERS (quick, easy, cheap, effective, rugged, and safe) extraction, followed by detection and quantification using liquid chromatography coupled to mass spectrometry was developed. The analytical method was evaluated for the determination of 23 antibiotics (including parent compounds and some metabolites) in fish, mussels and clams. Recoveries ranged between 30% and 70% for most of the compounds and method detection and quantification limits (MDLs and MQLs) were between 0.01 and 0.31 ng/g dry weigh (dw) and 0.02-1.03 ng/g (dw) respectively. Real seafood samples were analysed using this method. Nine antibiotics were found at levels above MDLs; however none of them exceed the maximum residue limits (MRL) established by the authorities. Tetracycline was the most ubiquitous compound, presenting also the highest concentration: 5.63 ng/g (dw) in fish from Netherlands. In addition, an alternative technique based on microbial growth inhibition was explored as semiquantitative detection method of antibiotics in seafood. This methodology could be applied as a fast screening technique for the detection of macrolides and β-lactams in seafood but further research is needed for other antibiotics families. Copyright © 2016 Elsevier Ltd. All rights reserved.

Beta lactam antibiotics residues in cow’s milk: comparison of efficacy of three screening tests used in Bosnia and Herzegovina

PubMed Central

Fejzić, Nihad; Begagić, Muris; Šerić-Haračić, Sabina; Smajlović, Muhamed

2014-01-01

Beta lactam antibiotics are widely used in therapy of cattle, particularly for the treatment of mastitis. Over 95% of residue testing in dairies in Bosnia and Herzegovina is for Beta lactams. The aim of this paper is to compare the efficacy of three most common screening tests for Beta lactam residues in cow’s milk in our country. The tests used in the study are SNAP β Lactam test (Idexx), Rosa Charm β Lactam test (Charm Sciences) and Inhibition MRL test (A&M). Study samples included: standardized concentrations of penicillin solution (0, 2, 3, 4, 5 and 6 ppb). In addition we tested milk samples from three equal size study groups (not receiving any antibiotic therapy, treated with Beta lactams for mastitis and treated with Beta lactams for diseases other than mastitis). Sensitivity and specificity were determined for each test, using standard penicillin concentrations with threshold value set at concentration of 4 ppb (Maximum residue level – MLR). Additionally we determined proportions of presumably false negative and false positive results for each test using results of filed samples testing. Agreement of test results for each test pair was assessed through Kappa coefficients interpreted by Landis-Koch scale. Detection level of all tests was shown to be well below MRL. This alongside with effects of natural inhibitors in milk contributed to finding of positive results in untreated and treated animals after the withholding period. Screening tests for beta lactam residues are important tools for ensuring that milk for human consumption is free from antibiotics residues. PMID:25172975

Distribution of POPs, pesticides and antibiotic residues in organic honeys from different production areas.

PubMed

Chiesa, Luca Maria; Panseri, Sara; Nobile, Maria; Ceriani, Federica; Arioli, Francesco

2018-06-22

Demand for honey is increasing, especially if it is organic and if its nutritional properties are linked to untreated environments in order to guarantee quality for health. Sources of contamination of honey can be divided into environmental and apicultural. Therefore, the distribution of persistent organic pollutants, pesticides and antibiotic residues from geographical areas with different contamination sources (high anthropic impact, intensive farming, husbandry and low anthropic impact) was investigated in order to confirm the potential transfer of xenobiotics into the supply chain and to give beekeepers tools for the selection of areas dedicated to organic production. The presence of polychlorinated biphenyls, polybrominated diphenyl ether and polycyclic aromatic hydrocarbons was confirmed, not only in proximity to highly urbanised centres, where the concentrations were higher, but in all environment contexts, confirming their ubiquity. No antibiotics or neonicotinoids were detected in 95 organic honeys, demonstrating the absence of apicultural treatments and consequently the good quality of honey of different areas. These results are important due to the undefined regulatory European situation on honey antibiotic limits.[Figure: see text].

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.

Risk assessment of antibiotic residues in different water matrices in India: key issues and challenges.

PubMed

Mutiyar, Pravin K; Mittal, Atul K

2014-06-01

Global detection of antibiotic substances in water matrices has considerably increased in the recent past. However, in India research on this issue is limited or generalised in the literature. Risks associated with the presence of antibiotics in the environment can be quantified using a hazard quotient (HQ) approach. Here, HQs were developed using the measured environmental concentration (MEC) approach for antibiotic residues in Indian water matrices previously reported in the literature. In the present study, environmental risk assessment, using the HQ index [HQ = measured environmental concentration (MEC)/predicted no effect concentration (PNEC)] for different antibiotics, was performed according to the guidelines of European Medicine Evaluation Agency (EMEA). MEC and PNEC levels were obtained from the literature. PNEC values were also calculated from EC50 using a safety factor when no PNECs were reported in the literature. HQs were obtained for industrial effluents (HQ = 10(4)) that were greater than any previously reported values. Ciprofloxacin, a fluoroquinolone antibiotic, seemed to present the greatest risk in India. The HQ indices for Indian water matrices were in the following order: industrial effluents > lake water > river water > hospital effluents > treated sewage ≃ groundwater. A very high HQ represents a potential environmental concern for aquatic environments in India and demands that immediate attention be devoted to regulating these compounds, especially in pharmaceutical industrial wastewater.

Synergistic interactions between phenolic compounds identified in grape pomace extract with antibiotics of different classes against Staphylococcus aureus and Escherichia coli.

PubMed

Sanhueza, Loreto; Melo, Ricardo; Montero, Ruth; Maisey, Kevin; Mendoza, Leonora; Wilkens, Marcela

2017-01-01

Synergy could be an effective strategy to potentiate and recover antibiotics nowadays useless in clinical treatments against multi-resistant bacteria. In this study, synergic interactions between antibiotics and grape pomace extract that contains high concentration of phenolic compounds were evaluated by the checkerboard method in clinical isolates of Staphylococcus aureus and Escherichia coli. To define which component of the extract is responsible for the synergic effect, phenolic compounds were identified by RP-HPLC and their relative abundance was determined. Combinations of extract with pure compounds identified there in were also evaluated. Results showed that the grape pomace extract combined with representatives of different classes of antibiotics as β-lactam, quinolone, fluoroquinolone, tetracycline and amphenicol act in synergy in all S. aureus and E. coli strains tested with FICI values varying from 0.031 to 0.155. The minimal inhibitory concentration (MIC) was reduced 4 to 75 times. The most abundant phenolic compounds identified in the extract were quercetin, gallic acid, protocatechuic acid and luteolin with relative abundance of 26.3, 24.4, 16.7 and 11.4%, respectively. All combinations of the extract with the components also showed synergy with FICI values varying from 0.031 to 0.5 and MIC reductions of 4 to 125 times with both bacteria strains. The relative abundance of phenolic compounds has no correlation with the obtained synergic effect, suggesting that the mechanism by which the synergic effect occurs is by a multi-objective action. It was also shown that combinations of grape pomace extract with antibiotics are not toxic for the HeLa cell line at concentrations in which the synergistic effect was observed (47 μg/mL of extract and 0.6-375 μg/mL antibiotics). Therefore, these combinations are good candidates for testing in animal models in order to enhance the effect of antibiotics of different classes and thus restore the currently unused

Amino acid sequence requirements at residues 69 and 238 for the SME-1 beta-lactamase to confer resistance to beta-lactam antibiotics.

PubMed

Majiduddin, Fahd K; Palzkill, Timothy

2003-03-01

Carbapenem antibiotics have been used to counteract resistant strains of bacteria harboring beta-lactamases and extended-spectrum beta-lactamases. Four enzymes from the class A group of beta-lactamases, NMC-A, IMI-1, SME-1, and KPC-1, efficiently hydrolyze carbapenem antibiotics. Sequence comparisons and structural information indicate that cysteines at amino acid residues 69 and 238, which are conserved in all four of these enzymes, form a disulfide bond that is unique to these beta-lactamases. To test whether this disulfide bond is required for catalytic activity, the codons for residues Cys69 and Cys238 were randomized individually and simultaneously by PCR-based mutagenesis to create random replacement libraries for these positions. Mutants that were able to confer resistance to ampicillin, imipenem, or cefotaxime were selected from these libraries. The results indicate that positions Cys69 and Cys238 are critical for hydrolysis of all of the antibiotics tested, suggesting that the disulfide bond is generally required for this enzyme to catalyze the hydrolysis of beta-lactam antibiotics.

Amino Acid Sequence Requirements at Residues 69 and 238 for the SME-1 β-Lactamase To Confer Resistance to β-Lactam Antibiotics

PubMed Central

Majiduddin, Fahd K.; Palzkill, Timothy

2003-01-01

Carbapenem antibiotics have been used to counteract resistant strains of bacteria harboring β-lactamases and extended-spectrum β-lactamases. Four enzymes from the class A group of β-lactamases, NMC-A, IMI-1, SME-1, and KPC-1, efficiently hydrolyze carbapenem antibiotics. Sequence comparisons and structural information indicate that cysteines at amino acid residues 69 and 238, which are conserved in all four of these enzymes, form a disulfide bond that is unique to these β-lactamases. To test whether this disulfide bond is required for catalytic activity, the codons for residues Cys69 and Cys238 were randomized individually and simultaneously by PCR-based mutagenesis to create random replacement libraries for these positions. Mutants that were able to confer resistance to ampicillin, imipenem, or cefotaxime were selected from these libraries. The results indicate that positions Cys69 and Cys238 are critical for hydrolysis of all of the antibiotics tested, suggesting that the disulfide bond is generally required for this enzyme to catalyze the hydrolysis of β-lactam antibiotics. PMID:12604542

State of the art in the validation of screening methods for the control of antibiotic residues: is there a need for further development?

PubMed

Gaudin, Valérie

2017-09-01

Screening methods are used as a first-line approach to detect the presence of antibiotic residues in food of animal origin. The validation process guarantees that the method is fit-for-purpose, suited to regulatory requirements, and provides evidence of its performance. This article is focused on intra-laboratory validation. The first step in validation is characterisation of performance, and the second step is the validation itself with regard to pre-established criteria. The validation approaches can be absolute (a single method) or relative (comparison of methods), overall (combination of several characteristics in one) or criterion-by-criterion. Various approaches to validation, in the form of regulations, guidelines or standards, are presented and discussed to draw conclusions on their potential application for different residue screening methods, and to determine whether or not they reach the same conclusions. The approach by comparison of methods is not suitable for screening methods for antibiotic residues. The overall approaches, such as probability of detection (POD) and accuracy profile, are increasingly used in other fields of application. They may be of interest for screening methods for antibiotic residues. Finally, the criterion-by-criterion approach (Decision 2002/657/EC and of European guideline for the validation of screening methods), usually applied to the screening methods for antibiotic residues, introduced a major characteristic and an improvement in the validation, i.e. the detection capability (CCβ). In conclusion, screening methods are constantly evolving, thanks to the development of new biosensors or liquid chromatography coupled to tandem-mass spectrometry (LC-MS/MS) methods. There have been clear changes in validation approaches these last 20 years. Continued progress is required and perspectives for future development of guidelines, regulations and standards for validation are presented here.

Effects of temperature and antibiotics on persistence of antibiotic-resistant bacteria and antibiotic resistance genes in poultry litter

USDA-ARS?s Scientific Manuscript database

The effect of low, residual concentrations of antibiotics in manure and other environmental matrices is not well understood. It has been hypothesized that antibiotic concentrations below clinical MIC (minimal inhibitory concentrations) are still capable of selecting for resistance. The objective of ...

Environmental and Public Health Implications of Water Reuse: Antibiotics, Antibiotic Resistant Bacteria, and Antibiotic Resistance Genes

PubMed Central

Hong, Pei-Ying; Al-Jassim, Nada; Ansari, Mohd Ikram; Mackie, Roderick I.

2013-01-01

Water scarcity is a global problem, and is particularly acute in certain regions like Africa, the Middle East, as well as the western states of America. A breakdown on water usage revealed that 70% of freshwater supplies are used for agricultural irrigation. The use of reclaimed water as an alternative water source for agricultural irrigation would greatly alleviate the demand on freshwater sources. This paradigm shift is gaining momentum in several water scarce countries like Saudi Arabia. However, microbial problems associated with reclaimed water may hinder the use of reclaimed water for agricultural irrigation. Of particular concern is that the occurrence of antibiotic residues in the reclaimed water can select for antibiotic resistance genes among the microbial community. Antibiotic resistance genes can be associated with mobile genetic elements, which in turn allow a promiscuous transfer of resistance traits from one bacterium to another. Together with the pathogens that are present in the reclaimed water, antibiotic resistant bacteria can potentially exchange mobile genetic elements to create the “perfect microbial storm”. Given the significance of this issue, a deeper understanding of the occurrence of antibiotics in reclaimed water, and their potential influence on the selection of resistant microorganisms would be essential. In this review paper, we collated literature over the past two decades to determine the occurrence of antibiotics in municipal wastewater and livestock manure. We then discuss how these antibiotic resistant bacteria may impose a potential microbial risk to the environment and public health, and the knowledge gaps that would have to be addressed in future studies. Overall, the collation of the literature in wastewater treatment and agriculture serves to frame and identify potential concerns with respect to antibiotics, antibiotic resistant bacteria, and antibiotic resistance genes in reclaimed water. PMID:27029309

A survey to identify barriers of implementing an antibiotic checklist.

PubMed

van Daalen, F V; Geerlings, S E; Prins, J M; Hulscher, M E J L

2016-04-01

A checklist is an effective implementation tool, but addressing barriers that might impact on the effectiveness of its use is crucial. In this paper, we explore barriers to the uptake of an antibiotic checklist that aims to improve antibiotic use in daily hospital care. We performed an online questionnaire survey among medical specialists and residents with various professional backgrounds from nine Dutch hospitals. The questionnaire consisted of 23 statements on anticipated barriers hindering the uptake of the checklist. Furthermore, it gave the possibility to add comments. We included 219 completed questionnaires (122 medical specialists and 97 residents) in our descriptive analysis. The top six anticipated barriers included: (1) lack of expectation of improvement of antibiotic use, (2) lack of expected patients' satisfaction by checklist use, (3) lack of feasibility of the checklist, (4) negative previous experiences with other checklists, (5) the complexity of the antibiotic checklist and (6) lack of nurses' expectation of checklist use. Remarkably, 553 comments were made, mostly (436) about the content of the checklist. These insights can be used to improve the specific content of the checklist and to develop an implementation strategy that addresses the identified barriers.

Identifying and exploiting genes that potentiate the evolution of antibiotic resistance.

PubMed

Gifford, Danna R; Furió, Victoria; Papkou, Andrei; Vogwill, Tom; Oliver, Antonio; MacLean, R Craig

2018-06-01

There is an urgent need to develop novel approaches for predicting and preventing the evolution of antibiotic resistance. Here, we show that the ability to evolve de novo resistance to a clinically important β-lactam antibiotic, ceftazidime, varies drastically across the genus Pseudomonas. This variation arises because strains possessing the ampR global transcriptional regulator evolve resistance at a high rate. This does not arise because of mutations in ampR. Instead, this regulator potentiates evolution by allowing mutations in conserved peptidoglycan biosynthesis genes to induce high levels of β-lactamase expression. Crucially, blocking this evolutionary pathway by co-administering ceftazidime with the β-lactamase inhibitor avibactam can be used to eliminate pathogenic P. aeruginosa populations before they can evolve resistance. In summary, our study shows that identifying potentiator genes that act as evolutionary catalysts can be used to both predict and prevent the evolution of antibiotic resistance.

Effect of temperature on sulfonamide antibiotics degradation, and on antibiotic resistance determinants and hosts in animal manures.

PubMed

Lin, Hui; Zhang, Jin; Chen, Hongjin; Wang, Jianmei; Sun, Wanchun; Zhang, Xin; Yang, Yuyi; Wang, Qiang; Ma, Junwei

2017-12-31

Animal manure is a main reservoir of antibiotic residues and antibiotic resistance. Here, the effect of temperature on sulfonamide antibiotics (SAs), sulfonamide-resistant (SR) genes/bacteria was investigated by aerobically incubating swine and chicken manures at different temperatures. In swine manure, the SAs concentration declined with increasing temperature, with a minimum at 60°C. In chicken manure, the greatest degradation of SAs was noted at 30°C. The reduction of relative abundance of antibiotic resistance genes (ARGs) and sul-positive hosts in swine manure was more pronounced during thermophilic than mesospheric incubation; neither temperature conditions effectively reduced these parameters in chicken manure. The relationship between the residual levels/distribution profiles of SAs, ARGs (sul1, sul2 and intI1), cultivable SR bacteria and sul-positive hosts was further established. The antibiotic residual profile, rather than antibiotic concentration, acted as an important factor in the prevalence of ARGs and sul-positive hosts in manure. Corynebacterium and Leucobacter from the phylum Actinobacteria tend to be main carriers of sul1 and intI1; the relative abundance of sul2 was significantly correlated with the relative abundance of cultivable SR bacteria. Overall, differences in resistant bacterial communities also constitute a dominant factor affecting ARG variation. This study contributes to management options for reducing the pollution of antibiotics and antibiotic resistance within manure. Copyright © 2017 Elsevier B.V. All rights reserved.

Presence, concentrations and risk assessment of selected antibiotic residues in sediments and near-bottom waters collected from the Polish coastal zone in the southern Baltic Sea - Summary of 3years of studies.

PubMed

Siedlewicz, Grzegorz; Białk-Bielińska, Anna; Borecka, Marta; Winogradow, Aleksandra; Stepnowski, Piotr; Pazdro, Ksenia

2018-04-01

Concentrations of selected antibiotic compounds from different groups were measured in sediment samples (14 analytes) and in near-bottom water samples (12 analytes) collected in 2011-2013 from the southern Baltic Sea (Polish coastal zone). Antibiotics were determined at concentration levels of a few to hundreds of ng g -1 d.w. in sediments and ng L -1 in near-bottom waters. The most frequently detected compounds were sulfamethoxazole, trimethoprim, oxytetracycline in sediments and sulfamethoxazole and trimethoprim in near-bottom waters. The occurrence of the identified antibiotics was characterized by spatial and temporal variability. A statistically important correlation was observed between sediment organic matter content and the concentrations of sulfachloropyridazine and oxytetracycline. Risk assessment analyses revealed a potential high risk of sulfamethoxazole contamination in near-bottom waters and of contamination by sulfamethoxazole, trimethoprim and tetracyclines in sediments. Both chemical and risk assessment analyses show that the coastal area of the southern Baltic Sea is highly exposed to antibiotic residues. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antibiotic Resistances in Livestock: A Comparative Approach to Identify an Appropriate Regression Model for Count Data

PubMed Central

Hüls, Anke; Frömke, Cornelia; Ickstadt, Katja; Hille, Katja; Hering, Johanna; von Münchhausen, Christiane; Hartmann, Maria; Kreienbrock, Lothar

2017-01-01

Antimicrobial resistance in livestock is a matter of general concern. To develop hygiene measures and methods for resistance prevention and control, epidemiological studies on a population level are needed to detect factors associated with antimicrobial resistance in livestock holdings. In general, regression models are used to describe these relationships between environmental factors and resistance outcome. Besides the study design, the correlation structures of the different outcomes of antibiotic resistance and structural zero measurements on the resistance outcome as well as on the exposure side are challenges for the epidemiological model building process. The use of appropriate regression models that acknowledge these complexities is essential to assure valid epidemiological interpretations. The aims of this paper are (i) to explain the model building process comparing several competing models for count data (negative binomial model, quasi-Poisson model, zero-inflated model, and hurdle model) and (ii) to compare these models using data from a cross-sectional study on antibiotic resistance in animal husbandry. These goals are essential to evaluate which model is most suitable to identify potential prevention measures. The dataset used as an example in our analyses was generated initially to study the prevalence and associated factors for the appearance of cefotaxime-resistant Escherichia coli in 48 German fattening pig farms. For each farm, the outcome was the count of samples with resistant bacteria. There was almost no overdispersion and only moderate evidence of excess zeros in the data. Our analyses show that it is essential to evaluate regression models in studies analyzing the relationship between environmental factors and antibiotic resistances in livestock. After model comparison based on evaluation of model predictions, Akaike information criterion, and Pearson residuals, here the hurdle model was judged to be the most appropriate model. PMID

Antibiotics in agroecosystems: Introduction to the special section

USDA-ARS?s Scientific Manuscript database

The presence of antibiotic drug residues, antibiotic resistant bacteria, and antibiotic resistance genes in agroecosystems has become a significant area of research in recent years, and is a growing public health concern. While antibiotics are utilized for human medicine and agricultural practices, ...

The effect of different treatment technologies on the fate of antibiotic resistance genes and class 1 integrons after the application of residual municipal wastewater solids to soil

USDA-ARS?s Scientific Manuscript database

Land-application of residual wastewater solids is an important environmental source of antibiotic resistance genes (ARGs). Treatment technologies exist that can reduce ARG levels in residual solids prior to land-application, but the effect of these technologies on ARG levels in soil following land-a...

A Transposon Screen Identifies Genetic Determinants of Vibrio cholerae Resistance to High-Molecular-Weight Antibiotics

PubMed Central

Delgado, Fernanda; Umans, Benjamin D.; Gerding, Matthew A.; Davis, Brigid M.

2016-01-01

Gram-negative bacteria are notoriously resistant to a variety of high-molecular-weight antibiotics due to the limited permeability of their outer membrane (OM). The basis of OM barrier function and the genetic factors required for its maintenance remain incompletely understood. Here, we employed transposon insertion sequencing to identify genes required for Vibrio cholerae resistance to vancomycin and bacitracin, antibiotics that are thought to be too large to efficiently penetrate the OM. The screen yielded several genes whose protein products are predicted to participate in processes important for OM barrier functions and for biofilm formation. In addition, we identified a novel factor, designated vigA (for vancomycin inhibits growth), that has not previously been characterized or linked to outer membrane function. The vigA open reading frame (ORF) codes for an inner membrane protein, and in its absence, cells became highly sensitive to glycopeptide antibiotics (vancomycin and ramoplanin) and bacitracin but not to other large antibiotics or detergents. In contrast to wild-type (WT) cells, the vigA mutant was stained with fluorescent vancomycin. These observations suggest that VigA specifically prevents the periplasmic accumulation of certain large antibiotics without exerting a general role in the maintenance of OM integrity. We also observed marked interspecies variability in the susceptibilities of Gram-negative pathogens to glycopeptides and bacitracin. Collectively, our findings suggest that the OM barrier is not absolute but rather depends on specific OM-antibiotic interactions. PMID:27216069

Residues of veterinary antibiotics in manures from feedlot livestock in eight provinces of China.

PubMed

Zhao, Ling; Dong, Yuan Hua; Wang, Hui

2010-02-01

The residue levels of selected fluoroquinolones, sulfonamides and tetracyclines in 143 animal dung samples collected in 2007 from large-scale livestock and poultry feedlots in 8 provinces were determined by using ultrasonic extraction and liquid chromatography. Recoveries from spiked pig dung samples (spike level=1mg/kg) ranged from 73.9 to 102.0% for fluoroquinolones, from 81.6 to 92.3% for sulfonamides, and from 57.2 to 72.6% for tetracyclines. Relative standard deviations of the recoveries were less than 10% within the same day. Method quantification limits were measured from 0.031 to 0.150 mg/kg for fluoroquinolones, from 0.023 to 0.082 mg/kg for sulfonamides, and 0.091 to 0.182 mg/kg for tetracyclines in spiked pig manure samples. Analysis of 61 pig, 54 chicken and 28 cow dung samples collected in China revealed that in pig and cow dung, up to 33.98 and 29.59 mg/kg ciprofloxacin, 33.26 and 46.70 mg/kg enrofloxacin, 59.06 and 59.59 mg/kg oxytetracycline, and 21.06 and 27.59 mg/kg chlortetracycline could be detected, respectively. A maximum concentration of 99.43 mg/kg fleroxacin, 225.45 mg/kg norfloxacin, 45.59 mg/kg ciprofloxacin and 1420.76 mg/kg enrofloxacin could be detected in chicken dung. No appreciable sulfonamide antibiotic concentrations (less than 10mg/kg) were found in any animal dung, and only sulfadimidine was observed, at a maximum concentration of 6.04 mg/kg, in chicken dung. Both enrofloxacin and chlortetracycline were detected with a very high occurrence in three animal manure samples. The residue levels for most antibiotics showed significant statistical differences among the sampling districts and the animal species. Copyright 2009 Elsevier B.V. All rights reserved.

Potential ligand-binding residues in rat olfactory receptors identified by correlated mutation analysis

NASA Technical Reports Server (NTRS)

Singer, M. S.; Oliveira, L.; Vriend, G.; Shepherd, G. M.

1995-01-01

A family of G-protein-coupled receptors is believed to mediate the recognition of odor molecules. In order to identify potential ligand-binding residues, we have applied correlated mutation analysis to receptor sequences from the rat. This method identifies pairs of sequence positions where residues remain conserved or mutate in tandem, thereby suggesting structural or functional importance. The analysis supported molecular modeling studies in suggesting several residues in positions that were consistent with ligand-binding function. Two of these positions, dominated by histidine residues, may play important roles in ligand binding and could confer broad specificity to mammalian odor receptors. The presence of positive (overdominant) selection at some of the identified positions provides additional evidence for roles in ligand binding. Higher-order groups of correlated residues were also observed. Each group may interact with an individual ligand determinant, and combinations of these groups may provide a multi-dimensional mechanism for receptor diversity.

Multiresidue determination of fluoroquinolone, sulfonamide, trimethoprim, and chloramphenicol antibiotics in urban waters in China.

PubMed

Peng, Xianzhi; Tan, Jianhua; Tang, Caiming; Yu, Yiyi; Wang, Zhendi

2008-01-01

A feasible method has been optimized to simultaneously determine multiclass antibiotic residues, including sulfonamides, fluoroquinolones, trimethoprim, and chloramphenicol in urban riverine water and wastewater by off-line solid phase extraction and high-performance liquid chromatography coupled with a diode-array ultraviolet detector and a fluorescence detector. Internal standard and standard addition methods were used in combination to identify and quantify these antibiotics to compensate for the matrix interference. The method quantification limits (MQLs) were determined to be 0.035 to 0.100 microg/L and 0.100 to 0.300 microg/L for the riverine water and wastewater, respectively. Recoveries of the investigated antibiotics ranged from 63 to 126%. Sulfamethoxazole was the most frequently detected antibiotic residue in Guangzhou section of the Major Pearl River, South China, with a maximum level of 0.510 microg/L. Fluoroquinolone antibiotics were relatively less detected with a maximum level of 0.459 microg/L. The maximum concentration of sulfamethoxazole reached 5.597 microg/L in the raw wastewater from a large-scale sewage treatment plant in Guangzhou city. Around 30% of sulfamethoxazole might survive the primary clarification and biotreatment processes in the sewage treatment plant. None of the investigated antibiotics have been found above MQLs in the final effluent after chlorine disinfection.

Fate of antibiotic and metal resistance genes during two-phase anaerobic digestion of residue sludge revealed by metagenomic approach.

PubMed

Wu, Ying; Cui, Erping; Zuo, Yiru; Cheng, Weixiao; Chen, Hong

2018-05-01

The prevalence and persistence of antibiotic resistance genes in wastewater treatment plants (WWTPs) is of growing interest, and residual sludge is among the main sources for the release of antibiotic resistance genes (ARGs). Moreover, heavy metals concentrated in dense microbial communities of sludge could potentially favor co-selection of ARGs and metal resistance genes (MRGs). Residual sludge treatment is needed to limit the spread of resistance from WWTPs into the environment. This study aimed to explore the fate of ARGs and MRGs during thermophilic two-phase (acidogenic/methanogenic phase) anaerobic digestion by metagenomic analysis. The occurrence and abundance of mobile genetic elements were also determined based on the SEED database. Among the 27 major ARG subtypes detected in feed sludge, large reductions (> 50%) in 6 ARG subtypes were achieved by acidogenic phase (AP), while 63.0% of the ARG subtypes proliferated in the following methanogenic phase (MP). In contrast, a 2.8-fold increase in total MRG abundance was found in AP, while the total abundance during MP decreased to the same order of magnitude as in feed sludge. The distinct dynamics of ARGs and MRGs during the two-phase anaerobic digestion are noteworthy, and more specific treatments are required to limit their proliferation in the environment.

Evaluation and validation of a multi-residue method based on biochip technology for the simultaneous screening of six families of antibiotics in muscle and aquaculture products.

PubMed

Gaudin, Valérie; Hedou, Celine; Soumet, Christophe; Verdon, Eric

2016-01-01

The Evidence Investigator™ system (Randox, UK) is a biochip and semi-automated system. The microarray kit II (AM II) is capable of detecting several compounds belonging to different families of antibiotics: quinolones, ceftiofur, thiamphenicol, streptomycin, tylosin and tetracyclines. The performance of this innovative system was evaluated for the detection of antibiotic residues in new matrices, in muscle of different animal species and in aquaculture products. The method was validated according to the European Decision No. EC/2002/657 and the European guideline for the validation of screening methods, which represents a complete initial validation. The false-positive rate was equal to 0% in muscle and in aquaculture products. The detection capabilities CCβ for 12 validated antibiotics (enrofloxacin, difloxacin, ceftiofur, desfuroyl ceftiofur cysteine disulfide, thiamphenicol, florfenicol, tylosin, tilmicosin, streptomycin, dihydrostreptomycin, tetracycline, doxycycline) were all lower than the respective maximum residue limits (MRLs) in muscle from different animal origins (bovine, ovine, porcine, poultry). No cross-reactions were observed with other antibiotics, neither with the six detected families nor with other families of antibiotics. The AM II kit could be applied to aquaculture products but with higher detection capabilities from those in muscle. The detection capabilities CCβ in aquaculture products were respectively at 0.25, 0.10 and 0.5 of the respective MRL in aquaculture products for enrofloxacin, tylosin and oxytetracycline. The performance of the AM II kit has been compared with other screening methods and with the performance characteristics previously determined in honey.

Drug and chemical residues in domestic animals.

PubMed

Mussman, H C

1975-02-01

Given the large number of chemical substances that may find their way into the food supply, a system is needed to monitor their presence. The U. S. Department of Agriculture's Meat and Poultry Inspection Program routinely tests for chemical residues in animals coming to slaughter. Pesticides, heavy metals, growth promotants (hormones and hormonelike agents), and antibiotics are included. Samples are taken statistically so that inferences as to national incidence of residues can be drawn. When a problem is identified, a more selective sampling is designed to help follow up on the initial regulatory action. In testing for pesticides, only DDT and dieldrin are found with any frequency and their levels are decreasing; violative residues of any chlorinated hydrocarbon are generally a result of an industrial accident rather than agricultural usage. Analyses for heavy metals have revealed detectable levels of mercury, lead, and others, but none at levels that are considered a health hazard. Of the hormone or hormonelike substances, only diethylstilbestrol has been a residue problem and its future is uncertain. The most extensive monitoring for veterinary drugs is on the antimicrobials, including sulfonamides, streptomycin, and the tetracycline group of antibiotics that constitute the bulk of the violations; their simultaneous use prophylactically and therapeutically has contributed to the problem in certain cases. A strong, well-designed user education program on proper application of pesticides, chemicals, and veterinary drugs appears to be one method of reducing the incidence of unwanted residues.

(Electro)Sensing of Phenicol Antibiotics-A Review.

PubMed

Pilehvar, Sanaz; Gielkens, Kristoffer; Trashin, Stanislav A; Dardenne, Freddy; Blust, Ronny; De Wael, Karolien

2016-10-25

The presence of residues from frequent antibiotic use in animal feed can cause serious health risks by contaminating products meant for human consumption such as meat and milk. The present paper gives an overview of the electrochemical methods developed for the detection of phenicol antibiotic residues (chloramphenicol, thiamphenicol, and florfenicol) in different kinds of foodstuffs. Electrochemical sensors based on different biomolecules and nanomaterials are described. The detection limit of various developed methods with their advantages and disadvantages will be highlighted.

Machine Learning Leveraging Genomes from Metagenomes Identifies Influential Antibiotic Resistance Genes in the Infant Gut Microbiome

PubMed Central

Olm, Matthew R.; Morowitz, Michael J.

2018-01-01

ABSTRACT Antibiotic resistance in pathogens is extensively studied, and yet little is known about how antibiotic resistance genes of typical gut bacteria influence microbiome dynamics. Here, we leveraged genomes from metagenomes to investigate how genes of the premature infant gut resistome correspond to the ability of bacteria to survive under certain environmental and clinical conditions. We found that formula feeding impacts the resistome. Random forest models corroborated by statistical tests revealed that the gut resistome of formula-fed infants is enriched in class D beta-lactamase genes. Interestingly, Clostridium difficile strains harboring this gene are at higher abundance in formula-fed infants than C. difficile strains lacking this gene. Organisms with genes for major facilitator superfamily drug efflux pumps have higher replication rates under all conditions, even in the absence of antibiotic therapy. Using a machine learning approach, we identified genes that are predictive of an organism’s direction of change in relative abundance after administration of vancomycin and cephalosporin antibiotics. The most accurate results were obtained by reducing annotated genomic data to five principal components classified by boosted decision trees. Among the genes involved in predicting whether an organism increased in relative abundance after treatment are those that encode subclass B2 beta-lactamases and transcriptional regulators of vancomycin resistance. This demonstrates that machine learning applied to genome-resolved metagenomics data can identify key genes for survival after antibiotics treatment and predict how organisms in the gut microbiome will respond to antibiotic administration. IMPORTANCE The process of reconstructing genomes from environmental sequence data (genome-resolved metagenomics) allows unique insight into microbial systems. We apply this technique to investigate how the antibiotic resistance genes of bacteria affect their ability to

Antibiotic Application and Emergence of Multiple Antibiotic Resistance (MAR) in Global Catfish Aquaculture.

PubMed

Chuah, Li-Oon; Effarizah, M E; Goni, Abatcha Mustapha; Rusul, Gulam

2016-06-01

Catfish is one of the most cultivated species worldwide. Antibiotics are usually used in catfish farming as therapeutic and prophylactic agents. In the USA, only oxytetracycline, a combination of sulfadimethoxine and ormetoprim, and florfenicol are approved by the Food Drug Administration for specific fish species (e.g., catfish and salmonids) and their specific diseases. Misuse of antibiotics as prophylactic agents in disease prevention, however, is common and contributes in the development of antibiotic resistance. Various studies had reported on antibiotic residues and/or resistance in farmed species, feral fish, water column, sediments, and, in a lesser content, among farm workers. Ninety percent of the world aquaculture production is carried out in developing countries, which lack regulations and enforcement on the use of antibiotics. Hence, efforts are needed to promote the development and enforcement of such a regulatory structure. Alternatives to antibiotics such as antibacterial vaccines, bacteriophages and their lysins, and probiotics have been applied to curtail the increasing emergence of antibiotic-resistant bacteria due to the imprudent application of antibiotics in aquaculture.

Regulation of veterinary antibiotics in Australia.

PubMed

Dyke, T M

2003-01-01

The Australian Pesticides and Veterinary Medicines Authority (APVMA)* registers veterinary antibiotic products before they can be supplied, distributed or sold in Australia. Extensive scientific assessment on all new veterinary antibiotic products is undertaken for the APVMA by experts in other government agencies including the Therapeutic Goods Administration (toxicology), the National Occupational Health and Safety Commission (occupational health and safety), Environment Australia (environmental hazards) and state departments of agriculture or primary industry (efficacy and safety) as well as APVMA assessments on food residues, trade and manufacturing. The National Health and Medical Research Council Expert Advisory Group on Antimicrobial Resistance provides advice to the APVMA on the potential transfer of antibiotic resistance from the use of antibiotics in animals to humans, and the impact transfer may have on public health. Food Standards Australia New Zealand (previously Australia New Zealand Food Authority) set maximum residue levels for human foods. The APVMA monitors registered product use through compliance activities and an adverse experience reporting program, and reviews registered products as necessary. The import, manufacture, supply and use of veterinary antibiotics are regulated by Commonwealth and State governments in Australia.

Investigation to identify a resource-efficient case-control methodology for determining antibiotics associated with Clostridium difficile infection.

PubMed

Chung, Philip; Currie, Brian; Guo, Yi; Talansky, Moshe; Brown, Shakara; Ostrowsky, Belinda

2014-10-01

Antimicrobial exposure remains an important risk factor for developing Clostridium difficile infection (CDI). Efficient method to identify antibiotics associated with CDI is important for formulating strategies to curtail their use. As a prelude to a more extensive Agency for Healthcare Research and Quality-funded project (Evaluation & Research on Antimicrobial Stewardship's Effect on Clostridium difficile), we undertook an exploratory evaluation to determine a resource-efficient method for identifying antibiotic targets for antimicrobial stewardship interventions. The study compared a series of 6 focused case-control studies. Cases consisted of patients with laboratory-confirmed CDI admitted from July-October 2009. Controls were selected from patients without CDI hospitalized during the same period. Five groups of controls were matched to cases (2:1 ratio) using group-specific matching criteria, including admission date, age, type of admission, length of stay (LOS) to discharge, and/or LOS to CDI diagnosis. The final control group was selected from patients who received antibiotics during hospitalization. Data, including demographics and antibiotic usage, were compared between case and control groups. A total of 126 cases were matched to 6 groups of 252 controls. For control groups 1-5, the use of piperacillin and tazobactam, ceftriaxone or cefepime, ciprofloxacin or moxifloxacin, intravenous vancomycin, azithromycin, and antibiotics of last resort were significantly more frequent in case than control patients. For the final control group, the associations between ceftriaxone or cefepime, and ciprofloxacin or moxifloxacin use and CDI no longer persisted. This could in part be explained by differences in comorbidities between case and control patients even with stringent matching criteria. Use of a simple matching strategy to conduct case-control studies is an efficient and feasible compromise strategy, especially in resource-limited settings, to identify high

Behavior of antibiotics and antibiotic resistance genes in eco-agricultural system: A case study.

PubMed

Cheng, Weixiao; Li, Jianan; Wu, Ying; Xu, Like; Su, Chao; Qian, Yanyun; Zhu, Yong-Guan; Chen, Hong

2016-03-05

This study aims to determine abundance and persistence of antibiotics and antibiotic resistance genes (ARGs) in eco-agricultural system (EAS), which starts from swine feces to anaerobic digestion products, then application of anaerobic digestion solid residue (ADSR) and anaerobic digestion liquid residue (ADLR) to the soil to grow ryegrass, one of swine feed. Oxytetracycline had the highest concentration in manure reaching up to 138.7 mg/kg. Most of antibiotics could be effectively eliminated by anaerobic digestion and removal rates ranged from 11% to 86%. ARGs abundance fluctuated within EAS. TetQ had the highest relative abundance and the relative abundance of tetG had the least variation within the system, which indicates that tetG is persistent in the agricultural environment and requires more attention. Compared to the relative abundance in manure, tetC and tetM increased in biogas residue while three ribosomal protection proteins genes (tetO, tetQ, tetW) decreased (p<0.05), with other genes showing no significant change after anaerobic fermentation (p>0.05). Most ARGs in downstream components (soils and fishpond) of EAS showed significantly higher relative abundance than the control agricultural system (p<0.05), except for tetG and sulI. Copyright © 2015 Elsevier B.V. All rights reserved.

Presence of antibiotic residues in various environmental compartments of Shandong province in eastern China: Its potential for resistance development and ecological and human risk.

PubMed

Hanna, Nada; Sun, Pan; Sun, Qiang; Li, Xuewen; Yang, Xiwei; Ji, Xiang; Zou, Huiyun; Ottoson, Jakob; Nilsson, Lennart E; Berglund, Björn; Dyar, Oliver James; Tamhankar, Ashok J; Stålsby Lundborg, Cecilia

2018-05-01

To investigate the occurrence of antibiotic residues in different types of environmental samples including water samples in rural Shandong province, China. Further, to characterize the potential ecological risk for development of antibiotic resistance in the environment, and the potential direct human health risk of exposure to antibiotics via drinking water and vegetables. Environmental samples (n = 214) (river water, waste water, drinking water, sediments, manure, soil and edible parts of vegetables) were collected in twelve villages in Shandong province in eastern China. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to determine the concentration of antibiotic residues. The ratio of the measured environmental concentrations (MEC) to the predicted no-effect concentrations (PNEC) was used to evaluate the ecological risk (risk quotient, RQ) for development of antibiotic resistance. The potential risks to human health through exposure to antibiotics in drinking water were assessed by comparing measured environmental concentrations (MEC) and predicted no-effect concentration in drinking water (PNEC DW ), and in vegetables by comparing estimated daily intake (EDI) to ADI. Sulfapyridine, sulfamethoxazole, ciprofloxacin, enrofloxacin, levofloxacin, norfloxacin, chloramphenicol, florfenicol, doxycycline, and metronidazole were detected at concentrations ranging between 0.3 and 3.9 ng/L in river water, 1.3 and 12.5 ng/L in waste water, 0.5 and 21.4 ng/L in drinking water, 0.31 and 1.21 μg/kg in river sediment, 0.82 and 1.91 μg/kg in pig manure, 0.1 and 11.68 μg/kg in outlet sediment, 0.5 and 2.5 μg/kg in soil, and 6.3 and 27.2 μg/kg in vegetables. The RQs for resistance development were >1 for enrofloxacin, levofloxacin, and ranged between 0.1 and 1 for ciprofloxacin. MECs/PNEC DW ratios were <1 from exposure to antibiotics through drinking water for both adults and children. EDI/ADI ratios were <0.1 from

Positive selection moments identify potential functional residues in human olfactory receptors

NASA Technical Reports Server (NTRS)

Singer, M. S.; Weisinger-Lewin, Y.; Lancet, D.; Shepherd, G. M.

1996-01-01

Correlated mutation analysis and molecular models of olfactory receptors have provided evidence that residues in the transmembrane domains form a binding pocket for odor ligands. As an independent test of these results, we have calculated positive selection moments for the alpha-helical sixth transmembrane domain (TM6) of human olfactory receptors. The moments can be used to identify residues that have been preferentially affected by positive selection and are thus likely to interact with odor ligands. The results suggest that residue 622, which is commonly a serine or threonine, could form critical H-bonds. In some receptors a dual-serine subsite, formed by residues 622 and 625, could bind hydroxyl determinants on odor ligands. The potential importance of these residues is further supported by site-directed mutagenesis in the beta-adrenergic receptor. The findings should be of practical value for future physiological studies, binding assays, and site-directed mutagenesis.

Air-drying beds reduce the quantities of antibiotic resistance genes and class 1 integrons in residual municipal wastewater solids.

PubMed

Burch, Tucker R; Sadowsky, Michael J; LaPara, Timothy M

2013-09-03

This study investigated whether air-drying beds reduce antibiotic resistance gene (ARG) concentrations in residual municipal wastewater solids. Three laboratory-scale drying beds were operated for a period of nearly 100 days. Real-time PCR was used to quantify 16S rRNA genes, 16S rRNA genes specific to fecal bacteria (AllBac) and human fecal bacteria (HF183), the integrase gene of class 1 integrons (intI1), and five ARGs representing a cross-section of antibiotic classes and resistance mechanisms (erm(B), sul1, tet(A), tet(W), and tet(X)). Air-drying beds were capable of reducing all gene target concentrations by 1 to 5 orders of magnitude, and the nature of this reduction was consistent with both a net decrease in the number of bacterial cells and a lack of selection within the microbial community. Half-lives varied between 1.5 d (HF183) and 5.4 d (tet(X)) during the first 20 d of treatment. After the first 20 d of treatment, however, half-lives varied between 8.6 d (tet(X)) and 19.3 d (AllBac), and 16S rRNA gene, intI1, and sul1 concentrations did not change (P > 0.05). These results demonstrate that air-drying beds can reduce ARG and intI1 concentrations in residual municipal wastewater solids within timeframes typical of operating practices.

Moral Polemics of Far-Reaching Economic Consequences of Antibiotics Overuse.

PubMed

Vochozka, Marek; Maroušková, Anna; Šuleř, Petr

2017-08-01

The unethical overuse of antibiotics to seek to achieve a shortening of the treatment period raises the cost of health services and poses a threat to humanity due to the gradual development of antibiotic resistance. Other consequences of our modern passion for antibiotics have appeared. Small concentrations of antibiotic residues in sewage waters slow down the metabolism of anaerobic microorganism thereby reducing the overall performance of the anaerobic fermentation used to detoxify and digest sewage and other collected organic wastes. Reduced biogas yields represents a serious threat to the energy self-sufficiency of some waste-water treatment plants, so it might change them from energy producers into energy consumers. Morally justifiable production of renewable energy from bio-waste is also threatened by antibiotic residues that remain in the bio-waste.

Antibiotic discovery throughout the Small World Initiative: A molecular strategy to identify biosynthetic gene clusters involved in antagonistic activity.

PubMed

Davis, Elizabeth; Sloan, Tyler; Aurelius, Krista; Barbour, Angela; Bodey, Elijah; Clark, Brigette; Dennis, Celeste; Drown, Rachel; Fleming, Megan; Humbert, Allison; Glasgo, Elizabeth; Kerns, Trent; Lingro, Kelly; McMillin, MacKenzie; Meyer, Aaron; Pope, Breanna; Stalevicz, April; Steffen, Brittney; Steindl, Austin; Williams, Carolyn; Wimberley, Carmen; Zenas, Robert; Butela, Kristen; Wildschutte, Hans

2017-06-01

The emergence of bacterial pathogens resistant to all known antibiotics is a global health crisis. Adding to this problem is that major pharmaceutical companies have shifted away from antibiotic discovery due to low profitability. As a result, the pipeline of new antibiotics is essentially dry and many bacteria now resist the effects of most commonly used drugs. To address this global health concern, citizen science through the Small World Initiative (SWI) was formed in 2012. As part of SWI, students isolate bacteria from their local environments, characterize the strains, and assay for antibiotic production. During the 2015 fall semester at Bowling Green State University, students isolated 77 soil-derived bacteria and genetically characterized strains using the 16S rRNA gene, identified strains exhibiting antagonistic activity, and performed an expanded SWI workflow using transposon mutagenesis to identify a biosynthetic gene cluster involved in toxigenic compound production. We identified one mutant with loss of antagonistic activity and through subsequent whole-genome sequencing and linker-mediated PCR identified a 24.9 kb biosynthetic gene locus likely involved in inhibitory activity in that mutant. Further assessment against human pathogens demonstrated the inhibition of Bacillus cereus, Listeria monocytogenes, and methicillin-resistant Staphylococcus aureus in the presence of this compound, thus supporting our molecular strategy as an effective research pipeline for SWI antibiotic discovery and genetic characterization. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Intraoperative near-infrared fluorescence imaging and spectroscopy identifies residual tumor cells in wounds

NASA Astrophysics Data System (ADS)

Holt, David; Parthasarathy, Ashwin B.; Okusanya, Olugbenga; Keating, Jane; Venegas, Ollin; Deshpande, Charuhas; Karakousis, Giorgos; Madajewski, Brian; Durham, Amy; Nie, Shuming; Yodh, Arjun G.; Singhal, Sunil

2015-07-01

Surgery is the most effective method to cure patients with solid tumors, and 50% of all cancer patients undergo resection. Local recurrences are due to tumor cells remaining in the wound, thus we explore near-infrared (NIR) fluorescence spectroscopy and imaging to identify residual cancer cells after surgery. Fifteen canines and two human patients with spontaneously occurring sarcomas underwent intraoperative imaging. During the operation, the wounds were interrogated with NIR fluorescence imaging and spectroscopy. NIR monitoring identified the presence or absence of residual tumor cells after surgery in 14/15 canines with a mean fluorescence signal-to-background ratio (SBR) of ˜16. Ten animals showed no residual tumor cells in the wound bed (mean SBR<2, P<0.001). None had a local recurrence at >1-year follow-up. In five animals, the mean SBR of the wound was >15, and histopathology confirmed tumor cells in the postsurgical wound in four/five canines. In the human pilot study, neither patient had residual tumor cells in the wound bed, and both remain disease free at >1.5-year follow up. Intraoperative NIR fluorescence imaging and spectroscopy identifies residual tumor cells in surgical wounds. These observations suggest that NIR imaging techniques may improve tumor resection during cancer operations.

Intraoperative near-infrared fluorescence imaging and spectroscopy identifies residual tumor cells in wounds

PubMed Central

Holt, David; Parthasarathy, Ashwin B.; Okusanya, Olugbenga; Keating, Jane; Venegas, Ollin; Deshpande, Charuhas; Karakousis, Giorgos; Madajewski, Brian; Durham, Amy; Nie, Shuming; Yodh, Arjun G.; Singhal, Sunil

2015-01-01

Abstract. Surgery is the most effective method to cure patients with solid tumors, and 50% of all cancer patients undergo resection. Local recurrences are due to tumor cells remaining in the wound, thus we explore near-infrared (NIR) fluorescence spectroscopy and imaging to identify residual cancer cells after surgery. Fifteen canines and two human patients with spontaneously occurring sarcomas underwent intraoperative imaging. During the operation, the wounds were interrogated with NIR fluorescence imaging and spectroscopy. NIR monitoring identified the presence or absence of residual tumor cells after surgery in 14/15 canines with a mean fluorescence signal-to-background ratio (SBR) of ∼16. Ten animals showed no residual tumor cells in the wound bed (mean SBR<2, P<0.001). None had a local recurrence at >1-year follow-up. In five animals, the mean SBR of the wound was >15, and histopathology confirmed tumor cells in the postsurgical wound in four/five canines. In the human pilot study, neither patient had residual tumor cells in the wound bed, and both remain disease free at >1.5-year follow up. Intraoperative NIR fluorescence imaging and spectroscopy identifies residual tumor cells in surgical wounds. These observations suggest that NIR imaging techniques may improve tumor resection during cancer operations. PMID:26160347

Antibiotic resistance in the wild: an eco-evolutionary perspective.

PubMed

Hiltunen, Teppo; Virta, Marko; Laine, Anna-Liisa

2017-01-19

The legacy of the use and misuse of antibiotics in recent decades has left us with a global public health crisis: antibiotic-resistant bacteria are on the rise, making it harder to treat infections. At the same time, evolution of antibiotic resistance is probably the best-documented case of contemporary evolution. To date, research on antibiotic resistance has largely ignored the complexity of interactions that bacteria engage in. However, in natural populations, bacteria interact with other species; for example, competition and grazing are import interactions influencing bacterial population dynamics. Furthermore, antibiotic leakage to natural environments can radically alter bacterial communities. Overall, we argue that eco-evolutionary feedback loops in microbial communities can be modified by residual antibiotics and evolution of antibiotic resistance. The aim of this review is to connect some of the well-established key concepts in evolutionary biology and recent advances in the study of eco-evolutionary dynamics to research on antibiotic resistance. We also identify some key knowledge gaps related to eco-evolutionary dynamics of antibiotic resistance, and review some of the recent technical advantages in molecular microbiology that offer new opportunities for tackling these questions. Finally, we argue that using the full potential of evolutionary theory and active communication across the different fields is needed for solving this global crisis more efficiently.This article is part of the themed issue 'Human influences on evolution, and the ecological and societal consequences'. © 2016 The Authors.

Antibiotic resistance in the wild: an eco-evolutionary perspective

PubMed Central

Virta, Marko

2017-01-01

The legacy of the use and misuse of antibiotics in recent decades has left us with a global public health crisis: antibiotic-resistant bacteria are on the rise, making it harder to treat infections. At the same time, evolution of antibiotic resistance is probably the best-documented case of contemporary evolution. To date, research on antibiotic resistance has largely ignored the complexity of interactions that bacteria engage in. However, in natural populations, bacteria interact with other species; for example, competition and grazing are import interactions influencing bacterial population dynamics. Furthermore, antibiotic leakage to natural environments can radically alter bacterial communities. Overall, we argue that eco-evolutionary feedback loops in microbial communities can be modified by residual antibiotics and evolution of antibiotic resistance. The aim of this review is to connect some of the well-established key concepts in evolutionary biology and recent advances in the study of eco-evolutionary dynamics to research on antibiotic resistance. We also identify some key knowledge gaps related to eco-evolutionary dynamics of antibiotic resistance, and review some of the recent technical advantages in molecular microbiology that offer new opportunities for tackling these questions. Finally, we argue that using the full potential of evolutionary theory and active communication across the different fields is needed for solving this global crisis more efficiently. This article is part of the themed issue ‘Human influences on evolution, and the ecological and societal consequences'. PMID:27920384

Determination of fluoroquinolone antibiotic residues in the plasma of Eurasian griffon vultures (Gyps fulvus) in Spain.

PubMed

Casas-Díaz, Encarna; Cristòfol, Carles; Cuenca, Rafaela; Agustí, Susana; Carneiro, Manuela; Marco, Ignasi; Lavín, Santiago; Margalida, Antoni

2016-07-01

Due to the possible toxicological impact, the accumulation of pharmaceuticals in wildlife as a consequence of human practices is of growing concern. The consumption of carrion at feeding stations - the so-called 'vulture restaurants' - with no management of the veterinary drugs it contains may expose scavengers to pharmaceuticals. To demonstrate this, we analyzed plasma from Eurasian griffon vultures (Gyps fulvus) originating from two different areas of Spain for antibiotics such as enrofloxacin and ciprofloxacin, its primary metabolite. Quinolone residues were detected in about 65% (n=106) of birds, of which 15.1% (16/106) had quantifiable amounts of enrofloxacin (0.049±0.102μg/mL) and 5.7% (6/106) of ciprofloxacin (0.009±0.007μg/mL). The differences in exposure between the two sampled areas are attributable to different types of carrion management: the vultures that fed in areas with a high density of dead livestock (supplied directly to feeding stations) were more prone to exposure than those that sought food in areas where carcass availability is more unpredictable. Our findings are evidence that vultures have access to medicated livestock and that there are quantifiable levels of livestock antibiotics in vulture plasma. However, the vultures analyzed in this study had maximum antibiotic concentrations of only 0.4μg/mL, much less than the concentrations used in the clinical treatment of scavengers and a level that is probably too small to cause intoxication. Copyright © 2016 Elsevier B.V. All rights reserved.

Determination of six polyether antibiotic residues in foods of animal origin by solid phase extraction combined with liquid chromatography-tandem mass spectrometry.

PubMed

Ha, Jing; Song, Ge; Ai, Lian-Feng; Li, Jian-Chen

2016-04-01

A new method using solid phase extraction (SPE) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the determination of six polyether antibiotics, including lasalocid, salinomycin, monensin, narasin, madubamycin and nigericin residues, in foods of animal origin. The samples were extracted with acetonitrile and purified by ENVI-Carb SPE columns after comparing the impurity effect and maneuverability of several SPE cartridges. Subsequently, the analytes were separated on a Hypersil Gold column (2.1×150mm, 5μm) and analyzed by MS/MS detection. The limit of quantization (LOQ) for milk and chicken was 0.4μg/kg, and for chicken livers and eggs, it was 1μg/kg. The linearity was satisfactory with a correlation coefficient of >0.9995 at concentrations ranging from 2 to 100μg/L. The average recoveries of the analytes fortified at three levels ranged from 68.2 to 114.3%, and the relative standard deviations ranged from 4.5 to 12.1%. The method was suitable for quantitative analysis and confirmation of polyether antibiotic residues in foods of animal origin. Copyright © 2016 Elsevier B.V. All rights reserved.

Distribution of Penicillin G Residues in Culled Dairy Cow Muscles: Implications for Residue Monitoring

USDA-ARS?s Scientific Manuscript database

The U.S. Food and Drug Administration sets tolerances for veterinary drug residues in muscle, but does not specify which type of muscle should be analyzed. In order to determine if antibiotic residue levels are dependent on muscle type, 7 culled dairy cows were dosed with Penicillin G (Pen G) from ...

Identifying and Predicting Profiles of Medical Noncompliance: Pediatric Caregivers' Antibiotic Stewardship.

PubMed

Smith, Rachel A; Kim, Youllee; M'Ikanatha, Nkuchia M

2018-05-14

Sometimes compliance with medical recommendations is problematic. We investigated pediatric caregivers' (N = 606) patterns of noncompliance with antibiotic stewardship based on the obstacle hypothesis. We tested predictors of noncompliance framed by the obstacle hypothesis, dissonance theory, and psychological reactance. The results revealed four profiles of caregivers' stewardship: one marked by compliance (Stewards) and three marked by types of noncompliance (Stockers, Persuaders, and Dissenters). The covariate analysis showed that, although psychological reactance predicted being noncompliant, it was types of obstacles and discrepant experiences that predicted caregivers' patterns of noncompliance with antibiotic stewardship. Campaign planning often focuses on identifying the belief most associated with the targeted outcome, such as compliance. Noncompliance research, however, points out that persuaders may be successful to the extent to which they anticipate obstacles to compliance and address them in their influence attempts. A shift from medical noncompliance to patient engagement also affords an opportunity to consider how some recommendations create obstacles for others and to find positive ways to embrace conflicting needs, tensions, and reasons for refusal in order to promote collective goals.

Overexpression of antibiotic resistance genes in hospital effluents over time

PubMed Central

Baker-Austin, Craig; Verner-Jeffreys, David W.; Ryan, Jim J.; Micallef, Christianne; Maskell, Duncan J.; Pearce, Gareth P.

2017-01-01

Objectives: Effluents contain a diverse abundance of antibiotic resistance genes that augment the resistome of receiving aquatic environments. However, uncertainty remains regarding their temporal persistence, transcription and response to anthropogenic factors, such as antibiotic usage. We present a spatiotemporal study within a river catchment (River Cam, UK) that aims to determine the contribution of antibiotic resistance gene-containing effluents originating from sites of varying antibiotic usage to the receiving environment. Methods: Gene abundance in effluents (municipal hospital and dairy farm) was compared against background samples of the receiving aquatic environment (i.e. the catchment source) to determine the resistome contribution of effluents. We used metagenomics and metatranscriptomics to correlate DNA and RNA abundance and identified differentially regulated gene transcripts. Results: We found that mean antibiotic resistance gene and transcript abundances were correlated for both hospital (ρ = 0.9, two-tailed P <0.0001) and farm (ρ = 0.5, two-tailed P  <0.0001) effluents and that two β-lactam resistance genes (blaGES and blaOXA) were overexpressed in all hospital effluent samples. High β-lactam resistance gene transcript abundance was related to hospital antibiotic usage over time and hospital effluents contained antibiotic residues. Conclusions: We conclude that effluents contribute high levels of antibiotic resistance genes to the aquatic environment; these genes are expressed at significant levels and are possibly related to the level of antibiotic usage at the effluent source. PMID:28175320

Analysis of beta-lactam antibiotics in incurred raw milk by rapid test methods and liquid chromatography coupled with electrospray ionization tandem mass spectrometry.

PubMed

Riediker, S; Diserens, J M; Stadler, R H

2001-09-01

A recently developed confirmatory LC-MS method has been applied to the quantification of five major beta-lactam antibiotics in suspect raw bovine milk samples that gave a positive response with receptor-based (BetaStar) and rapid microbial inhibitory screen tests (Delvotest SP). In total, 18 presumptive positive raw milk samples were reanalyzed; 16 samples showed traces of antibiotic residues that could be identified and quantified by the LC-MS method, ranging from the limits of confirmation up to 38 microg/kg. Of the positive samples, only five (approximately 30%) were found to be violative of EU maximum residue limits. The most frequently detected antibiotic residues were cloxacillin and penicillin G, the former often in combination with amoxicillin or ampicillin. This study compares the results obtained by the three methods on identical samples and addresses how these relate to certain criteria such as sensitivity and selectivity. Furthermore, the limitations of the LC-MS method and the potential impact of the presence of frequently more than one residue in the same milk sample on the response of the rapid test methods are discussed.

Bacteriocins - exploring alternatives to antibiotics in mastitis treatment.

PubMed

Pieterse, Reneé; Todorov, Svetoslav D

2010-07-01

Mastitis is considered to be the most costly disease affecting the dairy industry. Management strategies involve the extensive use of antibiotics to treat and prevent this disease. Prophylactic dosages of antibiotics used in mastitis control programmes could select for strains with resistance to antibiotics. In addition, a strong drive towards reducing antibiotic residues in animal food products has lead to research in finding alternative antimicrobial agents. In this review we have focus on the pathogenesis of the mastitis in dairy cows, existing antibiotic treatments and possible alternative for application of bacteriocins from lactic acid bacteria in the treatment and prevention of this disease.

Validation of a Five Plate Test, the STAR protocol, for the screening of antibiotic residues in muscle from different animal species according to European Decision 2002/657/EC.

PubMed

Gaudin, V; Hedou, C; Rault, A; Verdon, E

2010-07-01

The STAR protocol is a Five Plate Test (FPT) developed several years ago at the Community Reference Laboratory (CRL) for the screening of antimicrobial residues in milk and muscle. This paper presents the validation of this method according to European Decision 2002/657/EC and to an internal guideline for validation. A validation protocol based on 'simulated tissues' and on a list of 16 representative antimicrobials to be validated was implemented in our laboratory during several months for the STAR protocol. The performance characteristics of the method were determined (specificity, detection capabilities CCbeta, applicability, ruggedness). In conclusion, the STAR protocol is applicable to the broad-spectrum detection of antibiotic residues in muscles of different animal species (pig, cattle, sheep, poultry). The method has good specificity (false-positive rate = 4%). The detection capabilities were determined for 16 antibiotics from different families in relation to their respective maximum residue limit (MRL): beta-lactams (penicillins and cephalosporins < or = MRL), tetracyclines (< or = MRL and < or = 2.5 MRL), macrolides (2 MRL), quinolones (< or = 2 MRL), some sulphonamides (< or = 3 MRL), and trimethoprim (2 MRL). However, the sensitivity of the STAR protocol towards aminoglycosides (> 8 MRL) and florfenicol (< or = 10 MRL) was unsatisfactory (>MRL). The two objectives of this study were met: firstly, to validate the STAR protocol according to European Decision 2002/657/EC, then to demonstrate that the validation guideline developed to implement this decision is applicable to microbiological plate tests even for muscle. The use of simulated tissue appeared a good compromise between spiked discs with antibiotic solutions and incurred tissues. In addition, the choice of a list of representative antibiotics allowed the reduction of the scope of the validation, which was already costly in time and effort.

Validation of a multi-residue method for the determination of several antibiotic groups in honey by LC-MS/MS.

PubMed

Bohm, Detlef A; Stachel, Carolin S; Gowik, Petra

2012-07-01

The presented multi-method was developed for the confirmation of 37 antibiotic substances from the six antibiotic groups: macrolides, lincosamides, quinolones, tetracyclines, pleuromutilines and diamino-pyrimidine derivatives. All substances were analysed simultaneously in a single analytical run with the same procedure, including an extraction with buffer, a clean-up by solid-phase extraction, and the measurement by liquid chromatography tandem mass spectrometry in ESI+ mode. The method was validated on the basis of an in-house validation concept with factorial design by combination of seven factors to check the robustness in a concentration range of 5-50 μg kg(-1). The honeys used were of different types with regard to colour and origin. The values calculated for the validation parameters-decision limit CCα (range, 7.5-12.9 μg kg(-1)), detection capability CCβ (range, 9.4-19.9 μg kg(-1)), within-laboratory reproducibility RSD(wR) (<20% except for tulathromycin with 23.5% and tylvalosin with 21.4 %), repeatability RSD(r) (<20% except for tylvalosin with 21.1%), and recovery (range, 92-106%)-were acceptable and in agreement with the criteria of Commission Decision 2002/657/EC. The validation results showed that the method was applicable for the residue analysis of antibiotics in honey to substances with and without recommended concentrations, although some changes had been tested during validation to determine the robustness of the method.

[Antibiotic Residue in Environmental Water in Vietnam].

PubMed

Harada, Kazuo

2018-01-01

　The increasing prevalence of antimicrobial resistance (AMR) has caused intractable infections worldwide. Nearly 50% of the healthy population of Southeast Asia carries extended-spectrum β-lactamase (ESBL)-producing Escherichia coli. The overuse of antimicrobial agents in the agriculture, aquaculture, and medical care sectors causes environmental pollution, facilitating the spread of AMR. However, there is a lack of data pertaining to antimicrobial residues in environmental water in such regions. We investigated a total of 49 chemicals, including β-lactams, sulfonamides, quinolones, and tetracyclines. Water samples were collected from rivers in city centers, and ponds in livestock and aquaculture farms, in Ha Noi, Thai Binh, and Can Tho in Vietnam. We detected antimicrobial agents at 87 of 111 sampling sites (78.4%). Among the target analytes, sulfamethoxazole, sulfamethazine, trimethoprim, cephalexin, and ofloxacin were detected frequently. The residual levels of each antimicrobial agent ranged from 0.1 to 10000 ng/L. Moreover, we detected multi-drug resistant E. coli in fishes sampled from these rivers, suggesting unwanted effects of antimicrobial residues in the environment.

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.

Using robust Bayesian network to estimate the residuals of fluoroquinolone antibiotic in soil.

PubMed

Li, Xuewen; Xie, Yunfeng; Li, Lianfa; Yang, Xunfeng; Wang, Ning; Wang, Jinfeng

2015-11-01

Prediction of antibiotic pollution and its consequences is difficult, due to the uncertainties and complexities associated with multiple related factors. This article employed domain knowledge and spatial data to construct a Bayesian network (BN) model to assess fluoroquinolone antibiotic (FQs) pollution in the soil of an intensive vegetable cultivation area. The results show: (1) The relationships between FQs pollution and contributory factors: Three factors (cultivation methods, crop rotations, and chicken manure types) were consistently identified as predictors in the topological structures of three FQs, indicating their importance in FQs pollution; deduced with domain knowledge, the cultivation methods are determined by the crop rotations, which require different nutrients (derived from the manure) according to different plant biomass. (2) The performance of BN model: The integrative robust Bayesian network model achieved the highest detection probability (pd) of high-risk and receiver operating characteristic (ROC) area, since it incorporates domain knowledge and model uncertainty. Our encouraging findings have implications for the use of BN as a robust approach to assessment of FQs pollution and for informing decisions on appropriate remedial measures.

Occurrence of veterinary antibiotics and progesterone in broiler manure and agricultural soil in Malaysia.

PubMed

Ho, Yu Bin; Zakaria, Mohamad Pauzi; Latif, Puziah Abdul; Saari, Nazamid

2014-08-01

Repeated applications of animal manure as fertilizer are normal agricultural practices that may release veterinary antibiotics and hormones into the environment from treated animals. Broiler manure samples and their respective manure-amended agricultural soil samples were collected in selected locations in the states of Selangor, Negeri Sembilan and Melaka in Malaysia to identify and quantify veterinary antibiotic and hormone residues in the environment. The samples were analyzed using ultrasonic extraction followed by solid phase extraction (SPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The broiler manure samples were found to be contaminated with at least six target analytes, namely, doxycycline, enrofloxacin, flumequine, norfloxacin, trimethoprim and tylosin. These analytes were detected in broiler manure samples with maximum concentrations reaching up to 78,516 μg kg(-1) dry weight (DW) (doxycycline). For manure-amended agricultural soil samples, doxycycline and enrofloxacin residues were detected in every soil sample. The maximum concentration of antibiotic detected in soil was 1331 μg kg(-1) DW (flumequine). The occurrence of antibiotics and hormones in animal manure at high concentration poses a risk of contaminating agricultural soil via fertilization with animal manure. Some physico-chemical parameters such as pH, total organic carbon (TOC) and metal content played a considerable role in the fate of the target veterinary antibiotics and progesterone in the environment. It was suggested that these parameters can affect the adsorption of pharmaceuticals to solid environmental matrices. Copyright © 2014 Elsevier B.V. All rights reserved.

STUDY TO IDENTIFY IMPORTANT PARAMETERS FOR CHARACTERIZING PESTICIDE RESIDUE TRANSFER EFFICIENCIES

EPA Science Inventory

To reduce the uncertainty associated with current estimates of children's exposure to pesticides by dermal contact and non-dietary ingestion, residue transfer data are required. Prior to conducting exhaustive studies, a screening study to identify the important parameters for...

Overexpression of antibiotic resistance genes in hospital effluents over time.

PubMed

Rowe, Will P M; Baker-Austin, Craig; Verner-Jeffreys, David W; Ryan, Jim J; Micallef, Christianne; Maskell, Duncan J; Pearce, Gareth P

2017-06-01

Effluents contain a diverse abundance of antibiotic resistance genes that augment the resistome of receiving aquatic environments. However, uncertainty remains regarding their temporal persistence, transcription and response to anthropogenic factors, such as antibiotic usage. We present a spatiotemporal study within a river catchment (River Cam, UK) that aims to determine the contribution of antibiotic resistance gene-containing effluents originating from sites of varying antibiotic usage to the receiving environment. Gene abundance in effluents (municipal hospital and dairy farm) was compared against background samples of the receiving aquatic environment (i.e. the catchment source) to determine the resistome contribution of effluents. We used metagenomics and metatranscriptomics to correlate DNA and RNA abundance and identified differentially regulated gene transcripts. We found that mean antibiotic resistance gene and transcript abundances were correlated for both hospital ( ρ  = 0.9, two-tailed P  <0.0001) and farm ( ρ  = 0.5, two-tailed P   <0.0001) effluents and that two β-lactam resistance genes ( bla GES and bla OXA ) were overexpressed in all hospital effluent samples. High β-lactam resistance gene transcript abundance was related to hospital antibiotic usage over time and hospital effluents contained antibiotic residues. We conclude that effluents contribute high levels of antibiotic resistance genes to the aquatic environment; these genes are expressed at significant levels and are possibly related to the level of antibiotic usage at the effluent source. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

Chlortetracycline and Oxytetracycline Residues in Poultry Tissues and Eggs

PubMed Central

Meredith, W. E.; Weiser, H. H.; Winter, A. R.

1965-01-01

A pad-plate method of assaying residual amounts of chlortetracycline (CTC) and oxytetracycline (OTC) using Bacillus cereus 213 was used to determine amounts of antibiotic left in tissues and eggs of poultry fed 1,000 and 200 ppm of CTC and OTC in basal feed mixtures. The effects of various methods of cooking the tissues and eggs and the potentiating effect of terephthalic acid (TPA) were studied. It was found that normal methods of roasting, frying, and autoclaving poultry tissue destroyed all residual CTC and OTC, even with the potentiating effect of TPA. The largest amounts of residual antibiotic were found in the liver, then breast, and then thigh tissue when assayed for CTC. Tissue assays for CTC revealed that it was not taken up as extensively as CTC and the largest amounts were found in the liver, then breast. OTC residue was seldom found in the thigh tissue. Terephthalic acid in 0.5% concentration increased the concentration found in all cases. Cooking by poaching and scrambling eggs did not destroy the antibiotic in all cases. PMID:14264853

Lysine succinylation of Mycobacterium tuberculosis isocitrate lyase (ICL) fine-tunes the microbial resistance to antibiotics.

PubMed

Zhou, Mingliang; Xie, Longxiang; Yang, Zhaozhen; Zhou, Jiahai; Xie, Jianping

2017-04-01

Lysine succinylation (Ksucc) is a newly identified protein posttranslational modification (PTM), which may play an important role in cellular physiology. However, the role of lysine succinylation in antibiotic resistance remains elusive. Isocitrate lyase (ICL) is crucial for broad-spectrum antibiotics tolerance in Mycobacterium tuberculosis (Mtb). We previously found that MtbICL (Rv0467) has at least three succinylated lysine residues, namely K189, K322, and K334.To explore the effect of succinylation on the activity of MtbICL, mutants' mimicry of the lysine succinylation were generated by site-directed mutagenesis. ICL-K189E mutant strain is more sensitive than the wild-type to rifampicin and streptomycin, but not isoniazid. For the in vitro activity of the purified isocitrate lyase, only K189E mutant showed significantly decreased activity. Crystal structure analysis showed that Lys189 Glu dramatically increased the pKa of Glu188 and decreased the pKa of Lys190, whereas had negligible effect on other residues within 5 Å as well as disruption of the electrostatic interaction between Lys189 and Glu182, which might prevent the closure of the active site loop and cause severe reduction of the enzyme activity. Considering the genetic, biochemical, and crystallographical evidences together, the succinylation of specific ICL residue can fine-tune the bacterial resistance to selected antibiotics. The decreased enzymatic activity resulting from the succinylation-changed electrostatic interaction might underlie this phenotype. This study provided the first insight into the link between lysine succinylation and antibiotic resistance.

Development of a suspect and non-target screening approach to detect veterinary antibiotic residues in a complex biological matrix using liquid chromatography/high-resolution mass spectrometry.

PubMed

Solliec, Morgan; Roy-Lachapelle, Audrey; Sauvé, Sébastien

2015-12-30

Swine manure can contain a wide range of veterinary antibiotics, which could enter the environment via manure spreading on agricultural fields. A suspect and non-target screening method was applied to swine manure samples to attempt to identify veterinary antibiotics and pharmaceutical compounds for a future targeted analysis method. A combination of suspect and non-target screening method was developed to identify various veterinary antibiotic families using liquid chromatography coupled with high-resolution mass spectrometry (LC/HRMS). The sample preparation was based on the physicochemical parameters of antibiotics for the wide scope extraction of polar compounds prior to LC/HRMS analysis. The amount of data produced was processed by applying restrictive thresholds and filters to significantly reduce the number of compounds found and eliminate matrix components. The suspect and non-target screening was applied on swine manure samples and revealed the presence of seven common veterinary antibiotics and some of their relative metabolites, including tetracyclines, β-lactams, sulfonamides and lincosamides. However, one steroid and one analgesic were also identified. The occurrence of the identified compounds was validated by comparing their retention times, isotopic abundance patterns and fragmentation patterns with certified standards. This identification method could be very useful as an initial step to screen for and identify emerging contaminants such as veterinary antibiotics and pharmaceuticals in environmental and biological matrices prior to quantification. Copyright © 2015 John Wiley & Sons, Ltd.

Presence and biological activity of antibiotics used in fuel ethanol and corn co-product production.

PubMed

Compart, D M Paulus; Carlson, A M; Crawford, G I; Fink, R C; Diez-Gonzalez, F; Dicostanzo, A; Shurson, G C

2013-05-01

Antibiotics are used in ethanol production to control bacteria from competing with yeast for nutrients during starch fermentation. However, there is no published scientific information on whether antibiotic residues are present in distillers grains (DG), co-products from ethanol production, or whether they retain their biological activity. Therefore, the objectives of this study were to quantify concentrations of various antibiotic residues in DG and determine whether residues were biologically active. Twenty distillers wet grains and 20 distillers dried grains samples were collected quarterly from 9 states and 43 ethanol plants in the United States. Samples were analyzed for DM, CP, NDF, crude fat, S, P, and pH to describe the nutritional characteristics of the samples evaluated. Samples were also analyzed for the presence of erythromycin, penicillin G, tetracycline, tylosin, and virginiamycin M1, using liquid chromatography and mass spectrometry. Additionally, virginiamycin residues were determined, using a U.S. Food and Drug Administration-approved bioassay method. Samples were extracted and further analyzed for biological activity by exposing the sample extracts to 10(4) to 10(7) CFU/mL concentrations of sentinel bacterial strains Escherichia coli ATCC 8739 and Listeria monocytogenes ATCC 19115. Extracts that inhibited bacterial growth were considered to have biological activity. Physiochemical characteristics varied among samples but were consistent with previous findings. Thirteen percent of all samples contained low (≤1.12 mg/kg) antibiotic concentrations. Only 1 sample extract inhibited growth of Escherichia coli at 10(4) CFU/mL, but this sample contained no detectable concentrations of antibiotic residues. No extracts inhibited Listeria monocytogenes growth. These data indicate that the likelihood of detectable concentrations of antibiotic residues in DG is low; and if detected, they are found in very low concentrations. The inhibition in only 1 DG

Aptamer-Based Biosensors for Antibiotic Detection: A Review.

PubMed

Mehlhorn, Asol; Rahimi, Parvaneh; Joseph, Yvonne

2018-06-11

Antibiotic resistance and, accordingly, their pollution because of uncontrolled usage has emerged as a serious problem in recent years. Hence, there is an increased demand to develop robust, easy, and sensitive methods for rapid evaluation of antibiotics and their residues. Among different analytical methods, the aptamer-based biosensors (aptasensors) have attracted considerable attention because of good selectivity, specificity, and sensitivity. This review gives an overview about recently-developed aptasensors for antibiotic detection. The use of various aptamer assays to determine different groups of antibiotics, like β-lactams, aminoglycosides, anthracyclines, chloramphenicol, (fluoro)quinolones, lincosamide, tetracyclines, and sulfonamides are presented in this paper.

Dietary risk ranking for residual antibiotics in cultured aquatic products around Tai Lake, China.

PubMed

Song, Chao; Li, Le; Zhang, Cong; Qiu, Liping; Fan, Limin; Wu, Wei; Meng, Shunlong; Hu, Gengdong; Chen, Jiazhang; Liu, Ying; Mao, Aimin

2017-10-01

Antibiotics are widely used in aquaculture and therefore may be present as a dietary risk in cultured aquatic products. Using the Tai Lake Basin as a study area, we assessed the presence of 15 antibiotics in 5 widely cultured aquatic species using a newly developed dietary risk ranking approach. By assigning scores to each factor involved in the ranking matrices, the scores of dietary risks per antibiotic and per aquatic species were calculated. The results indicated that fluoroquinolone antibiotics posed the highest dietary risk in all aquatic species. Then, the total scores per aquatic species were summed by all 15 antibiotic scores of antibiotics, it was found that Crab (Eriocheir sinensis) had the highest dietary risks. Finally, the most concerned antibiotic category and aquatic species were selected. This study highlighted the importance of dietary risk ranking in the production and consumption of cultured aquatic products around Tai Lake. Copyright © 2017 Elsevier Inc. All rights reserved.

Residual antibiofilm effects of various concentrations of double antibiotic paste used during regenerative endodontics after different application times.

PubMed

Jenks, Daniel B; Ehrlich, Ygal; Spolnik, Kenneth; Gregory, Richard L; Yassen, Ghaeth H

2016-10-01

We investigated the residual antibiofilm effects of different concentrations of double antibiotic paste (DAP) applied on radicular dentin for 1 or 4 weeks. Dentin samples were prepared (n=120), sterilized and pretreated for 1 or 4 weeks with the clinically used concentration of DAP (500mg/mL), low concentrations of DAP (1, 5 or 50mg/mL) loaded into a methylcellulose system, calcium hydroxide (Ca(OH) 2 ), or placebo paste. After the assigned treatment time, treatment pastes were rinsed off and the samples were kept independently in phosphate buffered saline for 3 weeks. Pretreated dentin samples were then inoculated with Enterococcus faecalis and bacterial biofilms were allowed to grow for an additional 3 weeks. Biofilms were then retrieved from dentin using biofilm disruption assays, diluted, spiral plated, and quantified. Fisher's Exact and Wilcoxon rank sum tests were used for statistical comparisons (α=0.05). Dentin pretreatment for 4 weeks with 5, 50 or 500mg/mL of DAP demonstrated significantly higher residual antibiofilm effects and complete eradication of E. faecalis biofilms in comparison to a 1 week pretreatment with similar concentrations. However, dentin pretreated with 1mg/mL of DAP or Ca(OH) 2 did not provide a substantial residual antibiofilm effect regardless of the application time. Dentin pretreatment with 5mg/mL of DAP or higher for 4 weeks induced significantly higher residual antibiofilm effects in comparison to a 1 week pretreatment with the same concentrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ecotoxicological assessment of antibiotics: A call for improved consideration of microorganisms.

PubMed

Brandt, Kristian K; Amézquita, Alejandro; Backhaus, Thomas; Boxall, Alistair; Coors, Anja; Heberer, Thomas; Lawrence, John R; Lazorchak, James; Schönfeld, Jens; Snape, Jason R; Zhu, Yong-Guan; Topp, Edward

2015-12-01

Antibiotics play a pivotal role in the management of infectious disease in humans, companion animals, livestock, and aquaculture operations at a global scale. Antibiotics are produced, consumed, and released into the environment at an unprecedented scale causing concern that the presence of antibiotic residues may adversely impact aquatic and terrestrial ecosystems. Here we critically review the ecotoxicological assessment of antibiotics as related to environmental risk assessment (ERA). We initially discuss the need for more specific protection goals based on the ecosystem service concept, and suggest that the ERA of antibiotics, through the application of a mode of toxic action approach, should make more use of ecotoxicological endpoints targeting microorganisms (especially bacteria) and microbial communities. Key ecosystem services provided by microorganisms and associated ecosystem service-providing units (e.g. taxa or functional groups) are identified. Approaches currently available for elucidating ecotoxicological effects on microorganisms are reviewed in detail and we conclude that microbial community-based tests should be used to complement single-species tests to offer more targeted protection of key ecosystem services. Specifically, we propose that ecotoxicological tests should not only assess microbial community function, but also microbial diversity (‘species’ richness) and antibiotic susceptibility. Promising areas for future basic and applied research of relevance to ERA are highlighted throughout the text. In this regard, the most fundamental knowledge gaps probably relate to our rudimentary understanding of the ecological roles of antibiotics in nature and possible adverse effects of environmental pollution with subinhibitory levels of antibiotics.

Near-infrared fluorescence-based multiplex lateral flow immunoassay for the simultaneous detection of four antibiotic residue families in milk.

PubMed

Chen, Yiqiang; Chen, Qian; Han, Miaomiao; Liu, Jiangyang; Zhao, Peng; He, Lidong; Zhang, Yuan; Niu, Yiming; Yang, Wenjun; Zhang, Liying

2016-05-15

In this study, we developed a novel near-infrared fluorescence based multiplex lateral flow immunoassay by conjugating a near-infrared label to broad-specificity monoclonal antibody/receptor as detection complexes. Different antigens were dispensed onto separate test zones of nitrocellulose membrane to serve as capture reagents. This assay format allowed the simultaneous detection of four families of antibiotics (β-lactams, tetracyclines, quinolones and sulfonamides) in milk within 20 min. Qualitative and quantitative analysis of target antibiotics were realized by imaging the fluorescence intensity of the near-infrared label captured on respective test lines. For qualitative analysis, the cut-off values of β-lactams, tetracyclines, quinolones and sulfonamides were determined to be 8 ng/mL, 2 ng/mL, 4 ng/mL and 8 ng/mL respectively, which were much lower than the conventional gold nanoparticle based lateral flow immunoassay. For quantitative analysis, the detection ranges were 0.26-3.56 ng/mL for β-lactams, 0.04-0.98 ng/mL for tetracyclines, 0.08-2.0 ng/mL for quinolones, and 0.1-3.98 ng/mL for sulfonamides, with linear correlation coefficients higher than 0.97. The mean spiked recoveries ranged from 93.7% to 108.2% with coefficient of variations less than 16.3%. These results demonstrated that this novel immunoassay is a promising approach for rapidly screening the four families of antibiotic residues in milk. Copyright © 2015 Elsevier B.V. All rights reserved.

Bacteriocins – Exploring Alternatives to Antibiotics in Mastitis Treatment

PubMed Central

Pieterse, Reneé; Todorov, Svetoslav D.

2010-01-01

Mastitis is considered to be the most costly disease affecting the dairy industry. Management strategies involve the extensive use of antibiotics to treat and prevent this disease. Prophylactic dosages of antibiotics used in mastitis control programmes could select for strains with resistance to antibiotics. In addition, a strong drive towards reducing antibiotic residues in animal food products has lead to research in finding alternative antimicrobial agents. In this review we have focus on the pathogenesis of the mastitis in dairy cows, existing antibiotic treatments and possible alternative for application of bacteriocins from lactic acid bacteria in the treatment and prevention of this disease. PMID:24031528

Paenibacillus polymyxa PKB1 produces variants of polymyxin B-type antibiotics.

PubMed

Shaheen, Mohamed; Li, Jingru; Ross, Avena C; Vederas, John C; Jensen, Susan E

2011-12-23

Polymyxins are cationic lipopeptide antibiotics active against many species of Gram-negative bacteria. We sequenced the gene cluster for polymyxin biosynthesis from Paenibacillus polymyxa PKB1. The 40.8 kb gene cluster comprises three nonribosomal peptide synthetase-encoding genes and two ABC transporter-like genes. Disruption of a peptide synthetase gene abolished all antibiotic production, whereas deletion of one or both transporter genes only reduced antibiotic production. Computational analysis of the peptide synthetase modules suggested that the enzyme system produces variant forms of polymyxin B (1 and 2), with D-2,4-diaminobutyrate instead of L-2,4-diaminobutyrate in amino acid position 3. Two antibacterial metabolites were resolved by HPLC and identified by high-resolution mass spectrometry and MS/MS sequencing as the expected variants 3 and 4 of polymyxin B(1) (1) and B(2) (2). Stereochemical analysis confirmed the presence of both D-2,4-diaminobutyrate and L-2,4-diaminobutyrate residues. Copyright © 2011 Elsevier Ltd. All rights reserved.

Antibiotic, Pesticide, and Microbial Contaminants of Honey: Human Health Hazards

PubMed Central

Al-Waili, Noori; Salom, Khelod; Al-Ghamdi, Ahmed; Ansari, Mohammad Javed

2012-01-01

Agricultural contamination with pesticides and antibiotics is a challenging problem that needs to be fully addressed. Bee products, such as honey, are widely consumed as food and medicine and their contamination may carry serious health hazards. Honey and other bee products are polluted by pesticides, heavy metals, bacteria and radioactive materials. Pesticide residues cause genetic mutations and cellular degradation and presence of antibiotics might increase resistant human or animal's pathogens. Many cases of infant botulisms have been attributed to contaminated honey. Honey may be very toxic when produced from certain plants. Ingestion of honey without knowing its source and safety might be problematic. Honey should be labeled to explore its origin, composition, and clear statement that it is free from contaminants. Honey that is not subjected for analysis and sterilization should not be used in infants, and should not be applied to wounds or used for medicinal purposes. This article reviews the extent and health impact of honey contamination and stresses on the introduction of a strict monitoring system and validation of acceptable minimal concentrations of pollutants or identifying maximum residue limits for bee products, in particular, honey. PMID:23097637

High-performance thin-layer chromatography screening of multi class antibiotics in animal food by bioluminescent bioautography and electrospray ionization mass spectrometry.

PubMed

Chen, Yisheng; Schwack, Wolfgang

2014-08-22

The world-wide usage and partly abuse of veterinary antibiotics resulted in a pressing need to control residues in animal-derived foods. Large-scale screening for residues of antibiotics is typically performed by microbial agar diffusion tests. This work employing high-performance thin-layer chromatography (HPTLC) combined with bioautography and electrospray ionization mass spectrometry introduces a rapid and efficient method for a multi-class screening of antibiotic residues. The viability of the bioluminescent bacterium Aliivibrio fischeri to the studied antibiotics (16 species of 5 groups) was optimized on amino plates, enabling detection sensitivity down to the strictest maximum residue limits. The HPTLC method was developed not to separate the individual antibiotics, but for cleanup of sample extracts. The studied antibiotics either remained at the start zones (tetracyclines, aminoglycosides, fluoroquinolones, and macrolides) or migrated into the front (amphenicols), while interfering co-extracted matrix compounds were dispersed at hRf 20-80. Only after a few hours, the multi-sample plate image clearly revealed the presence or absence of antibiotic residues. Moreover, molecular information as to the suspected findings was rapidly achieved by HPTLC-mass spectrometry. Showing remarkable sensitivity and matrix-tolerance, the established method was successfully applied to milk and kidney samples. Copyright © 2014 Elsevier B.V. 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.

Distribution of veterinary drug residues among muscles

USDA-ARS?s Scientific Manuscript database

The U.S. Food and Drug Administration sets tolerances for veterinary drug residues in muscle, but does not specify which muscle should be sampled for analysis. The goal of this research was to determine if antibiotic residue levels are dependent on muscle type. In this study, penicillin G (Pen G) d...

High-throughput method for the determination of residues of β-lactam antibiotics in bovine milk by LC-MS/MS.

PubMed

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

2015-01-01

This study describes the development and validation procedures for scope extension of a method for the determination of β-lactam antibiotic residues (ampicillin, amoxicillin, penicillin G, penicillin V, oxacillin, cloxacillin, dicloxacillin, nafcillin, ceftiofur, cefquinome, cefoperazone, cephapirine, cefalexin and cephalonium) in bovine milk. Sample preparation was performed by liquid-liquid extraction (LLE) followed by two clean-up steps, including low temperature purification (LTP) and a solid phase dispersion clean-up. Extracts were analysed using a liquid chromatography-electrospray-tandem mass spectrometry system (LC-ESI-MS/MS). Chromatographic separation was performed in a C18 column, using methanol and water (both with 0.1% of formic acid) as mobile phase. Method validation was performed according to the criteria of Commission Decision 2002/657/EC. Main validation parameters such as linearity, limit of detection, decision limit (CCα), detection capability (CCβ), accuracy, and repeatability were determined and were shown to be adequate. The method was applied to real samples (more than 250) and two milk samples had levels above maximum residues limits (MRLs) for cloxacillin - CLX and cefapirin - CFAP.

Surface modeling of soil antibiotics.

PubMed

Shi, Wen-jiao; Yue, Tian-xiang; Du, Zheng-ping; Wang, Zong; Li, Xue-wen

2016-02-01

Large numbers of livestock and poultry feces are continuously applied into soils in intensive vegetable cultivation areas, and then some veterinary antibiotics are persistent existed in soils and cause health risk. For the spatial heterogeneity of antibiotic residues, developing a suitable technique to interpolate soil antibiotic residues is still a challenge. In this study, we developed an effective interpolator, high accuracy surface modeling (HASM) combined vegetable types, to predict the spatial patterns of soil antibiotics, using 100 surface soil samples collected from an intensive vegetable cultivation area located in east of China, and the fluoroquinolones (FQs), including ciprofloxacin (CFX), enrofloxacin (EFX) and norfloxacin (NFX), were analyzed as the target antibiotics. The results show that vegetable type is an effective factor to be combined to improve the interpolator performance. HASM achieves less mean absolute errors (MAEs) and root mean square errors (RMSEs) for total FQs (NFX+CFX+EFX), NFX, CFX and EFX than kriging with external drift (KED), stratified kriging (StK), ordinary kriging (OK) and inverse distance weighting (IDW). The MAE of HASM for FQs is 55.1 μg/kg, and the MAEs of KED, StK, OK and IDW are 99.0 μg/kg, 102.8 μg/kg, 106.3 μg/kg and 108.7 μg/kg, respectively. Further, RMSE simulated by HASM for FQs (CFX, EFX and NFX) are 106.2 μg/kg (88.6 μg/kg, 20.4 μg/kg and 39.2 μg/kg), and less 30% (27%, 22% and 36%), 33% (27%, 27% and 43%), 38% (34%, 23% and 41%) and 42% (32%, 35% and 51%) than the ones by KED, StK, OK and IDW, respectively. HASM also provides better maps with more details and more consistent maximum and minimum values of soil antibiotics compared with the measured data. The better performance can be concluded that HASM takes the vegetable type information as global approximate information, and takes local sampling data as its optimum control constraints. Copyright © 2015 Elsevier B.V. All rights reserved.

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%.

Patterns of chemical residues detected in US beef carcasses between 1991 and 1993.

PubMed

Gibbons, S N; Kaneene, J B; Lloyd, J W

1996-08-01

A study of data from 12 states in the Food Safety Inspection Service's Residue Violation Information System was conducted to describe patterns of violative chemical residues in US beef during 1991, 1992, and 1993. In 1991, 3,249 violative residues were found in 2,734 carcasses in the 12 states included in the study. In 1992, 3,132 violative residues were found in 2,813 carcasses, and in 1993, 2,317 violative residues were found in 2,051 carcasses. During each of the 3 years, the Calf Antibiotic and Sulfonamide Test and Swab Test On Premises projects detected most of the violative residues, and producers/independent growers and dairy farms were recorded as the responsible sources for most of the violations. Also, most of the animals found to have violative residues were bob calves and culled cows. In bob calves, neomycin was the most frequently identified violative chemical, followed by tetracycline, gentamicin, oxytetracycline, and penicillin. In culled cows, penicillin was the most frequently identified violative chemical and was the chemical most frequently found in combination with other chemicals in cows with multiple violative residues. Distribution patterns of violative chemical residues by slaughter class and residue type varied among the 5 Food Safety Inspection Service regions. These specific regional characteristics support the need for customized intervention, education, assessment, and prevention programs.

DNA-aptamers binding aminoglycoside antibiotics.

PubMed

Nikolaus, Nadia; Strehlitz, Beate

2014-02-21

Aptamers are short, single stranded DNA or RNA oligonucleotides that are able to bind specifically and with high affinity to their non-nucleic acid target molecules. This binding reaction enables their application as biorecognition elements in biosensors and assays. As antibiotic residues pose a problem contributing to the emergence of antibiotic-resistant pathogens and thereby reducing the effectiveness of the drug to fight human infections, we selected aptamers targeted against the aminoglycoside antibiotic kanamycin A with the aim of constructing a robust and functional assay that can be used for water analysis. With this work we show that aptamers that were derived from a Capture-SELEX procedure targeting against kanamycin A also display binding to related aminoglycoside antibiotics. The binding patterns differ among all tested aptamers so that there are highly substance specific aptamers and more group specific aptamers binding to a different variety of aminoglycoside antibiotics. Also the region of the aminoglycoside antibiotics responsible for aptamer binding can be estimated. Affinities of the different aptamers for their target substance, kanamycin A, are measured with different approaches and are in the micromolar range. Finally, the proof of principle of an assay for detection of kanamycin A in a real water sample is given.

Determination of antibiotic residues in manure, soil, and surface waters

USGS Publications Warehouse

Christian, T.; Schneider, R.J.; Farber, H.A.; Skutlarek, D.; Meyer, M.T.; Goldbach, H.E.

2003-01-01

In the last years more and more often detections of antimicrobially active compounds ("antibiotics") in surface waters have been reported. As a possible input pathway in most cases municipal sewage has been discussed. But as an input from the realm of agriculture is conceivable as well, in this study it should be investigated if an input can occur via the pathway application of liquid manure on fields with the subsequent mechanisms surface run-off/interflow, leaching, and drift. For this purpose a series of surface waters, soils, and liquid manures from North Rhine-Westphalia (Northwestern Germany) were sampled and analyzed for up to 29 compounds by HPLC-MS/MS. In each of the surface waters antibiotics could be detected. The highest concentrations were found in samples from spring (300 ng/L of erythromycin). Some of the substances detected (e.g., tylosin), as well as characteristics in the landscape suggest an input from agriculture in some particular cases. In the investigation of different liquid manure samples by a fast immunoassay method sulfadimidine could be detected in the range of 1...2 mg/kg. Soil that had been fertilized with this liquid manure showed a content of sulfadimidine extractable by accelerated solvent extraction (ASE) of 15 ??g/kg dry weight even 7 months after the application. This indicates the high stability of some antibiotics in manure and soil.

Occurrence of Veterinary Antibiotics in Swine Manure from Large-scale Feedlots in Zhejiang Province, China.

PubMed

Wang, Hua; Chu, Yixuan; Fang, Chengran

2017-04-01

The occurrence and distribution of five sulfonamides and three tetracyclines in swine manure sampled from large-scale feedlots in different areas of Zhejiang Province, China were detected using solid-phase extraction and high-performance liquid chromatography. All eight test antibiotics were detected in most of the manure samples. The dominant antibiotics in swine manure were sulfadiazine, sulfamerazine, sulfadimidine, tetracycline, and chlortetracycline. The maximum concentration of residual antibiotic reached up to 57.95 mg/kg (chlortetracycline). The concentrations and distribution of both types of antibiotics in swine manure of different areas varied greatly. Relatively higher concentrations of sulfonamides were found in swine manure from the Zhejiang area in this experiment compared with previous studies. The results revealed that antibiotics were extensively used in feedlots in this district and that animal manure might act as a non-specific source of antibiotic residues in farmlands and aquatic environments.

Fighting antibiotic resistance in Portuguese hospitals: Understanding antibiotic prescription behaviours to better design antibiotic stewardship programmes.

PubMed

Simões, Alexandra S; Alves, Daniela A; Gregório, João; Couto, Isabel; Dias, Sónia; Póvoa, Pedro; Viveiros, Miguel; Gonçalves, Luzia; Lapão, Luís V

2018-06-01

Since physicians play an important role in antibiotic usage, it is vital to understand their antibiotic-prescribing behaviour and knowledge on antimicrobial resistance in order to develop and implement effective antibiotic stewardship interventions. The aim of this study was to evaluate Portuguese physicians' knowledge and to understand prescription behaviours, difficulties and barriers in their antibiotic prescription process in order to promote better and well-adapted antibiotic stewardship policies. This study was conducted in 2016 using a self-administered questionnaire to physicians in two tertiary public hospitals from two different regions in Portugal. Participating physicians [response rate 47.6% (30/63)] identified antibiotic resistance as a global problem; however, one-third did not recognise antibiotic resistance as a major problem on their own hospital. Factors that most influenced antibiotic prescription were 'microbiology laboratory results', 'patient clinical situation' and patient 'co-morbidities'. On the other hand, 'colleagues' opinion' and 'costs control' were considered as less determining factors. Regarding difficulties and bottlenecks in the antibiotic prescription process, participant physicians reported 'lack of (or delayed) microbiological results' and 'no access to antibiotic susceptibility patterns' as major barriers. 'Education and training' was considered the most effective intervention to improve antibiotic prescription. These results suggest that the design and implementation of antibiotic stewardship interventions should provide better data management and sharing tools between physicians and the microbiology laboratory, especially through the creation of antimicrobial prescribing guidelines according to hospital epidemiology, and easy access to hospital antibiotic susceptibility patterns and epidemiological data. Copyright © 2018 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights

Antibiotics involved in the occurrence of antibiotic-resistant bacteria: a nationwide multilevel study suggests differences within antibiotic classes.

PubMed

Gbaguidi-Haore, Houssein; Dumartin, Catherine; L'Hériteau, François; Péfau, Muriel; Hocquet, Didier; Rogues, Anne-Marie; Bertrand, Xavier

2013-02-01

To identify the antibiotics potentially the most involved in the occurrence of antibiotic-resistant bacteria from an ecological perspective in French healthcare facilities (HCFs). This study was based on data from the French antimicrobial surveillance network (ATB-RAISIN, 2007-09). Antibiotics were expressed in defined daily doses per 1000 patient-days. Antibiotic-resistant bacteria were considered as count data adjusted for patient-days. These were third-generation cephalosporin (3GC)- and ciprofloxacin-resistant Escherichia coli, cefotaxime-resistant Enterobacter cloacae, methicillin-resistant Staphylococcus aureus and ceftazidime-, imipenem- and ciprofloxacin-resistant Pseudomonas aeruginosa. Three-level negative binomial regression models were built to take into account the hierarchical structure of data: level 1, repeated measures each year (count outcome, time, antibiotics); level 2, HCFs (type and size); and level 3, regions (geographical area). A total of 701 HCFs from 20 French regions and up to 1339 HCF-years were analysed. The use of ceftriaxone, but not of cefotaxime, was positively correlated with incidence rates of 3GC- and ciprofloxacin-resistant E. coli. In contrast, both 3GCs were positively correlated with the incidence rate of cefotaxime-resistant E. cloacae. Higher levels of use of ciprofloxacin and/or ofloxacin, but not of levofloxacin, were associated with higher incidence rates of 3GC- and ciprofloxacin-resistant E. coli, cefotaxime-resistant E. cloacae, methicillin-resistant S. aureus and ceftazidime- and ciprofloxacin-resistant P. aeruginosa. Our study suggests differences within antibiotic classes in promoting antibiotic resistance. We identified ceftriaxone, ciprofloxacin and ofloxacin as priority targets in public health strategies designed to reduce antibiotic use and antibiotic-resistant bacteria in French HCFs.

[Release of antibiotics into urban wastewater: A secondary-data based analysis for the input assessment using the city of Dresden as an example].

PubMed

Timpel, Patrick; Gurke, Robert; Marx, Conrad; Knoth, Holger; Fauler, Joachim

2016-02-01

Antibiotics are essential for the successful treatment of bacterial infections. Recently, the increasing number of resistant bacteria and the occurrence of residues of antibiotics in the environment has become the focus of scientific interest. The aim of the cooperative project ANTI-Resist was to investigate the release of antibiotics and the occurrence and distribution of antibiotic resistance in the urban waste water system of the city of Dresden.This article presents the main results of the secondary data analysis for the determination of outpatient and inpatient antibiotic consumption and provides an insight into the complexity of the topic antibiotics in waste water.Based on the data of outpatient prescriptions provided by the AOK PLUS for the period 2005 to 2013, thirteen focus substances were identified to estimate antibiotic consumption. Furthermore, delivery data from the pharmacies of three hospitals in Dresden were available.Depending on the substances investigated, seasonality and age dependency were determined. The results at a regional level were mostly in good accordance with general trends throughout Germany. It should be noted that the total amount of antibiotics used remained nearly constant over the whole period investigated, but the prescription of fluoroquinolones increased. This must be questioned when taking into account the increasingly critical situation in the treatment of Gram-negative bacteria in particular. Examinations of waste water conducted indicated that sewage treatment plants are not able to remove antibiotics or their metabolites completely from waste water. The residues are released into surface waters via the treatment plants. The impact cannot be assessed at the moment and further investigations are necessary.

Routine administration of antibiotics to patients suffering accidental gallbladder perforation during laparoscopic cholecystectomy is not necessary.

PubMed

Guzmán-Valdivia, Gilberto

2008-12-01

Accidental rupture of the gallbladder is an event which occurs in up to 20% of laparoscopic cholecystectomies, mainly in those where dissection is difficult, or during extraction when the gallbladder is withdrawn directly through the laparoscope port. It has been commonly assumed that contamination by bile in the abdominal cavity could be a cause of infection and lead to the formation of a residual abscess or even to surgical wound infection. It is common practice, therefore, for the surgeon to prescribe the application of an antibiotic at the moment when gallbladder perforation occurs. To compare 2 groups of similar patients, to determine whether administration of antibiotics, started during surgery, is actually useful in reducing the risk of residual abscess or infection in the surgical wound. The study considered a total of 166 patients who had suffered accidental perforation of the gallbladder during elective laparoscopic cholecystectomy. This total was divided at random into 2 groups: group A (80 patients) who received a dose of 1 g of Cefotaxime at the moment of gallbladder rupture, followed by 2 more doses at intervals of 8 hours in the immediate postoperative period; and group B (86 patients) who did not receive any antibiotic treatment at all. The dependent variables observed were surgical wound infection and residual abscess: and the control variables were age, sex, length of operation time, intercurrent illnesses, and American Society of Anesthesiologists (ASA) classification. Two patients (2.5%) in group A developed a surgical wound infection, against 3 cases (3.4%) in group B, the result having no statistical significance. No patients developed residual abscess. In a multivariant analysis, the following were identified as independent factors significantly associated with the onset of surgical wound infection (P<0.001): diabetes mellitus, being over 60 years of age, operation time lasting longer than 70 minutes, and ASA 3. Routine application of an

Occurrence and diversity of antibiotic resistance in untreated hospital wastewater.

PubMed

Wang, Qiang; Wang, Panliang; Yang, Qingxiang

2018-04-15

Antibiotics, antibiotic-resistant bacteria (ARB), antibiotic-resistance genes (ARGs), and mobile genetic elements (MGEs) have been reported in many environments. However, the investigation of their occurrence and diversity in untreated hospital wastewater is still insufficient. High concentrations of antibiotic residues were found in hospital wastewater using solid-phase extraction and UPLC-MS/MS analysis. The concentrations of six of 14 antibiotics reached μg/L levels in the hospital wastewater, which is higher than reported in other aquatic environments. Results of high-throughput sequencing analysis indicated that sequences affiliated to genera Escherichia and Acinetobacter were the predominant in the cultivable multiple-antibiotic-resistant bacteria (CMARB) recovered from the wastewater of three hospitals in China, with compositions of 34%-74%. Notably, several genera containing clinically pathogenic or opportunistic CMARB (e.g., Escherichia, Acinetobacter, Aeromonas, Myroides, Enterococcus, Proteus, Pseudomonas, and Streptococcus) were detected at high relative abundances in the wastewaters of the three hospitals. High-capacity quantitative PCR showed that 131-139 unique ARGs of the 178 targeted genes were detected in the hospital wastewaters. The high prevalence of five MGEs and 12 ARGs was confirmed with qPCR, and some positive correlations between ARGs and MGEs were identified, such as between intI1 and qnrD, intI2 and sul3, intI3 and tetX, Tn916/Tn1545 and sul2, and ISCR1 and sul3. These results suggest that highly abundant antibiotic-resistant pathogens and highly mobile ARGs already exist in the human body, and that their release from hospitals without effective treatment poses high risks to environments and human health. Copyright © 2017 Elsevier B.V. All rights reserved.

Occurrence of antibiotics and antibiotic resistance genes in soils from wastewater irrigation areas in the Pearl River Delta region, southern China.

PubMed

Pan, Min; Chu, L M

2018-05-15

The occurrence and distribution of tetracycline (TC) and sulfamethazine (SMZ), and the corresponding antibiotic resistance genes (ARGs) were investigated in six agricultural sites in the Pearl River Delta (PRD) region in southern China. Irrigation water and irrigated soils at two different depths (0-10 and 10-20cm) were analyzed. The total concentrations of TC and SMZ in irrigation water ranged from 69.3 to 234ng/L and from 4.00 to 58.2ng/L, respectively, while the total concentrations of TC and SMZ in irrigated soils ranged from 5.00 to 21.9μg/kg and from 1.30 to 4.20μg/kg, respectively. After long-term irrigation with domestic and fishpond wastewater in the field, the residual TC and SMZ and their corresponding ARGs in soils were significantly higher in fishpond-irrigated soils (Dongguan and Shenzhen) than in domestic wastewater-irrigated soils (Foshan, Guangzhou, Huizhou and Zhongshan). The concentrations of antibiotics and their ARGs were significantly higher in irrigation water than in irrigated soils, which indicated that wastewater was the primary source of antibiotics in the soil environments. The domestic and fishpond wastewater were important repositories of antibiotics and their ARGs, which require effective treatment before their discharge into the environment. Other factors such as soil physicochemical properties, manure application, irrigation water sources and cropping patterns also affect the antibiotic concentrations and ARG abundances. The residual antibiotic concentrations statistically correlated with the corresponding ARGs in irrigation water and irrigated soils, both of which decreased with increasing soil depth, indicating that the concentration of antibiotics in the environment exerted a selection pressure on the microorganisms in the environment. Copyright © 2017 Elsevier B.V. All rights reserved.

Bacterial Community Shift Drives Antibiotic Resistance Promotion during Drinking Water Chlorination.

PubMed

Jia, Shuyu; Shi, Peng; Hu, Qing; Li, Bing; Zhang, Tong; Zhang, Xu-Xiang

2015-10-20

For comprehensive insights into the effects of chlorination, a widely used disinfection technology, on bacterial community and antibiotic resistome in drinking water, this study applied high-throughput sequencing and metagenomic approaches to investigate the changing patterns of antibiotic resistance genes (ARGs) and bacterial community in a drinking water treatment and distribution system. At genus level, chlorination could effectively remove Methylophilus, Methylotenera, Limnobacter, and Polynucleobacter, while increase the relative abundance of Pseudomonas, Acidovorax, Sphingomonas, Pleomonas, and Undibacterium in the drinking water. A total of 151 ARGs within 15 types were detectable in the drinking water, and chlorination evidently increased their total relative abundance while reduced their diversity in the opportunistic bacteria (p < 0.05). Residual chlorine was identified as the key contributing factor driving the bacterial community shift and resistome alteration. As the dominant persistent ARGs in the treatment and distribution system, multidrug resistance genes (mainly encoding resistance-nodulation-cell division transportation system) and bacitracin resistance gene bacA were mainly carried by chlorine-resistant bacteria Pseudomonas and Acidovorax, which mainly contributed to the ARGs abundance increase. The strong correlation between bacterial community shift and antibiotic resistome alteration observed in this study may shed new light on the mechanism behind the chlorination effects on antibiotic resistance.

Management Options For Reducing The Release Of Antibiotics And Antibiotic Resistance Genes To The Environment

EPA Science Inventory

Background: There is growing concern worldwide about the role of polluted soil and water - 77 environments in the development and dissemination of antibiotic resistance. 78 Objective: To identify management options for reducing the spread of antibiotics and 79 antibiotic resist...

Investigating antibiotics, antibiotic resistance genes, and microbial contaminants in groundwater in relation to the proximity of urban areas.

PubMed

Szekeres, Edina; Chiriac, Cecilia Maria; Baricz, Andreea; Szőke-Nagy, Tiberiu; Lung, Ildiko; Soran, Maria-Loredana; Rudi, Knut; Dragos, Nicolae; Coman, Cristian

2018-05-01

Groundwater is an essential public and drinking water supply and its protection is a goal for global policies. Here, we investigated the presence and prevalence of antibiotic residues, antibiotic resistance genes (ARGs), mobile genetic elements (MGEs), and microbial contamination in groundwater environments at various distances from urban areas. Antibiotic concentrations ranged from below detection limit to 917 ng/L, being trimethoprim, macrolide, and sulfonamide the most abundant antibiotic classes. A total of eleven ARGs (aminoglycoside, β-lactam, chloramphenicol, Macrolide-Lincosamide-Streptogramin B - MLSB, sulfonamide, and tetracycline), one antiseptic resistance gene, and two MGEs were detected by qPCR with relative abundances ranging from 6.61 × 10 -7 to 2.30 × 10 -1 copies/16S rRNA gene copies. ARGs and MGEs were widespread in the investigated groundwater environments, with increased abundances not only in urban, but also in remote areas. Distinct bacterial community profiles were observed, with a higher prevalence of Betaproteobacteria and Bacteroidetes in the less-impacted areas, and that of Firmicutes in the contaminated groundwater. The combined characteristics of increased species diversity, distinct phylogenetic composition, and the possible presence of fecal and/or pathogenic bacteria could indicate different types of contamination. Significant correlations between ARGs, MGEs and specific taxa within the groundwater bacterial community were identified, revealing the potential hosts of resistance types. Although no universal marker gene could be determined, a co-selection of int1, qacEΔ1 and sulI genes, a proxy group for anthropogenic pollution, with the tetC, tetO, tetW resistance genes was identified. As the tet group was observed to follow the pattern of environmental contamination for the groundwater samples investigated in this study, our results strongly support the proposal of this group of genes as an environmental tracer of

Different removal behaviours of multiple trace antibiotics in municipal wastewater chlorination.

PubMed

Li, Bing; Zhang, Tong

2013-06-01

The chlorination behaviours of 12 antibiotics belonging to six classes at environmentally relevant concentrations were systematically examined under typical conditions relevant to municipal wastewater chlorination. Cefotaxime, cefalexin, ampicillin and tetracycline were completely removed under all three initial free chlorine dosages (5 mg/L, 10 mg/L, and 15 mg/L). The removal efficiencies of sulphamethoxazole, sulphadiazine, roxithromycin, anhydro-erythromycin, ofloxacin, and trimethoprim were closely correlated to the residual free chlorine concentration, and no further significant mass removal was observed after the residual free chlorine concentration decreased to less than ≈ 0.75 mg/L. Ammonia plays a critical role during chlorination because of its competition with antibiotics for free chlorine to form combined chlorine, which reacts slowly with these antibiotics. Except for norfloxacin and ciprofloxacin, the removal behaviours of the 10 other target antibiotics under ammonia nitrogen concentrations ranging from 2 to 15 mg/L were characterised by a rapid initial removal rate upon contact with free chlorine during the first 5 s-1 min (depending on the specific antibiotic and ammonia nitrogen concentration) and then a much slower removal rate. Free chlorine was responsible for the reaction with antibiotics during the rapid stage (first 5 s-1 min), whereas combined chlorine reacted with antibiotics in the subsequent slow stage. Combined chlorine can remove norfloxacin and ciprofloxacin at a relatively faster rate. The presence of suspended solids at 30 mg/L slightly decreased the antibiotic removal rate. The kinetic rate constants decreased by 2.1-13.9%, while the half-lives increased by 2.0-15.0% compared to those of a 0 mg/L suspended solid for the target antibiotics. Copyright © 2013 Elsevier Ltd. All rights reserved.

Amino Acid Residues That Contribute to Substrate Specificity of Class A β-Lactamase SME-1

PubMed Central

Majiduddin, Fahd K.; Palzkill, Timothy

2005-01-01

Carbapenem antibiotics are used as antibiotics of last resort because they possess a broad spectrum of antimicrobial activity and are not easily hydrolyzed by β-lactamases. Recently, class A enzymes, such as the SME-1, NMC-A, and IMI-1 β-lactamases, have been identified with the capacity to hydrolyze carbapenem antibiotics. Traditional class A β-lactamases, such as TEM-1 and SHV-1, are unable to hydrolyze carbapenem antibiotics and exhibit some differences in sequence from those that are able to hydrolyze carbapenem antibiotics. The positions that differ may contribute to the unique substrate specificity of the class A carbapenemase SME-1. Codons in the SME-1 gene representing residues 104, 105, 132, 167, 237, and 241 were randomized by site-directed mutagenesis, and functional mutants were selected for the ability to hydrolyze imipenem, ampicillin, or cefotaxime. Although several positions are important for hydrolysis of β-lactam antibiotics, no single position was found to uniquely contribute to carbapenem hydrolysis. The results of this study support a model whereby the carbapenemase activity of SME-1 is due to a highly distributed set of interactions that subtly alter the structure of the active-site pocket. PMID:16048956

Amino acid residues that contribute to substrate specificity of class A beta-lactamase SME-1.

PubMed

Majiduddin, Fahd K; Palzkill, Timothy

2005-08-01

Carbapenem antibiotics are used as antibiotics of last resort because they possess a broad spectrum of antimicrobial activity and are not easily hydrolyzed by beta-lactamases. Recently, class A enzymes, such as the SME-1, NMC-A, and IMI-1 beta-lactamases, have been identified with the capacity to hydrolyze carbapenem antibiotics. Traditional class A beta-lactamases, such as TEM-1 and SHV-1, are unable to hydrolyze carbapenem antibiotics and exhibit some differences in sequence from those that are able to hydrolyze carbapenem antibiotics. The positions that differ may contribute to the unique substrate specificity of the class A carbapenemase SME-1. Codons in the SME-1 gene representing residues 104, 105, 132, 167, 237, and 241 were randomized by site-directed mutagenesis, and functional mutants were selected for the ability to hydrolyze imipenem, ampicillin, or cefotaxime. Although several positions are important for hydrolysis of beta-lactam antibiotics, no single position was found to uniquely contribute to carbapenem hydrolysis. The results of this study support a model whereby the carbapenemase activity of SME-1 is due to a highly distributed set of interactions that subtly alter the structure of the active-site pocket.

RecA Inhibitors Potentiate Antibiotic Activity and Block Evolution of Antibiotic Resistance.

PubMed

Alam, Md Kausar; Alhhazmi, Areej; DeCoteau, John F; Luo, Yu; Geyer, C Ronald

2016-03-17

Antibiotic resistance arises from the maintenance of resistance mutations or genes acquired from the acquisition of adaptive de novo mutations or the transfer of resistance genes. Antibiotic resistance is acquired in response to antibiotic therapy by activating SOS-mediated DNA repair and mutagenesis and horizontal gene transfer pathways. Initiation of the SOS pathway promotes activation of RecA, inactivation of LexA repressor, and induction of SOS genes. Here, we have identified and characterized phthalocyanine tetrasulfonic acid RecA inhibitors that block antibiotic-induced activation of the SOS response. These inhibitors potentiate the activity of bactericidal antibiotics, including members of the quinolone, β-lactam, and aminoglycoside families in both Gram-negative and Gram-positive bacteria. They reduce the ability of bacteria to acquire antibiotic resistance mutations and to transfer mobile genetic elements conferring resistance. This study highlights the advantage of including RecA inhibitors in bactericidal antibiotic therapies and provides a new strategy for prolonging antibiotic shelf life. Copyright © 2016 Elsevier Ltd. All rights reserved.

Current perspectives on the dynamics of antibiotic resistance in different reservoirs.

PubMed

Caniça, Manuela; Manageiro, Vera; Jones-Dias, Daniela; Clemente, Lurdes; Gomes-Neves, Eduarda; Poeta, Patrícia; Dias, Elsa; Ferreira, Eugénia

2015-09-01

Antibiotic resistance consists of a dynamic web. In this review, we describe the path by which different antibiotic residues and antibiotic resistance genes disseminate among relevant reservoirs (human, animal, and environmental settings), evaluating how these events contribute to the current scenario of antibiotic resistance. The relationship between the spread of resistance and the contribution of different genetic elements and events is revisited, exploring examples of the processes by which successful mobile resistance genes spread across different niches. The importance of classic and next generation molecular approaches, as well as action plans and policies which might aid in the fight against antibiotic resistance, are also reviewed. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

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.

Isolation and Purification of Antibiotic Material from Physarum gyrosum

PubMed Central

Schroeder, H. R.; Mallette, M. F.

1973-01-01

The myxomycete Physarum gyrosum was cultured in its plasmodial stage on agar plates containing 0.025 M phosphate buffer at pH 6.5, 2% bakers' yeast, and 0.2% glucose and was supplemented with live Escherichia coli. Extracts of these plasmodia contained several antibiotic substances. Antibiotic materials were partially purified by dialysis of the agar medium-mold mixture, evaporation of the dialyzate, and butanol extraction of the residue. Further purification in two paper and two thin-layer chromatographic systems gave one product which was pure in six thin-layer chromatographic systems. Antibiotic activity against some gram-positive and gram-negative bacteria and yeasts was demonstrated with partially purified extracts and a paper-chromatographically separated fraction. One pure antibiotic was effective against Bacillus cereus. PMID:4799591

Aerobic digestion reduces the quantity of antibiotic resistance genes in residual municipal wastewater solids

PubMed Central

Burch, Tucker R.; Sadowsky, Michael J.; LaPara, Timothy M.

2012-01-01

Numerous initiatives have been undertaken to circumvent the problem of antibiotic resistance, including the development of new antibiotics, the use of narrow spectrum antibiotics, and the reduction of inappropriate antibiotic use. We propose an alternative but complimentary approach to reduce antibiotic resistant bacteria (ARB) by implementing more stringent technologies for treating municipal wastewater, which is known to contain large quantities of ARB and antibiotic resistance genes (ARGs). In this study, we investigated the ability of conventional aerobic digestion to reduce the quantity of ARGs in untreated wastewater solids. A bench-scale aerobic digester was fed untreated wastewater solids collected from a full-scale municipal wastewater treatment facility. The reactor was operated under semi-continuous flow conditions for more than 200 days at a residence time of approximately 40 days. During this time, the quantities of tet(A), tet(W), and erm(B) decreased by more than 90%. In contrast, intI1 did not decrease, and tet(X) increased in quantity by 5-fold. Following operation in semi-continuous flow mode, the aerobic digester was converted to batch mode to determine the first-order decay coefficients, with half-lives ranging from as short as 2.8 days for tet(W) to as long as 6.3 days for intI1. These results demonstrated that aerobic digestion can be used to reduce the quantity of ARGs in untreated wastewater solids, but that rates can vary substantially depending on the reactor design (i.e., batch vs. continuous-flow) and the specific ARG. PMID:23407455

Aerobic digestion reduces the quantity of antibiotic resistance genes in residual municipal wastewater solids.

PubMed

Burch, Tucker R; Sadowsky, Michael J; Lapara, Timothy M

2013-01-01

Numerous initiatives have been undertaken to circumvent the problem of antibiotic resistance, including the development of new antibiotics, the use of narrow spectrum antibiotics, and the reduction of inappropriate antibiotic use. We propose an alternative but complimentary approach to reduce antibiotic resistant bacteria (ARB) by implementing more stringent technologies for treating municipal wastewater, which is known to contain large quantities of ARB and antibiotic resistance genes (ARGs). In this study, we investigated the ability of conventional aerobic digestion to reduce the quantity of ARGs in untreated wastewater solids. A bench-scale aerobic digester was fed untreated wastewater solids collected from a full-scale municipal wastewater treatment facility. The reactor was operated under semi-continuous flow conditions for more than 200 days at a residence time of approximately 40 days. During this time, the quantities of tet(A), tet(W), and erm(B) decreased by more than 90%. In contrast, intI1 did not decrease, and tet(X) increased in quantity by 5-fold. Following operation in semi-continuous flow mode, the aerobic digester was converted to batch mode to determine the first-order decay coefficients, with half-lives ranging from as short as 2.8 days for tet(W) to as long as 6.3 days for intI1. These results demonstrated that aerobic digestion can be used to reduce the quantity of ARGs in untreated wastewater solids, but that rates can vary substantially depending on the reactor design (i.e., batch vs. continuous-flow) and the specific ARG.

Antibiotics and Antibiotic Resistance

MedlinePlus

... Medicine Safely Antibiotics and Antibiotic Resistance Antibiotics and Antibiotic Resistance Share Tweet Linkedin Pin it More sharing options ... throughout the world are becoming resistant to antibiotics. Antibiotic resistance has been called one of the world's most ...

Reconnaissance of 47 antibiotics and associated microbial risks in seafood sold in the United States.

PubMed

Done, Hansa Y; Halden, Rolf U

2015-01-23

Aquaculture production has nearly tripled in the last two decades, bringing with it a significant increase in the use of antibiotics. Using liquid chromatography/tandem mass spectrometry (LC-MS/MS), the presence of 47 antibiotics was investigated in U.S. purchased shrimp, salmon, catfish, trout, tilapia, and swai originating from 11 different countries. All samples (n=27) complied with U.S. FDA regulations and five antibiotics were detected above the limits of detection: oxytetracycline (in wild shrimp, 7.7ng/g of fresh weight; farmed tilapia, 2.7; farmed salmon, 8.6; farmed trout with spinal deformities, 3.9), 4-epioxytetracycline (farmed salmon, 4.1), sulfadimethoxine (farmed shrimp, 0.3), ormetoprim (farmed salmon, 0.5), and virginiamycin (farmed salmon marketed as antibiotic-free, 5.2). A literature review showed that sub-regulatory levels of antibiotics, as found here, can promote resistance development; publications linking aquaculture to this have increased more than 8-fold from 1991 to 2013. Although this study was limited in size and employed sample pooling, it represents the largest reconnaissance of antibiotics in U.S. seafood to date, providing data on previously unmonitored antibiotics and on farmed trout with spinal deformities. Results indicate low levels of antibiotic residues and general compliance with U.S. regulations. The potential for development of microbial drug resistance was identified as a key concern and research priority. Copyright © 2014 Elsevier B.V. All rights reserved.

Botanical alternatives to antibiotics for use in organic poultry production.

PubMed

Diaz-Sanchez, Sandra; D'Souza, Doris; Biswas, Debrabrata; Hanning, Irene

2015-06-01

The development of antibiotic resistant pathogens has resulted from the use of sub-therapeutic concentrations of antibiotics delivered in poultry feed. Furthermore, there are a number of consumer concerns regarding the use of antibiotics in food animals including residue contamination of poultry products and antibiotic resistant bacterial pathogens. These issues have resulted in recommendations to reduce the use of antibiotics as growth promoters in livestock in the United States. Unlike conventional production, organic systems are not permitted to use antibiotics. Thus, both conventional and organic poultry production need alternative methods to improve growth and performance of poultry. Herbs, spices, and various other plant extracts are being evaluated as alternatives to antibiotics and some do have growth promoting effects, antimicrobial properties, and other health-related benefits. This review aims to provide an overview of herbs, spices, and plant extracts, currently defined as phytobiotics as potential feed additives. © 2015 Poultry Science Association Inc.

21 CFR 510.110 - Antibiotics used in food-producing animals.

Code of Federal Regulations, 2011 CFR

2011-04-01

... residues of antibiotics in milk from intramammary infusion preparations were requested within 60 days and... remain in edible products from treated animals, all injectable, intramammary infusion, intrauterine, and...

21 CFR 510.110 - Antibiotics used in food-producing animals.

Code of Federal Regulations, 2010 CFR

2010-04-01

... residues of antibiotics in milk from intramammary infusion preparations were requested within 60 days and... remain in edible products from treated animals, all injectable, intramammary infusion, intrauterine, and...

Factors influencing variation of bulk milk antibiotic residue occurrence, somatic cell count, and total bacterial count in dairy sheep flocks.

PubMed

Gonzalo, C; Carriedo, J A; García-Jimeno, M C; Pérez-Bilbao, M; de la Fuente, L F

2010-04-01

To study the variations of bulk tank milk variables in dairy ewe flocks and to identify the main target practices and flock groups to improve milk quality and safety, a total of 71,228 records of antibiotic residue (AR) and milk yield and 68,781 records of somatic cell count (SCC) and total bacterial count (TBC) were obtained over 5 yr from the same 209 dairy ewe flocks of the Assaf breed belonging to the Consortium for Ovine Promotion of Castilla-León (Spain). Based on a logistic regression model, year, month, semester, SCC, TBC, dry therapy, and milk yield significantly contributed to AR variation. High SCC was associated with increased AR violations. When antibiotic dry therapy was implemented, AR occurrence was higher than when this practice was not used. A polynomial monthly distribution throughout the year was observed for AR occurrence; the highest values were in autumn, coinciding with low milk yields per flock. Yearly occurrences drastically diminished from 2004 (1.36%) to 2008 (0.30%), probably as a result of effective educational programs. The mixed-model ANOVA of factors influencing variation in SCC and TBC indicated that year, month, AR, dry therapy group, milking type, and year interactions were significant variation factors for SCC and TBC; mathematical model accounted for 74.1 and 35.4% of total variance for each variable, respectively. Differences in management and hygiene practice caused significant SCC and TBC variations among flocks and within flocks throughout the 5-yr study. Over time, continuously dry treated flocks showed lower logSCC (5.80) and logTBC (4.92) than untreated (6.10 and 5.18, respectively) or discontinuously dry treated (6.01 and 5.05, respectively) flocks. Continuously dry treated flocks had lower AR occurrences than did discontinuously dry treated flocks. As a whole, AR occurrence and SCC and TBC bulk tank milk variables can be used for monitoring mammary health and milk hygiene and safety in dairy sheep throughout time

Antibiotic-resistant bacteria in the guts of insects feeding on plants: prospects for discovering plant-derived antibiotics.

PubMed

Ignasiak, Katarzyna; Maxwell, Anthony

2017-12-01

Although plants produce many secondary metabolites, currently none of these are commercial antibiotics. Insects feeding on specific plants can harbour bacterial strains resistant to known antibiotics suggesting that compounds in the plant have stimulated resistance development. We sought to determine whether the occurrence of antibiotic-resistant bacteria in insect guts was a widespread phenomenon, and whether this could be used as a part of a strategy to identify antibacterial compounds from plants. Six insect/plant pairs were selected and the insect gut bacteria were identified and assessed for antibiotic susceptibilities compared with type strains from culture collections. We found that the gut strains could be more or less susceptible to antibiotics than the type strains, or show no differences. Evidence of antibacterial activity was found in the plant extracts from five of the six plants, and, in one case Catharanthus roseus (Madagascar Periwinkle), compounds with antibacterial activity were identified. Bacterial strains isolated from insect guts show a range of susceptibilities to antibiotics suggesting a complex interplay between species in the insect gut microbiome. Extracts from selected plants can show antibacterial activity but it is not easy to isolate and identify the active components. We found that vindoline, present in Madagascar Periwinkle extracts, possessed moderate antibacterial activity. We suggest that plant-derived antibiotics are a realistic possibility given the advances in genomic and metabolomic methodologies.

Prevalence and correlates of antibiotic sharing in the Philippines: antibiotic misconceptions and community-level access to non-medical sources of antibiotics.

PubMed

Barber, Daniel A; Casquejo, Efren; Ybañez, Purita L; Pinote, Magdaleno T; Casquejo, Luz; Pinote, Lucia S; Estorgio, Magdalena; Young, April M

2017-05-01

To identify sociodemographic, knowledge and attitudinal correlates to antibiotic sharing among a community-based sample of adults (age 18 and older) in a low-income setting of the Philippines and to explore community-level data on informal antibiotic distribution in roadside stands (i.e., sari-sari stands). Participants (n = 307) completed self-administered surveys. Correlates to antibiotic sharing were assessed using logistic regression with Firth's bias-adjusted estimates. Study staff also visited 106 roadside stands and collected data on availability and characteristics of antibiotics in the stands. 78% had shared antibiotics in their lifetime, most often with family members. In multivariable analysis, agreement with the belief that it is safe to prematurely stop an antibiotic course (OR: 2.8, CI: 1.3-5.8) and concerns about antibiotic side effects (OR: 2.1, CI: 1.1-4.4) were significantly associated with increased odds of reported antibiotic sharing. Antibiotic sharing was not associated with sociodemographic characteristics or antibiotic knowledge. Antibiotics were widely available in 60% of sampled sari-sari stands, in which 59% of antibiotics were missing expiration dates. Amoxicillin and cephalexin were the most commonly available antibiotics for sale at the stands (60% and 21%, respectively). Antibiotic sharing was common and was associated with misconceptions about proper antibiotic use. Antibiotics were widely available in sari-sari stands, and usually without expiration information. This study suggests that multipronged and locally tailored approaches to curbing informal antibiotic access are needed in the Philippines and similar Southeast-Asian countries. © 2017 John Wiley & Sons Ltd.

Accelerated Biodegradation of Veterinary Antibiotics in Agricultural Soil following Long-Term Exposure, and Isolation of a Sulfamethazine-degrading sp.

PubMed

Topp, Edward; Chapman, Ralph; Devers-Lamrani, Marion; Hartmann, Alain; Marti, Romain; Martin-Laurent, Fabrice; Sabourin, Lyne; Scott, Andrew; Sumarah, Mark

2013-01-01

The World Health Organization has identified antibiotic resistance as one of the top three threats to global health. There is concern that the use of antibiotics as growth promoting agents in livestock production contributes to the increasingly problematic development of antibiotic resistance. Many antibiotics are excreted at high rates, and the land application of animal manures represents a significant source of environmental exposure to these agents. To evaluate the long-term effects of antibiotic exposure on soil microbial populations, a series of field plots were established in 1999 that have since received annual applications of a mixture of sulfamethazine (SMZ), tylosin (TYL), and chlortetracycline (CTC). During the first 6 yr (1999-2004) soils were treated at concentrations of 0, 0.01 0.1, and 1.0 mg kg soil, in subsequent years at concentrations of 0, 0.1, 1.0, and 10 mg kg soil. The lower end of this concentration range is within that which would result from an annual application of manure from medicated swine. Following ten annual applications, the fate of the drugs in the soil was evaluated. Residues of SMZ and TYL, but not CTC were removed much more rapidly in soil with a history of exposure to 10 mg/kg drugs than in untreated control soil. Residues of C-SMZ were rapidly and thoroughly mineralized to CO in the historically treated soils, but not in the untreated soil. A SMZ-degrading sp. was isolated from the treated soil. Overall, these results indicate that soil bacteria adapt to long-term exposure to some veterinary antibiotics resulting in sharply reduced persistence. Accelerated biodegradation of antibiotics in matrices exposed to agricultural, wastewater, or pharmaceutical manufacturing effluents would attenuate environmental exposure to antibiotics, and merits investigation in the context of assessing potential risks of antibiotic resistance development in environmental matrices. Copyright © by the American Society of Agronomy, Crop Science

The determinants of the antibiotic resistance process.

PubMed

Franco, Beatriz Espinosa; Altagracia Martínez, Marina; Sánchez Rodríguez, Martha A; Wertheimer, Albert I

2009-01-01

The use of antibiotic drugs triggers a complex interaction involving many biological, sociological, and psychological determinants. Resistance to antibiotics is a serious worldwide problem which is increasing and has implications for morbidity, mortality, and health care both in hospitals and in the community. To analyze current research on the determinants of antibiotic resistance and comprehensively review the main factors in the process of resistance in order to aid our understanding and assessment of this problem. We conducted a MedLine search using the key words "determinants", "antibiotic", and "antibiotic resistance" to identify publications between 1995 and 2007 on the determinants of antibiotic resistance. Publications that did not address the determinants of antibiotic resistance were excluded. The process and determinants of antibiotic resistance are described, beginning with the development of antibiotics, resistance and the mechanisms of resistance, sociocultural determinants of resistance, the consequences of antibiotic resistance, and alternative measures proposed to combat antibiotic resistance. Analysis of the published literature identified the main determinants of antibiotic resistance as irrational use of antibiotics in humans and animal species, insufficient patient education when antibiotics are prescribed, lack of guidelines for treatment and control of infections, lack of scientific information for physicians on the rational use of antibiotics, and lack of official government policy on the rational use of antibiotics in public and private hospitals.

Emergence of antibiotic-resistant extremophiles (AREs).

PubMed

Gabani, Prashant; Prakash, Dhan; Singh, Om V

2012-09-01

Excessive use of antibiotics in recent years has produced bacteria that are resistant to a wide array of antibiotics. Several genetic and non-genetic elements allow microorganisms to adapt and thrive under harsh environmental conditions such as lethal doses of antibiotics. We attempt to classify these microorganisms as antibiotic-resistant extremophiles (AREs). AREs develop strategies to gain greater resistance to antibiotics via accumulation of multiple genes or plasmids that harbor genes for multiple drug resistance (MDR). In addition to their altered expression of multiple genes, AREs also survive by producing enzymes such as penicillinase that inactivate antibiotics. It is of interest to identify the underlying molecular mechanisms by which the AREs are able to survive in the presence of wide arrays of high-dosage antibiotics. Technologically, "omics"-based approaches such as genomics have revealed a wide array of genes differentially expressed in AREs. Proteomics studies with 2DE, MALDI-TOF, and MS/MS have identified specific proteins, enzymes, and pumps that function in the adaptation mechanisms of AREs. This article discusses the molecular mechanisms by which microorganisms develop into AREs and how "omics" approaches can identify the genetic elements of these adaptation mechanisms. These objectives will assist the development of strategies and potential therapeutics to treat outbreaks of pathogenic microorganisms in the future.

Development of a field testing protocol for identifying Deepwater Horizon oil spill residues trapped near Gulf of Mexico beaches.

PubMed

Han, Yuling; Clement, T Prabhakar

2018-01-01

The Deepwater Horizon (DWH) accident, one of the largest oil spills in U.S. history, contaminated several beaches located along the Gulf of Mexico (GOM) shoreline. The residues from the spill still continue to be deposited on some of these beaches. Methods to track and monitor the fate of these residues require approaches that can differentiate the DWH residues from other types of petroleum residues. This is because, historically, the crude oil released from sources such as natural seeps and anthropogenic discharges have also deposited other types of petroleum residues on GOM beaches. Therefore, identifying the origin of these residues is critical for developing effective management strategies for monitoring the long-term environmental impacts of the DWH oil spill. Advanced fingerprinting methods that are currently used for identifying the source of oil spill residues require detailed laboratory studies, which can be cost-prohibitive. Also, most agencies typically use untrained workers or volunteers to conduct shoreline monitoring surveys and these worker will not have access to advanced laboratory facilities. Furthermore, it is impractical to routinely fingerprint large volumes of samples that are collected after a major oil spill event, such as the DWH spill. In this study, we propose a simple field testing protocol that can identify DWH oil spill residues based on their unique physical characteristics. The robustness of the method is demonstrated by testing a variety of oil spill samples, and the results are verified by characterizing the samples using advanced chemical fingerprinting methods. The verification data show that the method yields results that are consistent with the results derived from advanced fingerprinting methods. The proposed protocol is a reliable, cost-effective, practical field approach for differentiating DWH residues from other types of petroleum residues.

Development of a field testing protocol for identifying Deepwater Horizon oil spill residues trapped near Gulf of Mexico beaches

PubMed Central

Han, Yuling

2018-01-01

The Deepwater Horizon (DWH) accident, one of the largest oil spills in U.S. history, contaminated several beaches located along the Gulf of Mexico (GOM) shoreline. The residues from the spill still continue to be deposited on some of these beaches. Methods to track and monitor the fate of these residues require approaches that can differentiate the DWH residues from other types of petroleum residues. This is because, historically, the crude oil released from sources such as natural seeps and anthropogenic discharges have also deposited other types of petroleum residues on GOM beaches. Therefore, identifying the origin of these residues is critical for developing effective management strategies for monitoring the long-term environmental impacts of the DWH oil spill. Advanced fingerprinting methods that are currently used for identifying the source of oil spill residues require detailed laboratory studies, which can be cost-prohibitive. Also, most agencies typically use untrained workers or volunteers to conduct shoreline monitoring surveys and these worker will not have access to advanced laboratory facilities. Furthermore, it is impractical to routinely fingerprint large volumes of samples that are collected after a major oil spill event, such as the DWH spill. In this study, we propose a simple field testing protocol that can identify DWH oil spill residues based on their unique physical characteristics. The robustness of the method is demonstrated by testing a variety of oil spill samples, and the results are verified by characterizing the samples using advanced chemical fingerprinting methods. The verification data show that the method yields results that are consistent with the results derived from advanced fingerprinting methods. The proposed protocol is a reliable, cost-effective, practical field approach for differentiating DWH residues from other types of petroleum residues. PMID:29329313

Genomic Analysis Reveals Distinct Concentration-Dependent Evolutionary Trajectories for Antibiotic Resistance in Escherichia coli

PubMed Central

Mogre, Aalap; Sengupta, Titas; Veetil, Reshma T.; Ravi, Preethi; Seshasayee, Aswin Sai Narain

2014-01-01

Evolution of bacteria under sublethal concentrations of antibiotics represents a trade-off between growth and resistance to the antibiotic. To understand this trade-off, we performed in vitro evolution of laboratory Escherichia coli under sublethal concentrations of the aminoglycoside kanamycin over short time durations. We report that fixation of less costly kanamycin-resistant mutants occurred earlier in populations growing at lower sublethal concentration of the antibiotic, compared with those growing at higher sublethal concentrations; in the latter, resistant mutants with a significant growth defect persisted longer. Using deep sequencing, we identified kanamycin resistance-conferring mutations, which were costly or not in terms of growth in the absence of the antibiotic. Multiple mutations in the C-terminal end of domain IV of the translation elongation factor EF-G provided low-cost resistance to kanamycin. Despite targeting the same or adjacent residues of the protein, these mutants differed from each other in the levels of resistance they provided. Analysis of one of these mutations showed that it has little defect in growth or in synthesis of green fluorescent protein (GFP) from an inducible plasmid in the absence of the antibiotic. A second class of mutations, recovered only during evolution in higher sublethal concentrations of the antibiotic, deleted the C-terminal end of the ATP synthase shaft. This mutation confers basal-level resistance to kanamycin while showing a strong growth defect in the absence of the antibiotic. In conclusion, the early dynamics of the development of resistance to an aminoglycoside antibiotic is dependent on the levels of stress (concentration) imposed by the antibiotic, with the evolution of less costly variants only a matter of time. PMID:25281544

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.

The determinants of the antibiotic resistance process

PubMed Central

Franco, Beatriz Espinosa; Altagracia Martínez, Marina; Sánchez Rodríguez, Martha A; Wertheimer, Albert I

2009-01-01

Background: The use of antibiotic drugs triggers a complex interaction involving many biological, sociological, and psychological determinants. Resistance to antibiotics is a serious worldwide problem which is increasing and has implications for morbidity, mortality, and health care both in hospitals and in the community. Objectives: To analyze current research on the determinants of antibiotic resistance and comprehensively review the main factors in the process of resistance in order to aid our understanding and assessment of this problem. Methods: We conducted a MedLine search using the key words “determinants”, “antibiotic”, and “antibiotic resistance” to identify publications between 1995 and 2007 on the determinants of antibiotic resistance. Publications that did not address the determinants of antibiotic resistance were excluded. Results: The process and determinants of antibiotic resistance are described, beginning with the development of antibiotics, resistance and the mechanisms of resistance, sociocultural determinants of resistance, the consequences of antibiotic resistance, and alternative measures proposed to combat antibiotic resistance. Conclusions: Analysis of the published literature identified the main determinants of antibiotic resistance as irrational use of antibiotics in humans and animal species, insufficient patient education when antibiotics are prescribed, lack of guidelines for treatment and control of infections, lack of scientific information for physicians on the rational use of antibiotics, and lack of official government policy on the rational use of antibiotics in public and private hospitals. PMID:21694883

Effects of pesticides and antibiotics on penaeid shrimp with special emphases on behavioral and biomarker responses.

PubMed

Tu, Huynh Thi; Silvestre, Frederic; Phuong, Nguyen Thanh; Kestemont, Patrick

2010-04-01

The purpose of the present study is to provide information on the current state of knowledge regarding the effects of pesticides and antibiotics used in aquaculture on penaeid shrimp, one of the most common aquatic products for human consumption, with a special emphasis on the use of behavioral, physiological, and biochemical response. These include behavior; feeding rate changes; respiration rate, oxygen consumption, and osmoregulation alterations; nucleic acids, protein, and glycogen synthesis; cholinesterase activity inhibition; ATPase activity; and oxidative stress responses. This paper also deals with residues of antibiotics and pesticides in penaeid shrimp. Antibiotics and pesticides used in aquaculture may have adverse effects on treated animals and human consumers health if they are not correctly used. As a complement to the measurement of antibiotic and pesticide residues in tissues, the use of behavioral and biomarker responses can provide more relevant biological information on the potential adverse effects of antibiotics and pesticides on penaeid shrimp health. (c) 2009 SETAC.

DEVELOPMENT OF AN ANTIBIOTIC OPTIONS INDEX FOR ANTIBIOTIC RESISTANCE MONITORING.

PubMed

Manomayitthikan, Taweesuk; Borlace, Glenn N; Kessomboon, Nusaraporn

2016-11-01

Using antibiogram data to indicate the overall antibiotic resistance of a pathogen is complicated by the multiple antibiotic susceptibilities reported in the antibiogram. The objectives of this study were to develop and determine the benefits of an Antibiotic Options Index (AOI); an index that summarizes antibiotic susceptibility data for a pathogen by presenting it as the availability of antibiotic treatment options. The AOI was calculated using antibiogram data for the seven most commonly isolated pathogens from the National Antimicrobial Resistance Surveillance Center of Thailand between 1998 and 2014 and was classified as acceptable (AOI ≥ 0.8) or unacceptable (AOI < 0.8) based on the availability of treatment options. The AOI identified two problematic pathogens: Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus (MRSA). For A. baumannii, the probability of having at least two viable antibiotic treatment options (AOIm2) decreased from an acceptable level (0.93) in 1998 to an unacceptable level (0.53) in 2014 and for MRSA the AOIm2 decreased from an acceptable level (0.82) in 1998 to an unacceptable level (0.47) in 2014. By including the idea that the problem with increasing antibiotic resistance is a problem with treating infections, the AOI effectively compiles susceptibility data to present it as the probability of having effective antibiotic treatment. This index is calculated from widely available antibiogram data, making it more suitable to be used to monitor antibiotic resistance at the hospital, provincial and national levels.

Fabric phase sorptive extraction of selected penicillin antibiotic residues from intact milk followed by high performance liquid chromatography with diode array detection.

PubMed

Samanidou, Victoria; Michaelidou, Katia; Kabir, Abuzar; Furton, Kenneth G

2017-06-01

Fabric phase sorptive extraction (FPSE), a novel sorbent-based microextraction method, was evaluated as a simple and rapid strategy for the extraction of four penicillin antibiotic residues (benzylpenicillin, cloxacillin, dicloxacillin and oxacillin) from cows' milk, without prior protein precipitation. Time-consuming solvent evaporation and reconstitution steps were eliminated successfully from the sample preparation workflow. FPSE utilizes a flexible fabric substrate, chemically coated with sol-gel derived, highly efficient, organic-inorganic hybrid sorbent as the extraction medium. Herein short-chain poly(ethylene glycol) provided optimum extraction sensitivity for the selected penicillins, which were analysed using an RP-HPLC method, validated according to the European Decision 657/2002/EC. The limit of quantitation was 10μg/kg for benzylpenicillin, 20μg/kg for cloxacillin, 25μg/kg dicloxacillin and 30μg/kg oxacillin. These are a similar order of magnitude with those reported in the literature and (with the exception of benzylpenicillin) are less than the maximum residue limits (MRL) set by European legislation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Validation of a quantitative and confirmatory method for residue analysis of aminoglycoside antibiotics in poultry, bovine, equine and swine kidney through liquid chromatography-tandem mass spectrometry.

PubMed

Almeida, M P; Rezende, C P; Souza, L F; Brito, R B

2012-01-01

The use of aminoglycoside antibiotics in food animals is approved in Brazil. Accordingly, Brazilian food safety legislation sets maximum levels for these drugs in tissues from these animals in an effort to guarantee that food safety is not compromised. Aiming to monitor the levels of these drugs in tissues from food animals, the validation of a quantitative, confirmatory method for the detection of residues of 10 aminoglycosides antibiotics in poultry, swine, equine and bovine kidney, with extraction using a solid phase and detection and quantification by LC-MS/MS was performed. The procedure is an adaptation of the US Department of Agriculture, Food Safety and Inspection Service (USDA-FSIS) qualitative method, with the inclusion of additional clean-up and quantification at lower levels, which proved more efficient. Extraction was performed using a phosphate buffer containing trifluoroacetic acid followed by neutralization, purification on a cationic exchange SPE cartridge, with elution with methanol/acetic acid, evaporation, and dilution in ion-pair solvent. The method was validated according to the criteria and requirements of the European Commission Decision 2002/657/EC, showing selectivity with no matrix interference. Linearity was established for all analytes using the method of weighted minimum squares. CCα and CCβ varied between 1036 and 12,293 µg kg(-1), and between 1073 and 14,588 µg kg(-1), respectively. The limits of quantification varied between 27 and 688 µg kg(-1). The values of recovery for all analytes in poultry kidney, fortified in the range of 500-1500 µg kg(-1), were higher than 90%, and the relative standard deviations were lower than 15%, except spectinomycin (21.8%). Uncertainty was estimated using a simplified methodology of 'bottom-up' and 'top-down' strategies. The results showed that this method is effective for the quantification and confirmation of aminoglycoside residues and could be used by the Brazilian programme of residue

Management Options for Reducing the Release of Antibiotics and Antibiotic Resistance Genes to the Environment

PubMed Central

Pruden, Amy; Amézquita, Alejandro; Collignon, Peter; Brandt, Kristian K.; Graham, David W.; Lazorchak, James M.; Suzuki, Satoru; Silley, Peter; Snape, Jason R.; Topp, Edward; Zhang, Tong; Zhu, Yong-Guan

2013-01-01

Background: There is growing concern worldwide about the role of polluted soil and water environments in the development and dissemination of antibiotic resistance. Objective: Our aim in this study was to identify management options for reducing the spread of antibiotics and antibiotic-resistance determinants via environmental pathways, with the ultimate goal of extending the useful life span of antibiotics. We also examined incentives and disincentives for action. Methods: We focused on management options with respect to limiting agricultural sources; treatment of domestic, hospital, and industrial wastewater; and aquaculture. Discussion: We identified several options, such as nutrient management, runoff control, and infrastructure upgrades. Where appropriate, a cross-section of examples from various regions of the world is provided. The importance of monitoring and validating effectiveness of management strategies is also highlighted. Finally, we describe a case study in Sweden that illustrates the critical role of communication to engage stakeholders and promote action. Conclusions: Environmental releases of antibiotics and antibiotic-resistant bacteria can in many cases be reduced at little or no cost. Some management options are synergistic with existing policies and goals. The anticipated benefit is an extended useful life span for current and future antibiotics. Although risk reductions are often difficult to quantify, the severity of accelerating worldwide morbidity and mortality rates associated with antibiotic resistance strongly indicate the need for action. PMID:23735422

Prevalence and Comparing of Some Microbiological Properties, Somatic Cell Count and Antibiotic Residue of Organic and Conventional Raw Milk Produced in Turkey

PubMed Central

Şengül, Mustafa; Erkaya, Tuba; Aksakal, Vecihi

2017-01-01

The aim of this study was to investigate the effects of production systems and milk collection periods on the somatic cell count (SCC), some microbiological properties, total aerobic mesophilic bacteria (TAMB), coliform, Staphylococcus aureus (S. aureus), yeast and mould) and antibiotic residue of milk; in Turkey. Milk samples were collected from 9 conventional farms and 9 organic farms during one year time, at six different months (December 2013 to October 2014), and all farms were selected from the same geographical locations. All organically managed farms had organic production certificates given by the Republic of Turkey Ministry of Food, Agriculture and Livestock. The count of TAMB, coliform, and coagulase positive S. aureus were affected by production systems at the level of p<0.01; yeast and mold, and somatic cell count (SCC) were affected at the level of p<0.05. But, differences according to months were statistically significant only on TAMB (p<0.01) and coliform (p<0.05) counts. The general means of TAMB, coliform and yeast and mould counts of the organic milk (OM) were significantly lower (p<0.05), while the general means of SCC and coagulase positive S. aureus count of the OM was significantly higher (p<0.05) compared to conventional milk (CM). Antibiotic residue was determined in one of the CM sample and in two of the OM samples. Our study is the first research that compared conventional and organic milk in Turkey. This study indicated that the microbiological quality of OM was the higher in terms of TAMB, coliform and yeast and mould, whereas was the lower in relation to SCC and coagulase positive S. aureus counts. But, the quality of both milk types should be improved. PMID:28515650

Crystal Structure of StaL, A Glycopeptide Antibiotic Sulfotransferase from Streptomyces Toyocaensis

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

Shi,R.; Lamb, S.; Bhat, S.

2007-01-01

Over the past decade, antimicrobial resistance has emerged as a major public health crisis. Glycopeptide antibiotics such as vanco-mycin and teicoplanin are clinically important for the treatment of Gram-positive bacterial infections. StaL is a 3'-phosphoadenosine 5'-phosphosulfate-dependent sulfotransferase capable of sulfating the cross-linked heptapeptide substrate both in vivo and in vitro, yielding the product A47934 [GenBank], unique teicoplanin-class glycopeptide antibiotic. The sulfonation reaction catalyzed by StaL constitutes the final step in A47934 [GenBank] biosynthesis. Here we report the crystal structure of StaL and its complex with the cofactor product 3'-phosphoadenosine 5'-phosphate. This is only the second prokaryotic sulfotransferase to be structurallymore » characterized. StaL belongs to the large sulfotransferase family and shows higher similarity to cytosolic sulfotransferases (ST) than to the bacterial ST (Stf0). StaL has a novel dimerization motif, different from any other STs that have been structurally characterized. We have also applied molecular modeling to investigate the binding mode of the unique substrate, desulfo-A47934. Based on the structural analysis and modeling results, a series of residues was mutated and kinetically characterized. In addition to the conserved residues (Lys{sup 12}, His{sup 67}, and Ser{sup 98}), molecular modeling, fluorescence quenching experiments, and mutagenesis studies identified several other residues essential for substrate binding and/or activity, including Trp{sup 34}, His{sup 43}, Phe{sup 77}, Trp{sup 132}, and Glu{sup 205}.« less

The scourge of antibiotic resistance: the important role of the environment.

PubMed

Finley, Rita L; Collignon, Peter; Larsson, D G Joakim; McEwen, Scott A; Li, Xian-Zhi; Gaze, William H; Reid-Smith, Richard; Timinouni, Mohammed; Graham, David W; Topp, Edward

2013-09-01

Antibiotic resistance and associated genes are ubiquitous and ancient, with most genes that encode resistance in human pathogens having originated in bacteria from the natural environment (eg, β-lactamases and fluoroquinolones resistance genes, such as qnr). The rapid evolution and spread of "new" antibiotic resistance genes has been enhanced by modern human activity and its influence on the environmental resistome. This highlights the importance of including the role of the environmental vectors, such as bacterial genetic diversity within soil and water, in resistance risk management. We need to take more steps to decrease the spread of resistance genes in environmental bacteria into human pathogens, to decrease the spread of resistant bacteria to people and animals via foodstuffs, wastes and water, and to minimize the levels of antibiotics and antibiotic-resistant bacteria introduced into the environment. Reducing this risk must include improved management of waste containing antibiotic residues and antibiotic-resistant microorganisms.

[Micromonospora resistence to definite antibiotics and their ability to produce structurally analogous antibiotics].

PubMed

Bibikova, M V; Ivanitskaia, L P; Tikhonova, A S

1980-01-01

Thirty six cultures of Micromonospora freshly isolated from soil samples were studied with respect to their sensitivity to a number of antibiotics of various structures and modes of action. It was found that all of them were highly sensitive to penicillin, ristomycin, tetracycline, rifampicin, streptomycin, olivomycin, carminomycin and dactinomycin. Significant differences in sensitivity of the Micromonospora cultures were revealed only with respect to gentamicin, tobramicin, erythromycin and lincomycin. Seven cultures were resistant to gentamicin and tobramicin and sensitive to all of the other antibiotics. Broad spectrum antibiotics were isolated from these cultures. The study of the antibiotic chemistry showed that they were 2-desoxystreptamine-containing aminoglycosides. Two cultures proved to be resistant to erythromycin and lincomycin. When identified with the use of antibiotic resistant staphylococcal strains, the crude antibiotic substances isolated from these cultures appeared to be not active against staphylococci resistant to erythromycin and lincomycin. By their chromatograpi- behaviour the antibiotics were close to macrolides. Therefore, it was found that production of aminoglycoside and macrolide antibiotics was most characteristic of Micromonospora. A certain correlation between resistance of Micromonospora to these 2 antibiotic groups and capacity for their production was shown.

Intraoperative Molecular Imaging of Lung Adenocarcinoma Can Identify Residual Tumor Cells at the Surgical Margins

PubMed Central

Keating, Jane J.; Okusanya, Olugbenga T.; De Jesus, Elizabeth; Judy, Ryan; Jiang, Jack; Deshpande, Charuhas; Nie, Shuming; Low, Philip; Singhal, Sunil

2017-01-01

Purpose During lung surgery, identification of surgical margins is challenging. We hypothesized that molecular imaging with a fluorescent probe to pulmonary adenocarcinomas could enhance residual tumor during resection. Procedures Mice with flank tumors received a contrast agent targeting folate receptor alpha. Optimal dose and time of injection was established. Margin detection was compared using traditional methods versus molecular imaging. A pilot study was then performed in 3 humans with lung adenocarcinoma. Results The peak tumor-to background ratio (TBR) of murine tumors was 3.9. Fluorescence peaked at 2 hours and was not improved beyond 0.1 mg/kg. Traditional inspection identified 30% of mice with positive margins. Molecular imaging identified an additional 50% of residual tumor deposits (P<0.05). The fluorescent probe visually enhanced all human tumors with a mean TBR of 3.5. Conclusions Molecular imaging is an important adjunct to traditional inspection to identify surgical margins after tumor resection. PMID:26228697

Screening the Biosphere: The Fungicolous Fungus Trichoderma phellinicola, a Prolific Source of Hypophellins, New 17-, 18-, 19-, and 20-Residue Peptaibiotics1)

PubMed Central

Röhrich, Christian René; Iversen, Anita; Jaklitsch, Walter Michael; Voglmayr, Hermann; Vilcinskas, Andreas; Nielsen, Kristian Fog; Thrane, Ulf; von Döhren, Hans; Brückner, Hans; Degenkolb, Thomas

2013-01-01

To investigate the significance of antibiotics for the producing organism(s) in the natural habitat, we screened a specimen of the fungicolous fungus Trichoderma phellinicola (syn. Hypocrea phellinicola) growing on its natural host Phellinus ferruginosus. Results revealed that a particular group of non-ribosomal antibiotic polypeptides, peptaibiotics, which contain the non-proteinogenic marker amino acid, α-aminoisobutyric acid, was biosynthesized in the natural habitat by the fungicolous producer and, consequently, released into the host. By means of liquid chromatography coupled to electrospray high-resolution time-of-flight mass spectrometry, we detected ten 20-residue peptaibols in the specimen. Sequences of peptaibiotics found in vivo were independently confirmed by analyzing the peptaibiome of an agar plate culture of T. phellinicola CBS 119283 (ex-type) grown under laboratory conditions. Notably, this strain could be identified as a potent producer of 39 new 17-, 18-, and 19-residue peptaibiotics, which display the same building scheme as the 20-residue peptaibols found in the specimen. Two of the 19-residue peptaibols are tentatively assigned to carry tyrosinol, a novel C-terminal residue, as deduced from high-resolution tandem mass-spectrometry data. For the new peptaibiotics produced by T. phellinicola, the name ‘hypophellin(s)’, based on the teleomorph name, is introduced. PMID:23681726

A Common Platform for Antibiotic Dereplication and Adjuvant Discovery.

PubMed

Cox, Georgina; Sieron, Arthur; King, Andrew M; De Pascale, Gianfranco; Pawlowski, Andrew C; Koteva, Kalinka; Wright, Gerard D

2017-01-19

Solving the antibiotic resistance crisis requires the discovery of new antimicrobial drugs and the preservation of existing ones. The discovery of inhibitors of antibiotic resistance, antibiotic adjuvants, is a proven example of the latter. A major difficulty in identifying new antibiotics is the frequent rediscovery of known compounds, necessitating laborious "dereplication" to identify novel chemical entities. We have developed an antibiotic resistance platform (ARP) that can be used for both the identification of antibiotic adjuvants and for antibiotic dereplication. The ARP is a cell-based array of mechanistically distinct individual resistance elements in an identical genetic background. In dereplication mode, we demonstrate the rapid identification, and thus discrimination, of common antibiotics. In adjuvant discovery mode, we show that the ARP can be harnessed in screens to identify inhibitors of resistance. The ARP is therefore a powerful tool that has broad application in confronting the resistance crisis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Metagenomics of urban sewage identifies an extensively shared antibiotic resistome in China.

PubMed

Su, Jian-Qiang; An, Xin-Li; Li, Bing; Chen, Qing-Lin; Gillings, Michael R; Chen, Hong; Zhang, Tong; Zhu, Yong-Guan

2017-07-19

Antibiotic-resistant pathogens are challenging treatment of infections worldwide. Urban sewage is potentially a major conduit for dissemination of antibiotic resistance genes into various environmental compartments. However, the diversity and abundance of such genes in wastewater are not well known. Here, seasonal and geographical distributions of antibiotic resistance genes and their host bacterial communities from Chinese urban sewage were characterized, using metagenomic analyses and 16S rRNA gene-based Illumina sequencing, respectively. In total, 381 different resistance genes were detected, and these genes were extensively shared across China, with no geographical clustering. Seasonal variation in abundance of resistance genes was observed, with average concentrations of 3.27 × 10 11 and 1.79 × 10 12 copies/L in summer and winter, respectively. Bacterial communities did not exhibit geographical clusters, but did show a significant distance-decay relationship (P < 0.01). The core, shared resistome accounted for 57.7% of the total resistance genes, and was significantly associated with the core microbial community (P < 0.01). The core human gut microbiota was also strongly associated with the shared resistome, demonstrating the potential contribution of human gut microbiota to the dissemination of resistance elements via sewage disposal. This study provides a baseline for investigating environmental dissemination of resistance elements and raises the possibility of using the abundance of resistance genes in sewage as a tool for antibiotic stewardship.

An inter-residue network model to identify mutational-constrained regions on the Ebola coat glycoprotein

PubMed Central

Quinlan, Devin S.; Raman, Rahul; Tharakaraman, Kannan; Subramanian, Vidya; del Hierro, Gabriella; Sasisekharan, Ram

2017-01-01

Recently, progress has been made in the development of vaccines and monoclonal antibody cocktails that target the Ebola coat glycoprotein (GP). Based on the mutation rates for Ebola virus given its natural sequence evolution, these treatment strategies are likely to impose additional selection pressure to drive acquisition of mutations in GP that escape neutralization. Given the high degree of sequence conservation among GP of Ebola viruses, it would be challenging to determine the propensity of acquiring mutations in response to vaccine or treatment with one or a cocktail of monoclonal antibodies. In this study, we analyzed the mutability of each residue using an approach that captures the structural constraints on mutability based on the extent of its inter-residue interaction network within the three-dimensional structure of the trimeric GP. This analysis showed two distinct clusters of highly networked residues along the GP1-GP2 interface, part of which overlapped with epitope surfaces of known neutralizing antibodies. This network approach also permitted us to identify additional residues in the network of the known hotspot residues of different anti-Ebola antibodies that would impact antibody-epitope interactions. PMID:28397835

Antibiotic Resistance Markers in Burkholderia pseudomallei Strain Bp1651 Identified by Genome Sequence Analysis

PubMed Central

Sue, David; Gee, Jay E.; Elrod, Mindy G.; Hoffmaster, Alex R.; Randall, Linnell B.; Chirakul, Sunisa; Tuanyok, Apichai; Schweizer, Herbert P.; Weigel, Linda M.

2017-01-01

ABSTRACT Burkholderia pseudomallei Bp1651 is resistant to several classes of antibiotics that are usually effective for treatment of melioidosis, including tetracyclines, sulfonamides, and β-lactams such as penicillins (amoxicillin-clavulanic acid), cephalosporins (ceftazidime), and carbapenems (imipenem and meropenem). We sequenced, assembled, and annotated the Bp1651 genome and analyzed the sequence using comparative genomic analyses with susceptible strains, keyword searches of the annotation, publicly available antimicrobial resistance prediction tools, and published reports. More than 100 genes in the Bp1651 sequence were identified as potentially contributing to antimicrobial resistance. Most notably, we identified three previously uncharacterized point mutations in penA, which codes for a class A β-lactamase and was previously implicated in resistance to β-lactam antibiotics. The mutations result in amino acid changes T147A, D240G, and V261I. When individually introduced into select agent-excluded B. pseudomallei strain Bp82, D240G was found to contribute to ceftazidime resistance and T147A contributed to amoxicillin-clavulanic acid and imipenem resistance. This study provides the first evidence that mutations in penA may alter susceptibility to carbapenems in B. pseudomallei. Another mutation of interest was a point mutation affecting the dihydrofolate reductase gene folA, which likely explains the trimethoprim resistance of this strain. Bp1651 was susceptible to aminoglycosides likely because of a frameshift in the amrB gene, the transporter subunit of the AmrAB-OprA efflux pump. These findings expand the role of penA to include resistance to carbapenems and may assist in the development of molecular diagnostics that predict antimicrobial resistance and provide guidance for treatment of melioidosis. PMID:28396541

Magnetic solid-phase extraction based on carbon nanotubes for the determination of polyether antibiotic and s-triazine drug residues in animal food with LC-MS/MS.

PubMed

Liu, Xiaoxing; Xie, Shuyu; Ni, Tengteng; Chen, Dongmei; Wang, Xu; Pan, Yuanhu; Wang, Yulian; Huang, Lingli; Cheng, Guyue; Qu, Wei; Liu, Zhenli; Tao, Yanfei; Yuan, Zonghui

2017-06-01

Carbon nanotubes-magnetic nanoparticles, comprising ferroferric oxide nanoparticles and carbon nanotubes, were prepared through a simple one-step synthesis method and subsequently applied to magnetic solid-phase extraction for the determination of polyether antibiotic and s-triazine drug residues in animal food coupled with liquid chromatography with tandem mass spectrometry. The nanocomposites were characterized by transmission electron microscopy, X-ray diffraction, and vibrating sample magnetometry. The components within the nanocomposites endowed the material with high extraction performance and manipulative convenience. Compared with carbon nanotubes, the as-prepared carbon nanotubes-magnetic nanoparticles showed better extraction and separation efficiencies for polyether antibiotics and s-triazine drugs thanks to the contribution of the iron-containing magnetic nanoparticles. Various experimental parameters affecting the extraction efficiency had been investigated in detail. Under the optimal conditions, the good linearity ranging from 1 to 200 μg/kg for diclazuril, toltrazuril, toltrazuril sulfone, lasalocid, monensin, salinomycin, narasin, nanchangmycin, and maduramicin, low limits of detection ranging from 1 to 5 μg/kg, and satisfactory spiked recoveries (77.1-91.2%, with the inter relative standard deviation values from 4.0 to 12.2%) were shown. It was confirmed that this novel method was an efficient pretreatment and enrichment procedure and could be successfully applied for extraction and determination of polyether and s-triazine drug residues in complex matrices. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Assessment of oxytetracycline and tetracycline antibiotics in manure samples in different cities of Khuzestan Province, Iran.

PubMed

Alavi, Nadali; Babaei, Ali Akbar; Shirmardi, Mohammad; Naimabadi, Abolfazl; Goudarzi, Gholamreza

2015-11-01

Tetracyclines (TCs), a class of antibiotics with a broad spectrum, are the most frequently used antibiotics in animal production. The major concern is that the widespread use of the antibiotics may lead to the emergence of new strains of bacteria that are resistant to these antibiotics. The objective of this study was to determine the residual levels of oxytetracycline and tetracycline in 80 animal manure samples that were collected from the livestock and poultry feedlots in Khuzestan Province. The residual levels of the antibiotics in the samples were extracted by using solid-phase extraction (SPE) method and subsequently were measured by liquid chromatography. Recoveries from the spiked poultry manure samples ranged from 65 to 113% for tetracycline and 86 to 132% for oxytetracycline. Relative standard deviations of the recoveries were less than 5.7% within the same day. Method detection limit (MDL) measured for oxytetracycline and tetracycline in the manure were 0.011 and 0.01 mg/kg, respectively. Analysis of the collected 50 chickens and 30 cow manure samples showed that the highest concentration of tetracycline was related to Behbahan City (5.36 mg/kg) and the lowest concentration was detected for Ramhormoz (0.05 mg/kg). The highest and lowest concentrations of oxytetracycline were respectively observed for Behbahan (13.77 mg/kg) and Ramhormoz (0.047 mg/kg). Based on the results, in chicken manure, there was significant statistical difference between the residual TC concentrations among five cities (p(value) < 0.05). However, no significant relationship was observed between oxytetracyclin (OTC) residual concentrations among five cities (p(value) > 0.05).

A potent synthetic inorganic antibiotic with activity against drug-resistant pathogens.

PubMed

Hubick, Shelby; Jayaraman, Arumugam; McKeen, Alexander; Reid, Shelby; Alcorn, Jane; Stavrinides, John; Sterenberg, Brian T

2017-02-06

The acronymously named "ESKAPE" pathogens represent a group of bacteria that continue to pose a serious threat to human health, not only due to their propensity for repeated emergence, but also due to their ability to "eskape" antibiotic treatment. The evolution of multi-drug resistance in these pathogens alone has greatly outpaced the development of new therapeutics, necessitating an alternative strategy for antibiotic development that considers the evolutionary mechanisms driving antibiotic resistance. In this study, we synthesize a novel inorganic antibiotic, phosphopyricin, which has antibiotic activity against the Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE). We show that this potent antibiotic is bactericidal, and exhibits low toxicity in an acute dose assay in mice. As a synthetic compound that does not occur naturally, phosphopyricin would be evolutionarily foreign to microbes, thereby slowing the evolution of resistance. In addition, it loses antibiotic activity upon exposure to light, meaning that the active antibiotic will not accumulate in the general environment where strong selective pressures imposed by antibiotic residuals are known to accelerate resistance. Phosphopyricin represents an innovation in antimicrobials, having a synthetic core, and a photosensitive chemical architecture that would reduce accumulation in the environment.

Antibiotics in the surface water of the Yangtze Estuary: occurrence, distribution and risk assessment.

PubMed

Yan, Caixia; Yang, Yi; Zhou, Junliang; Liu, Min; Nie, Minghua; Shi, Hao; Gu, Lijun

2013-04-01

The occurrence and distribution of five groups of antibiotics were investigated in the surface water of Yangtze Estuary over four seasons. Of the 20 antibiotics, only sulfamerazine was not detected at all sampling sites, indicating widespread occurrence of antibiotic residues in the study area. Detection frequencies and concentrations of antibiotics were generally higher in January, indicating that low flow conditions and low temperature might enhance the persistence of antibiotics in water. Antibiotic levels varied with location, with the highest concentrations being observed around river discharge and sewage outfall. Furthermore, a positive correlation between total antibiotic and DOC concentrations revealed the significant role played by DOC. Risk assessment based on single compound exposure showed that sulfapyridine and sulfamethoxazole could cause medium risk to daphnid in the Yangtze Estuary. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Residues of tetracycline and quinolones in wild fish living around a salmon aquaculture center in Chile].

PubMed

Fortt Z, Antonia; Cabello C, Felipe; Buschmann R, Alejandro

2007-02-01

The presence of residues of tetracycline, quinolones and antiparasitic drugs was investigated in wild fish captured around salmon aquaculture pens in Cochamó, Region X, Chile. Residues of both antibiotics were found in the meta [corrected] of two species of wild fish that are consumed by humans, robalo (Elginops maclovinus) and cabrilla (Sebastes capensis) [corrected] These findings suggest that the antibiotic usage in salmon aquaculture in Chile has nvironmental implications that may affect human and animal health. More studies are needed in Chile to determine the relevance of these findings for human and animal health and the environment to regulate this use of antibiotics.

Irrigation waters and pipe-based biofilms as sources for antibiotic-resistant bacteria.

PubMed

Blaustein, Ryan A; Shelton, Daniel R; Van Kessel, Jo Ann S; Karns, Jeffrey S; Stocker, Matthew D; Pachepsky, Yakov A

2016-01-01

The presence of antibiotic-resistant bacteria in environmental surface waters has gained recent attention. Wastewater and drinking water distribution systems are known to disseminate antibiotic-resistant bacteria, with the biofilms that form on the inner-surfaces of the pipeline as a hot spot for proliferation and gene exchange. Pipe-based irrigation systems that utilize surface waters may contribute to the dissemination of antibiotic-resistant bacteria in a similar manner. We conducted irrigation events at a perennial stream on a weekly basis for 1 month, and the concentrations of total heterotrophic bacteria, total coliforms, and fecal coliforms, as well as the concentrations of these bacterial groups that were resistant to ampicillin and tetracycline, were monitored at the intake water. Prior to each of the latter three events, residual pipe water was sampled and 6-in. sections of pipeline (coupons) were detached from the system, and biofilm from the inner-wall was removed and analyzed for total protein content and the above bacteria. Isolates of biofilm-associated bacteria were screened for resistance to a panel of seven antibiotics, representing five antibiotic classes. All of the monitored bacteria grew substantially in the residual water between irrigation events, and the biomass of the biofilm steadily increased from week to week. The percentages of biofilm-associated isolates that were resistant to antibiotics on the panel sometimes increased between events. Multiple-drug resistance was observed for all bacterial groups, most often for fecal coliforms, and the distributions of the numbers of antibiotics that the total coliforms and fecal coliforms were resistant to were subject to change from week to week. Results from this study highlight irrigation waters as a potential source for antibiotic-resistant bacteria, which can subsequently become incorporated into and proliferate within irrigation pipe-based biofilms.

MALDI-FTICR MS Imaging as a Powerful Tool to Identify Paenibacillus Antibiotics Involved in the Inhibition of Plant Pathogens

NASA Astrophysics Data System (ADS)

Debois, Delphine; Ongena, Marc; Cawoy, Hélène; De Pauw, Edwin

2013-08-01

Nowadays, microorganisms are more and more often used as biocontrol agents for crop protection against diseases. Among them, bacteria of Bacillus and Paenibacillus genders are already used as commercial biocontrol agents. Their mode of action is supposed to be related to their production of antibiotics, such as cyclic lipopeptides, which exhibit great antimicrobial activities. We chose to work with a Paenibacillus polymyxa strain (Pp56) very resistant to various microorganisms. The bacteria were grown simultaneously with Fusarium oxysporum and we applied matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance (MALDI-FTICR) mass spectrometry to identify the antibiotics compounds present in the fungus growth inhibition area. We, therefore, identified fusaricidins A, B, and C and numerous members of the LI-F antibiotics family. MALDI-FTICR mass spectrometry imaging was then used to follow the diffusion of lipopeptides involved in the inhibitory activity over time. We analyzed the molecular content of the inhibitory area at different Pp56 and Fusarium incubation durations and concluded that some lipopeptides such as fusaricidin B and a mixture of LI-F05b/06b/08a were mainly involved in the defense mechanism of Pp56. Our study confirms that MALDI imaging may be a powerful tool to quickly determine which molecular species is involved in an antagonism with another microorganism, avoiding time-consuming steps of extraction, purification, and activity tests, which are still commonly used in microbiology.

Development of an enzyme immunoassay for the antibiotic cefquinome and its application for residue determination in cow's milk after therapeutical mastitis treatment.

PubMed

Thal, Johannes; Steffen, Monika; Meier, Bianca; Schneider, Elisabeth; Adriany, Ansgar; Usleber, Ewald

2011-01-01

The aim of this study was to develop and evaluate an enzyme immunoassay (EIA) for the cephalosporin antibiotic in milk, in combination with a new microbiological test system (brilliant black reduction test, BRT-P). Polyclonal antibodies against cefquinome were produced in rabbits, using cefquinome-keyhole limpet hemocyanine as the immunogen. These antibodies and a cefquinome-glucose oxidase conjugate were used in a competitive indirect EIA. The detection limit for cefquinome in milk was 1.5 ng ml(-1), recoveries were 80-128% at 4-40 ng ml(-1). Cross-reactivities with other cephalosporins/penicillins were all <1%. The EIA was used to determine cefquinome in incurred raw milk, the BRT-P (detection limit ≈ 20 ng ml(-1)) and a receptor assay (ßeta-s.t.a.r., detection limit ≈ 15 ng ml(-1)) were used in parallel. Five lactating cows, suffering from clinical mastitis, were treated with cefquinome by simultaneous intramammary and intramuscular injection. Cefquinome residues (maximum 10-27 μg ml(-1)) were most exclusively found in the udder quarter which was treated intramammary, residue levels in the other three quarters were low (<20 ng ml(-1)). Even in milk from intramammary-dosed quarters, residue levels fell below European Union maximum residue level (MRL, 20 μg kg(-1)) 2 days before the end of the withdrawal period. EIA, BRT-P, and ßeta-s.t.a.r. results showed acceptable agreement for milk samples, but the newly developed EIA is superior in aspects of sensitivity. In conclusion, this is the first one description of immunoassay and microbiological tests capable to determine cefquinome in milk at the MRL in incurred sample material.

Analysis of veterinary drug residue monitoring results for commercial livestock products in Taiwan between 2011 and 2015.

PubMed

Lee, Hsin-Chun; Chen, Chi-Min; Wei, Jen-Ting; Chiu, Hsiu-Yi

2018-04-01

Antibiotics have been widely used in the treatment of livestock diseases. However, the emergence of issues related to drug resistance prompted governments to enact a series of laws regulating the use of antibiotics in livestock. Following control of the problem of drug resistant bacteria, public attention has shifted to the recurring incidence of human health and safety issues caused by residual veterinary drugs in livestock products. To guarantee the safety and hygiene of meat, milk, and eggs from food-producing animals, governments and relevant agencies established laws and regulations for the use of veterinary drugs. It is, therefore, necessary to monitor the content of residual drugs in livestock products at regular intervals to assess whether the regulations have resulted in the effective management of food product safety, and to prevent and manage sudden problems related to this issue. A 2011-2015 livestock product post-marketing monitoring program launched by the Taiwan Food and Drug Administration (TFDA) inspected 1487 livestock products. Over the past 5 years, there were 34 samples identified that did not conform to the regulations; these samples included residue drugs such as β-agonists, chloramphenicols, β-lactam antibiotics, sulfa drugs, enrofloxacin, and lincomycin. Inspections of commercial livestock products with the consistent cooperation of agricultural authorities did not detect the drugs that were banned by the government, whereas the detection of other drugs decreased annually with an increase in the post-market monitoring sample size. In the future, the TFDA will continue to monitor the status of residual veterinary drugs in commercial livestock products, adjust the sampling of food products annually according to monitoring results, and closely cooperate with agricultural authorities on source management. Copyright © 2017. Published by Elsevier B.V.

Some chemical and physical properties of nisin, a small-protein antibiotic produced by Lactococcus lactis.

PubMed Central

Liu, W; Hansen, J N

1990-01-01

Nisin is a small gene-encoded antimicrobial protein produced by Lactococcus lactis that contains unusual dehydroalanine and dehydrobutyrine residues. The reactivity of these residues toward nucleophiles was explored by reacting nisin with a variety of mercaptans. The kinetics of reaction with 2-mercaptoethane-sulfonate and thioglycolate indicated that the reaction pathway includes a binding step. Reaction of nisin at high pH resulted in the formation of multimeric products, apparently as a result of intramolecular and intermolecular reactions between nucleophilic groups and the dehydro residues. One of the nucleophiles had a pKa of about 9.8. The unique vinyl protons of the dehydro residues that give readily identifiable proton nuclear magnetic resonances were used to observe the addition of nucleophiles to the dehydro moiety. After reaction with nucleophiles, nisin lost its antibiotic activity and no longer showed the dehydro resonances, indicating that the dehydro groups had been modified. The effect of pH on the solubility of nisin was determined; the solubility was quite high at low pH (57 mg/ml at pH 2) and was much lower at high pH (0.25 mg/ml at pH 8 to 12), as measured before significant pH-induced chemical modification had occurred. High-performance liquid chromatography on a C18 column was an effective technique for separating unmodified nisin from its reaction products. The cyanogen bromide cleavage products of nisin were about 90% less active toward inhibition of bacterial spore outgrowth than was native nisin. These results are consistent with earlier observations, which suggested that the dehydro residues of nisin have a role in the mechanism of antibiotic action, in which they act as electrophilic Michael acceptors toward nucleophiles in the cellular target. Images PMID:2119570

Multiclass method for the determination of 62 antibiotics in milk.

PubMed

Moretti, Simone; Cruciani, Gabriele; Romanelli, Sara; Rossi, Rosanna; Saluti, Giorgio; Galarini, Roberta

2016-09-01

A multiclass method for screening and confirmatory analysis of antimicrobial residues in milk has been developed and validated. Sixty-two antibiotics belonging to ten different drug families (amphenicols, cephalosporins, lincosamides, macrolides, penicillin, pleuromutilins, quinolones, rifamycins, sulfonamides and tetracyclines) have been included. After the addition of an aqueous solution of EDTA, the milk samples were extracted twice with acetonitrile, evaporated and dissolved in ammonium acetate. After centrifugation, 10 µl were analysed using LC-Q-Orbitrap operating in positive electrospray ionization mode. The method was validated in bovine milk in the range 2-150 µg kg(-1) for all antibiotics; for four compounds with maximum residue limits higher than 100 µg kg(-1) , the validation interval has been extended until 333 µg kg(-1) . The estimated performance characteristics were satisfactory complying with the requirements of Commission Decision 2002/657/EC. Good accuracies were obtained also taking advantage from the versatility of the hybrid mass analyser. Identification criteria were achieved verifying the mass accuracy and ion ratio of two ions, including the pseudomolecular one, where possible. Finally, the developed procedure was applied to 13 real cases of suspect milk samples (microbiological assay) confirming the presence of one or more antibiotics, although frequently, the maximum residue limits were not exceeded. The availability of rapid multiclass confirmatory methods can avoid wastes of suspect, but compliant, raw milk samples. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Oral versus inhaled antibiotics for bronchiectasis.

PubMed

Spencer, Sally; Felix, Lambert M; Milan, Stephen J; Normansell, Rebecca; Goeminne, Pieter C; Chalmers, James D; Donovan, Tim

2018-03-27

Bronchiectasis is a chronic inflammatory disease characterised by a recurrent cycle of respiratory bacterial infections associated with cough, sputum production and impaired quality of life. Antibiotics are the main therapeutic option for managing bronchiectasis exacerbations. Evidence suggests that inhaled antibiotics may be associated with more effective eradication of infective organisms and a lower risk of developing antibiotic resistance when compared with orally administered antibiotics. However, it is currently unclear whether antibiotics are more effective when administered orally or by inhalation. To determine the comparative efficacy and safety of oral versus inhaled antibiotics in the treatment of adults and children with bronchiectasis. We identified studies through searches of the Cochrane Airways Group's Specialised Register (CAGR), which is maintained by the Information Specialist for the group. The Register contains trial reports identified through systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, AMED, and PsycINFO, and handsearching of respiratory journals and meeting abstracts. We also searched ClinicalTrials.gov and the WHO trials portal. We searched all databases in March 2018 and imposed no restrictions on language of publication. We planned to include studies which compared oral antibiotics with inhaled antibiotics. We would have considered short-term use (less than four weeks) for treating acute exacerbations separately from longer-term use as a prophylactic (4 weeks or more). We would have considered both intraclass and interclass comparisons. We planned to exclude studies if the participants received continuous or high-dose antibiotics immediately before the start of the trial, or if they have received a diagnosis of cystic fibrosis (CF), sarcoidosis, active allergic bronchopulmonary aspergillosis or active non-tuberculous Mycobacterial infection

Adverse consequences of neonatal antibiotic exposure.

PubMed

Cotten, Charles M

2016-04-01

Antibiotics have not only saved lives and improved outcomes, but they also influence the evolving microbiome. This review summarizes reports on neonatal infections and variation in antibiotic utilization, discusses the emergence of resistant organisms, and presents data from human neonates and animal models demonstrating the impact of antibiotics on the microbiome, and how microbiome alterations impact health. The importance of antibiotic stewardship is also discussed. Infections increase neonatal morbidity and mortality. Furthermore, the clinical presentation of infections can be subtle, prompting clinicians to empirically start antibiotics when infection is a possibility. Antibiotic-resistant infections are a growing problem. Cohort studies have identified extensive center variations in antibiotic usage and associations between antibiotic exposures and outcomes. Studies of antibiotic-induced microbiome alterations and downstream effects on the developing immune system have increased our understanding of the mechanisms underlying the associations between antibiotics and adverse outcomes. The emergence of resistant microorganisms and recent evidence linking antibiotic practice variations with health outcomes has led to the initiation of antibiotic stewardship programs. The review encourages practitioners to assess local antibiotic use with regard to local microbiology, and to adopt steps to reduce infections and use antibiotics wisely.

Occurrence and human dietary assessment of fluoroquinolones antibiotics in cultured fish around tai lake, China.

PubMed

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

2017-11-01

Fluoroquinolone antibiotics are widely used in the production of aquatic products and considered to be a significant contributing factor to the burden of both natural and aquaculture environments. However, the main types of fluoroquinolones present in aquaculture systems have not been determined. The objectives of the present study were to explore the occurrence of residual fluoroquinolone antibiotics in fish muscle tissues sampled from across the entire aquaculture season in the Tai Lake basin in China and to assess the dietary risks associated with the upcoming vendible fish in the last month of the aquaculture season. Fluoroquinolones were detected in 95.69% of all fish samples, and the concentrations ranged from the limit of quantification (LOQ) to 47 108.00 μg · kg -1 . Enrofloxacin contributed the most among the 9 fluoroquinolone antibiotics tested. Of the 4 fish species studied, enrofloxacin was present in bream at significant (p < 0.05) concentrations in August, with an average value of 321.45 μg · kg -1 , while enrofloxacin concentrations peaked in crab and shrimp in September, with average values of 6949.60 and 460.82 μg · kg -1 , respectively. However, different patterns were observed in perch, suggesting that other categories of antibiotics may be used in the production of this fish. Dietary risk assessment showed that the residual levels and estimated daily intake in bream, perch, and shrimp were far below the maximum residual level and acceptable daily intake. However, the average residual level in crab exceeded the maximum residual level, and the estimated daily intake value accounted for 78.49% of the acceptable daily intake, indicating potential consumption risk. In summary, the present study aims to guide the production and consumption of aquatic products. Environ Toxicol Chem 2017;36:2899-2905. © 2017 SETAC. © 2017 SETAC.

Fractionation and analysis of veterinary antibiotics and their related degradation products in agricultural soils and drainage waters following swine manure amendment.

PubMed

Solliec, Morgan; Roy-Lachapelle, Audrey; Gasser, Marc-Olivier; Coté, Caroline; Généreux, Mylène; Sauvé, Sébastien

2016-02-01

The fate of antimicrobial active compound residues in the environment, and especially antibiotics used in swine husbandry are of particular interest for their potential toxicity and contribution to antibiotic resistance. The presence of relatively high concentrations of bioactive compounds has been reported in agricultural areas but few information is available on their degradation products. Veterinary antibiotics reach terrestrial environments through many routes, including application of swine manure to soils. The objectives of this project were first, to develop an analytical method able to quantify and identify veterinary antibiotics and their degradation products in manure, soil and water samples; and second, to study the distribution of these target compounds in soils and drainage waters. A brief evaluation of their potential toxicity in the environment was also made. In order to achieve these objectives, liquid chromatography coupled to high-resolution mass spectrometry was used for its ability to quantify contaminants with sensitivity and selectivity, and its capacity to identify degradation products. Samples of manure, soil and water came from a long-term experimental site where swine manure containing veterinary antibiotics has been applied for many years. In this study, tetracycline antibiotics were found at several hundred μg L(-1) in the swine manure slurry used for fertilization, several hundred of ng L(-1) in drainage waters and several ng g(-1) in soils, while degradation products were sometimes found at concentrations higher than the parent compounds. Copyright © 2015 Elsevier B.V. All rights reserved.

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

Antibiotics in the aquatic environment of Vietnam: Sources, concentrations, risk and control strategy.

PubMed

Binh, Vu Ngan; Dang, Nhung; Anh, Nguyen Thi Kieu; Ky, Le Xuan; Thai, Phong K

2018-04-01

The presence of antibiotics in the aquatic environment is a serious concern because it may lead to the emergence of antibiotic resistance, thus lowering the therapeutic effect of antibiotics. In Vietnam, the problem is aggravated by the irrational use of antibiotics in different sectors of agriculture and human health service. Moreover, the residues of antibiotics in the aquatic environment can be spread widely due to the lack of proper wastewater treatment systems. In this paper, we aim to comprehensively review all relevant sources that discharge antibiotics to the aquatic environment in Vietnam. Apart from the common source of antibiotics from aquaculture, other activities that release considerable amounts of antibiotics into water environment are also included. Environmental concentrations of antibiotics related to those sources are studied to demonstrate their contributions to the presence of antibiotics in the aquatic environment in Vietnam. As antibiotic-contained water may be used as water supply for irrigation and even human consumption in rural areas, the essence of wastewater treatment is highlighted. Finally, we also discuss the new National Action plan from the Ministry of Health for controlling the issue of antibiotic resistance in Vietnam. Copyright © 2018 Elsevier Ltd. All rights reserved.

The mycobacterial antibiotic resistance determinant WhiB7 acts as a transcriptional activator by binding the primary sigma factor SigA (RpoV).

PubMed

Burian, Ján; Yim, Grace; Hsing, Michael; Axerio-Cilies, Peter; Cherkasov, Artem; Spiegelman, George B; Thompson, Charles J

2013-12-01

Tuberculosis therapeutic options are limited by the high intrinsic antibiotic resistance of Mycobacterium tuberculosis. The putative transcriptional regulator WhiB7 is crucial for the activation of systems that provide resistance to diverse antibiotic classes. Here, we used in vitro run-off, two-hybrid assays, as well as mutagenic, complementation and protein pull-down experiments, to characterize WhiB7 as an auto-regulatory, redox-sensitive transcriptional activator in Mycobacterium smegmatis. We provide the first direct biochemical proof that a WhiB protein promotes transcription and also demonstrate that this activity is sensitive to oxidation (diamide). Its partner protein for transcriptional activation was identified as SigA, the primary sigma factor subunit of RNA polymerase. Residues required for the interaction mapped to region 4 of SigA (including R515H) or adjacent domains of WhiB7 (including E63D). WhiB7's ability to provide a specific spectrum of antibiotic-resistance was dependent on these residues as well as its C-terminal AT-hook module that binds to an AT-rich motif immediately upstream of the -35 hexamer recognized by SigA. These experimentally established constrains, combined with protein structure predictions, were used to generate a working model of the WhiB7-SigA-promoter complex. Inhibitors preventing WhiB7 interactions could allow the use of previously ineffective antibiotics for treatment of mycobacterial diseases.

The future of antibiotics

PubMed Central

2014-01-01

Antibiotic resistance continues to spread even as society is experiencing a market failure of new antibiotic research and development (R&D). Scientific, economic, and regulatory barriers all contribute to the antibiotic market failure. Scientific solutions to rekindle R&D include finding new screening strategies to identify novel antibiotic scaffolds and transforming the way we think about treating infections, such that the goal is to disarm the pathogen without killing it or modulate the host response to the organism without targeting the organism for destruction. Future economic strategies are likely to focus on ‘push’ incentives offered by public-private partnerships as well as increasing pricing by focusing development on areas of high unmet need. Such strategies can also help protect new antibiotics from overuse after marketing. Regulatory reform is needed to re-establish feasible and meaningful traditional antibiotic pathways, to create novel limited-use pathways that focus on highly resistant infections, and to harmonize regulatory standards across nations. We need new antibiotics with which to treat our patients. But we also need to protect those new antibiotics from misuse when they become available. If we want to break the cycle of resistance and change the current landscape, disruptive approaches that challenge long-standing dogma will be needed. PMID:25043962

No evidential correlation between veterinary antibiotic degradation ability and resistance genes in microorganisms during the biodegradation of doxycycline.

PubMed

Wen, Xin; Wang, Yan; Zou, Yongde; Ma, Baohua; Wu, Yinbao

2018-01-01

Biodegradation of antibiotic residues in the environment by microorganisms may lead to the generation of antibiotic resistance genes (ARGs), which are of great concern to human health. The aim of this study was to determine whether there is a relationship between the ability to degrade antibiotic doxycycline (DOX) and the development of resistance genes in microorganisms. We isolated and identified ten bacterial strains from a vegetable field that had received long-term manure application as fertilizer and were capable of surviving in a series of DOX concentrations (25, 50, 80, and 100mg/L). Our results showed no evidential correlation between DOX degradation ability and the development of resistance genes among the isolated microorganisms that had high DOX degradation capability (P > 0.05). This was based on the fact that Escherichia sp. and Candida sp. were the most efficient bacterial strains to degrade DOX (92.52% and 91.63%, respectively), but their tetracycline resistance genes showed a relatively low risk of antibiotic resistance in a 7-day experiment. Moreover, the tetM of the ribosomal protection protein genes carried by these two preponderant bacteria was five-fold higher than that carried by other isolates (P < 0.05). Pearson correlations between the C t /C 0 of DOX and tet resistance genes of three isolates, except for Escherichia sp. and Candida sp., showed remarkable negative correlations (P < 0.05), mainly because tetG markedly increased during the DOX degradation process. Our results concluded that the biodegradation of antibiotic residues may not necessarily lead to the development of ARGs in the environment. In addition, the two bacteria that we isolated, namely, Escherichia sp. and Candida sp., are potential candidates for the engineering of environmentally friendly bacteria. Copyright © 2017 Elsevier Inc. All rights reserved.

The Comprehensive Antibiotic Resistance Database

PubMed Central

McArthur, Andrew G.; Waglechner, Nicholas; Nizam, Fazmin; Yan, Austin; Azad, Marisa A.; Baylay, Alison J.; Bhullar, Kirandeep; Canova, Marc J.; De Pascale, Gianfranco; Ejim, Linda; Kalan, Lindsay; King, Andrew M.; Koteva, Kalinka; Morar, Mariya; Mulvey, Michael R.; O'Brien, Jonathan S.; Pawlowski, Andrew C.; Piddock, Laura J. V.; Spanogiannopoulos, Peter; Sutherland, Arlene D.; Tang, Irene; Taylor, Patricia L.; Thaker, Maulik; Wang, Wenliang; Yan, Marie; Yu, Tennison

2013-01-01

The field of antibiotic drug discovery and the monitoring of new antibiotic resistance elements have yet to fully exploit the power of the genome revolution. Despite the fact that the first genomes sequenced of free living organisms were those of bacteria, there have been few specialized bioinformatic tools developed to mine the growing amount of genomic data associated with pathogens. In particular, there are few tools to study the genetics and genomics of antibiotic resistance and how it impacts bacterial populations, ecology, and the clinic. We have initiated development of such tools in the form of the Comprehensive Antibiotic Research Database (CARD; http://arpcard.mcmaster.ca). The CARD integrates disparate molecular and sequence data, provides a unique organizing principle in the form of the Antibiotic Resistance Ontology (ARO), and can quickly identify putative antibiotic resistance genes in new unannotated genome sequences. This unique platform provides an informatic tool that bridges antibiotic resistance concerns in health care, agriculture, and the environment. PMID:23650175

Effects of chlortetracycline on the fate of multi-antibiotic resistance genes and the microbial community during swine manure composting.

PubMed

Chen, Zhiqiang; Wang, Yao; Wen, Qinxue

2018-06-01

Excessive use of antibiotics in breeding industry leads to accumulation of antibiotic residuals and antibiotic resistance genes (ARGs) in environment from improperly treated livestock excrements. Four commonly used veterinary antibiotics including chlortetracycline (CTC), sulfamerazine (SMZ), enrofloxacin (ENR) and erythromycin (ERY) were monitored in the swine manure composting. Co-resistance and cross-resistance effects among relative ARGs, correlations between ARGs and bacterial community under multiple antibiotics residual during the composting were investigated in this research. With CTC addition up to 20 mg/kg, more than 99% of CTC removal was achieved after composting, and most of the other antibiotics can be thoroughly removed as well. The variations in ARGs during the composting were strongly correlated to the compositions of the microbial community, Bacteroides and Sporosarcina were main ARGs carriers in the thermophlic phase. Clostridium Ⅺ, Clostridium sensu stricto, and Pseudoxanthomonas, might spread ARGs in cooling and maturing stage. Most of the tested ARGs in swine manure can be effectively reduced through composting, thus makes the compost products safe for soil fertilization. Copyright © 2017 Elsevier Ltd. All rights reserved.

Microbial screening for quinolones residues in cow milk by bio-optical method.

PubMed

Appicciafuoco, Brunella; Dragone, Roberto; Frazzoli, Chiara; Bolzoni, Giuseppe; Mantovani, Alberto; Ferrini, Anna Maria

2015-03-15

The use of antibiotics on lactating cows should be monitored for the possible risk of milk contamination with residues. Accordingly, Maximum Residue Levels (MRLs) are established by the European Commission to guarantee consumers safety. As pointed out by Dec 2002/657/EC, screening is the first step in the strategy for antibiotic residue control, thus playing a key role in the whole control procedure. However, current routine screening methods applied in milk chain still fail to detect residues of quinolones at concentrations of interest. This paper reports the findings of a new bio-optical method for the screening of quinolones residues in bovine milk, based on E. coli ATCC 11303 growth inhibition. The effect of blank and spiked cow milk samples (aliquots equivalents to 0.8%, v/v) is evaluated in Mueller Hinton Broth (MHb) and MHb enriched with MgSO4 2% (MHb-Mg) inoculated with the test strain at the concentration of 10(4)CFU/mL. The presence of quinolones inhibits the cellular growth in MHb, while this effect is neutralized in MHb-Mg allowing both detection and presumptive identification of quinolones. Growth of the test strain is monitored at 37 °C in a Bioscreen C automated system, and Optical Density (OD) at 600 nm is recorded every 10 min after shaking for 10s. Growth curves (OD vs. time) of E. coli ATCC 11303 are assessed in milk samples, with and without quinolones, and their differences in terms of ΔOD (ΔOD600nm=ODMHb-Mg-ODMHb) are calculated. The presence of quinolones is detected by the cellular growth inhibition (OD vs time, none increase in the value OD) and presumptively identified through the increase of the slope of ΔOD600nm curve (ΔOD vs. time), after about 3h of incubation. The detection limit for ciprofloxacin and enrofloxacin is at the level of MRL, for marbofloxacin is at 2-fold the MRL whereas for danofloxacin is at 4-fold the MRL. Although the sensitivity of the method could be further improved and the procedure automated, it is a

A potent synthetic inorganic antibiotic with activity against drug-resistant pathogens

PubMed Central

Hubick, Shelby; Jayaraman, Arumugam; McKeen, Alexander; Reid, Shelby; Alcorn, Jane; Stavrinides, John; Sterenberg, Brian T.

2017-01-01

The acronymously named “ESKAPE” pathogens represent a group of bacteria that continue to pose a serious threat to human health, not only due to their propensity for repeated emergence, but also due to their ability to “eskape” antibiotic treatment12. The evolution of multi-drug resistance in these pathogens alone has greatly outpaced the development of new therapeutics, necessitating an alternative strategy for antibiotic development that considers the evolutionary mechanisms driving antibiotic resistance. In this study, we synthesize a novel inorganic antibiotic, phosphopyricin, which has antibiotic activity against the Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE). We show that this potent antibiotic is bactericidal, and exhibits low toxicity in an acute dose assay in mice. As a synthetic compound that does not occur naturally, phosphopyricin would be evolutionarily foreign to microbes, thereby slowing the evolution of resistance. In addition, it loses antibiotic activity upon exposure to light, meaning that the active antibiotic will not accumulate in the general environment where strong selective pressures imposed by antibiotic residuals are known to accelerate resistance. Phosphopyricin represents an innovation in antimicrobials, having a synthetic core, and a photosensitive chemical architecture that would reduce accumulation in the environment. PMID:28165020

Comparison of microbial growth inhibition screening assays with high-pressure liquid chromatography for detection of experimentally incurred penicillin G residues in calves.

PubMed

Musser, Jeffrey M B; Anderson, Kevin L; Boison, Joe O

2002-01-01

Twelve calves were fed milk replacer containing 3.33 ppm penicillin G for one feeding, and 12 calves were fed the medicated milk replacer once daily at a rate of 12% of their body weight for 14 days. Two calves served as controls. Calves were slaughtered 4 to 13 hours after being fed. Kidney, liver, muscle, and urine samples were assayed for penicillin by high-pressure liquid chromatography (HPLC). Penicillin G was not detected in any muscle samples and concentrations of penicillin exceeded the tolerance level (0.05 microg/g) in kidney or liver tissue from 13 of 24 treated-calf carcasses examined by HPLC. The Live Animal Swab Test identified all 13 carcasses with violative drug residues. Using kidney as the test matrix, the Swab Test on Premises identified 10 of 13 carcasses with violative drug residues, while the Calf Antibiotic Sulfa Test identified seven of 13 carcasses with violative residues.

Expedient antibiotics production: Final report

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

Bienkowski, P.R.; Byers, C.H.; Lee, D.D.

The literature on the manufacture, separation and purification, and clinical uses of antibiotics was reviewed, and a bibliography of the pertinent material was completed. Five antimicrobial drugs, penicillin V and G, (and amoxicillin with clavulanic acid), Cephalexin (a cephalosporin), tetracycline and oxytetracycline, Bacitracin (topical), and sulfonamide (chemically produced) were identified for emergency production. Plants that manufacture antibiotics in the continental United States, Mexico, and Puerto Rico have been identified along with potential alternate sites such as those where SCP, enzyme, and fermentation ethanol are produced. Detailed process flow sheets and process descriptions have been derived from the literature and documented.more » This investigation revealed that a typical antibiotic-manufacturing facility is composed of two main sections: (1) a highly specialized, but generic, fermentation unit and (2) a multistep, complex separation and purification unit which is specific to a particular antibiotic product. The fermentation section requires specialized equipment for operation in a sterile environment which is not usually available in other industries. The emergency production of antibiotics under austere conditions will be feasible only if a substantial reduction in the complexity and degree of separation and purity normally required can be realized. Detailed instructions were developed to assist state and federal officials who would be directing the resumption of antibiotic production after a nuclear attack. 182 refs., 54 figs., 26 tabs.« less

Dissemination of health information through social networks: twitter and antibiotics.

PubMed

Scanfeld, Daniel; Scanfeld, Vanessa; Larson, Elaine L

2010-04-01

This study reviewed Twitter status updates mentioning "antibiotic(s)" to determine overarching categories and explore evidence of misunderstanding or misuse of antibiotics. One thousand Twitter status updates mentioning antibiotic(s) were randomly selected for content analysis and categorization. To explore cases of potential misunderstanding or misuse, these status updates were mined for co-occurrence of the following terms: "cold + antibiotic(s)," "extra + antibiotic(s)," "flu + antibiotic(s)," "leftover + antibiotic(s)," and "share + antibiotic(s)" and reviewed to confirm evidence of misuse or misunderstanding. Of the 1000 status updates, 971 were categorized into 11 groups: general use (n = 289), advice/information (n = 157), side effects/negative reactions (n = 113), diagnosis (n = 102), resistance (n = 92), misunderstanding and/or misuse (n = 55), positive reactions (n = 48), animals (n = 46), other (n = 42), wanting/needing (n = 19), and cost (n = 8). Cases of misunderstanding or abuse were identified for the following combinations: "flu + antibiotic(s)" (n = 345), "cold + antibiotic(s)" (n = 302), "leftover + antibiotic(s)" (n = 23), "share + antibiotic(s)" (n = 10), and "extra + antibiotic(s)" (n = 7). Social media sites offer means of health information sharing. Further study is warranted to explore how such networks may provide a venue to identify misuse or misunderstanding of antibiotics, promote positive behavior change, disseminate valid information, and explore how such tools can be used to gather real-time health data. 2010 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Occurrence of antibiotics as emerging contaminant substances in aquatic environment.

PubMed

Milić, Nataša; Milanović, Maja; Letić, Nevena Grujić; Sekulić, Maja Turk; Radonić, Jelena; Mihajlović, Ivana; Miloradov, Mirjana Vojinović

2013-01-01

The occurrence of pharmaceutical residues in the environment has become a subject of growing concern. Due to the constant input of the emerging contaminants in the surface water via wastewater which leads to the long-term adverse effects on the aquatic and terrestrial organisms, special attention is being paid to their presence in the aquatic environment. Most of the emerging substances, especially pharmaceuticals, could not be completely removed using the wastewater treatment. Pharmaceuticals are usually water soluble and poorly degradable. They can pass through all natural filtrations and then reach the groundwater and, finally, the drinking water. The trace levels of antibiotics could have a negative impact on the environment and public health because of their inherent bioactivity. This article is an overview of the presence of the antibiotic residual concentrations, methods and levels of detection and possible risks to both health and environment.

Comparative outcomes of β-lactam antibiotics in outpatient parenteral antibiotic therapy: treatment success, readmissions and antibiotic switches.

PubMed

Lee, Boeun; Tam, Idy; Weigel, Bernard; Breeze, Janis L; Paulus, Jessica K; Nelson, Jason; Allison, Genève M

2015-08-01

β-Lactam antibiotics are commonly used in outpatient parenteral antimicrobial therapy (OPAT), but data regarding outcomes of long-term therapy are limited. The purpose of this study was to compare treatment success, readmission and antibiotic switch rates in patients treated with β-lactam antibiotics as OPAT. We carried out a retrospective review of all patients, discharged from Tufts Medical Center with cefazolin, ceftriaxone, ertapenem or oxacillin, between January 2009 and June 2013. A competing risks analysis was used to compare the cumulative incidence of first occurrence of treatment success, antibiotic switch and 30 day readmission for each drug. Four hundred patients were identified (cefazolin n = 38, ceftriaxone n = 104, ertapenem n = 128 and oxacillin n = 130). Baseline demographics were similar. Treatment success rates were higher for ceftriaxone and ertapenem (cefazolin 61%, ceftriaxone 81%, ertapenem 73% and oxacillin 58%; P < 0.001). Thirty-day all-cause readmissions were similar (cefazolin 21%, ceftriaxone 14%, ertapenem 20% and oxacillin 15%; P = 0.46). In 400 OPAT courses, 37 out of 50 antibiotic switches were accomplished without readmission. Adverse drug events (ADEs) were the most common reason for outpatient antibiotic switches (31/37, 84%). The ADE rate was higher for the oxacillin group (cefazolin 2.0 versus ceftriaxone 1.5 versus ertapenem 2.9 versus oxacillin 8.4 per 1000 OPAT days; P < 0.001). OPAT with β-lactam antibiotics is effective, but antibiotic switches for adverse events were more frequent with oxacillin use. Clinicians should be cognizant of the risk of readmissions and ADEs in OPAT patients, as the value of OPAT lies in reducing patient morbidity and readmissions by managing ADEs and preventing clinical failures. © 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.

Discharge of swine wastes risks water quality and food safety: Antibiotics and antibiotic resistance genes from swine sources to the receiving environments.

PubMed

He, Liang-Ying; Ying, Guang-Guo; Liu, You-Sheng; Su, Hao-Chang; Chen, Jun; Liu, Shuang-Shuang; Zhao, Jian-Liang

2016-01-01

Swine feedlots are widely considered as a potential hotspot for promoting the dissemination of antibiotic resistance genes (ARGs) in the environment. ARGs could enter the environment via discharge of animal wastes, thus resulting in contamination of soil, water, and food. We investigated the dissemination and diversification of 22 ARGs conferring resistance to sulfonamides, tetracyclines, chloramphenicols, and macrolides as well as the occurrence of 18 corresponding antibiotics from three swine feedlots to the receiving water, soil environments and vegetables. Most ARGs and antibiotics survived the on-farm waste treatment processes in the three swine farms. Elevated diversity of ARGs was observed in the receiving environments including river water and vegetable field soils when compared with respective controls. The variation of ARGs along the vertical soil profiles of vegetable fields indicated enrichment and migration of ARGs. Detection of various ARGs and antibiotic residues in vegetables fertilized by swine wastes could be of great concern to the general public. This research demonstrated the contribution of swine wastes to the occurrence and development of antibiotic resistance determinants in the receiving environments and potential risks to food safety and human health. Copyright © 2016 Elsevier Ltd. All rights reserved.

Combining modelling and mutagenesis studies of synaptic vesicle protein 2A to identify a series of residues involved in racetam binding.

PubMed

Shi, Jiye; Anderson, Dina; Lynch, Berkley A; Castaigne, Jean-Gabriel; Foerch, Patrik; Lebon, Florence

2011-10-01

LEV (levetiracetam), an antiepileptic drug which possesses a unique profile in animal models of seizure and epilepsy, has as its unique binding site in brain, SV2A (synaptic vesicle protein 2A). Previous studies have used a chimaeric and site-specific mutagenesis approach to identify three residues in the putative tenth transmembrane helix of SV2A that, when mutated, alter binding of LEV and related racetam derivatives to SV2A. In the present paper, we report a combined modelling and mutagenesis study that successfully identifies another 11 residues in SV2A that appear to be involved in ligand binding. Sequence analysis and modelling of SV2A suggested residues equivalent to critical functional residues of other MFS (major facilitator superfamily) transporters. Alanine scanning of these and other SV2A residues resulted in the identification of residues affecting racetam binding, including Ile273 which differentiated between racetam analogues, when mutated to alanine. Integrating mutagenesis results with docking analysis led to the construction of a mutant in which six SV2A residues were replaced with corresponding SV2B residues. This mutant showed racetam ligand-binding affinity intermediate to the affinities observed for SV2A and SV2B.

Antibiotic use in heavy pigs: Comparison between urine and muscle samples from food chain animals analysed by HPLC-MS/MS.

PubMed

Chiesa, Luca Maria; Nobile, Maria; Panseri, Sara; Arioli, Francesco

2017-11-15

The antibiotic overuse in zoothechnics, due to prophylactic and therapeutic treatments, or to their growth-promoting activity, is a major cause for the onset of widespread antibiotic resistance. Of particular relevance to this study, is the antibiotic abuse in pig breeding. Despite the comprehensive literature on residue controls in pig muscle, data on pig urine, a non-invasive, on-farm collectable matrix, are lacking. Therefore, we validated an HPLC-MS/MS method to detect 29 antimicrobials from eight classes and applied it to 43 anonymous pig urine and muscle paired samples and fulfilled the parameters in agreement with the Commission Decision 2002/657/UE. The analytical limits were moreover much lower than the maximum residue limits (MRLs) required by the Commission Regulation 37/2010/UE. In the samples, antibiotics were usually detected at higher frequencies and concentrations in urine than muscle. Urine proved a useful tool to detect antibiotic administration and their excessive use in pig farming is depicted. Copyright © 2017. Published by Elsevier Ltd.

Automatic phylogenetic classification of bacterial beta-lactamase sequences including structural and antibiotic substrate preference information.

PubMed

Ma, Jianmin; Eisenhaber, Frank; Maurer-Stroh, Sebastian

2013-12-01

Beta lactams comprise the largest and still most effective group of antibiotics, but bacteria can gain resistance through different beta lactamases that can degrade these antibiotics. We developed a user friendly tree building web server that allows users to assign beta lactamase sequences to their respective molecular classes and subclasses. Further clinically relevant information includes if the gene is typically chromosomal or transferable through plasmids as well as listing the antibiotics which the most closely related reference sequences are known to target and cause resistance against. This web server can automatically build three phylogenetic trees: the first tree with closely related sequences from a Tachyon search against the NCBI nr database, the second tree with curated reference beta lactamase sequences, and the third tree built specifically from substrate binding pocket residues of the curated reference beta lactamase sequences. We show that the latter is better suited to recover antibiotic substrate assignments through nearest neighbor annotation transfer. The users can also choose to build a structural model for the query sequence and view the binding pocket residues of their query relative to other beta lactamases in the sequence alignment as well as in the 3D structure relative to bound antibiotics. This web server is freely available at http://blac.bii.a-star.edu.sg/.

Seasonal and temporal variation in release of antibiotics in hospital wastewater: estimation using continuous and grab sampling.

PubMed

Diwan, Vishal; Stålsby Lundborg, Cecilia; Tamhankar, Ashok J

2013-01-01

The presence of antibiotics in the environment and their subsequent impact on resistance development has raised concerns globally. Hospitals are a major source of antibiotics released into the environment. To reduce these residues, research to improve knowledge of the dynamics of antibiotic release from hospitals is essential. Therefore, we undertook a study to estimate seasonal and temporal variation in antibiotic release from two hospitals in India over a period of two years. For this, 6 sampling sessions of 24 hours each were conducted in the three prominent seasons of India, at all wastewater outlets of the two hospitals, using continuous and grab sampling methods. An in-house wastewater sampler was designed for continuous sampling. Eight antibiotics from four major antibiotic groups were selected for the study. To understand the temporal pattern of antibiotic release, each of the 24-hour sessions were divided in three sub-sampling sessions of 8 hours each. Solid phase extraction followed by liquid chromatography/tandem mass spectrometry (LC-MS/MS) was used to determine the antibiotic residues. Six of the eight antibiotics studied were detected in the wastewater samples. Both continuous and grab sampling methods indicated that the highest quantities of fluoroquinolones were released in winter followed by the rainy season and the summer. No temporal pattern in antibiotic release was detected. In general, in a common timeframe, continuous sampling showed less concentration of antibiotics in wastewater as compared to grab sampling. It is suggested that continuous sampling should be the method of choice as grab sampling gives erroneous results, it being indicative of the quantities of antibiotics present in wastewater only at the time of sampling. Based on our studies, calculations indicate that from hospitals in India, an estimated 89, 1 and 25 ng/L/day of fluroquinolones, metronidazole and sulfamethoxazole respectively, might be getting released into the

Screening blood samples to estimate when oxytetverycline residues exceed regulatory tolerances in poultry muscle

USDA-ARS?s Scientific Manuscript database

The presence of antibiotic residues in edible animal products is a human food safety concern. To address this potential problem, the government samples edible tissues, such as muscle, to monitor for residues. Due to loss of valuable product and analytical difficulties only a small percentage of po...

Evaluation of a microbiological indicator test for antibiotic detection in ewe and goat milk.

PubMed

Comunian, R; Paba, A; Dupré, I; Daga, E S; Scintu, M F

2010-12-01

Antibiotics are widely used for therapeutic and prophylactic purposes in dairy animals. The presence of residual antibiotics in milk could cause potentially serious problems in human health and have technological implication in the manufacturing of dairy products. The aim of this study was to evaluate Delvotest Accelerator (DSM Food Specialties, Delft, the Netherlands), a new system for a fully automated microbial test to detect antibiotic residues in ewe and goat milk. Forty-three samples of raw, whole, refrigerated bulk-tank milk samples (22 of ewe milk and 21 of goat milk) were analyzed during the whole lactation period. Four concentrations of 4 antibiotics were diluted in milk: penicillin G at 1, 2, 3, and 4 μg/L; sulfadiazine at 25, 50, 100, and 200 μg/L; tetracycline at 50, 100, 200, and 400 μg/L; and gentamicin at 25, 50, 100, and 200 μg/L. The detection limit of the Delvotest Accelerator was calculated as the range of antibiotic concentrations within which 95% of positive result lie. The range of detection limit of penicillin G and sulfadiazine was easily detected by Delvotest Accelerator at or below the European Union maximum residue limits, both for ewe and goat milk samples. In contrast, the system showed a lower ability to detect tetracycline and gentamicin both for ewe and goat milk samples. Very low percentages of false-positive outcomes were obtained. Lactation phase did not seem to be a crucial factor affecting the ability of the Delvotest Accelerator to detect spiked milk samples. A higher detection ability was observed for goat milk samples compared with ewe milk samples. A negative correlation between the percentage of positive milk samples detected and milk fat, protein, and lactose contents was observed for gentamicin only. Copyright © 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The mycobacterial antibiotic resistance determinant WhiB7 acts as a transcriptional activator by binding the primary sigma factor SigA (RpoV)

PubMed Central

Burian, Ján; Yim, Grace; Hsing, Michael; Axerio-Cilies, Peter; Cherkasov, Artem; Spiegelman, George B.; Thompson, Charles J.

2013-01-01

Tuberculosis therapeutic options are limited by the high intrinsic antibiotic resistance of Mycobacterium tuberculosis. The putative transcriptional regulator WhiB7 is crucial for the activation of systems that provide resistance to diverse antibiotic classes. Here, we used in vitro run-off, two-hybrid assays, as well as mutagenic, complementation and protein pull-down experiments, to characterize WhiB7 as an auto-regulatory, redox-sensitive transcriptional activator in Mycobacterium smegmatis. We provide the first direct biochemical proof that a WhiB protein promotes transcription and also demonstrate that this activity is sensitive to oxidation (diamide). Its partner protein for transcriptional activation was identified as SigA, the primary sigma factor subunit of RNA polymerase. Residues required for the interaction mapped to region 4 of SigA (including R515H) or adjacent domains of WhiB7 (including E63D). WhiB7’s ability to provide a specific spectrum of antibiotic-resistance was dependent on these residues as well as its C-terminal AT-hook module that binds to an AT-rich motif immediately upstream of the −35 hexamer recognized by SigA. These experimentally established constrains, combined with protein structure predictions, were used to generate a working model of the WhiB7–SigA-promoter complex. Inhibitors preventing WhiB7 interactions could allow the use of previously ineffective antibiotics for treatment of mycobacterial diseases. PMID:23990327

Antibiotic Adjuvants: Rescuing Antibiotics from Resistance.

PubMed

Wright, Gerard D

2016-11-01

Rooted in the mechanism of action of antibiotics and subject to bacterial evolution, antibiotic resistance is difficult and perhaps impossible to overcome. Nevertheless, strategies can be used to minimize the emergence and impact of resistance. Antibiotic adjuvants offer one such approach. These are compounds that have little or no antibiotic activity themselves but act to block resistance or otherwise enhance antibiotic action. Antibiotic adjuvants are therefore delivered in combination with antibiotics and can be divided into two groups: Class I agents that act on the pathogen, and Class II agents that act on the host. Adjuvants offer a means to both suppress the emergence of resistance and rescue the activity of existing drugs, offering an orthogonal strategy complimentary to new antibiotic discovery VIDEO ABSTRACT. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Prevalence of antibiotic resistance genes in the bacterial flora of integrated fish farming environments of Pakistan and Tanzania.

PubMed

Shah, Syed Q A; Colquhoun, Duncan J; Nikuli, Hamisi L; Sørum, Henning

2012-08-21

The use of a wide variety of antimicrobials in human and veterinary medicine, including aquaculture, has led to the emergence of antibiotic resistant pathogens. In the present study, bacteria from water, sediments, and fish were collected from fish farms in Pakistan and Tanzania with no recorded history of antibiotic use. The isolates were screened for the presence of resistance genes against various antimicrobials used in aquaculture and animal husbandry. Resistant isolates selected by disk diffusion and genotyped by Southern hybridization were further screened by polymerase chain reaction (PCR) and amplicon sequencing. The prominent resistance genes identified encoded tetracycline [tetA(A) and tetA(G)], trimethoprim [dfrA1, dfrA5, dfrA7, dfrA12, and dfrA15], amoxicillin [bla(TEM)], streptomycin [strA-strB], chloramphenicol [cat-1], and erythromycin resistance [mefA]. The int1 gene was found in more than 30% of the bacterial isolates in association with gene cassettes. MAR indices ranged from 0.2 to 1. The bla(NDM-1) gene was not identified in ertapenem resistant isolates. It is hypothesized that integrated fish farming practices utilizing domestic farm and poultry waste along with antibiotic residues from animal husbandry may have contributed to a pool of resistance genes in the aquaculture systems studied.

Evaluation of chemical labeling methods for identifying functional arginine residues of proteins by mass spectrometry.

PubMed

Wanigasekara, Maheshika S K; Chowdhury, Saiful M

2016-09-07

Arginine residues undergo several kinds of post-translational modifications (PTMs). These PTMs are associated with several inflammatory diseases, such as rheumatoid arthritis, atherosclerosis, and diabetes. Mass spectrometric studies of arginine modified proteins and peptides are very important, not only to identify the reactive arginine residues but also to understand the tandem mass spectrometry behavior of these peptides for assigning the sequences unambiguously. Herein, we utilize tandem mass spectrometry to report the performance of two widely used arginine labeling reagents, 1,2-cyclohexanedione (CHD) and phenylglyoxal (PG) with several arginine containing peptides and proteins. Time course labeling studies were performed to demonstrate the selectivity of the reagents in proteins or protein digests. Structural studies on the proteins were also explored to better understand the reaction sites and position of arginine residues. We found CHD showed better labeling efficiencies compared to phenylglyoxal. Reactive arginine profiling on a purified albumin protein clearly pointed out the cellular glycation modification site for this protein with high confidence. We believe these detailed mass-spectrometric studies will provide significant input to profile reactive arginine residues in large-scale studies; therefore, targeted proteomics can be performed to the short listed reactive sites for cellular arginine modifications. Copyright © 2016 Elsevier B.V. All rights reserved.

Characterisation of the selective binding of antibiotics vancomycin and teicoplanin by the VanS receptor regulating type A vancomycin resistance in the enterococci.

PubMed

Hughes, C S; Longo, E; Phillips-Jones, M K; Hussain, R

2017-08-01

A-type resistance towards "last-line" glycopeptide antibiotic vancomycin in the leading hospital acquired infectious agent, the enterococci, is the most common in the UK. Resistance is regulated by the VanR A S A two-component system, comprising the histidine sensor kinase VanS A and the partner response regulator VanR A . The nature of the activating ligand for VanS A has not been identified, therefore this work sought to identify and characterise ligand(s) for VanS A . In vitro approaches were used to screen the structural and activity effects of a range of potential ligands with purified VanS A protein. Of the screened ligands (glycopeptide antibiotics vancomycin and teicoplanin, and peptidoglycan components N-acetylmuramic acid, D-Ala-D-Ala and Ala-D-y-Glu-Lys-D-Ala-D-Ala) only glycopeptide antibiotics vancomycin and teicoplanin were found to bind VanS A with different affinities (vancomycin 70μM; teicoplanin 30 and 170μM), and were proposed to bind via exposed aromatic residues tryptophan and tyrosine. Furthermore, binding of the antibiotics induced quicker, longer-lived phosphorylation states for VanS A , proposing them as activators of type A vancomycin resistance in the enterococci. Copyright © 2017 Diamond Light Source Ltd. Published by Elsevier B.V. All rights reserved.

Electrochemical oxidation of tetracycline antibiotics using a Ti/IrO2 anode for wastewater treatment of animal husbandry.

PubMed

Miyata, M; Ihara, I; Yoshid, G; Toyod, K; Umetsu, K

2011-01-01

In animal husbandry, antibiotics are widely used to treat and prevent diseases or to promote growth. The use of antibiotics for domestic animals enables to promote safety of livestock products and enhance productivity. Tetracycline antibiotics (TCs) are one of the primarily used groups of antibiotics for cattle and swine. However, the unintentional spreading of antibiotics from animal waste to the environment may leave out drug residues, promoting resistant strains of bacteria, and will adversely affect the ecosystem and human health. To prevent the spread of veterinary antibiotics in the environment, it is required to treat residual antibiotics in livestock wastewater. In this study, we investigated the electrochemical oxidation of TCs to treat livestock wastewater. The concentrations of TCs in aqueous solutions were reduced from 100 mg/L to less than 0.6 mg/L by 6 h of electrochemical treatment using a Ti/IrO2 anode with Na2SO4 electrolyte. The concentration of oxytetracycline (OTC) in livestock wastewater was also reduced from 100 mg/L to less than 0.7 mg/L by the same treatment. Thus, the electrochemical oxidation using a Ti/IrO2 anode with Na2SO4 electrolyte was found to be effective for degradation of TCs. The results suggest that the electrochemical oxidation method is a promising treatment for TCs in livestock wastewater.

Identifying Residual Speech Sound Disorders in Bilingual Children: A Japanese-English Case Study

PubMed Central

Preston, Jonathan L.; Seki, Ayumi

2012-01-01

Purpose The purposes are to (1) describe the assessment of residual speech sound disorders (SSD) in bilinguals by distinguishing speech patterns associated with second language acquisition from patterns associated with misarticulations, and (2) describe how assessment of domains such as speech motor control and phonological awareness can provide a more complete understanding of SSDs in bilinguals. Method A review of Japanese phonology is provided to offer a context for understanding the transfer of Japanese to English productions. A case study of an 11-year-old is presented, demonstrating parallel speech assessments in English and Japanese. Speech motor and phonological awareness tasks were conducted in both languages. Results Several patterns were observed in the participant’s English that could be plausibly explained by the influence of Japanese phonology. However, errors indicating a residual SSD were observed in both Japanese and English. A speech motor assessment suggested possible speech motor control problems, and phonological awareness was judged to be within the typical range of performance in both languages. Conclusion Understanding the phonological characteristics of L1 can help clinicians recognize speech patterns in L2 associated with transfer. Once these differences are understood, patterns associated with a residual SSD can be identified. Supplementing a relational speech analysis with measures of speech motor control and phonological awareness can provide a more comprehensive understanding of a client’s strengths and needs. PMID:21386046

Dissemination of antibiotic resistance genes and human pathogenic bacteria from a pig feedlot to the surrounding stream and agricultural soils.

PubMed

Fang, Hua; Han, Lingxi; Zhang, Houpu; Long, Zhengnan; Cai, Lin; Yu, Yunlong

2018-05-29

The dissemination of antibiotic resistance genes (ARGs), human pathogenic bacteria (HPB), and antibiotic-resistant HPB (ARHPB) from animal feedlot to nearby environment poses a potentially high risk to environmental ecology and public health. Here, a metagenomic analysis was employed to explore the dissemination of ARGs, HPB, and ARHPB from a pig feedlot to surrounding stream and agricultural soils. In total, not detectable (ND)-1,628.4 μg/kg of antibiotic residues, 18 types of ARGs, 48 HPB species, and 216 ARB isolates were detected in all samples. Antibiotic residues from pig feedlot mainly migrated into stream sediments and greenhouse soil. The dominant ARGs and HPB species from pig feedlot spread into stream sediments (tetracycline resistance genes, Clostridium difficile, and Mycobacterium tuberculosis), stream water (multidrug resistance (MDR) genes, Shigella flexneri, and Bordetella pertussis), and greenhouse soil (MDR genes, Bacillus anthracis, and Brucella melitensis). It is concerning that 54.4% of 216 ARB isolates from all samples were potential ARHPB species, and genome sequencing and functional annotation of 4 MDR HPB isolates showed 9 ARG types. Our findings revealed the potential migration and dissemination of antibiotic residues, ARGs, HPB, and ARHPB from pig feedlot to surrounding stream and agricultural soils via pig sewage discharge and manure fertilization. Copyright © 2018 Elsevier B.V. All rights reserved.

Broad-spectrum antibiotics in Norwegian hospitals.

PubMed

Holen, Øyunn; Alberg, Torunn; Blix, Hege Salvesen; Smith, Ingrid; Neteland, Marion Iren; Eriksen, Hanne Merete

2017-03-01

BACKGROUND One of the objectives in the action plan to reduce antimicrobial resistance in the health services in Norway is to reduce the use of broad-spectrum antibiotics in Norwegian hospitals. This study describes the use of certain broad-spectrum antibiotics mentioned in the action plan in Norwegian hospitals, and assesses prescribing practices in relation to the Norwegian guidelines for antibiotic use in hospitals.MATERIAL AND METHOD Data were analysed from a nationwide non-identifiable point prevalence survey in May 2016 where all systemic use of antibiotics was recorded.RESULTS Broad-spectrum antibiotics accounted for 33 % of all antibiotics prescribed. Altogether 84 % of all broad-spectrum antibiotics were prescribed as treatment, 8 % were for prophylactic use, and 8 % were classified as other/unknown. Lower respiratory tract infections were the most frequent indication for treatment with broad-spectrum antibiotics, involving 30 % of all broad-spectrum treatment.INTERPRETATION This point prevalence survey in Norwegian hospitals in spring 2016 indicates a possibility for reducing the use of broad-spectrum antibiotics in the treatment of lower respiratory tract infections and for prophylactic use. Reduction of healthcare-associated infections may also contribute.

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

UPLC-MS/MS analysis of antibiotics in pharmaceutical effluent in Tunisia: ecotoxicological impact and multi-resistant bacteria dissemination.

PubMed

Tahrani, Leyla; Mehri, Ines; Reyns, Tim; Anthonissen, Roel; Verschaeve, Luc; Khalifa, Anis Bel Haj; Loco, Joris Van; Abdenaceur, Hassen; Mansour, Hedi Ben

2018-05-01

The UPLC MS/MS analysis showed the presence of the two antibiotics in the pharmaceutical industry discharges during 3 months; norfloxacin and spiramycin which were quantified with the mean concentrations of 226.7 and 84.2 ng mL -1 , respectively. Sixteen resistant isolates were obtained from the pharmaceutical effluent and identified by sequencing. These isolates belong to different genera, namely Citrobacter, Acinetobacter, Pseudomonas, Delftia, Shewanella, and Rheinheimera. The antibiotic resistance phenotypes of these isolates were determined (27 tested antibiotics-discs). All the studied isolates were found resistant to amoxicillin and gentamicin, and 83.33% of isolates were resistant to ciprofloxacin. Multiple antibiotic resistances were revealed against β-lactams, quinolones, and aminoglycosides families. Our overall results suggest that the obtained bacterial isolates may constitute potential candidates for bioremediation and can be useful for biotechnological applications. Genotoxic effects were assessed by a battery of biotests; the pharmaceutical wastewater was genotoxic according to the bacterial Vitotox test and micronuclei test. Genotoxicity was also evaluated by the comet test; the tail DNA damages reached 38 and 22% for concentrated sample (10×) and non-concentrated sample (1×), respectively. However, the histological sections of kidney and liver's mice treated by pharmaceutical effluent showed normal histology and no visible structural effects or alterations as cytolysis, edema, or ulcerative necrosis were observed. Residual antibiotics can reach water environment through wastewater and provoke dissemination of the antibiotics resistance and induce genotoxic effects.

Treatment of tetracycline antibiotics by laccase in the presence of 1-hydroxybenzotriazole.

PubMed

Suda, Tomoyo; Hata, Takayuki; Kawai, Shingo; Okamura, Hideo; Nishida, Tomoaki

2012-01-01

Tetracycline antibiotics are widely used in human and veterinary medicine; however, residual amounts of these antibiotics in the environment are of concern since they could contribute to selection of resistant bacteria. In this study, tetracycline (TC), chlortetracycline (CTC), doxycycline (DC) and oxytetracycline (OTC) were treated with laccase from the white rot fungus Trametes versicolor in the presence of the redox mediator 1-hydroxybenzotriazole (HBT). High performance liquid chromatography demonstrated that DC and CTC were completely eliminated after 15 min, while TC and CTC were eliminated after 1 h. This system also resulted in a complete loss of inhibition of growth of Escherichia coli and Bacillus subtilis and the green alga Pseudokirchneriella subcapitata with decreasing tetracycline antibiotic concentration. These results suggest that the laccase-HBT system is effective in eliminating tetracycline antibiotics and removing their ecotoxicity. Copyright © 2011 Elsevier Ltd. All rights reserved.

Genomic characterization of a new endophytic Streptomyces kebangsaanensis identifies biosynthetic pathway gene clusters for novel phenazine antibiotic production

PubMed Central

Remali, Juwairiah; Sarmin, Nurul ‘Izzah Mohd; Ng, Chyan Leong; Tiong, John J.L.; Aizat, Wan M.; Keong, Loke Kok

2017-01-01

Background Streptomyces are well known for their capability to produce many bioactive secondary metabolites with medical and industrial importance. Here we report a novel bioactive phenazine compound, 6-((2-hydroxy-4-methoxyphenoxy) carbonyl) phenazine-1-carboxylic acid (HCPCA) extracted from Streptomyces kebangsaanensis, an endophyte isolated from the ethnomedicinal Portulaca oleracea. Methods The HCPCA chemical structure was determined using nuclear magnetic resonance spectroscopy. We conducted whole genome sequencing for the identification of the gene cluster(s) believed to be responsible for phenazine biosynthesis in order to map its corresponding pathway, in addition to bioinformatics analysis to assess the potential of S. kebangsaanensis in producing other useful secondary metabolites. Results The S. kebangsaanensis genome comprises an 8,328,719 bp linear chromosome with high GC content (71.35%) consisting of 12 rRNA operons, 81 tRNA, and 7,558 protein coding genes. We identified 24 gene clusters involved in polyketide, nonribosomal peptide, terpene, bacteriocin, and siderophore biosynthesis, as well as a gene cluster predicted to be responsible for phenazine biosynthesis. Discussion The HCPCA phenazine structure was hypothesized to derive from the combination of two biosynthetic pathways, phenazine-1,6-dicarboxylic acid and 4-methoxybenzene-1,2-diol, originated from the shikimic acid pathway. The identification of a biosynthesis pathway gene cluster for phenazine antibiotics might facilitate future genetic engineering design of new synthetic phenazine antibiotics. Additionally, these findings confirm the potential of S. kebangsaanensis for producing various antibiotics and secondary metabolites. PMID:29201559

Detection of antibiotics in chicken eggs obtained from supermarkets in Ho Chi Minh City, Vietnam.

PubMed

Yamaguchi, Takahiro; Okihashi, Masahiro; Harada, Kazuo; Konishi, Yoshimasa; Uchida, Kotaro; Hoang Ngoc Do, Mai; Thi Bui, Long; Nguyen, Thinh Duc; Phan, Ha Bich; Dang Thien Bui, Huong; Nguyen, Phuc Do; Kajimura, Keiji; Kumeda, Yuko; Van Dang, Chinh; Hirata, Kazumasa; Yamamoto, Yoshimasa

2017-06-03

The residual levels of antibiotics in Vietnamese eggs were monitored from 2014 to 2015. A total of 111 egg packages, distributed by 11 different companies, were collected from supermarkets in Ho Chi Minh City and the levels of 28 antibiotics were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) screening method. Sixteen samples tested positive for antibiotics; a total of eight compounds (enrofloxacin, ciprofloxacin, norfloxacin, sulfadimethoxine, sulfamethazine, sulfamonomethoxine, tilmicosin and trimethoprim) were detected. Enrofloxacin was detected in eight samples, with two samples exhibiting concentrations exceeding 1,000 µg kg -1 . Tilmicosin was detected in three samples at a range of 49-568 µg kg -1 . We observed that two of the 11 companies frequently sold antibiotic-contaminated eggs (detection rates of 56 and 60%), suggesting that a number of companies do not regulate the use of antibiotics in egg-laying hens. Our findings indicate that livestock farmers require instruction regarding antibiotic use and that continual antibiotic monitoring is essential in Vietnam.

Newly identified essential amino acid residues affecting ^8-sphingolipid desaturase activity revealed by site-directed mutagenesis

USDA-ARS?s Scientific Manuscript database

In order to identify amino acid residues crucial for the enzymatic activity of ^8-sphingolipid desaturases, a sequence comparison was performed among ^8-sphingolipid desaturases and ^6-fatty acid desaturase from various plants. In addition to the known conserved cytb5 (cytochrome b5) HPGG motif and...

Approach to osteomyelitis treatment with antibiotic loaded PMMA.

PubMed

Wentao, Zhang; Lei, Guangyu; Liu, Yang; Wang, Wei; Song, Tao; Fan, Jinzhu

2017-01-01

To reduce the incidence of osteomyelitis infection, local antibiotic impregnated delivery systems are commonly used as a promising and effective approach to deliver high antibiotic concentrations at the infection site. The objective of this review was to provide a literature review regarding approach to osteomyelitis treatment with antibiotic loaded PMMA. Literature study regarding osteomyelitis treatment with antibiotic loaded carriers using key terms Antibiotic, osteomyelitis, biodegradable PMMA through published articles. Hands searching of bibliographies of identified articles were also undertaken. We concluded that Antibiotic-impregnated PMMA beads are useful options for the treatment of osteomyelitis for prolonged drug therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Experimental antibiotic treatment identifies potential pathogens of white band disease in the endangered Caribbean coral Acropora cervicornis.

PubMed

Sweet, M J; Croquer, A; Bythell, J C

2014-08-07

Coral diseases have been increasingly reported over the past few decades and are a major contributor to coral decline worldwide. The Caribbean, in particular, has been noted as a hotspot for coral disease, and the aptly named white syndromes have caused the decline of the dominant reef building corals throughout their range. White band disease (WBD) has been implicated in the dramatic loss of Acropora cervicornis and Acropora palmata since the 1970s, resulting in both species being listed as critically endangered on the International Union for Conservation of Nature Red list. The causal agent of WBD remains unknown, although recent studies based on challenge experiments with filtrate from infected hosts concluded that the disease is probably caused by bacteria. Here, we report an experiment using four different antibiotic treatments, targeting different members of the disease-associated microbial community. Two antibiotics, ampicillin and paromomycin, arrested the disease completely, and by comparing with community shifts brought about by treatments that did not arrest the disease, we have identified the likely candidate causal agent or agents of WBD. Our interpretation of the experimental treatments is that one or a combination of up to three specific bacterial types, detected consistently in diseased corals but not detectable in healthy corals, are likely causal agents of WBD. In addition, a histophagous ciliate (Philaster lucinda) identical to that found consistently in association with white syndrome in Indo-Pacific acroporas was also consistently detected in all WBD samples and absent in healthy coral. Treatment with metronidazole reduced it to below detection limits, but did not arrest the disease. However, the microscopic disease signs changed, suggesting a secondary role in disease causation for this ciliate. In future studies to identify a causal agent of WBD via tests of Henle-Koch's postulates, it will be vital to experimentally control for populations

Monitoring and determination of sulfonamide antibiotics (sulfamethoxydiazine, sulfamethazine, sulfamethoxazole and sulfadiazine) in imported Pangasius catfish products in Thailand using liquid chromatography coupled with tandem mass spectrometry.

PubMed

Jansomboon, Worawat; Boontanon, Suwanna Kitpati; Boontanon, Narin; Polprasert, Chongrak; Thi Da, Chau

2016-12-01

This research aimed to monitor the concentrations of sulfamethoxydiazine (SMD), sulfamethazine (SMT), sulfamethoxazole (SMX) and sulfadiazine (SDZ) in imported Pangasius catfish products in Thailand. The residues of the four sulfonamides (SAs) were analyzed by extraction process and liquid chromatography coupled with tandem mass spectrometry. The highest concentrations found were 10.97ng/g for SMD, 6.23ng/g for SMT, 11.13ng/g for SDZ and 245.91ng/g for SMX, which was higher than the European Union (EU) standard (100ng/g). Moreover, all samples contaminated with SMX also contained SMT, indicating that more than one antibiotic was used for production in the country of origin. Because Thai standards for antibiotics in food have not been completely set, all contaminated discovered would not be considered to be an illegal food, in which antibiotic residues may affect human health in the long term. Therefore, antibiotic residues in Pangasius catfish products should be continually regulated and monitored. Copyright © 2016 Elsevier Ltd. All rights reserved.

Gain-of-function mutations in beet DODA2 identify key residues for betalain pigment evolution.

PubMed

Bean, Alexander; Sunnadeniya, Rasika; Akhavan, Neda; Campbell, Annabelle; Brown, Matthew; Lloyd, Alan

2018-05-13

The key enzymatic step in betalain biosynthesis involves conversion of l-3,4-dihydroxyphenylalanine (l-DOPA) to betalamic acid. One class of enzymes capable of this is 3,4-dihydroxyphenylalanine 4,5-dioxygenase (DODA). In betalain-producing species, multiple paralogs of this gene are maintained. This study demonstrates which paralogs function in the betalain pathway and determines the residue changes required to evolve a betalain-nonfunctional DODA into a betalain-functional DODA. Functionalities of two pairs of DODAs were tested by expression in beets, Arabidopsis and yeast, and gene silencing was performed by virus-induced gene silencing. Site-directed mutagenesis identified amino acid residues essential for betalamic acid production. Beta vulgaris and Mirabilis jalapa both possess a DODA1 lineage that functions in the betalain pathway and at least one other lineage, DODA2, that does not. Site-directed mutagenesis resulted in betalain biosynthesis by a previously nonfunctional DODA, revealing key residues required for evolution of the betalain pathway. Divergent functionality of DODA paralogs, one clade involved in betalain biosynthesis but others not, is present in various Caryophyllales species. A minimum of seven amino acid residue changes conferred betalain enzymatic activity to a betalain-nonfunctional DODA paralog, providing insight into the evolution of the betalain pigment pathway in plants. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

OXIDATION OF ANTIBIOTICS IN WASTEWATER: IDENTIFYING PRODUCTS AND IMPACTS ON ANTIBACTERIAL ACTIVITY

EPA Science Inventory

It is hypothesized that advanced oxidation can be applied effectively and in an economically responsible manner for the removal of the antibacterial activity of antibiotics. Ultimately, this study will develop a set of recommendations for the application of advanced oxidation ...

Genomic Microbial Epidemiology Is Needed to Comprehend the Global Problem of Antibiotic Resistance and to Improve Pathogen Diagnosis

PubMed Central

Wyrsch, Ethan R.; Roy Chowdhury, Piklu; Chapman, Toni A.; Charles, Ian G.; Hammond, Jeffrey M.; Djordjevic, Steven P.

2016-01-01

Contamination of waste effluent from hospitals and intensive food animal production with antimicrobial residues is an immense global problem. Antimicrobial residues exert selection pressures that influence the acquisition of antimicrobial resistance and virulence genes in diverse microbial populations. Despite these concerns there is only a limited understanding of how antimicrobial residues contribute to the global problem of antimicrobial resistance. Furthermore, rapid detection of emerging bacterial pathogens and strains with resistance to more than one antibiotic class remains a challenge. A comprehensive, sequence-based genomic epidemiological surveillance model that captures essential microbial metadata is needed, both to improve surveillance for antimicrobial resistance and to monitor pathogen evolution. Escherichia coli is an important pathogen causing both intestinal [intestinal pathogenic E. coli (IPEC)] and extraintestinal [extraintestinal pathogenic E. coli (ExPEC)] disease in humans and food animals. ExPEC are the most frequently isolated Gram negative pathogen affecting human health, linked to food production practices and are often resistant to multiple antibiotics. Cattle are a known reservoir of IPEC but they are not recognized as a source of ExPEC that impact human or animal health. In contrast, poultry are a recognized source of multiple antibiotic resistant ExPEC, while swine have received comparatively less attention in this regard. Here, we review what is known about ExPEC in swine and how pig production contributes to the problem of antibiotic resistance. PMID:27379026

Genomic Microbial Epidemiology Is Needed to Comprehend the Global Problem of Antibiotic Resistance and to Improve Pathogen Diagnosis.

PubMed

Wyrsch, Ethan R; Roy Chowdhury, Piklu; Chapman, Toni A; Charles, Ian G; Hammond, Jeffrey M; Djordjevic, Steven P

2016-01-01

Contamination of waste effluent from hospitals and intensive food animal production with antimicrobial residues is an immense global problem. Antimicrobial residues exert selection pressures that influence the acquisition of antimicrobial resistance and virulence genes in diverse microbial populations. Despite these concerns there is only a limited understanding of how antimicrobial residues contribute to the global problem of antimicrobial resistance. Furthermore, rapid detection of emerging bacterial pathogens and strains with resistance to more than one antibiotic class remains a challenge. A comprehensive, sequence-based genomic epidemiological surveillance model that captures essential microbial metadata is needed, both to improve surveillance for antimicrobial resistance and to monitor pathogen evolution. Escherichia coli is an important pathogen causing both intestinal [intestinal pathogenic E. coli (IPEC)] and extraintestinal [extraintestinal pathogenic E. coli (ExPEC)] disease in humans and food animals. ExPEC are the most frequently isolated Gram negative pathogen affecting human health, linked to food production practices and are often resistant to multiple antibiotics. Cattle are a known reservoir of IPEC but they are not recognized as a source of ExPEC that impact human or animal health. In contrast, poultry are a recognized source of multiple antibiotic resistant ExPEC, while swine have received comparatively less attention in this regard. Here, we review what is known about ExPEC in swine and how pig production contributes to the problem of antibiotic resistance.

Antibiotic identification, use, and self-medication for respiratory illnesses among urban Latinos

PubMed Central

Landers, Timothy F.; Ferng, Yu-hui; McLoughlin, Jennifer Wong; Barrett, Angela E.; Larson, Elaine

2010-01-01

Purpose The purpose of this study was to describe the extent to which antibiotic and nonantibiotic medications commonly used for upper respiratory infections (URIs) were correctly identified by a sample of urban dwelling Latinas and the association of medication identification with antibiotic use and self-medication. Data sources One hundred women completed an interview and were asked to identify whether a list of 39 medications (17 antibiotics, 22 nonantibiotics) were antibiotics or not, whether anyone in the household had used the medication, their ages, and the source of the medication. Results Overall, participants correctly identified 62% of nonantibiotics and 34% of antibiotics. Seventy three (73%) women in the study reported antibiotic use by at least one member of the household in the past year. Among users, self-medication was reported in 67.2% of antibiotics for adults, but in only 2.4% of children. There was no difference in antibiotic recognition between those who self-medicated and those who did not, but antibiotic self-medication was associated with a significantly lower recognition of nonantibiotics (p = .01). Implications for practice Measures to improve antibiotic utilization should address self-medication and consider the cultural and social context in which antibiotic use occurs. PMID:20854641

Use of antibiotics in paediatric long-term care facilities.

PubMed

Murray, M T; Johnson, C L; Cohen, B; Jackson, O; Jones, L K; Saiman, L; Larson, E L; Neu, N

2018-06-01

Adult long-term care (LTC) facilities have high rates of antibiotic use, raising concerns about antimicrobial resistance. Few studies have examined antibiotic use in paediatric LTC facilities. To describe antibiotic use in three paediatric LTC facilities and to describe the factors associated with use. A retrospective cohort study was conducted from September 2012 to December 2015 in three paediatric LTC facilities. Medical records were reviewed for demographics, healthcare-associated infections (HAIs), antimicrobial use and diagnostic testing. Logistic regression was used to identify predictors for antibiotic use. The association between susceptibility testing results and appropriate antibiotic coverage was determined using Chi-squared test. Fifty-eight percent (413/717) of residents had at least one HAI, and 79% (325/413) of these residents were treated with at least one antibiotic course, totalling 2.75 antibiotic courses per 1000 resident-days. Length of enrolment greater than one year, having a neurological disorder, having a tracheostomy, and being hospitalized at least once during the study period were significantly associated with receiving antibiotics when controlling for facility (all P < 0.001). Diagnostic testing was performed for 40% of antibiotic-treated HAIs. Eighty-six percent of antibiotic courses for identified bacterial pathogens (201/233) provided appropriate coverage. Access to susceptibility testing was not associated with appropriate antibiotic choice (P = 0.26). Use of antibiotics in paediatric LTC facilities is widespread. There is further need to assess antibiotic use in paediatric LTC facilities. Evaluation of the adverse outcomes associated with inappropriate antibiotic use, including the prevalence of resistant organisms in paediatric LTC facilities, is critical. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Effects of multiple antibiotics exposure on denitrification process in the Yangtze Estuary sediments.

PubMed

Yin, Guoyu; Hou, Lijun; Liu, Min; Zheng, Yanling; Li, Xiaofei; Lin, Xianbiao; Gao, Juan; Jiang, Xiaofen; Wang, Rong; Yu, Chendi

2017-03-01

Denitrification is a dominant reactive nitrogen removal pathway in most estuarine and coastal ecosystems, and plays a significant role in regulating N 2 O release. Although multiple antibiotics residues are widely detected in aquatic environment, combined effects of antibiotics on denitrification remain indistinct. In this work, 5 classes of antibiotics (sulfonamides, chloramphenicols, tetracyclines, macrolides, and fluoroquinolones) were selected to conduct orthogonal experiments in order to explore their combined effects on denitrification. 15 N-based denitrification and N 2 O release rates were determined in the orthogonal experiments, while denitrifying functional genes were examined to illustrate the microbial mechanism of the combined antibiotics effect. Denitrification rates were inhibited by antibiotics treatments, and synergistic inhibition effect was observed for multiple antibiotics exposure. Different classes of antibiotics had different influence on N 2 O release rates, but multiple antibiotics exposure mostly led to stimulatory effect. Abundances of denitrifying functional genes were inhibited by multiple antibiotics exposure due to the antimicrobial properties, and different inhibition on denitrifiers may be the major mechanism for the variations of N 2 O release rates. Combined effects of antibiotics on denitrification may lead to nitrate retention and N 2 O release in estuarine and coastal ecosystems, and consequently cause cascading environmental problems, such as greenhouse effects and hyper-eutrophication. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Prophylactic antibiotics for manual removal of retained placenta in vaginal birth.

PubMed

Chongsomchai, Chompilas; Lumbiganon, Pisake; Laopaiboon, Malinee

2014-10-20

Retained placenta is a potentially life-threatening condition because of its association with postpartum hemorrhage. Manual removal of placenta increases the likelihood of bacterial contamination in the uterine cavity. To compare the effectiveness and side-effects of routine antibiotic use for manual removal of placenta in vaginal birth in women who received antibiotic prophylaxis and those who did not and to identify the appropriate regimen of antibiotic prophylaxis for this procedure. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2014). All randomized controlled trials comparing antibiotic prophylaxis and placebo or non antibiotic use to prevent endometritis after manual removal of placenta in vaginal birth. There are no included trials. In future updates, if we identify eligible trials, two review authors will independently assess trial quality and extract data No studies that met the inclusion criteria were identified. There are no randomized controlled trials to evaluate the effectiveness of antibiotic prophylaxis to prevent endometritis after manual removal of placenta in vaginal birth.

Dissemination of health information through social networks: Twitter and antibiotics

PubMed Central

Scanfeld, Vanessa; Larson, Elaine L.

2010-01-01

Background This study reviewed Twitter status updates mentioning “antibiotic(s)” to determine overarching categories and explore evidence of misunderstanding or misuse of antibiotics. Methods One thousand Twitter status updates mentioning antibiotic(s) were randomly selected for content analysis and categorization. To explore cases of potential misunderstanding or misuse, these status updates were mined for co-occurrence of the following terms: “cold + antibiotic(s),” “extra antibiotic(s),” “flu + antibiotic(s),” “leftover antibiotic(s),” and “share antibiotic(s)” and reviewed to confirm evidence of misuse or misunderstanding. Results Of the 1,000 status updates, 971 were categorized into 11 groups: General Use (n=289), Advice/Information (n=157), Side Effects/Negative Reactions (n=113), Diagnosis (n=102), Resistance (n=92), Misunderstanding and/or Misuse (n=55), Positive Reactions (n=48), Animals (n=46), Other (n=42), Wanting/Needing (n=19), and Cost (n=8). Cases of misunderstanding or abuse were identified for the following combinations: “flu + antibiotic(s)” (n=345), “cold + antibiotic(s)” (n=302), “leftover antibiotic(s)” (n=23), “share antibiotic(s)” (n=10), and “extra antibiotic(s)” (n=7). Conclusions Social media sites offer means of health information sharing. Further study is warranted to explore how such networks may provide a venue to identify misuse or misunderstanding of antibiotics, promote positive behavior change, disseminate valid information, and explore how such tools can be used to gather real-time health data. PMID:20347636

Development of an antibiotic spectrum score based on veterans affairs culture and susceptibility data for the purpose of measuring antibiotic de-escalation: a modified Delphi approach.

PubMed

Madaras-Kelly, Karl; Jones, Makoto; Remington, Richard; Hill, Nicole; Huttner, Benedikt; Samore, Matthew

2014-09-01

Development of a numerical score to measure the microbial spectrum of antibiotic regimens (spectrum score) and method to identify antibiotic de-escalation events based on application of the score. Web-based modified Delphi method. Physician and pharmacist antimicrobial stewards practicing in the United States recruited through infectious diseases-focused listservs. Three Delphi rounds investigated: organisms and antibiotics to include in the spectrum score, operationalization of rules for the score, and de-escalation measurement. A 4-point ordinal scale was used to score antibiotic susceptibility for organism-antibiotic domain pairs. Antibiotic regimen scores, which represented combined activity of antibiotics in a regimen across all organism domains, were used to compare antibiotic spectrum administered early (day 2) and later (day 4) in therapy. Changes in spectrum score were calculated and compared with Delphi participants' judgments on de-escalation with 20 antibiotic regimen vignettes and with non-Delphi steward judgments on de-escalation of 300 pneumonia regimen vignettes. Method sensitivity and specificity to predict expert de-escalation status were calculated. Twenty-four participants completed all Delphi rounds. Expert support for concepts utilized in metric development was identified. For vignettes presented in the Delphi, the sign of change in score correctly classified de-escalation in all vignettes except those involving substitution of oral antibiotics. The sensitivity and specificity of the method to identify de-escalation events as judged by non-Delphi stewards were 86.3% and 96.0%, respectively. Identification of de-escalation events based on an algorithm that measures microbial spectrum of antibiotic regimens generally agreed with steward judgments of de-escalation status.

Isolation and characterization of lipopeptide antibiotics produced by Bacillus subtilis.

PubMed

Chen, H; Wang, L; Su, C X; Gong, G H; Wang, P; Yu, Z L

2008-09-01

Antibiotics from Bacillus subtilis JA show strong pathogen inhibition ability, which has potential market application; yet, the composition of these antibiotics has not been elucidated. The aim of this paper is to isolate and identify these antibiotics. The antagonistic activity of JA was tested in vitro; it exhibited strong inhibition against some important phytopathogens and postharvest pathogens. Crude antibiotic production was extracted with methanol from the precipitate by adding 6 mol l(-1) HCl to the bacillus-free culture broth. The crude extract was run on Diamonsil C18 column (5 microm, 250 x 4.6 mm) in HPLC system to separate the antibiotics. Major antibiotics were classified into three lipopeptide families according to electrospray ionization-mass spectrometry analysis. Subsequently, the classification of antibiotics was confirmed with typical collision-induced dissociation fragments. Three kinds of antibiotics were isolated from B. subtilis JA and were identified to the lipopeptide families, surfactin, iturin and fengycin. These compounds could function as biocontrol agents against a large spectrum of pathogens. This study provided a reliable and rapid method for isolation and structural characterization of lipopeptide antibiotics from B. subtilis.

Insights into an evolutionary strategy leading to antibiotic resistance

NASA Astrophysics Data System (ADS)

Hou, Chun-Feng D.; Liu, Jian-Wei; Collyer, Charles; Mitić, Nataša; Pedroso, Marcelo Monteiro; Schenk, Gerhard; Ollis, David L.

2017-01-01

Metallo-β-lactamases (MBLs) with activity towards a broad-spectrum of β-lactam antibiotics have become a major threat to public health, not least due to their ability to rapidly adapt their substrate preference. In this study, the capability of the MBL AIM-1 to evade antibiotic pressure by introducing specific mutations was probed by two alternative methods, i.e. site-saturation mutagenesis (SSM) of active site residues and in vitro evolution. Both approaches demonstrated that a single mutation in AIM-1 can greatly enhance a pathogen’s resistance towards broad spectrum antibiotics without significantly compromising the catalytic efficiency of the enzyme. Importantly, the evolution experiments demonstrated that relevant amino acids are not necessarily in close proximity to the catalytic centre of the enzyme. This observation is a powerful demonstration that MBLs have a diverse array of possibilities to adapt to new selection pressures, avenues that cannot easily be predicted from a crystal structure alone.

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.

The abundance of antibiotic resistance genes in human guts has correlation to the consumption of antibiotics in animal

PubMed Central

Hu, Yongfei; Yang, Xi; Lu, Na; Zhu, Baoli

2014-01-01

Increasing evidence has accumulated to support that the human gut is a reservoir for antibiotic resistance genes. We previously identified more than 1000 genes displaying high similarity with known antibiotic resistance genes in the human gut gene set generated from the Chinese, Danish, and Spanish populations. Here, first, we add our new understanding of antibiotic resistance genes in the US and the Japanese populations; next, we describe the structure of a vancomycin-resistant operon in a Danish sample; and finally, we provide discussions on the correlation of the abundance of resistance genes in human gut with the antibiotic consumption in human medicine and in animal husbandry. These results, combined with those we published previously, provide comprehensive insights into the antibiotic resistance genes in the human gut microbiota at a population level. PMID:24637798

The abundance of antibiotic resistance genes in human guts has correlation to the consumption of antibiotics in animal.

PubMed

Hu, Yongfei; Yang, Xi; Lu, Na; Zhu, Baoli

2014-01-01

Increasing evidence has accumulated to support that the human gut is a reservoir for antibiotic resistance genes. We previously identified more than 1000 genes displaying high similarity with known antibiotic resistance genes in the human gut gene set generated from the Chinese, Danish, and Spanish populations. Here, first, we add our new understanding of antibiotic resistance genes in the US and the Japanese populations; next, we describe the structure of a vancomycin-resistant operon in a Danish sample; and finally, we provide discussions on the correlation of the abundance of resistance genes in human gut with the antibiotic consumption in human medicine and in animal husbandry. These results, combined with those we published previously, provide comprehensive insights into the antibiotic resistance genes in the human gut microbiota at a population level.

Metagenomic analysis reveals the influences of milk containing antibiotics on the rumen microbes of calves.

PubMed

Li, Wei; Han, Yunsheng; Yuan, Xue; Wang, Guan; Wang, Zhibo; Pan, Qiqi; Gao, Yan; Qu, Yongli

2017-04-01

Milk containing antibiotics is used as cost-effective feed for calves, which may lead to antibiotic residues-associated food safety problems. This study aims to investigate the influence of antibiotics on rumen microbes. Through metagenomic sequencing, the rumen microbial communities of calves fed with pasteurized milk containing antibiotics (B1), milk containing antibiotics (B2) and fresh milk (B3) were explored. Each milk group included calves in 2 (T1), 3 (T2) and 6 (T3) months of age. Using FastQC software and SOAPdenovo 2, the filtered data, respectively, were performed with quality control and sequence splicing. Following KEGG annotation was conducted for the uploaded sequences using KAAS software. Using R software, both species abundance analysis and differential abundance analysis were performed. In the B1 samples, the species abundance of Bacteroidetes gradually decreased along with the extension of feeding time, while that of Fibrobacteres gradually increased. The species abundances of Proteobacteria (p value = 0.01) and Spirochaetes (p value = 0.03) had significant differences among T1, T2 and T3 samples. Meanwhile, only the species abundance of Spirochaetes (p value = 0.04) had significant difference among B1, B2 and B3 samples. Cell cycle involving GSK3β, CDK2 and CDK7 was significantly enriched for the differentially expressed genes in the T1 versus T2 and T1 versus T3 comparison groups. Milk containing antibiotics might have a great influence on these rumen microbes and lead to antibiotic residues-associated food safety problems. Furthermore, GSK3β, CDK2 and CDK7 in rumen bacteria might affect milk fat metabolism in early growth stages of calves.

Antibiotic Cycling and Antibiotic Mixing: Which One Best Mitigates Antibiotic Resistance?

PubMed Central

Peña-Miller, Rafael; Gori, Fabio; Iredell, Jonathan

2017-01-01

Abstract Can we exploit our burgeoning understanding of molecular evolution to slow the progress of drug resistance? One role of an infection clinician is exactly that: to foresee trajectories to resistance during antibiotic treatment and to hinder that evolutionary course. But can this be done at a hospital-wide scale? Clinicians and theoreticians tried to when they proposed two conflicting behavioral strategies that are expected to curb resistance evolution in the clinic, these are known as “antibiotic cycling” and “antibiotic mixing.” However, the accumulated data from clinical trials, now approaching 4 million patient days of treatment, is too variable for cycling or mixing to be deemed successful. The former implements the restriction and prioritization of different antibiotics at different times in hospitals in a manner said to “cycle” between them. In antibiotic mixing, appropriate antibiotics are allocated to patients but randomly. Mixing results in no correlation, in time or across patients, in the drugs used for treatment which is why theorists saw this as an optimal behavioral strategy. So while cycling and mixing were proposed as ways of controlling evolution, we show there is good reason why clinical datasets cannot choose between them: by re-examining the theoretical literature we show prior support for the theoretical optimality of mixing was misplaced. Our analysis is consistent with a pattern emerging in data: neither cycling or mixing is a priori better than the other at mitigating selection for antibiotic resistance in the clinic. Key words: antibiotic cycling, antibiotic mixing, optimal control, stochastic models. PMID:28096304

History of Antibiotics Research.

PubMed

Mohr, Kathrin I

2016-01-01

For thousands of years people were delivered helplessly to various kinds of infections, which often reached epidemic proportions and have cost the lives of millions of people. This is precisely the age since mankind has been thinking of infectious diseases and the question of their causes. However, due to a lack of knowledge, the search for strategies to fight, heal, and prevent the spread of communicable diseases was unsuccessful for a long time. It was not until the discovery of the healing effects of (antibiotic producing) molds, the first microscopic observations of microorganisms in the seventeenth century, the refutation of the abiogenesis theory, and the dissolution of the question "What is the nature of infectious diseases?" that the first milestones within the history of antibiotics research were set. Then new discoveries accelerated rapidly: Bacteria could be isolated and cultured and were identified as possible agents of diseases as well as producers of bioactive metabolites. At the same time the first synthetic antibiotics were developed and shortly thereafter, thousands of synthetic substances as well as millions of soil borne bacteria and fungi were screened for bioactivity within numerous microbial laboratories of pharmaceutical companies. New antibiotic classes with different targets were discovered as on assembly line production. With the beginning of the twentieth century, many of the diseases which reached epidemic proportions at the time-e.g., cholera, syphilis, plague, tuberculosis, or typhoid fever, just to name a few, could be combatted with new discovered antibiotics. It should be considered that hundred years ago the market launch of new antibiotics was significantly faster and less complicated than today (where it takes 10-12 years in average between the discovery of a new antibiotic until the launch). After the first euphoria it was quickly realized that bacteria are able to develop, acquire, and spread numerous resistance mechanisms

Microbial Contaminants of Cord Blood Units Identified by 16S rRNA Sequencing and by API Test System, and Antibiotic Sensitivity Profiling

PubMed Central

França, Luís; Simões, Catarina; Taborda, Marco; Diogo, Catarina; da Costa, Milton S.

2015-01-01

Over a period of ten months a total of 5618 cord blood units (CBU) were screened for microbial contamination under routine conditions. The antibiotic resistance profile for all isolates was also examined using ATB strips. The detection rate for culture positive units was 7.5%, corresponding to 422 samples.16S rRNA sequence analysis and identification with API test system were used to identify the culturable aerobic, microaerophilic and anaerobic bacteria from CBUs. From these samples we recovered 485 isolates (84 operational taxonomic units, OTUs) assigned to the classes Bacteroidia, Actinobacteria, Clostridia, Bacilli, Betaproteobacteria and primarily to the Gammaproteobacteria. Sixty-nine OTUs, corresponding to 447 isolates, showed 16S rRNA sequence similarities above 99.0% with known cultured bacteria. However, 14 OTUs had 16S rRNA sequence similarities between 95 and 99% in support of genus level identification and one OTU with 16S rRNA sequence similarity of 90.3% supporting a family level identification only. The phenotypic identification formed 29 OTUs that could be identified to the species level and 9 OTUs that could be identified to the genus level by API test system. We failed to obtain identification for 14 OTUs, while 32 OTUs comprised organisms producing mixed identifications. Forty-two OTUs covered species not included in the API system databases. The API test system Rapid ID 32 Strep and Rapid ID 32 E showed the highest proportion of identifications to the species level, the lowest ratio of unidentified results and the highest agreement to the results of 16S rRNA assignments. Isolates affiliated to the Bacilli and Bacteroidia showed the highest antibiotic multi-resistance indices and microorganisms of the Clostridia displayed the most antibiotic sensitive phenotypes. PMID:26512991

Microbial Contaminants of Cord Blood Units Identified by 16S rRNA Sequencing and by API Test System, and Antibiotic Sensitivity Profiling.

PubMed

França, Luís; Simões, Catarina; Taborda, Marco; Diogo, Catarina; da Costa, Milton S

2015-01-01

Over a period of ten months a total of 5618 cord blood units (CBU) were screened for microbial contamination under routine conditions. The antibiotic resistance profile for all isolates was also examined using ATB strips. The detection rate for culture positive units was 7.5%, corresponding to 422 samples.16S rRNA sequence analysis and identification with API test system were used to identify the culturable aerobic, microaerophilic and anaerobic bacteria from CBUs. From these samples we recovered 485 isolates (84 operational taxonomic units, OTUs) assigned to the classes Bacteroidia, Actinobacteria, Clostridia, Bacilli, Betaproteobacteria and primarily to the Gammaproteobacteria. Sixty-nine OTUs, corresponding to 447 isolates, showed 16S rRNA sequence similarities above 99.0% with known cultured bacteria. However, 14 OTUs had 16S rRNA sequence similarities between 95 and 99% in support of genus level identification and one OTU with 16S rRNA sequence similarity of 90.3% supporting a family level identification only. The phenotypic identification formed 29 OTUs that could be identified to the species level and 9 OTUs that could be identified to the genus level by API test system. We failed to obtain identification for 14 OTUs, while 32 OTUs comprised organisms producing mixed identifications. Forty-two OTUs covered species not included in the API system databases. The API test system Rapid ID 32 Strep and Rapid ID 32 E showed the highest proportion of identifications to the species level, the lowest ratio of unidentified results and the highest agreement to the results of 16S rRNA assignments. Isolates affiliated to the Bacilli and Bacteroidia showed the highest antibiotic multi-resistance indices and microorganisms of the Clostridia displayed the most antibiotic sensitive phenotypes.

Exploring the links between antibiotic occurrence, antibiotic resistance, and bacterial communities in water supply reservoirs.

PubMed

Huerta, Belinda; Marti, Elisabet; Gros, Meritxell; López, Pilar; Pompêo, Marcelo; Armengol, Joan; Barceló, Damià; Balcázar, Jose Luis; Rodríguez-Mozaz, Sara; Marcé, Rafael

2013-07-01

Antibiotic resistance represents a growing global health concern due to the overuse and misuse of antibiotics. There is, however, little information about how the selective pressure of clinical antibiotic usage can affect environmental communities in aquatic ecosystems and which bacterial groups might be responsible for dissemination of antibiotic resistance genes (ARGs) into the environment. In this study, chemical and biological characterization of water and sediments from three water supply reservoirs subjected to a wide pollution gradient allowed to draw an accurate picture of the concentration of antibiotics and prevalence of ARGs, in order to evaluate the potential role of ARGs in shaping bacterial communities, and to identify the bacterial groups most probably carrying and disseminating ARGs. Results showed significant correlation between the presence of ARG conferring resistance to macrolides and the composition of bacterial communities, suggesting that antibiotic pollution and the spreading of ARG might play a role in the conformation of bacterial communities in reservoirs. Results also pointed out the bacterial groups Actinobacteria and Firmicutes as the ones probably carrying and disseminating ARGs. The potential effect of antibiotic pollution and the presence of ARGs on the composition of bacterial communities in lacustrine ecosystems prompt the fundamental question about potential effects on bacterial-related ecosystem services supplied by lakes and reservoirs. Copyright © 2013 Elsevier B.V. All rights reserved.

Site-directed mutagenesis studies to probe the role of specific residues in the external loop (L3) of OmpF and OmpC porins in susceptibility of Serratia marcescens to antibiotics.

PubMed

Begic, Sanela; Worobec, Elizabeth A

2007-06-01

Serratia marcescens is a nosocomial bacterium with natural resistance to a broad spectrum of antibiotics, making treatment challenging. One factor contributing to this natural antibiotic resistance is reduced outer membrane permeability, controlled in part by OmpF and OmpC porin proteins. To investigate the direct role of these porins in the diffusion of antibiotics across the outer membrane, we have created an ompF-ompC porin-deficient strain of S. marcescens. A considerable similarity between the S. marcescens porins and those from other members of Enterobacteriaceae was detected by sequence alignment, with the exception of a change in a conserved region of the third external loop (L3) of the S. marcescens OmpC protein. Serratia marcescens OmpC has aspartic acid instead of glycine in position 112, methionine instead of aspartic acid in position 114, and glutamine in position 124, while in S. marcescens OmpF this is a glycine at position 124. To investigate the role of amino acid positions 112, 114, and 124 and how the observed changes within OmpC porin may play a part in pore permeability, 2 OmpC sites were altered in the Enterobacteriaceae consensus (D112G and M114D) through site-directed mutagenesis. Also, Q124G in OmpC, G124Q in OmpF, and double mutants of these amino acid residues were constructed. Antibiotic accumulation assays and minimal inhibitory concentrations of the strains harboring the mutated porins were performed, while liposome swelling experiments were performed on purified porins. Our results demonstrate that the amino acid at position 114 is not responsible for either antibiotic size or ionic selection, the amino acid at position 112 is responsible for size selection only, and position 124 is involved in both size and ionic selection.

Mechanisms of Antibiotic Resistance

PubMed Central

Munita, Jose M.; Arias, Cesar A.

2015-01-01

Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have emerged not only in the hospital environment but are now often identified in community settings, suggesting that reservoirs of antibiotic-resistant bacteria are present outside the hospital. The bacterial response to the antibiotic “attack” is the prime example of bacterial adaptation and the pinnacle of evolution. “Survival of the fittest” is a consequence of an immense genetic plasticity of bacterial pathogens that trigger specific responses that result in mutational adaptations, acquisition of genetic material or alteration of gene expression producing resistance to virtually all antibiotics currently available in clinical practice. Therefore, understanding the biochemical and genetic basis of resistance is of paramount importance to design strategies to curtail the emergence and spread of resistance and devise innovative therapeutic approaches against multidrug-resistant organisms. In this chapter, we will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice providing specific examples in relevant bacterial pathogens. PMID:27227291

Non-adherence to antibiotic therapy in patients visiting community pharmacies.

PubMed

Fernandes, Milene; Leite, Andreia; Basto, Maria; Nobre, Miguel Araújo; Vieira, Nuno; Fernandes, Rui; Nogueira, Paulo; Nicola, Paulo Jorge; Jorge, Paulo

2014-02-01

Patient non-adherence to antibiotic therapy may lead to therapeutic failure, re-infection, and bacterial resistance. Assessing the factors associated with this problem is important for promoting rational use of antibiotics. This study aimed to measure prevalence and reasons for non-adherence to antibiotic treatment and to identify associated factors. Patients were recruited for the study in community pharmacies in Lisbon, Portugal, from February to April, 2009. Data from prescriptions for oral antibiotics were collected for adult subjects. Adherence to treatment was assessed with a modified Portuguese version of the Morisky scale. Factors associated with non-adherence were identified through bivariate analysis and logistic regression models. A total of 243 patients were included in the study. They had a mean age 46.5 ± 16.6 years and 74.5 % of the sample was female. The prevalence of non-adherence was 57.7 % and was related to delays and failures in taking the prescribed medicine. Increasing age (OR 0.97), difficulty in buying the antibiotic (OR 2.34), duration of treatment (OR 1.28), difficulty with ingestion (OR 3.08), and satisfaction with the information given by physician (OR 0.33) were identified as independent factors associated with non-adherence. Non-adherence to antibiotics is common in the community setting. Factors related to the antibiotic, the patient, and the patient-physician relationship should be addressed to promote adherence. Pharmacists should provide information to patients about correct use of antibiotics and address barriers to adherence.

Occurrence and transformation of veterinary antibiotics and antibiotic resistance genes in dairy manure treated by advanced anaerobic digestion and conventional treatment methods.

PubMed

Wallace, Joshua S; Garner, Emily; Pruden, Amy; Aga, Diana S

2018-05-01

Manure treatment technologies are rapidly developing to minimize eutrophication of surrounding environments and potentially decrease the introduction of antibiotics and antibiotic resistant genes (ARGs) into the environment. While laboratory and pilot-scale manure treatment systems boast promising results, antibiotic and ARG removals in full-scale systems receiving continuous manure input have not been evaluated. The effect of treatment on ARGs is similarly lacking. This study examines the occurrence and transformation of sulfonamides, tetracyclines, tetracycline degradation products, and related ARGs throughout a full-scale advanced anaerobic digester (AAD) receiving continuous manure and antibiotic input. Manure samples were collected throughout the AAD system to evaluate baseline antibiotic and ARG input (raw manure), the effect of hygenization (post-pasteurized manure) and anaerobic digestion (post-digestion manure) on antibiotic and ARG levels. Antibiotics were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the ARGs tet(O), tet(W), sul1 and sul2 were analyzed by quantitative polymerase chain reaction (Q-PCR). Significant reductions in the concentrations of chlortetracycline, oxytetracycline, tetracycline and their degradation products were observed in manure liquids following treatment (p < 0.001), concomitant to significant increases in manure solids (p < 0.001). These results suggest sorption is the major removal route for tetracyclines during AAD. Significant decreases in the epimer-to-total residue ratios for chlortetracycline and tetracycline in manure solids further indicate degradation is desorption-limited. Moreover, sul1 and sul2 copies decreased significantly (p < 0.001) following AAD in the absence of sulfonamide antibiotics, while tetracyclines-resistant genes remained unchanged. A cross-sectional study of dairy farms utilizing natural aeration and liquid-solid separation treatments was additionally performed

Antibiotic Cycling and Antibiotic Mixing: Which One Best Mitigates Antibiotic Resistance?

PubMed

Beardmore, Robert Eric; Peña-Miller, Rafael; Gori, Fabio; Iredell, Jonathan

2017-04-01

Can we exploit our burgeoning understanding of molecular evolution to slow the progress of drug resistance? One role of an infection clinician is exactly that: to foresee trajectories to resistance during antibiotic treatment and to hinder that evolutionary course. But can this be done at a hospital-wide scale? Clinicians and theoreticians tried to when they proposed two conflicting behavioral strategies that are expected to curb resistance evolution in the clinic, these are known as "antibiotic cycling" and "antibiotic mixing." However, the accumulated data from clinical trials, now approaching 4 million patient days of treatment, is too variable for cycling or mixing to be deemed successful. The former implements the restriction and prioritization of different antibiotics at different times in hospitals in a manner said to "cycle" between them. In antibiotic mixing, appropriate antibiotics are allocated to patients but randomly. Mixing results in no correlation, in time or across patients, in the drugs used for treatment which is why theorists saw this as an optimal behavioral strategy. So while cycling and mixing were proposed as ways of controlling evolution, we show there is good reason why clinical datasets cannot choose between them: by re-examining the theoretical literature we show prior support for the theoretical optimality of mixing was misplaced. Our analysis is consistent with a pattern emerging in data: neither cycling or mixing is a priori better than the other at mitigating selection for antibiotic resistance in the clinic. : antibiotic cycling, antibiotic mixing, optimal control, stochastic models. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

21 CFR 333.150 - Labeling of first aid antibiotic drug products.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of first aid antibiotic drug products... First Aid Antibiotic Drug Products § 333.150 Labeling of first aid antibiotic drug products. (a... identifies the product as a “first aid antibiotic.” (b) Indications. The labeling of the product states...

Attitudes of pharmacists and physicians to antibiotic policies in hospitals.

PubMed

Adu, A; Simpson, J M; Armour, C L

1999-06-01

Antibiotic therapy in hospitals has substantial impact on patient outcome and the pharmacy drug budget. Antibiotic policies have been implemented by some hospitals to improve the quality of patient outcome and cost of antibiotic therapy. Antibiotic policies impose certain requirements on pharmacists and physicians. Pharmacists' and physicians' attitudes to and opinions about antibiotic policies are likely to affect the usefulness of such policies. To determine the attitudes of pharmacists and physicians to antibiotic policies in New South Wales (NSW) hospitals. Pharmacists and physicians in NSW public hospitals were surveyed to determine their attitudes to and opinions on antibiotic policies. A simple one-stage cluster sample of 241 pharmacists and a two-stage cluster sample of 701 physicians were obtained. Factor analysis was used to identify the attitudinal dimensions. General linear modelling was used to investigate the effects of predictor variables on outcome variables. The response rates were 91% and 77% for pharmacists and physicians, respectively. Factor analysis identified three dimensions of attitude to antibiotic policies: that they encourage rational antibiotic use; that they improve the quality of antibiotic prescribing and that they are associated with some problems. The reliability of these factors (Cronbach's alpha) ranged from 0.71 to 0.74, and was 0.90 for the overall attitude scale. Pharmacists and physicians had a positive overall attitude to antibiotic policies. Whereas physicians recognize that antibiotic policies improve the quality of prescribing, this was highly correlated with identification of problems (alpha = 0.71). In urban hospitals, pharmacists were more likely than physicians to associate antibiotics with problems. There was a positive overall attitude to hospital antibiotic policies expressed by pharmacists and physicians.

Effective antibiotics against 'Candidatus Liberibacter asiaticus' in HLB-affected citrus plants identified via the graft-based evaluation.

PubMed

Zhang, Muqing; Guo, Ying; Powell, Charles A; Doud, Melissa S; Yang, Chuanyu; Duan, Yongping

2014-01-01

Citrus huanglongbing (HLB), caused by three species of fastidious, phloem-limited 'Candidatus Liberibacter', is one of the most destructive diseases of citrus worldwide. To date, there is no established cure for this century-old and yet, newly emerging disease. As a potential control strategy for citrus HLB, 31 antibiotics were screened for effectiveness and phytotoxicity using the optimized graft-based screening system with 'Candidatus Liberibacter asiaticus' (Las)-infected citrus scions. Actidione and Oxytetracycline were the most phytotoxic to citrus with less than 10% of scions surviving and growing; therefore, this data was not used in additional analyses. Results of principal component (PCA) and hierarchical clustering analyses (HCA) demonstrated that 29 antibiotics were clustered into 3 groups: highly effective, partly effective, and not effective. In spite of different modes of actions, a number of antibiotics such as, Ampicillin, Carbenicillin, Penicillin, Cefalexin, Rifampicin and Sulfadimethoxine were all highly effective in eliminating or suppressing Candidatus Liberibacter asiaticus indicated by both the lowest Las infection rate and titers of the treated scions and inoculated rootstock. The non-effective group, including 11 antibiotics alone with three controls, such as Amikacin, Cinoxacin, Gentamicin, Kasugamycin, Lincomycin, Neomycin, Polymixin B and Tobramycin, did not eliminate or suppress Las in the tested concentrations, resulting in plants with increased titers of Las. The other 12 antibiotics partly eliminated or suppressed Las in the treated and graft-inoculated plants. The effective and non-phytotoxic antibiotics could be potential candidates for control of citrus HLB, either for the rescue of infected citrus germplasm or for restricted field application.

Empirical use of antibiotics and adjustment of empirical antibiotic therapies in a university hospital: a prospective observational study

PubMed Central

Mettler, Julian; Simcock, Mathew; Sendi, Pedram; Widmer, Andreas F; Bingisser, Roland; Battegay, Manuel; Fluckiger, Ursula; Bassetti, Stefano

2007-01-01

Background Several strategies to optimise the use of antibiotics have been developed. Most of these interventions can be classified as educational or restrictive. Restrictive measures are considered to be more effective, but the enforcement of these measures may be difficult and lead to conflicts with prescribers. Any intervention should be aimed at targets with the highest impact on antibiotic prescribing. The aim of the present study was to assess the adequacy of empirical and adjusted antibiotic therapies in a Swiss university hospital where no antibiotic use restrictions are enforced, and to identify risk factors for inadequate treatment and targets for intervention. Methods A prospective observational study was performed during 9 months. All patients admitted through the emergency department who received an antibiotic therapy within 24 hours of admission were included. Data on demographic characteristics, diagnoses, comorbidities, systemic inflammatory response syndrome (SIRS) parameters, microbiological tests, and administered antibiotics were collected prospectively. Antibiotic therapy was considered adequate if spectrum, dose, application modus, and duration of therapy were appropriate according to local recommendations or published guidelines. Results 2943 admitted patients were evaluated. Of these, 572 (19.4%) received antibiotics within 24 hours and 539 (94%) were analysed in detail. Empirical antibiotic therapy was inadequate in 121 patients (22%). Initial therapy was adjusted in 168 patients (31%). This adjusted antibiotic therapy was inadequate in 46 patients (27%). The main reason for inadequacy was the use of antibiotics with unnecessarily broad spectrum (24% of inadequate empirical, and 52% of inadequate adjusted therapies). In 26% of patients with inadequate adjusted therapy, antibiotics used were either ineffective against isolated pathogenic bacteria or antibiotic therapy was continued despite negative results of microbiological investigations

Experimental antibiotic treatment identifies potential pathogens of white band disease in the endangered Caribbean coral Acropora cervicornis

PubMed Central

Sweet, M. J.; Croquer, A.; Bythell, J. C.

2014-01-01

Coral diseases have been increasingly reported over the past few decades and are a major contributor to coral decline worldwide. The Caribbean, in particular, has been noted as a hotspot for coral disease, and the aptly named white syndromes have caused the decline of the dominant reef building corals throughout their range. White band disease (WBD) has been implicated in the dramatic loss of Acropora cervicornis and Acropora palmata since the 1970s, resulting in both species being listed as critically endangered on the International Union for Conservation of Nature Red list. The causal agent of WBD remains unknown, although recent studies based on challenge experiments with filtrate from infected hosts concluded that the disease is probably caused by bacteria. Here, we report an experiment using four different antibiotic treatments, targeting different members of the disease-associated microbial community. Two antibiotics, ampicillin and paromomycin, arrested the disease completely, and by comparing with community shifts brought about by treatments that did not arrest the disease, we have identified the likely candidate causal agent or agents of WBD. Our interpretation of the experimental treatments is that one or a combination of up to three specific bacterial types, detected consistently in diseased corals but not detectable in healthy corals, are likely causal agents of WBD. In addition, a histophagous ciliate (Philaster lucinda) identical to that found consistently in association with white syndrome in Indo-Pacific acroporas was also consistently detected in all WBD samples and absent in healthy coral. Treatment with metronidazole reduced it to below detection limits, but did not arrest the disease. However, the microscopic disease signs changed, suggesting a secondary role in disease causation for this ciliate. In future studies to identify a causal agent of WBD via tests of Henle–Koch's postulates, it will be vital to experimentally control for populations

[New antibiotics produced by Bacillus subtilis strains].

PubMed

Malanicheva, I A; Kozlov, D G; Efimenko, T A; Zenkova, V A; Kastrukha, G S; Reznikova, M I; Korolev, A M; Borshchevskaia, L N; Tarasova, O D; Sineokiĭ, S P; Efremenkova, O V

2014-01-01

Two Bacillus subtilis strains isolated from the fruiting body of a basidiomycete fungus Pholiota squarrosa exhibited a broad range of antibacterial activity, including those against methicillin-resistant Staphylococcus aureus INA 00761 (MRSA) and Leuconostoc mes6nteroides VKPM B-4177 resistant to glycopep-> tide antibiotics, as well as antifungal activity. The strains were identified as belonging to the "B. subtilis" com- plex based on their morphological and physiological characteristics, as well as by sequencing of the 16S rRNA gene fragments. Both strains (INA 01085 and INA 01086) produced insignificant amounts of polyene antibiotics (hexaen and pentaen, respectively). Strain INA 01086 produced also a cyclic polypeptide antibiotic containing Asp, Gly, Leu, Pro, Tyr, Thr, Trp, and Phe, while the antibiotic of strain INA 01085 contained, apart from these, two unidentified nonproteinaceous amino acids. Both polypeptide antibiotics were new compounds efficient against gram-positive bacteria and able to override the natural bacterial antibiotic resistance.

Occurrence and risk assessment of antibiotics in river water in Hong Kong.

PubMed

Deng, Wenjing; Li, Na; Zheng, Hailong; Lin, Huiying

2016-03-01

The occurrence and distribution of six typical antibiotics in the main rivers of Hong Kong were investigated using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ES-MS/MS). The results revealed that the antibiotics were widely distributed in the area studied. Of the target antibiotics, ofloxacin was the most frequently detected in the rivers, with a detection rate of 69.6% and a median concentration of 0.7ng/L. Sulfadimidine (n.d-580.4ng/L) and doxycycline (n.d-82.2ng/L), with detection frequencies of 65.2% and 30.4%, respectively, were found at the same level as in rivers in North America, Spain, France, Australia, and in the Yangtze and Pearl Rivers of China, while the other target antibiotics were found at lower levels. According to the ratios of the measured environmental concentration to the predicted no-effect concentration, ofloxacin and doxycycline could present a medium to low ecological risk to algae, while sulfonamides posed no obvious ecological risk to the relevant aquatic organisms (algae, Daphnia magna, and fish). A high detection rate of antibiotics occurred in densely populated areas, revealing that population activities might be greatly contributing to the increasing levels of antibiotics in the area. Thus, the residues of antibiotics present in the waters of Hong Kong need to be closely monitored. Copyright © 2015 Elsevier Inc. All rights reserved.

Inactivation/reactivation of antibiotic-resistant bacteria by a novel UVA/LED/TiO2 system.

PubMed

Xiong, Pei; Hu, Jiangyong

2013-09-01

In this study, an effective photocatalytic disinfection system was established using the newly emerged high power UVA/LED lamp. Crystallizing dish coated with TiO2 was prepared by 32-times impregnation-drying processes, and served as the supporting container for water samples. This study focused on the application of this UVA/LED system for the photocatalytic disinfection of selected antibiotic-resistant bacteria, Escherichia coli ATCC 700891. The disinfection performances were studied under various light intensities and illumination modes. Results show that higher light intensity could reach more significant inactivation of E. coli ATCC 700891. With the same UV dose, log-removal of antibiotic-resistant bacteria decreased with circle time in the studied range, while increased with duty circle. A "residual disinfecting effect" was found in the following dark period for bacteria collected at different phases of photocatalytic process. Residual disinfecting effect was found not significant for bacteria with 30 min periodic illumination. While residual disinfecting effect could kill almost all bacteria after 90 min UV periodic illumination within the following 240 min dark period. Copyright © 2013 Elsevier Ltd. All rights reserved.

Metagenomic analysis of antibiotic resistance genes (ARGs) during refuse decomposition.

PubMed

Liu, Xi; Yang, Shu; Wang, Yangqing; Zhao, He-Ping; Song, Liyan

2018-04-12

Landfill is important reservoirs of residual antibiotics and antibiotic resistance genes (ARGs), but the mechanism of landfill application influence on antibiotic resistance remains unclear. Although refuse decomposition plays a crucial role in landfill stabilization, its impact on the antibiotic resistance has not been well characterized. To better understand the impact, we studied the dynamics of ARGs and the bacterial community composition during refuse decomposition in a bench-scale bioreactor after long term operation (265d) based on metagenomics analysis. The total abundances of ARGs increased from 431.0ppm in the initial aerobic phase (AP) to 643.9ppm in the later methanogenic phase (MP) during refuse decomposition, suggesting that application of landfill for municipal solid waste (MSW) treatment may elevate the level of ARGs. A shift from drug-specific (bacitracin, tetracycline and sulfonamide) resistance to multidrug resistance was observed during the refuse decomposition and was driven by a shift of potential bacteria hosts. The elevated abundance of Pseudomonas mainly contributed to the increasing abundance of multidrug ARGs (mexF and mexW). Accordingly, the percentage of ARGs encoding an efflux pump increased during refuse decomposition, suggesting that potential bacteria hosts developed this mechanism to adapt to the carbon and energy shortage when biodegradable substances were depleted. Overall, our findings indicate that the use of landfill for MSW treatment increased antibiotic resistance, and demonstrate the need for a comprehensive investigation of antibiotic resistance in landfill. Copyright © 2018. Published by Elsevier B.V.

Think twice: A cognitive perspective of an antibiotic timeout intervention to improve antibiotic use.

PubMed

Jones, Makoto; Butler, Jorie; Graber, Christopher J; Glassman, Peter; Samore, Matthew H; Pollack, Lori A; Weir, Charlene; Goetz, Matthew Bidwell

2017-07-01

To understand clinicians' impressions of and decision-making processes regarding an informatics-supported antibiotic timeout program to re-evaluate the appropriateness of continuing vancomycin and piperacillin/tazobactam. We implemented a multi-pronged informatics intervention, based on Dual Process Theory, to prompt discontinuation of unwarranted vancomycin and piperacillin/tazobactam on or after day three in a large Veterans Affairs Medical Center. Two workflow changes were introduced to facilitate cognitive deliberation about continuing antibiotics at day three: (1) teams completed an electronic template note, and (2) a paper summary of clinical and antibiotic-related information was provided to clinical teams. Shortly after starting the intervention, six focus groups were conducted with users or potential users. Interviews were recorded and transcribed. Iterative thematic analysis identified recurrent themes from feedback. Themes that emerged are represented by the following quotations: (1) captures and controls attention ("it reminds us to think about it"), (2) enhances informed and deliberative reasoning ("it makes you think twice"), (3) redirects decision direction ("…because [there was no indication] I just [discontinued] it without even trying"), (4) fosters autonomy and improves team empowerment ("the template… forces the team to really discuss it"), and (5) limits use of emotion-based heuristics ("my clinical concern is high enough I think they need more aggressive therapy…"). Requiring template completion to continue antibiotics nudged clinicians to re-assess the appropriateness of specified antibiotics. Antibiotic timeouts can encourage deliberation on overprescribed antibiotics without substantially curtailing autonomy. An effective nudge should take into account clinician's time, workflow, and thought processes. Published by Elsevier Inc.

Phytotoxicity of vulpia residues: III. Biological activity of identified allelochemicals from Vulpia myuros.

PubMed

An, M; Pratley, J E; Haig, T

2001-02-01

Twenty compounds identified in vulpia (Vulpia myuros) residues as allelochemicals were individually and collectively tested for biological activity. Each exhibited characteristic allelochemical behavior toward the test plant, i.e., inhibition at high concentrations and stimulation or no effect at low concentrations, but individual activities varied. Allelopathins present in large quantities, such as syringic, vanillic, and succinic acids, possessed low activity, while those present in small quantities, such as catechol and hydrocinnamic acid, possessed strong inhibitory activity. The concept of a phytotoxic strength index was developed for quantifying the biological properties of each individual allelopathin in a concise, comprehensive, and meaningful format. The individual contribution of each allelopathin, assessed by comparing the phytotoxic strength index to the overall toxicity of vulpia residues, was variable according to structure and was influenced by its relative proportion in the residue. The majority of compounds possessed low or medium biological activity and contributed most of the vulpia phytotoxicity, while compounds with high biological activity were in the minority and only present at low concentration. Artificial mixtures of these pure allelochemicals also produced phytotoxicity. There were additive/synergistic effects evident in the properties of these mixtures. One such mixture, formulated from allelochemicals found in the same proportions as occur in vulpia extract, produced stronger activity than another formulated from the same set of compounds but in equal proportions. These results suggest that the exploration of the relative composition of a cluster of allelopathins may be more important than simply focusing on the identification of one or two compounds with strong biological activity and that synergism is fundamental to the understanding of allelopathy.

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.

Dual antibiotics for bronchiectasis.

PubMed

Felix, Lambert M; Grundy, Seamus; Milan, Stephen J; Armstrong, Ross; Harrison, Haley; Lynes, Dave; Spencer, Sally

2018-06-11

Bronchiectasis is a chronic respiratory disease characterised by abnormal and irreversible dilatation of the smaller airways and associated with a mortality rate greater than twice that of the general population. Antibiotics serve as front-line therapy for managing bacterial load, but their use is weighed against the development of antibiotic resistance. Dual antibiotic therapy has the potential to suppress infection from multiple strains of bacteria, leading to more successful treatment of exacerbations, reduced symptoms, and improved quality of life. Further evidence is required on the efficacy of dual antibiotics in terms of management of exacerbations and extent of antibiotic resistance. To evaluate the effects of dual antibiotics in the treatment of adults and children with bronchiectasis. We identified studies from the Cochrane Airways Group Specialised Register (CAGR), which includes the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine (AMED), and PsycINFO, as well as studies obtained by handsearching of journals/abstracts. We also searched the following trial registries: US National Institutes of Health Ongoing Trials Register, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform. We imposed no restriction on language of publication. We conducted our search in October 2017. We searched for randomised controlled trials comparing dual antibiotics versus a single antibiotic for short-term (< 4 weeks) or long-term management of bronchiectasis diagnosed in adults and/or children by bronchography, plain film chest radiography, or high-resolution computed tomography. Primary outcomes included exacerbations, length of hospitalisation, and serious adverse events. Secondary outcomes were response rates, emergence of resistance to antibiotics, systemic markers of infection, sputum

Toyota production system quality improvement initiative improves perioperative antibiotic therapy.

PubMed

Burkitt, Kelly H; Mor, Maria K; Jain, Rajiv; Kruszewski, Matthew S; McCray, Ellesha E; Moreland, Michael E; Muder, Robert R; Obrosky, David Scott; Sevick, Mary Ann; Wilson, Mark A; Fine, Michael J

2009-09-01

To assess the role of a Toyota production system (TPS) quality improvement (QI) intervention on appropriateness of perioperative antibiotic therapy and in length of hospital stay (LOS) among surgical patients. Pre-post quasi-experimental study using local and national retrospective cohorts. We used TPS methods to implement a multifaceted intervention to reduce nosocomial methicillin-resistant Staphylococcus aureus infections on a Veterans Affairs surgical unit, which led to a QI intervention targeting appropriate perioperative antibiotic prophylaxis. Appropriate perioperative antibiotic therapy was defined as selection of the recommended antibiotic agents for a duration not exceeding 24 hours from the time of the operation. The local computerized medical record system was used to identify patients undergoing the 25 most common surgical procedures and to examine changes in appropriate antibiotic therapy and LOS over time. Overall, 2550 surgical admissions were identified from the local computerized medical records. The proportion of surgical admissions receiving appropriate perioperative antibiotics was significantly higher (P <.01) in 2004 after initiation of the TPS intervention (44.0%) compared with the previous 4 years (range, 23.4%-29.8%) primarily because of improvements in compliance with antibiotic therapy duration rather than appropriate antibiotic selection. There was no statistically significant decrease in LOS over time. The use of TPS methods resulted in a QI intervention that was associated with an increase in appropriate perioperative antibiotic therapy among surgical patients, without affecting LOS.

Determination and removal of antibiotics in secondary effluent using a horizontal subsurface flow constructed wetland.

PubMed

Zhang, Chunhui; Ning, Ke; Zhang, Wenwen; Guo, Yuanjie; Chen, Jun; Liang, Chen

2013-04-01

Increased attention is currently being directed towards the potential negative effects of antibiotics and other PPCPs discharged into the aquatic environment via municipal WWTP secondary effluents. A number of analytical methods, such as high performance liquid chromatography technologies, including a high performance liquid chromatography-fluorescence method (HPLC-FLD), high performance liquid chromatography-UV detection method (HPLC-UV) and high performance liquid chromatography-mass spectrometry method (HPLC-MS), have been suggested as determination technologies for antibiotic residues in water. In this study, we implement a HPLC-MS/MS combined method to detect and analyze antibiotics in WWTP secondary effluent and apply a horizontal subsurface flow constructed wetland (CW) as an advanced wastewater treatment for removing antibiotics in the WWTP secondary effluent. The results show that there were 2 macrolides, 2 quinolones and 5 sulfas in WWTP secondary effluent among all the 22 antibiotics considered. After the CW advanced treatment, the concentration removal efficiencies and removal loads of 9 antibiotics were 53-100% and 0.004-0.7307 μg m(-2) per day, respectively.

Oral anti-pseudomonal antibiotics for cystic fibrosis.

PubMed

Remmington, Tracey; Jahnke, Nikki; Harkensee, Christian

2016-07-14

Pseudomonas aeruginosa is the most common bacterial pathogen causing lung infections in people with cystic fibrosis and appropriate antibiotic therapy is vital. Antibiotics for pulmonary exacerbations are usually given intravenously, and for long-term treatment, via a nebuliser. Oral anti-pseudomonal antibiotics with the same efficacy and safety as intravenous or nebulised antibiotics would benefit people with cystic fibrosis due to ease of treatment and avoidance of hospitalisation. This is an update of a previous review. To determine the benefit or harm of oral anti-pseudomonal antibiotic therapy for people with cystic fibrosis, colonised with Pseudomonas aeruginosa, in the:1. treatment of a pulmonary exacerbation; and2. long-term treatment of chronic infection. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.We contacted pharmaceutical companies and checked reference lists of identified trials.Date of last search: 08 July 2016. Randomised or quasi-randomised controlled trials comparing any dose of oral anti-pseudomonal antibiotics, to other combinations of inhaled, oral or intravenous antibiotics, or to placebo or usual treatment for pulmonary exacerbations and long-term treatment. Two authors independently selected the trials, extracted data and assessed quality. We contacted trial authors to obtain missing information. We included three trials examining pulmonary exacerbations (171 participants) and two trials examining long-term therapy (85 participants). We regarded the most important outcomes as quality of life and lung function. The analysis did not identify any statistically significant difference between oral anti-pseudomonal antibiotics and other treatments for these outcome measures for either pulmonary exacerbations or long-term treatment. One of the

Clostridium difficile infection: update on emerging antibiotic treatment options and antibiotic resistance

PubMed Central

Shah, Dhara; Dang, Minh-Duc; Hasbun, Rodrigo; Koo, Hoonmo L; Jiang, Zhi-Dong; DuPont, Herbert L; Garey, Kevin W

2010-01-01

Clostridium difficile infection (CDI) is the most common cause of identifiable diarrhea in hospitalized patients. The incidence and severity of CDIs are increasing. The increased incidence and severity of the disease has sparked interest in the optimal treatment of CDI as well as the use of new therapies and drug discovery. Current treatment strategies are inadequate with decreased response rates to metronidazole, and high recurrence rates with the use of metronidazole and oral vancomycin. Although incidence rates continue to be low, in vitro resistance to antibiotics used for the treatment of CDI has been noted. Recently, important data has emerged on new anti-C. difficile antibiotics such as rifaximin, rifalazil, fidaxomicin, nitazoxanide, tigecycline and ramoplanin. The purpose of this review is to provide an update on the in vitro susceptibility and new antibiotic treatment options for CDI. This review will focus primarily on scientific studies published in the last 36 months in order to provide an up-to-date review on the topic. PMID:20455684

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.

Antibiotic Resistance

MedlinePlus

... lives. But there is a growing problem of antibiotic resistance. It happens when bacteria change and become able ... resistant to several common antibiotics. To help prevent antibiotic resistance Don't use antibiotics for viruses like colds ...

Anaerobic stabilization and conversion of transformed intermediates of antibiotic pharmaceutical effluent in a fluidized bed reactor.

PubMed

Tamijevendane, S; Saravanane, R; Rajesh, R; Sivacoumar, R

2011-07-01

The formulation and implementation of regulatory standards for the ultimate disposal and reuse of transformed products of antibiotic drugs and solvents have been a pending issue in the waste management of pharmaceutical industries especially in the developing countries like India. A case study has been identified and the current issues in one of the major pharmaceutical industry (manufacturing cephalosporin drugs) located in Chennai, India, has been discussed for the possible implementation of anaerobically transformed intermediates of antibiotic pharmaceutical waste sludge. The objective of the study was to determine the effect of bioaugmentation on the convertibility of anaerobically transformed intermediates of antibiotic pharmaceutical waste sludge into residuals and biocompost. Cephalosporin is a common name refers to cephradine (C16H19N3O4S) and cephalexin (C16H17N3O4S.H2O). Based on the critical examination of results, the industry is looking for the alternatives of either direct disposal of 7-amino-3-deacetoxycephalosporanic acid (7-ADCA) and phenyl acetic acid or for further degradation and disposal, which will essentially require additional cost and maintenance. The present regulatory standard implemented in India does not envisage such disposal alternatives and hence this would invite suggestions and recommendations of the expertise for the possible implementation on the pending issue in the antibiotic based pharmaceutical industries. The presence of cephalosporin increases total strength (Chemical Oxygen Demand) of the effluent and indirectly increases the cost of the treatment. Hence the biotransformation of cephalosporin either alone or in combination with other energetic compounds, offers the potential for an economical and environment friendly disposal alternative for the anaerobically transformed intermediates of antibiotic pharmaceutical waste sludge.

Intraventricular antibiotics for bacterial meningitis in neonates.

PubMed

Shah, Sachin S; Ohlsson, Arne; Shah, Vibhuti S

2012-07-11

Neonatal meningitis may be caused by bacteria, especially gram-negative bacteria, which are difficult to eradicate from the cerebrospinal fluid (CSF) using safe doses of antibiotics. In theory, intraventricular administration of antibiotics would produce higher antibiotic concentrations in the CSF than intravenous administration alone, and eliminate the bacteria more quickly. However, ventricular taps may cause harm. To assess the effectiveness and safety of intraventricular antibiotics (with or without intravenous antibiotics) in neonates with meningitis (with or without ventriculitis) as compared to treatment with intravenous antibiotics alone. The Cochrane Library, Issue 2, 2007; MEDLINE; EMBASE; CINAHL and Science Citation Index were searched in June 2007. The Oxford Database of Perinatal Trials was searched in June 2004. Pediatric Research (abstracts of proceedings) were searched (1990 to April 2007) as were reference lists of identified trials and personal files. No language restrictions were applied.This search was updated in May 2011. Selection criteria for study inclusion were: randomised or quasi-randomised controlled trials in which intraventricular antibiotics with or without intravenous antibiotics were compared with intravenous antibiotics alone in neonates (< 28 days old) with meningitis. One of the following outcomes was required to be reported: mortality during initial hospitalisation; neonatal or infant mortality, or both; neurodevelopmental outcome; duration of hospitalisation; duration of culture positivity of CSF and side effects. All review authors abstracted information for outcomes reported and one review author checked for discrepancies and entered data into RevMan 5.1. Risk ratio (RR), risk difference (RD), number needed to treat for an additional beneficial outcome (NNTB) or number needed to treat for an additional harmful outcome (NNTH), and mean difference (MD), using the fixed-effect model are reported with 95% confidence intervals (CI

Ecotoxicological potential of antibiotic pollution-industrial wastewater: bioavailability, biomarkers, and occurrence in Mytilus galloprovincialis.

PubMed

Zouiten, Amina; Beltifa, Asma; Van Loco, Joris; Mansour, Hedi Ben; Reyns, Tim

2016-08-01

Environmental pollution by pharmaceutical residues has become a major problem in many countries worldwide. However, little is known about the concentrations of pharmaceuticals in water sources in Tunisia. Residues in the natural environment have been of increasing concern due to their impact on bacteria resistance development and toxicity to natural communities and ultimately to public health. In this work, we collected the wastewater sample from a pharmaceutical industry, which specializes in the antibiotics manufacture, during the years 2014-2015. Generally, this effluent is discharged into the marine environment and causes environmental problems. The Mediterranean mussel Mytilus galloprovincialis was commonly used as a model organism for its peculiar morphofunctional properties which also make it an excellent marine environmental biomonitoring species. The histological sections of mussel, which are exposed at different dilutions of pharmaceutical wastewater (PW), indicate a large pathological power revealed on the gills. On the other hand, genotoxicity of the studied effluent was evaluated using comet assay for quantification of DNA fragmentation in gill cells. Results show that PW exhibited a statistically significant (p < 0.001) genotoxic effect in a dose-dependent manner. However, the toxic effects of PW decreased significantly after its treatment with Bacillus atrophaeus. Toxicities can be imputed to the presence of antibiotics. In fact, chemical analysis of the gills of mussel M. galloprovincialis using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) showed the presence of some antibiotic residues. These concentrations decrease to half in mussels treated with PW biodegraded by B. atrophaeus.

Intimate contacted two-dimensional/zero-dimensional composite of bismuth titanate nanosheets supported ultrafine bismuth oxychloride nanoparticles for enhanced antibiotic residue degradation.

PubMed

Liu, Wenwen; Dai, Zhiqiang; Liu, Yi; Zhu, Anquan; Zhong, Donglin; Wang, Juan; Pan, Jun

2018-05-31

Constructing a two-dimensional/zero-dimensional (2D/0D) composite with matched crystal structure, suitable energy band structure as well as intimate contact interface is an effective way to improve carriers separation for achieving highly photocatalytic performance. In this work, a novel bismuth titanate/bismuth oxychloride (Bi 4 Ti 3 O 12 /BiOCl) composite consisting of 2D Bi 4 Ti 3 O 12 nanosheets and 0D BiOCl nanoparticles was constructed for the first time. Germinating ultrafine BiOCl nanoparticles on Bi 4 Ti 3 O 12 nanosheets can provide abundant contact interface and shorten migration distance of photoinduced carriers via two-step synthesis contained molten salt process and facile chemical transformation process. The obtained Bi 4 Ti 3 O 12 /BiOCl 2D/0D composites exhibited enhanced photocatalytic performance for antibiotic tetracycline hydrochloride degradation. The rate constant of optimal Bi 4 Ti 3 O 12 /BiOCl composite was about 4.4 times higher than that of bare Bi 4 Ti 3 O 12 although Bi 4 Ti 3 O 12 /BiOCl composite appeared lesser photoabsorption. The enhanced photocatalytic performance can be mainly ascribed to matched crystal structure, suitable energy band structure and intimate contact interface between Bi 4 Ti 3 O 12 nanosheets and ultrafine BiOCl nanoparticles as well as unique 2D/0D composite structure. Besides, a probable degradation mechanism on the basis of active species trapping experiments, electrochemical impedance spectroscopy, photocurrent responses and energy band structures was proposed. This work may be stretched to other 2D/0D composite photocatalysts construction, which is inspiring for antibiotic residue treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

Antibiotic alternatives: the substitution of antibiotics in animal husbandry?

PubMed Central

Cheng, Guyue; Hao, Haihong; Xie, Shuyu; Wang, Xu; Dai, Menghong; Huang, Lingli; Yuan, Zonghui

2014-01-01

It is a common practice for decades to use of sub-therapeutic dose of antibiotics in food-animal feeds to prevent animals from diseases and to improve production performance in modern animal husbandry. In the meantime, concerns over the increasing emergence of antibiotic-resistant bacteria due to the unreasonable use of antibiotics and an appearance of less novelty antibiotics have prompted efforts to develop so-called alternatives to antibiotics. Whether or not the alternatives could really replace antibiotics remains a controversial issue. This review summarizes recent development and perspectives of alternatives to antibiotics. The mechanism of actions, applications, and prospectives of the alternatives such as immunity modulating agents, bacteriophages and their lysins, antimicrobial peptides, pro-, pre-, and synbiotics, plant extracts, inhibitors targeting pathogenicity (bacterial quorum sensing, biofilm, and virulence), and feeding enzymes are thoroughly discussed. Lastly, the feasibility of alternatives to antibiotics is deeply analyzed. It is hard to conclude that the alternatives might substitute antibiotics in veterinary medicine in the foreseeable future. At the present time, prudent use of antibiotics and the establishment of scientific monitoring systems are the best and fastest way to limit the adverse effects of the abuse of antibiotics and to ensure the safety of animal-derived food and environment. PMID:24860564

A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance

PubMed Central

2014-01-01

Background Greater use of antibiotics during the past 50 years has exerted selective pressure on susceptible bacteria and may have favoured the survival of resistant strains. Existing information on antibiotic resistance patterns from pathogens circulating among community-based patients is substantially less than from hospitalized patients on whom guidelines are often based. We therefore chose to assess the relationship between the antibiotic resistance pattern of bacteria circulating in the community and the consumption of antibiotics in the community. Methods Both gray literature and published scientific literature in English and other European languages was examined. Multiple regression analysis was used to analyse whether studies found a positive relationship between antibiotic consumption and resistance. A subsequent meta-analysis and meta-regression was conducted for studies for which a common effect size measure (odds ratio) could be calculated. Results Electronic searches identified 974 studies but only 243 studies were considered eligible for inclusion by the two independent reviewers who extracted the data. A binomial test revealed a positive relationship between antibiotic consumption and resistance (p < .001) but multiple regression modelling did not produce any significant predictors of study outcome. The meta-analysis generated a significant pooled odds ratio of 2.3 (95% confidence interval 2.2 to 2.5) with a meta-regression producing several significant predictors (F(10,77) = 5.82, p < .01). Countries in southern Europe produced a stronger link between consumption and resistance than other regions. Conclusions Using a large set of studies we found that antibiotic consumption is associated with the development of antibiotic resistance. A subsequent meta-analysis, with a subsample of the studies, generated several significant predictors. Countries in southern Europe produced a stronger link between consumption and resistance than other

Global development of the studies focused on antibiotics in aquatic systems from 1945 to 2017.

PubMed

Zheng, Chun-Li; Cotner, James B; Sato, Chikashi; Li, Gang; Xu, Yao-Yang

2018-05-25

Antibiotics are used to fight diseases in humans and farm animals. Their residues, however, can enter aquatic environments and affect the resistance of non-target microbial strains, and the prevalence of antibiotic resistance genes (ARGs) potentially poses negative impacts on human health. In order to better understand how the studies of antibiotics have been conducted, we analyzed the publications on antibiotics in aquatic systems for the period of 1945-2017. We applied a bibliometric analysis method by coupling cluster analysis and network analysis. Results indicated that early research on antibiotics in water was mostly performed in America and Europe, while, in recent years, publications for the same subject were dominated by China and the USA. The majority of the articles were published in journal Chemosphere and the most representative subject categories of the seven sections were "Environmental science and ecology," "Chemistry," "Engineering," "Biochemistry and molecular biology," "Water resources," "Agriculture," and "Pharmacology and pharmacy." The most studied class of antibiotics was tetracyclines in wastewater. Antibiotic resistance, ARGs, Escherichia coli, and some mechanistic studies such as adsorption, toxicity, degradation, and kinetics were common topics in this field. ARGs present a major public health concern and much attention should be directed at the problems with antibiotics in the future studies of water.

Occurrence and risk assessment of four typical fluoroquinolone antibiotics in raw and treated sewage and in receiving waters in Hangzhou, China.

PubMed

Tong, Changlun; Zhuo, Xiajun; Guo, Yun

2011-07-13

A sensitive liquid chromatography-fluorescence detection method, combined with one-step solid-phase extraction, was established for detecting the residual levels of the four typical fluoroquinolone antibiotics (ofloxacin, norfloxacin, ciprofloxacin, and enrofloxacin) in influent, effluent, and surface waters from Hangzhou, China. For the various environmental water matrices, the overall recoveries were from 76.8 to 122%, and no obvious interferences of matrix effect were observed. The limit of quantitation of this method was estimated to be 17 ng/L for ciprofloxacin and norfloxacin, 20 ng/L for ofloxacin, and 27 ng/L for enrofloxacin. All of the four typical fluoroquinolone antibiotics were found in the wastewaters and surface waters. The residual contents of the four typical fluoroquinolone antibiotics in influent, effluent, and surface water samples are 108-1405, 54-429, and 7.0-51.6 ng/L, respectively. The removal rates of the selected fluoroquinolone antibiotics were 69.5 (ofloxacin), 61.3 (norfloxacin), and 50% (enrofloxacin), indicating that activated sludge treatment is effective except for ciprofloxacin and necessary to remove these fluoroquinolone antibiotics in municipal sewage. The risk to the aquatic environment was estimated by a ratio of measured environmental concentration and predicted no-effect concentration. At the concentrations, these fluoroquinolone antibiotics were found in influent, effluent, and surface waters, and they should not pose a risk for the aquatic environment.

Determination of 18 veterinary antibiotics in environmental water using high-performance liquid chromatography-q-orbitrap combined with on-line solid-phase extraction.

PubMed

Kim, Chansik; Ryu, Hong-Duck; Chung, Eu Gene; Kim, Yongseok

2018-05-01

The use of antibiotics and their occurrence in the environment have received significant attention in recent years owing to the generation of antibiotic-resistant bacteria. Antibiotic residues in water near livestock farming areas should be monitored to establish effective strategies for reducing the use of veterinary antibiotics. However, environmental water contamination resulting from veterinary antibiotics has not been studied extensively. In this work, we developed an analytical method for the simultaneous determination of multiple classes of veterinary antibiotic residues in environmental water using on-line solid-phase extraction (SPE)-high performance liquid chromatography (HPLC)-high resolution mass spectrometry (HRMS). Eighteen popular antibiotics (eight classes) were selected as target analytes based on veterinary antibiotics sales in South Korea in 2015. The developed method was validated by calibration-curve linearities, precisions, relative recoveries, and method detection limits (MDLs)/limits of quantification (LOQs) of the selected antibiotics, and applied to the analysis of environmental water samples (groundwater, river water, and wastewater-treatment-plant effluent). All calibration curves exhibited r 2  > 0.995 with MDLs ranging from 0.2 to 11.9 ng/L. Relative recoveries were between 50 and 150% with coefficients of variation below 20% for all analytes (spiked at 500 ng/L) in groundwater and river water samples. Relative standard deviations (RSDs) of standard-spiked samples were lower than 7% for all antibiotics. The on-line SPE system eliminates human-based SPE errors and affords excellent method reproducibility. Amoxicillin, ampicillin, clopidol, fenbendazole, flumequine, lincomycin, sulfadiazine, and trimethoprim were detected in environmental water samples in concentrations ranging from 1.26 to 127.49 ng/L. The developed method is a reliable analytical technique for the potential routine monitoring of veterinary antibiotics

Antibiotic resistance: a primer and call to action.

PubMed

Smith, Rachel A; M'ikanatha, Nkuchia M; Read, Andrew F

2015-01-01

During the past century, discoveries of microorganisms as causes of infections and antibiotics as effective therapeutic agents have contributed to significant gains in public health in many parts of the world. Health agencies worldwide are galvanizing attention toward antibiotic resistance, which is a major threat to public health (Centers for Disease Control and Prevention, 2013; World Health Organization, 2014). Some life scientists believe that we are approaching the post-antibiotic age (Davies & Davies, 2010). The growing threat of antimicrobial resistance is fueled by complex factors with biological, behavioral, and societal aspects. This primer provides an overview of antibiotic resistance and its growing burden on public health, the biological and behavioral mechanisms that increase antibiotic resistance, and examples of where health communication scholars can contribute to efforts to make our current antibiotic drugs last as long as possible. In addition, we identify compelling challenges for current communication theories and practices.

Degradation kinetics and mechanism of antibiotic ceftiofur in recycled water derived from beef farm

USDA-ARS?s Scientific Manuscript database

Ceftiofur is a third-generation cephalosporin antibiotic that has been widely used to treat bacterial infections in concentrated animal feeding operations (CAFOs). Land application of CAFO waste may lead to the loading of ceftiofur residues and its metabolites to the environment. To mitigate the pot...

Continuous versus intermittent antibiotics for bronchiectasis.

PubMed

Donovan, Tim; Felix, Lambert M; Chalmers, James D; Milan, Stephen J; Mathioudakis, Alexander G; Spencer, Sally

2018-06-03

Bronchiectasis is a chronic airway disease characterised by a destructive cycle of recurrent airway infection, inflammation and tissue damage. Antibiotics are a main treatment for bronchiectasis. The aim of continuous therapy with prophylactic antibiotics is to suppress bacterial load, but bacteria may become resistant to the antibiotic, leading to a loss of effectiveness. On the other hand, intermittent prophylactic antibiotics, given over a predefined duration and interval, may reduce antibiotic selection pressure and reduce or prevent the development of resistance. This systematic review aimed to evaluate the current evidence for studies comparing continuous versus intermittent administration of antibiotic treatment in bronchiectasis in terms of clinical efficacy, the emergence of resistance and serious adverse events. To evaluate the effectiveness of continuous versus intermittent antibiotics in the treatment of adults and children with bronchiectasis, using the primary outcomes of exacerbations, antibiotic resistance and serious adverse events. On 1 August 2017 and 4 May 2018 we searched the Cochrane Airways Review Group Specialised Register (CAGR), CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and AMED. On 25 September 2017 and 4 May 2018 we also searched www.clinicaltrials.gov, the World Health Organization (WHO) trials portal, conference proceedings and the reference lists of existing systematic reviews. We planned to include randomised controlled trials (RCTs) of adults or children with bronchiectasis that compared continuous versus intermittent administration of long-term prophylactic antibiotics of at least three months' duration. We considered eligible studies reported as full-text articles, as abstracts only and unpublished data. Two review authors independently screened the search results and full-text reports. We identified 268 unique records. Of these we retrieved and examined 126 full-text reports, representing 114 studies, but none of these studies

The multifaceted roles of antibiotics and antibiotic resistance in nature

PubMed Central

Sengupta, Saswati; Chattopadhyay, Madhab K.; Grossart, Hans-Peter

2013-01-01

Antibiotics are chemotherapeutic agents, which have been a very powerful tool in the clinical management of bacterial diseases since the 1940s. However, benefits offered by these magic bullets have been substantially lost in subsequent days following the widespread emergence and dissemination of antibiotic-resistant strains. While it is obvious that excessive and imprudent use of antibiotics significantly contributes to the emergence of resistant strains, antibiotic resistance is also observed in natural bacteria of remote places unlikely to be impacted by human intervention. Both antibiotic biosynthetic genes and resistance-conferring genes have been known to evolve billions of years ago, long before clinical use of antibiotics. Hence it appears that antibiotics and antibiotics resistance determinants have some other roles in nature, which often elude our attention because of overemphasis on the therapeutic importance of antibiotics and the crisis imposed by the antibiotic resistance in pathogens. In the natural milieu, antibiotics are often found to be present in sub-inhibitory concentrations acting as signaling molecules supporting the process of quorum sensing and biofilm formation. They also play an important role in the production of virulence factors and influence host–parasite interactions (e.g., phagocytosis, adherence to the target cell, and so on). The evolutionary and ecological aspects of antibiotics and antibiotic resistance in the naturally occurring microbial community are little understood. Therefore, the actual role of antibiotics in nature warrants in-depth investigations. Studies on such an intriguing behavior of the microorganisms promise insight into the intricacies of the microbial physiology and are likely to provide some lead in controlling the emergence and subsequent dissemination of antibiotic resistance. This article highlights some of the recent findings on the role of antibiotics and the genes that confer resistance to antibiotics

Antibiotic efficacy is linked to bacterial cellular respiration

PubMed Central

Lobritz, Michael A.; Belenky, Peter; Porter, Caroline B. M.; Gutierrez, Arnaud; Yang, Jason H.; Schwarz, Eric G.; Dwyer, Daniel J.; Khalil, Ahmad S.; Collins, James J.

2015-01-01

Bacteriostatic and bactericidal antibiotic treatments result in two fundamentally different phenotypic outcomes—the inhibition of bacterial growth or, alternatively, cell death. Most antibiotics inhibit processes that are major consumers of cellular energy output, suggesting that antibiotic treatment may have important downstream consequences on bacterial metabolism. We hypothesized that the specific metabolic effects of bacteriostatic and bactericidal antibiotics contribute to their overall efficacy. We leveraged the opposing phenotypes of bacteriostatic and bactericidal drugs in combination to investigate their activity. Growth inhibition from bacteriostatic antibiotics was associated with suppressed cellular respiration whereas cell death from most bactericidal antibiotics was associated with accelerated respiration. In combination, suppression of cellular respiration by the bacteriostatic antibiotic was the dominant effect, blocking bactericidal killing. Global metabolic profiling of bacteriostatic antibiotic treatment revealed that accumulation of metabolites involved in specific drug target activity was linked to the buildup of energy metabolites that feed the electron transport chain. Inhibition of cellular respiration by knockout of the cytochrome oxidases was sufficient to attenuate bactericidal lethality whereas acceleration of basal respiration by genetically uncoupling ATP synthesis from electron transport resulted in potentiation of the killing effect of bactericidal antibiotics. This work identifies a link between antibiotic-induced cellular respiration and bactericidal lethality and demonstrates that bactericidal activity can be arrested by attenuated respiration and potentiated by accelerated respiration. Our data collectively show that antibiotics perturb the metabolic state of bacteria and that the metabolic state of bacteria impacts antibiotic efficacy. PMID:26100898

Antibiotics for sore throat.

PubMed

Spinks, Anneliese; Glasziou, Paul P; Del Mar, Chris B

2013-11-05

Sore throat is a common reason for people to present for medical care. Although it remits spontaneously, primary care doctors commonly prescribe antibiotics for it. To assess the benefits of antibiotics for sore throat for patients in primary care settings. We searched CENTRAL 2013, Issue 6, MEDLINE (January 1966 to July week 1, 2013) and EMBASE (January 1990 to July 2013). Randomised controlled trials (RCTs) or quasi-RCTs of antibiotics versus control assessing typical sore throat symptoms or complications. Two review authors independently screened studies for inclusion and extracted data. We resolved differences in opinion by discussion. We contacted trial authors from three studies for additional information. We included 27 trials with 12,835 cases of sore throat. We did not identify any new trials in this 2013 update. 1. Symptoms Throat soreness and fever were reduced by about half by using antibiotics. The greatest difference was seen at day three. The number needed to treat to benefit (NNTB) to prevent one sore throat at day three was less than six; at week one it was 21. 2. Non-suppurative complications The trend was antibiotics protecting against acute glomerulonephritis but there were too few cases to be sure. Several studies found antibiotics reduced acute rheumatic fever by more than two-thirds within one month (risk ratio (RR) 0.27; 95% confidence interval (CI) 0.12 to 0.60). 3. Suppurative complications Antibiotics reduced the incidence of acute otitis media within 14 days (RR 0.30; 95% CI 0.15 to 0.58); acute sinusitis within 14 days (RR 0.48; 95% CI 0.08 to 2.76); and quinsy within two months (RR 0.15; 95% CI 0.05 to 0.47) compared to those taking placebo. 4. Subgroup analyses of symptom reduction Antibiotics were more effective against symptoms at day three (RR 0.58; 95% CI 0.48 to 0.71) if throat swabs were positive for Streptococcus, compared to RR 0.78; 95% CI 0.63 to 0.97 if negative. Similarly at week one the RR was 0.29 (95% CI 0.12 to 0

Antibiotic Stimulation of a Bacillus subtilis Migratory Response

PubMed Central

Liu, Yongjin; Kyle, Steven

2018-01-01

ABSTRACT Competitive interactions between bacteria reveal physiological adaptations that benefit fitness. Bacillus subtilis is a Gram-positive species with several adaptive mechanisms for competition and environmental stress. Biofilm formation, sporulation, and motility are the outcomes of widespread changes in a population of B. subtilis. These changes emerge from complex, regulated pathways for adapting to external stresses, including competition from other species. To identify competition-specific functions, we cultured B. subtilis with multiple species of Streptomyces and observed altered patterns of growth for each organism. In particular, when plated on agar medium near Streptomyces venezuelae, B. subtilis initiates a robust and reproducible mobile response. To investigate the mechanistic basis for the interaction, we determined the type of motility used by B. subtilis and isolated inducing metabolites produced by S. venezuelae. Bacillus subtilis has three defined forms of motility: swimming, swarming, and sliding. Streptomyces venezuelae induced sliding motility specifically in our experiments. The inducing agents produced by S. venezuelae were identified as chloramphenicol and a brominated derivative at subinhibitory concentrations. Upon further characterization of the mobile response, our results demonstrated that subinhibitory concentrations of chloramphenicol, erythromycin, tetracycline, and spectinomycin all activate a sliding motility response by B. subtilis. Our data are consistent with sliding motility initiating under conditions of protein translation stress. This report underscores the importance of hormesis as an early warning system for potential bacterial competitors and antibiotic exposure. IMPORTANCE Antibiotic resistance is a major challenge for the effective treatment of infectious diseases. Identifying adaptive mechanisms that bacteria use to survive low levels of antibiotic stress is important for understanding pathways to

Potential burden of antibiotic resistance on surgery and cancer chemotherapy antibiotic prophylaxis in the USA: a literature review and modelling study.

PubMed

Teillant, Aude; Gandra, Sumanth; Barter, Devra; Morgan, Daniel J; Laxminarayan, Ramanan

2015-12-01

The declining efficacy of existing antibiotics potentially jeopardises outcomes in patients undergoing medical procedures. We investigated the potential consequences of increases in antibiotic resistance on the ten most common surgical procedures and immunosuppressing cancer chemotherapies that rely on antibiotic prophylaxis in the USA. We searched the published scientific literature and identified meta-analyses and reviews of randomised controlled trials or quasi-randomised controlled trials (allocation done on the basis of a pseudo-random sequence-eg, odd/even hospital number or date of birth, alternation) to estimate the efficacy of antibiotic prophylaxis in preventing infections and infection-related deaths after surgical procedures and immunosuppressing cancer chemotherapy. We varied the identified effect sizes under different scenarios of reduction in the efficacy of antibiotic prophylaxis (10%, 30%, 70%, and 100% reductions) and estimated the additional number of infections and infection-related deaths per year in the USA for each scenario. We estimated the percentage of pathogens causing infections after these procedures that are resistant to standard prophylactic antibiotics in the USA. We estimate that between 38·7% and 50·9% of pathogens causing surgical site infections and 26·8% of pathogens causing infections after chemotherapy are resistant to standard prophylactic antibiotics in the USA. A 30% reduction in the efficacy of antibiotic prophylaxis for these procedures would result in 120,000 additional surgical site infections and infections after chemotherapy per year in the USA (ranging from 40,000 for a 10% reduction in efficacy to 280,000 for a 70% reduction in efficacy), and 6300 infection-related deaths (range: 2100 for a 10% reduction in efficacy, to 15,000 for a 70% reduction). We estimated that every year, 13,120 infections (42%) after prostate biopsy are attributable to resistance to fluoroquinolones in the USA. Increasing antibiotic

Review of Antibiotic and Non-Antibiotic Properties of Beta-lactam Molecules.

PubMed

Ochoa-Aguilar, Abraham; Ventura-Martinez, Rosa; Sotomayor-Sobrino, Marco Antonio; Gómez, Claudia; Morales-Espinoza, María del Rosario

2016-01-01

Beta-lactam molecules are a family of drugs commonly used for their antibiotic properties; however, recent research has shown that several members of this group present a large number of other effects such as neuroprotective, antioxidant, analgesic or immunomodulatory capabilities. These properties have been used in both preclinical and clinical studies in different diseases such as hypoxic neuronal damage or acute and chronic pain. The present work briefly reviews the antibiotic effect of these molecules, and will then focus specially on the non-antibiotic effects of three beta-lactam subfamilies: penicillins, cephalosporins and beta lactamase inhibitors, each of which have different molecular structure and pharmacokinetics and therefore have several potential clinical applications. A thorough search of bibliographic databases for peer-reviewed research was performed including only classic experiments or high quality reviews for the antibiotic mechanisms of beta-lactam molecules and only experimental research papers where included when the non-antibiotic properties of these molecules were searched. Only published articles from indexed journals were included. Quality of retrieved papers was assessed using standard tools. The characteristics of screened papers were described and findings of included studies were contextualized to either a mechanistic or a clinical framework. Seventy-eight papers were included in the review; the majority (56) were relative to the non-antibiotic properties of beta-lactam molecules. The non-antibiotic effects reviewed were divided accordingly to the amount of information available for each one. Twelve papers outlined the epileptogenic effects induced by beta-lactam molecules administration; these included both clinical and basic research as well as probable mechanistic explanations. Eighteen papers described a potential neuroprotective effect, mostly in basic in vitro and in vivo experiments. Analgesic properties where identified in

Characterization of extracellular polymeric substances in biofilms under long-term exposure to ciprofloxacin antibiotic using fluorescence excitation-emission matrix and parallel factor analysis.

PubMed

Gu, Chaochao; Gao, Pin; Yang, Fan; An, Dongxuan; Munir, Mariya; Jia, Hanzhong; Xue, Gang; Ma, Chunyan

2017-05-01

The presence of antibiotic residues in the environment has been regarded as an emerging concern due to their potential adverse environmental consequences such as antibiotic resistance. However, the interaction between antibiotics and extracellular polymeric substances (EPSs) of biofilms in wastewater treatment systems is not entirely clear. In this study, the effect of ciprofloxacin (CIP) antibiotic on biofilm EPS matrix was investigated and characterized using fluorescence excitation-emission matrix (EEM) and parallel factor (PARAFAC) analysis. Physicochemical analysis showed that the proteins were the major EPS fraction, and their contents increased gradually with an increase in CIP concentration (0-300 μg/L). Based on the characterization of biofilm tightly bound EPS (TB-EPS) by EEM, three fluorescent components were identified by PARAFAC analysis. Component C1 was associated with protein-like substances, and components C2 and C3 belonged to humic-like substances. Component C1 exhibited an increasing trend as the CIP addition increased. Pearson's correlation results showed that CIP correlated significantly with the protein contents and component C1, while strong correlations were also found among UV 254 , dissolved organic carbon, humic acids, and component C3. A combined use of EEM-PARAFAC analysis and chemical measurements was demonstrated as a favorable approach for the characterization of variations in biofilm EPS in the presence of CIP antibiotic.

Effective Antibiotics against ‘Candidatus Liberibacter asiaticus’ in HLB-Affected Citrus Plants Identified via the Graft-Based Evaluation

PubMed Central

Powell, Charles A.; Doud, Melissa S.; Yang, Chuanyu; Duan, Yongping

2014-01-01

Citrus huanglongbing (HLB), caused by three species of fastidious, phloem-limited ‘Candidatus Liberibacter’, is one of the most destructive diseases of citrus worldwide. To date, there is no established cure for this century-old and yet, newly emerging disease. As a potential control strategy for citrus HLB, 31 antibiotics were screened for effectiveness and phytotoxicity using the optimized graft-based screening system with ‘Candidatus Liberibacter asiaticus’ (Las)-infected citrus scions. Actidione and Oxytetracycline were the most phytotoxic to citrus with less than 10% of scions surviving and growing; therefore, this data was not used in additional analyses. Results of principal component (PCA) and hierarchical clustering analyses (HCA) demonstrated that 29 antibiotics were clustered into 3 groups: highly effective, partly effective, and not effective. In spite of different modes of actions, a number of antibiotics such as, Ampicillin, Carbenicillin, Penicillin, Cefalexin, Rifampicin and Sulfadimethoxine were all highly effective in eliminating or suppressing Candidatus Liberibacter asiaticus indicated by both the lowest Las infection rate and titers of the treated scions and inoculated rootstock. The non-effective group, including 11 antibiotics alone with three controls, such as Amikacin, Cinoxacin, Gentamicin, Kasugamycin, Lincomycin, Neomycin, Polymixin B and Tobramycin, did not eliminate or suppress Las in the tested concentrations, resulting in plants with increased titers of Las. The other 12 antibiotics partly eliminated or suppressed Las in the treated and graft-inoculated plants. The effective and non-phytotoxic antibiotics could be potential candidates for control of citrus HLB, either for the rescue of infected citrus germplasm or for restricted field application. PMID:25372135

Rationalizing antibiotic use to limit antibiotic resistance in India+

PubMed Central

2011-01-01

Antibiotic resistance, a global concern, is particularly pressing in developing nations, including India, where the burden of infectious disease is high and healthcare spending is low. The Global Antibiotic Resistance Partnership (GARP) was established to develop actionable policy recommendations specifically relevant to low- and middle-income countries where suboptimal access to antibiotics - not a major concern in high-income countries - is possibly as severe a problem as is the spread of resistant organisms. This report summarizes the situation as it is known regarding antibiotic use and growing resistance in India and recommends short and long term actions. Recommendations aim at (i) reducing the need for antibiotics; (ii) lowering resistance-enhancing drug pressure through improved antibiotic targeting, and (iii) eliminating antibiotic use for growth promotion in agriculture. The highest priority needs to be given to (i) national surveillance of antibiotic resistance and antibiotic use - better information to underpin decisions on standard treatment guidelines, education and other actions, as well as to monitor changes over time; (ii) increasing the use of diagnostic tests, which necessitates behavioural changes and improvements in microbiology laboratory capacity; (iii) setting up and/or strengthening infection control committees in hospitals; and (iv) restricting the use of antibiotics for non-therapeutic uses in agriculture. These interventions should help to reduce the spread of antibiotic resistance, improve public health directly, benefit the populace and reduce pressure on the healthcare system. Finally, increasing the types and coverage of childhood vaccines offered by the government would reduce the disease burden enormously and spare antibiotics. PMID:21985810

Analysis of copy number variations in Holstein cows identify potential mechanisms contributing to differences in residual feed intake

USDA-ARS?s Scientific Manuscript database

Genomic structural variation is an important and abundant source of genetic and phenotypic variation. In this study, we performed an initial analysis of CNVs using BovineHD SNP genotyping data from 147 Holstein cows identified as having high or low feed efficiency as estimated by residual feed intak...

Use and prescription of antibiotics in primary health care settings in China.

PubMed

Wang, Jin; Wang, Pan; Wang, Xinghe; Zheng, Yingdong; Xiao, Yonghong

2014-12-01

Appropriate antibiotic use is a key strategy to control antibacterial resistance. The first step in achieving this is to identify the major problems in antibiotic prescription in health care facilities, especially in primary health care settings, which is where most patients receive medical care. To identify current patterns of antibiotic use and explore the reasons for inappropriate prescription in primary health care settings in China. A total of 48 primary health care facilities in China were randomly selected from 6 provinces at various levels of economic development. Data for the years 2009 through 2011 from 39 qualifying facilities (23 city and 16 rural primary health care centers) were analyzed retrospectively. The study sample consisted of prescription records for 7311 outpatient visits and 2888 inpatient hospitalizations. General health center information, drug usage, disease diagnoses, and antibiotic use by outpatients and inpatients were surveyed. Cases of inappropriate antibiotic prescription were identified. Most staff in the primary health care facilities had less than a college degree, and the medical staff consisted primarily of physician assistants, assistant pharmacists, nurses, and nursing assistants. The median (range) governmental contribution to each facility was 34.0% (3.6%-92.5%) of total revenue. The facilities prescribed a median (range) of 28 (8-111) types of antibiotics, including 34 (10-115) individual agents. Antibiotics were included in 52.9% of the outpatient visit prescription records: of these, only 39.4% were prescribed properly. Of the inpatients, 77.5% received antibiotic therapy: of these, only 24.6% were prescribed properly. Antibiotics were prescribed for 78.0% of colds and 93.5% of cases of acute bronchitis. Of the antibiotic prescriptions, 28.0% contained cephalosporins and 15.7% fluoroquinolones. A total of 55.0% of the antibiotic prescriptions were for antibiotic combination therapy with 2 or more agents. In nonsurgical

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.

Antibiotic Resistance: A Primer and Call to Action

PubMed Central

Smith, Rachel A.; M’ikanatha, Nkuchia M.; Read, Andrew F.

2014-01-01

During the past century, discoveries of microorganisms as causes of infections and antibiotics as effective therapeutic agents have contributed to significant gains in public health in many parts of the world. Health agencies worldwide are galvanizing attention toward antibiotic resistance, which is a major threat to public health (Centers for Disease Control and Prevention [CDC], 2013; World Health Organization [WHO], 2014). Some life scientists believe that we are approaching the post-antibiotic age (Davies & Davies, 2010). The growing threat of antimicrobial resistance is fueled by complex factors with biological, behavioral and societal aspects. This primer provides an overview of antibiotic resistance and its growing burden on public health, the biological and behavioral mechanisms that increase antibiotic resistance, and examples of where health communication scholars can contribute to efforts to make our current antibiotic drugs last as long as possible. In addition, we identify compelling challenges for current communication theories and practices. PMID:25121990

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.

Long-term antibiotic exposure in soil is associated with changes in microbial community structure and prevalence of class 1 integrons.

PubMed

Cleary, David W; Bishop, Alistair H; Zhang, Lihong; Topp, Edward; Wellington, Elizabeth M H; Gaze, William H

2016-10-01

Antimicrobial resistance is one of the most significant challenges facing the global medical community and can be attributed to the use and misuse of antibiotics. This includes use as growth promoters or for prophylaxis and treatment of bacterial infection in intensively farmed livestock from where antibiotics can enter the environment as residues in manure. We characterised the impact of the long-term application of a mixture of veterinary antibiotics alone (tylosin, sulfamethazine and chlortetracycline) on class 1 integron prevalence and soil microbiota composition. Class 1 integron prevalence increased significantly (P < 0.005) from 0.006% in control samples to 0.064% in the treated plots. Soil microbiota was analysed using 16S rRNA gene sequencing and revealed significant alterations in composition. Of the 19 significantly different (P < 0.05) OTUs identified, 16 were of the Class Proteobacteria and these decreased in abundance relative to the control plots. Only one OTU, of the Class Cyanobacteria, was shown to increase in abundance significantly; a curiosity given the established sensitivity of this class to antibiotics. We hypothesise that the overrepresentation of Proteobacteria as OTUs that decreased significantly in relative abundance, coupled with the observations of an increase in integron prevalence, may represent a strong selective pressure on these taxa. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Prophylactic antibiotics for penetrating abdominal trauma.

PubMed

Brand, Martin; Grieve, Andrew

2013-11-18

antibiotics or placebo. Two authors screened the literature search results independently. We identified no trials meeting the inclusion criteria. There is currently no information from randomised controlled trials to support or refute the use of antibiotics for patients with penetrating abdominal trauma.

Correlates of parental antibiotic knowledge, demand, and reported use.

PubMed

Kuzujanakis, Marianne; Kleinman, Ken; Rifas-Shiman, Sheryl; Finkelstein, Jonathan A

2003-01-01

Clinicians cite parental misconceptions and requests for antibiotics as reasons for inappropriate prescribing. To identify misconceptions regarding antibiotics and predictors of parental demand for antibiotics and to determine if parental knowledge and attitudes are associated with use. Survey of parents in 16 Massachusetts communities. Domains included antibiotic-related knowledge, attitudes about antibiotics, antibiotic use during a 12-month period, demographics, and access to health information. Bivariate and multivariate analyses evaluated predictors of knowledge and proclivity to demand antibiotics. A multivariate model evaluated the associations of knowledge, demand, and demographic factors with parent-reported antibiotic use. A total of 1106 surveys were returned (response rates: 54% and 32% for commercially-insured and Medicaid-insured families). Misconceptions were common regarding bronchitis (92%) and green nasal discharge (78%). Two hundred sixty-five (24%) gave responses suggesting a proclivity to demand antibiotics. Antibiotic knowledge was associated with increased parental age and education, having more than 1 child, white race, and receipt of media information on resistance. Factors associated with a proclivity to demand antibiotics included decreased knowledge, pressure from day-care settings, lack of alternatives offered by clinicians, and lack of access to media information. Among all respondents, reported antibiotic use was associated with younger child age and day-care attendance. Among Medicaid-insured children only, less antibiotic knowledge and tendency to demand antibiotics were associated with higher rates of antibiotic use. Misconceptions regarding antibiotic use are widespread and potentially modifiable by clinicians and media sources. Particular attention should be paid to Medicaid-insured patients in whom such misconceptions may contribute to inappropriate prescribing.

A Systematic Review of Perioperative Versus Prophylactic Antibiotics for Cochlear Implantation.

PubMed

Anne, Samantha; Ishman, Stacey L; Schwartz, Seth

2016-11-01

Previous Cochrane review of prophylactic antibiotic use in clean and clean-contaminated ear surgery showed no benefit; however, these studies did not address cochlear implant (CI) surgery specifically. Systematically review effects of perioperative antibiotics on risk of infections and related complications in CI surgery SEARCH METHODS: PubMed, EMBASE, Medline, CINAHL, and Cochrane library were searched from inception to March 2015. Manual searches of bibliographies were also completed. We included all studies that describe perioperative antibiotic use in CI surgery. Outcome measures included infection, meningitis, implant extrusion, and adverse antibiotics effects. Two independent evaluators reviewed each abstract and article. One hundred and seventy-three studies were identified in search. Three met inclusion criteria and were reviewed. Articles were low quality; no randomized trials were identified. For included studies, numerous antibiotic types and dosing regimens were used. Recorded outcome measures were heterogeneous, and detailed information was frequently unavailable. Overall infection rate was low (3%-4.5%); single dose antibiotic prophylaxis showed low rate of complications (1%) in 2 studies. There is insufficient evidence to make definitive conclusions about the role of perioperative antibiotics in CI surgery. Reported infection rates are low; however, decision to use antibiotics should be based on assessment of risks and benefits to each patient. © The Author(s) 2016.

An antibiotic's journey from marketing authorization to use, Norway.

PubMed

Årdal, Christine; Blix, Hege Salvesen; Plahte, Jens; Røttingen, John-Arne

2017-03-01

Here we describe in detail marketing authorization and reimbursement procedures for medicinal products in Norway, with particular reference to nine novel antibiotics that received marketing authorization between 2005 and 2015. The description illustrates that, in places like Norway, with effective antibiotic stewardship policies and an associated low prevalence of antibiotic-resistant bacterial infection, there is little need for newer, more expensive antibiotics whose therapeutic superiority to existing compounds has not been demonstrated. Since resistance begins to emerge as soon as an antibiotic is used, Norway's practice of leaving newer antibiotics on the shelf is consistent with the goal of prolonging the effectiveness of newer antibiotics. An unintended consequence is that the country has signalled to the private sector that there is little commercial value in novel antibiotics, which may nevertheless still be needed to treat rare or emerging infections. Every country aims to improve infection control and to promote responsible antibiotic use. However, as progress is made, antibiotic-resistant bacteria should become less common and, consequently, the need for, and the commercial value of, novel antibiotics will probably be reduced. Nevertheless, antibiotic innovation continues to be essential. This dilemma will have to be resolved through the introduction of alternative reward systems for antibiotic innovation. The DRIVE-AB (Driving re-investment in research and development and responsible antibiotic use) research consortium in Europe has been tasked with identifying ways of meeting this challenge.

The use of antibiotics in cattle in North-East Benin: pharmaceutical inventory and risk practices of cattle breeders.

PubMed

Dognon, S R; Antoine-Moussiaux, N; Douny, C; Gustin, P; Moula, N; Scippo, M L; Youssao, A K I

2018-05-07

This study's aim is to inventory antibiotics used in cattle in North-East Benin and assess risk practices that could be the cause of both food chain contamination by antibiotic residues and selection of antibiotic-resistant bacteria in animals and humans. A survey was conducted among 98 cattle breeders in the districts of Banikoara, Kandi, Bembereke, and Kalale in North Benin. Semi-structured interviews were conducted, covering breeder status, breeding system, and antibiotic use. Multiple correspondence analysis and hierarchical classification analysis were conducted to establish a breeder typology. Breeders mainly belonged to the Fulani ethnic group (71.4 ± 8.9%) and almost all of them received "no formal education" (96.9 ± 3.4%). Cattle herds were mainly composed of a single breed, the Borgou (76.4 ± 8.1%) or the Fulani Zebu (16.0 ± 7.0%). Some herds were mixed. Antibiotics groups used in cattle breeding were tetracyclines, beta-lactams, sulfonamides, aminoglycosides, and macrolides, used by respectively 100%, 69.4 ± 9.1%, 56.1 ± 9.8%, 44.9 ± 9.8%, and 34.7 ± 9.4% of breeders. These drugs were purchased in local markets (59.0 ± 15.4%) and veterinary pharmacy (41.0 ± 15.4%). They were mainly used against respiratory diseases, lameness, mastitis, omphalitis and neonatal enteritis, and skin diseases. Only 49.0 ± 9.9% of breeders seek veterinary services to treat animals and 92.9 ± 5.1% of them did not respect antibiotic withdrawal times. These practices suggest that both contamination of bovine meat with antibiotic residues and selection of resistant bacteria are to be expected, resulting in adverse health effects on consumers.

Occurrence of antibiotics and antibiotic resistance genes in a sewage treatment plant and its effluent-receiving river.

PubMed

Xu, Jian; Xu, Yan; Wang, Hongmei; Guo, Changsheng; Qiu, Huiyun; He, Yan; Zhang, Yuan; Li, Xiaochen; Meng, Wei

2015-01-01

The extensive use of antibiotics has caused the contamination of both antibiotics and antibiotic resistance genes (ARGs) in the environment. In this study, the abundance and distribution of antibiotics and ARGs from a sewage treatment plant (STP) and its effluent-receiving river in Beijing China were characterized. Three classes of antibiotics including tetracycline, sulfonamide and quinolone were quantified by LC-MS/MS. In the secondary effluent they were detected at 195, 2001 and 3866 ng L(-1), respectively, which were higher than in the receiving river water. A total of 13 ARGs (6 tet genes: tetA, tetB, tetE, tetW, tetM and tetZ, 3 sulfonamide genes: sul1, sul2 and sul3, and 4 quinolone genes: gryA, parC, qnrC and qnrD) were determined by quantitative PCR. For all ARGs, sulfonamide resistance genes were present at relatively high concentrations in all samples, with the highest ARG concentration above 10(-1). ARGs remained relatively stable along each sewage treatment process. The abundances of detected ARGs from the STP were also higher than its receiving river. Bivariate correlation analysis showed that relative tet gene copies (tetB/16S-rRNA and tetW/16S-rRNA) were strongly correlated with the concentrations of tetracycline residues (r(2)>0.8, p<0.05), while no significant correlations occurred between sulfonamides and sul genes. A negative correlation between the relative abundance of quinolone resistance gene (qnrC/16S-rRNA) and the concentrations of enrofloxacin (ENR) was also determined. The difference of ARGs levels in the raw influent and secondary effluent suggested that the STP treatment process may induce to increase the abundance of resistance genes. The results showed that the sewage was an important repository of the resistance genes, which need to be effectively treated before discharge into the natural water body. Copyright © 2014 Elsevier Ltd. All rights reserved.

Resistance Mechanisms and the Future of Bacterial Enoyl-Acyl Carrier Protein Reductase (FabI) Antibiotics

PubMed Central

Yao, Jiangwei; Rock, Charles O.

2016-01-01

Missense mutations leading to clinical antibiotic resistance are a liability of single-target inhibitors. The enoyl-acyl carrier protein reductase (FabI) inhibitors have one intracellular protein target and drug resistance is increased by the acquisition of single-base-pair mutations that alter drug binding. The spectrum of resistance mechanisms to FabI inhibitors suggests criteria that should be considered during the development of single-target antibiotics that would minimize the impact of missense mutations on their clinical usefulness. These criteria include high-affinity, fast on/off kinetics, few drug contacts with residue side chains, and no toxicity. These stringent criteria are achievable by structure-guided design, but this approach will only yield pathogen-specific drugs. Single-step acquisition of resistance may limit the clinical application of broad-spectrum, single-target antibiotics, but appropriately designed pathogen-specific antibiotics have the potential to overcome this liability. PMID:26931811

Antibiotic prophylaxis in obstetric procedures.

PubMed

van Schalkwyk, Julie; Van Eyk, Nancy

2010-09-01

To review the evidence and provide recommendations on antibiotic prophylaxis for obstetrical procedures. Outcomes evaluated include need and effectiveness of antibiotics to prevent infections in obstetrical procedures. Published literature was retrieved through searches of Medline and The Cochrane Library on the topic of antibiotic prophylaxis in obstetrical procedures. Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. Searches were updated on a regular basis and articles published from January 1978 to June 2009 were incorporated in the guideline. Current guidelines published by the American College of Obstetrics and Gynecology were also incorporated. 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 under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care (Table 1). Implementation of this guideline should reduce the cost and harm resulting from the administration of antibiotics when they are not required and the harm resulting from failure to administer antibiotics when they would be beneficial. SUMMARY STATEMENTS: 1. Available evidence does not support the use of prophylactic antibiotics to reduce infectious morbidity following operative vaginal delivery. (II-1) 2. There is insufficient evidence to argue for or against the use of prophylactic antibiotics to reduce infectious morbidity for manual removal of the placenta. (III) 3. There is insufficient evidence to argue for or against the use of

Residue levels and discharge loads of antibiotics in wastewater treatment plants (WWTPs), hospital lagoons, and rivers within Lake Victoria Basin, Kenya.

PubMed

Kimosop, Selly Jemutai; Getenga, Z M; Orata, F; Okello, V A; Cheruiyot, J K

2016-09-01

The detection of antibiotics in water systems has instigated great environmental concern due to the toxicological effects associated with these compounds. Their discharge into the environment results from the ubiquity of use in medical, veterinary, and agricultural practices. Some of the effects of antibiotics include development of antibiotic-resistant bacteria, making it difficult to treat diseases, variation in natural microbial communities, and enzyme activities. In this study, the first comprehensive survey of some frequently used antibiotics namely ampicillin (AMP), amoxicillin (AMX), sulfamethoxazole (SMX), chloramphenicol (CAP), and ciprofloxacin (CPF) within Lake Victoria Basin of Kenya is presented. Sludge and wastewater samples were collected from wastewater treatment plants (WWTPs) and hospital lagoons within the study area. Samples were extracted and cleaned by solid-phase extraction, and analysis was carried out using high-performance liquid chromatography (HPLC). All wastewater samples and sludge collected contained quantifiable levels of the selected antibiotics. The highest concentrations were recorded for AMP with WWTPs and hospitals having 0.36 ± 0.04 and 0.79 ± 0.07 μg/L, respectively. In sludge samples, SMX recorded the highest concentrations of 276 ± 12 ng/g. The high levels in sludge indicate the preferential partition of antibiotics onto solid phase, posing great danger to consumers of crops grown in biosolid-amended soils. The daily discharge loads of antibiotics from nine WWTPs ranged between 80.75 and 3044.9 mg day(-1) with a total discharge of 6395.85 mg day(-1), signifying a high potential of water resource pollution within the region. This report will aid in the assessment of the risks posed by antibiotics released into the environment.

Plant Growth, Antibiotic Uptake, and Prevalence of Antibiotic Resistance in an Endophytic System of Pakchoi under Antibiotic Exposure

PubMed Central

Zhang, Hao; Li, Xunan; Yang, Qingxiang; Sun, Linlin; Yang, Xinxin; Zhou, Mingming; Deng, Rongzhen; Bi, Linqian

2017-01-01

Antibiotic contamination in agroecosystems may cause serious problems, such as the proliferation of various antibiotic resistant bacteria and the spreading of antibiotic resistance genes (ARGs) in the environment or even to human beings. However, it is unclear whether environmental antibiotics, antibiotic resistant bacteria, and ARGs can directly enter into, or occur in, the endophytic systems of plants exposed to pollutants. In this study, a hydroponic experiment exposing pakchoi (Brassica chinensis L.) to tetracycline, cephalexin, and sulfamethoxazole at 50% minimum inhibitory concentration (MIC) levels and MIC levels, respectively, was conducted to explore plant growth, antibiotic uptake, and the development of antibiotic resistance in endophytic systems. The three antibiotics promoted pakchoi growth at 50% MIC values. Target antibiotics at concentrations ranging from 6.9 to 48.1 µg·kg−1 were detected in the treated vegetables. Additionally, the rates of antibiotic-resistant endophytic bacteria to total cultivable endophytic bacteria significantly increased as the antibiotics accumulated in the plants. The detection and quantification of ARGs indicated that four types, tetX, blaCTX-M, and sul1 and sul2, which correspond to tetracycline, cephalexin, and sulfamethoxazole resistance, respectively, were present in the pakchoi endophytic system and increased with the antibiotic concentrations. The results highlight a potential risk of the development and spread of antibiotic resistance in vegetable endophytic systems. PMID:29099753

Plant Growth, Antibiotic Uptake, and Prevalence of Antibiotic Resistance in an Endophytic System of Pakchoi under Antibiotic Exposure.

PubMed

Zhang, Hao; Li, Xunan; Yang, Qingxiang; Sun, Linlin; Yang, Xinxin; Zhou, Mingming; Deng, Rongzhen; Bi, Linqian

2017-11-03

Antibiotic contamination in agroecosystems may cause serious problems, such as the proliferation of various antibiotic resistant bacteria and the spreading of antibiotic resistance genes (ARGs) in the environment or even to human beings. However, it is unclear whether environmental antibiotics, antibiotic resistant bacteria, and ARGs can directly enter into, or occur in, the endophytic systems of plants exposed to pollutants. In this study, a hydroponic experiment exposing pakchoi ( Brassica chinensis L.) to tetracycline, cephalexin, and sulfamethoxazole at 50% minimum inhibitory concentration (MIC) levels and MIC levels, respectively, was conducted to explore plant growth, antibiotic uptake, and the development of antibiotic resistance in endophytic systems. The three antibiotics promoted pakchoi growth at 50% MIC values. Target antibiotics at concentrations ranging from 6.9 to 48.1 µg·kg -1 were detected in the treated vegetables. Additionally, the rates of antibiotic-resistant endophytic bacteria to total cultivable endophytic bacteria significantly increased as the antibiotics accumulated in the plants. The detection and quantification of ARGs indicated that four types, tet X, bla CTX-M , and sul 1 and sul 2, which correspond to tetracycline, cephalexin, and sulfamethoxazole resistance, respectively, were present in the pakchoi endophytic system and increased with the antibiotic concentrations. The results highlight a potential risk of the development and spread of antibiotic resistance in vegetable endophytic systems.

The magnitude of antibiotic resistance to Helicobacter pylori in Africa and identified mutations which confer resistance to antibiotics: systematic review and meta-analysis.

PubMed

Jaka, Hyasinta; Rhee, Jee Ah; Östlundh, Linda; Smart, Luke; Peck, Robert; Mueller, Andreas; Kasang, Christa; Mshana, Stephen E

2018-04-24

Worldwide Helicobacter pylori (H.pylori) treatment is of great challenge due to increased antibiotic resistance. The burden of H. pylori antibiotic resistance in Africa is high with unclear information regarding the real magnitude. This systematic review and meta-analysis was conducted to investigate the magnitude of H.pylori antibiotic resistance in Africa to gain insight of the extent of the problem among H.pylori naïve treatment patients. The search was performed in the academic databases, Embase, PubMed, Web of Science and Africa Wide Information. ProQuest Dissertation and Theses, Scopus, Ethos, Africa Index Medicus (WHO), BioMed Central Proceedings, BASE, British Library, Open grey, Library of Congress and the New York Academy of Grey Literature Report were additionally searched for grey literature. Published articles from Africa on H.pylori antibiotic resistance between 1986 and June 2017 were systematically reviewed to estimate the H. pylori extent of resistance to macrolides, quinolones, amoxicillin, tetracycline and metronidazole. In 26 articles a total of 2085 isolates were tested for metronidazole, 1530 for amoxicillin, 1277 for tetracycline, 1752 for clarithromycin and 823 for quinolones.The overall pooled proportion of H.pylori resistance to quinolones, clarithromycin, tetracycline, metronidazole and amoxicillin were: (17.4%, 95%CI 12.8 - 21.9), (29.2%, 95%CI:26.7-31.8), (48.7%, 95%CI: 44.5-52.9), (75.8%, 95% CI: 74.1-.77.4) and (72.6%, 95% CI: 68.6-76.6), respectively. The commonest mutation detected were A2143G (49/97) for clarithromycin, RdxA (41/56) for metronidazole and D87I (16/40) for quinolones. Prevalence of metronidazole, clarithromycin, and amoxicillin resistance is high in developing world including Africa. This could impair the first line triple therapy of the H.pylori infection. There is a need of conducting surveillance of H.pylori susceptibility pattern in Africa for dual and triple resistance which can be used for the empirical

Fighting antibiotic resistance in the intensive care unit using antibiotics.

PubMed

Plantinga, Nienke L; Wittekamp, Bastiaan H J; van Duijn, Pleun J; Bonten, Marc J M

2015-01-01

Antibiotic resistance is a global and increasing problem that is not counterbalanced by the development of new therapeutic agents. The prevalence of antibiotic resistance is especially high in intensive care units with frequently reported outbreaks of multidrug-resistant organisms. In addition to classical infection prevention protocols and surveillance programs, counterintuitive interventions, such as selective decontamination with antibiotics and antibiotic rotation have been applied and investigated to control the emergence of antibiotic resistance. This review provides an overview of selective oropharyngeal and digestive tract decontamination, decolonization of methicillin-resistant Staphylococcus aureus and antibiotic rotation as strategies to modulate antibiotic resistance in the intensive care unit.

The Search for 'Evolution-Proof' Antibiotics.

PubMed

Bell, Graham; MacLean, Craig

2018-06-01

The effectiveness of antibiotics has been widely compromised by the evolution of resistance among pathogenic bacteria. It would be restored by the development of antibiotics to which bacteria cannot evolve resistance. We first discuss two kinds of 'evolution-proof' antibiotic. The first comprises literally evolution-proof antibiotics to which bacteria cannot become resistant by mutation or horizontal gene transfer. The second category comprises agents to which resistance may arise, but so rarely that it does not become epidemic. The likelihood that resistance to a novel agent will spread is evaluated here by a simple model that includes biological and therapeutic parameters governing the evolution of resistance within hosts and the transmission of resistant strains between hosts. This model leads to the conclusion that epidemic spread is unlikely if the frequency of mutations that confer resistance falls below a defined minimum value, and it identifies potential targets for intervention to prevent the evolution of resistance. Whether or not evolution-proof antibiotics are ever found, searching for them is likely to improve the deployment of new and existing agents by advancing our understanding of how resistance evolves. Copyright © 2017. Published by Elsevier Ltd.

Antibiotic therapy for Shigella dysentery.

PubMed

Prince Christopher R H; David, Kirubah V; John, Sushil M; Sankarapandian, Venkatesan

2010-01-20

Shigella dysentery is a relatively common illness and occasionally causes death, worldwide. Mild symptoms are self-limiting but in more severe cases, antibiotics are recommended for cure and preventing relapse. The antibiotics recommended are diverse, have regional differences in sensitivity, and have side effects. To evaluate the efficacy and safety of antibiotics for treating Shigella dysentery. In June 2009 we identified all relevant trials from the following databases: Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, issue 4), MEDLINE, EMBASE, LILACS and the metaRegister of Controlled Trials (mRCT). We also checked conference proceedings for relevant abstracts, and contacted researchers, organizations, and pharmaceutical companies. Randomized controlled trials of antibiotics for Shigella dysentery. Four authors, working in pairs, independently assessed trial eligibility, methodological quality, and extracted data. We calculated risk ratios (RR) with 95% confidence intervals (CI) for dichotomous data, and used the random-effects model for significant heterogeneity. We explored possible sources of heterogeneity, when present, in subgroup analyses of participant age and percentage of participants with confirmed Shigella infection. Sixteen trials (1748 participants), spanning four decades and with differing sensitivity to Shigella isolates, met the inclusion criteria. Seven were judged to be at risk of bias due to inadequate allocation concealment or blinding, and 12 due to incomplete reporting of outcome data. Limited data from one three-armed trial of people with moderately severe illness suggest that antibiotics reduce the episodes of diarrhoea at follow-up (furazolidone versus no drug RR 0.21, 95% CI 0.09 to 0.48, 73 participants; cotrimoxazole versus no drug RR 0.30, 95% CI 0.15 to 0.59, 76 participants).There was insufficient evidence to consider any class of

Antibiotic therapy for Shigella dysentery.

PubMed

Christopher, Prince Rh; David, Kirubah V; John, Sushil M; Sankarapandian, Venkatesan

2010-08-04

Shigella dysentery is a relatively common illness and occasionally causes death, worldwide. Mild symptoms are self-limiting but in more severe cases, antibiotics are recommended for cure and preventing relapse. The antibiotics recommended are diverse, have regional differences in sensitivity, and have side effects. To evaluate the efficacy and safety of antibiotics for treating Shigella dysentery. In June 2009 we identified all relevant trials from the following databases: Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, issue 4), MEDLINE, EMBASE, LILACS and the metaRegister of Controlled Trials (mRCT). We also checked conference proceedings for relevant abstracts, and contacted researchers, organizations, and pharmaceutical companies. Randomized controlled trials of antibiotics for Shigella dysentery. Four authors, working in pairs, independently assessed trial eligibility, methodological quality, and extracted data. We calculated risk ratios (RR) with 95% confidence intervals (CI) for dichotomous data, and used the random-effects model for significant heterogeneity. We explored possible sources of heterogeneity, when present, in subgroup analyses of participant age and percentage of participants with confirmed Shigella infection. Sixteen trials (1748 participants), spanning four decades and with differing sensitivity to Shigella isolates, met the inclusion criteria. Seven were judged to be at risk of bias due to inadequate allocation concealment or blinding, and 12 due to incomplete reporting of outcome data. Limited data from one three-armed trial of people with moderately severe illness suggest that antibiotics reduce the episodes of diarrhoea at follow-up (furazolidone versus no drug RR 0.21, 95% CI 0.09 to 0.48, 73 participants; cotrimoxazole versus no drug RR 0.30, 95% CI 0.15 to 0.59, 76 participants).There was insufficient evidence to consider any class of

Effect of Different Treatment Technologies on the Fate of Antibiotic Resistance Genes and Class 1 Integrons when Residual Municipal Wastewater Solids are Applied to Soil.

PubMed

Burch, Tucker R; Sadowsky, Michael J; LaPara, Timothy M

2017-12-19

Residual wastewater solids are a significant reservoir of antibiotic resistance genes (ARGs). While treatment technologies can reduce ARG levels in residual wastewater solids, the effects of these technologies on ARGs in soil during subsequent land-application are unknown. In this study we investigated the use of numerous treatment technologies (air drying, aerobic digestion, mesophilic anaerobic digestion, thermophilic anaerobic digestion, pasteurization, and alkaline stabilization) on the fate of ARGs and class 1 integrons in wastewater solids-amended soil microcosms. Six ARGs [erm(B), qnrA, sul1, tet(A), tet(W), and tet(X)], the integrase gene of class 1 integrons (intI1), and 16S rRNA genes were quantified using quantitative polymerase chain reaction. The quantities of ARGs and intI1 decreased in all microcosms, but thermophilic anaerobic digestion, alkaline stabilization, and pasteurization led to the most extensive decay of ARGs and intI1, often to levels similar to that of the control microcosms to which no wastewater solids had been applied. In contrast, the rates by which ARGs and intI1 declined using the other treatment technologies were generally similar, typically varying by less than 2 fold. These results demonstrate that wastewater solids treatment technologies can be used to decrease the persistence of ARGs and intI1 during their subsequent application to soil.

Iterative key-residues interrogation of a phytase with thermostability increasing substitutions identified in directed evolution.

PubMed

Shivange, Amol V; Roccatano, Danilo; Schwaneberg, Ulrich

2016-01-01

Bacterial phytases have attracted industrial interest as animal feed supplement due to their high activity and sufficient thermostability (required for feed pelleting). We devised an approach named KeySIDE,  an iterative Key-residues interrogation of the wild type with Substitutions Identified in Directed Evolution for improving Yersinia mollaretii phytase (Ymphytase) thermostability by combining key beneficial substitutions and elucidating their individual roles. Directed evolution yielded in a discovery of nine positions in Ymphytase and combined iteratively to identify key positions. The "best" combination (M6: T77K, Q154H, G187S, and K289Q) resulted in significantly improved thermal resistance; the residual activity improved from 35 % (wild type) to 89 % (M6) at 58 °C and 20-min incubation. Melting temperature increased by 3 °C in M6 without a loss of specific activity. Molecular dynamics simulation studies revealed reduced flexibility in the loops located next to helices (B, F, and K) which possess substitutions (Helix-B: T77K, Helix-F: G187S, and Helix-K: K289E/Q). Reduced flexibility in the loops might be caused by strengthened hydrogen bonding network (e.g., G187S and K289E/K289Q) and a salt bridge (T77K). Our results demonstrate a promising approach to design phytases in food research, and we hope that the KeySIDE might become an attractive approach for understanding of structure-function relationships of enzymes.

Antibiotic resistance rates and physician antibiotic prescription patterns of uncomplicated urinary tract infections in southern Chinese primary care

PubMed Central

Kung, Kenny; Au-Doung, Philip Lung Wai; Ip, Margaret; Lee, Nelson; Fung, Alice; Wong, Samuel Yeung Shan

2017-01-01

Uncomplicated urinary tract infections (UTI) are common in primary care. Whilst primary care physicians are called to be antimicrobial stewards, there is limited primary care antibiotic resistance surveillance and physician antibiotic prescription data available in southern Chinese primary care. The study aimed to investigate the antibiotic resistance rate and antibiotic prescription patterns in female patients with uncomplicated UTI. Factors associated with antibiotic resistance and prescription was explored. A prospective cohort study was conducted in 12 primary care group clinics in Hong Kong of patients presenting with symptoms of uncomplicated UTI from January 2012 to December 2013. Patients’ characteristics such as age, comorbidity, presenting symptoms and prior antibiotic use were recorded by physicians, as well as any empirical antibiotic prescription given at presentation. Urine samples were collected to test for antibiotic resistance of uropathogens. Univariate analysis was conducted to identify factors associated with antibiotic resistance and prescription. A total of 298 patients were included in the study. E. coli was detected in 107 (76%) out of the 141 positive urine samples. Antibiotic resistance rates of E. coli isolates for ampicillin, co-trimoxazole, ciprofloxacin, amoxicillin and nitrofurantoin were 59.8%, 31.8%, 23.4%, 1.9% and 0.9% respectively. E. coli isolates were sensitive to nitrofurantoin (98.1%) followed by amoxicillin (78.5%). The overall physician antibiotic prescription rate was 82.2%. Amoxicillin (39.6%) and nitrofurantoin (28.6%) were the most common prescribed antibiotics. Meanwhile, whilst physicians in public primary care prescribed more amoxicillin (OR: 2.84, 95% CI: 1.67 to 4.85, P<0.001) and nitrofurantoin (OR: 2.01, 95% CI: 1.14 to 3.55, P = 0.015), physicians in private clinics prescribed more cefuroxime and ciprofloxacin (P<0.05). Matching of antibiotic prescription and antibiotic sensitivity of E. coli isolates occurred

Ceramic Biocomposites as Biodegradable Antibiotic Carriers in the Treatment of Bone Infections

PubMed Central

Ferguson, Jamie; Diefenbeck, Michael; McNally, Martin

2017-01-01

Local release of antibiotic has advantages in the treatment of chronic osteomyelitis and infected fractures. The adequacy of surgical debridement is still key to successful clearance of infection but local antibiotic carriers seem to afford greater success rates by targeting the residual organisms present after debridement and delivering much higher local antibiotic concentrations compared with systemic antibiotics alone. Biodegradable ceramic carriers can be used to fill osseous defects, which reduces the dead space and provides the potential for subsequent repair of the osseous defect as they dissolve away. A dissolving ceramic antibiotic carrier also raises the possibility of single stage surgery with definitive closure and avoids the need for subsequent surgery for spacer removal. In this article we provide an overview of the properties of various biodegradable ceramics, including calcium sulphate, the calcium orthophosphate ceramics, calcium phosphate cement and polyphasic carriers. We summarise the antibiotic elution properties as investigated in previous animal studies as well as the clinical outcomes from clinical research investigating their use in the surgical management of chronic osteomyelitis. Calcium sulphate pellets have been shown to be effective in treating local infection, although newer polyphasic carriers may support greater osseous repair and reduce the risk of further fracture or the need for secondary reconstructive surgery. The use of ceramic biocomposites to deliver antibiotics together with BMPs, bisphosphonates, growth factors or living cells is under investigation and merits further study. We propose a treatment protocol, based on the Cierny-Mader classification, to help guide the appropriate selection of a suitable ceramic antibiotic carrier in the surgical treatment of chronic osteomyelitis. PMID:28529863

Evidence of Increased Antibiotic Resistance in Phylogenetically-Diverse Aeromonas Isolates from Semi-Intensive Fish Ponds Treated with Antibiotics.

PubMed

Patil, Hemant J; Benet-Perelberg, Ayana; Naor, Alon; Smirnov, Margarita; Ofek, Tamir; Nasser, Ahmed; Minz, Dror; Cytryn, Eddie

2016-01-01

The genus Aeromonas is ubiquitous in aquatic environments encompassing a broad range of fish and human pathogens. Aeromonas strains are known for their enhanced capacity to acquire and exchange antibiotic resistance genes and therefore, are frequently targeted as indicator bacteria for monitoring antimicrobial resistance in aquatic environments. This study evaluated temporal trends in Aeromonas diversity and antibiotic resistance in two adjacent semi-intensive aquaculture facilities to ascertain the effects of antibiotic treatment on antimicrobial resistance. In the first facility, sulfadiazine-trimethoprim was added prophylactically to fingerling stocks and water column-associated Aeromonas were monitored periodically over an 11-month fish fattening cycle to assess temporal dynamics in taxonomy and antibiotic resistance. In the second facility, Aeromonas were isolated from fish skin ulcers sampled over a 3-year period and from pond water samples to assess associations between pathogenic strains to those in the water column. A total of 1200 Aeromonas isolates were initially screened for sulfadiazine resistance and further screened against five additional antimicrobials. In both facilities, strong correlations were observed between sulfadiazine resistance and trimethoprim and tetracycline resistances, whereas correlations between sulfadiazine resistance and ceftriaxone, gentamicin, and chloramphenicol resistances were low. Multidrug resistant strains as well as sul1, tetA , and intI1 gene-harboring strains were significantly higher in profiles sampled during the fish cycle than those isolated prior to stocking and these genes were extremely abundant in the pathogenic strains. Five phylogenetically distinct Aeromonas clusters were identified using partial rpoD gene sequence analysis. Interestingly, prior to fingerling stocking the diversity of water column strains was high, and representatives from all five clusters were identified, including an A. salmonicida

Evidence of Increased Antibiotic Resistance in Phylogenetically-Diverse Aeromonas Isolates from Semi-Intensive Fish Ponds Treated with Antibiotics

PubMed Central

Patil, Hemant J.; Benet-Perelberg, Ayana; Naor, Alon; Smirnov, Margarita; Ofek, Tamir; Nasser, Ahmed; Minz, Dror; Cytryn, Eddie

2016-01-01

The genus Aeromonas is ubiquitous in aquatic environments encompassing a broad range of fish and human pathogens. Aeromonas strains are known for their enhanced capacity to acquire and exchange antibiotic resistance genes and therefore, are frequently targeted as indicator bacteria for monitoring antimicrobial resistance in aquatic environments. This study evaluated temporal trends in Aeromonas diversity and antibiotic resistance in two adjacent semi-intensive aquaculture facilities to ascertain the effects of antibiotic treatment on antimicrobial resistance. In the first facility, sulfadiazine-trimethoprim was added prophylactically to fingerling stocks and water column-associated Aeromonas were monitored periodically over an 11-month fish fattening cycle to assess temporal dynamics in taxonomy and antibiotic resistance. In the second facility, Aeromonas were isolated from fish skin ulcers sampled over a 3-year period and from pond water samples to assess associations between pathogenic strains to those in the water column. A total of 1200 Aeromonas isolates were initially screened for sulfadiazine resistance and further screened against five additional antimicrobials. In both facilities, strong correlations were observed between sulfadiazine resistance and trimethoprim and tetracycline resistances, whereas correlations between sulfadiazine resistance and ceftriaxone, gentamicin, and chloramphenicol resistances were low. Multidrug resistant strains as well as sul1, tetA, and intI1 gene-harboring strains were significantly higher in profiles sampled during the fish cycle than those isolated prior to stocking and these genes were extremely abundant in the pathogenic strains. Five phylogenetically distinct Aeromonas clusters were identified using partial rpoD gene sequence analysis. Interestingly, prior to fingerling stocking the diversity of water column strains was high, and representatives from all five clusters were identified, including an A. salmonicida cluster

Antibiotics for the neurological complications of Lyme disease.

PubMed

Cadavid, Diego; Auwaerter, Paul G; Rumbaugh, Jeffrey; Gelderblom, Harald

2016-12-08

Various central nervous system-penetrant antibiotics are bactericidal in vitro and in vivo against the causative agent of Lyme neuroborreliosis (LNB), Borrelia burgdorferi. These antibiotics are routinely used clinically to treat LNB, but their relative efficacy is not clear. To assess the effects of antibiotics for the treatment of LNB. On 25 October 2016 we searched the Cochrane Neuromuscular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase. We searched clinical trial registers on 26 October 2016. We reviewed the bibliographies of the randomized trials identified and contacted the authors and known experts in the field to identify additional published or unpublished data. There were no language restrictions when searching for studies. Randomized clinical trials of antibiotic treatment of LNB in adults and children that compared any antibiotic treatment, including combinations of treatments, versus any other treatment, placebo, or no treatment. We excluded studies of entities considered as post-Lyme syndrome. We used standard methodological procedures expected by Cochrane. We identified seven randomized studies involving 450 European participants with LNB for inclusion in this systematic review. We found no trials conducted in the United States. Marked heterogeneity among these studies prevented meta-analysis. None of the studies included a placebo control on the initial antibiotic treatment, and only one was blinded. None were delayed-start studies. All were active comparator studies, and most were not adequately powered for non-inferiority comparison. The trials investigated four antibiotics: penicillin G and ceftriaxone in four studies, doxycycline in three studies, and cefotaxime in two studies. One study tested a three-month course of oral amoxicillin versus placebo following initial treatment with intravenous ceftriaxone. One study was limited to children. The trials measured efficacy using heterogeneous

Bioavailability of Antibiotics at Soil-Water Interfaces: A Comparison of Measured Activities and Equilibrium Partitioning Estimates.

PubMed

Menz, Jakob; Müller, Julia; Olsson, Oliver; Kümmerer, Klaus

2018-06-05

There are growing concerns that antibiotic pollution impacts environmental microbiota and facilitates the propagation of antibiotic resistance. However, the prediction or analytical determination of bioavailable concentrations of antibiotics in soil is still subject to great uncertainty. Biological assays are increasingly recognized as valuable complementary tools that allow a more direct determination of the residual antibiotic activity. This study assessed the bioavailability of structurally diverse antibiotics at a soil-water interface applying activity-based analyses in conjunction with equilibrium partitioning (EqP) modeling. The activity against Gram-positive and Gram-negative bacteria of nine antibiotics from different classes was determined in the presence and absence of standard soil (LUFA St. 2.2). The addition of soil affected the activity of different antibiotics to highly varying degrees. Moreover, a highly significant correlation ( p < 0.0001) between the experimentally observed and the EqP-derived log EC 50 (half-maximal effective concentration) values was observed. The innovative experimental design of this study provided new insights on the bioavailability of antibiotics at soil-water interfaces. EqP appears to be applicable to a broad range of antibiotics for the purpose of screening-level risk assessment. However, EqP estimates cannot replace soil-specific ecotoxicity testing in higher-tier assessments, since their accuracy is still compromised by a number of factors.

Impact of antibiotic restrictions: the ethical perspective.

PubMed

Garau, J

2006-08-01

Antibiotic restrictions present difficult choices for physicians, patients and payors. Physicians must choose between the welfare of the patient and the directive of healthcare systems to restrict antibiotics. These may be supported with incentives or penalties, causing a conflict of interest. The patient has an expectation of best care, but will often be unaware of antibiotic restriction policies and is therefore not fully informed about his/her treatment. For payors, reducing the volume of antibiotic prescribing and/or prescribing less expensive antibiotics are apparently attractive targets for cost savings. However, we are only now beginning to understand the downstream consequences of restricting antibiotics on outcomes and costs. We are hampered by the lack of a universal ethical framework and information on outcomes. In addition, the concept of 'effective' or 'best' therapy will vary among different groups. Balancing the risks of treating or not treating with antibiotics is complex. Suboptimal therapy, that fails to eradicate the bacterial infection, exposes the patient to the risk of poor outcome, adverse events and the wider risk of antimicrobial resistance. Failure to treat where the risk of a poor outcome exceeds the risk of an adverse event is also ethically unacceptable. The key to rational antibiotic prescribing is to identify those patients who need antibiotic therapy and optimise therapy to achieve the fastest bacterial and clinical cure. We are only now beginning to assemble the information and tools to be able to make such decisions. Above all, we should treat on the basis of knowledge.

Optimal use of modern antibiotics: emerging trends.

PubMed

Polk, R

1999-08-01

Development of new antimicrobial drugs is an essential component in the effort to remain ahead of emerging microbial resistance. However, when new antibiotics are used with unrestrained enthusiasm, a predictable consequence is the further expansion of resistance. This problem is well known to the infectious diseases specialist and is increasingly appreciated by the nonspecialist and the public. A far more sensible strategy is to identify new ways to use these drugs to increase the duration of their usefulness. New methods to optimize antibiotic selection, dose, and duration of therapy are being investigated, and application of some of these strategies has been shown to have a favorable impact on resistance. Much of the classic thinking of how to use antibiotics is changing, and these newer strategies may result in prolongation of the era of the "antibiotic miracle."

[Antibiotics in the critically ill].

PubMed

Kolak, Radmila R

2010-01-01

Antibiotics are one the most common therapies administered in the intensive care unit setting. This review outlines the strategy for optimal use of antimicrobial agents in the critically ill. In severely ill patients, empirical antimicrobial therapy should be used when a suspected infection may impair the outcome. It is necessary to collect microbiological documentation before initiating empirical antimicrobial therapy. In addition to antimicrobial therapy, it is recommended to control a focus of infection and to modify factors that promote microbial growth or impair the host's antimicrobial defence. A judicious choice of antimicrobial therapy should be based on the host characteristics, the site of injection, the local ecology, and the pharmacokinetics/pharmacodynamics of antibiotics. This means treating empirically with broad-spectrum antimicrobials as soon as possible and narrowing the spectrum once the organism is identified (de-escalation), and limiting duration of therapy to the minimum effective period. Despite theoretical advantages, a combined antibiotic therapy is nor more effective than a mono-therapy in curing infections in most clinical trials involving intensive care patients. Nevertheless, textbooks and guidelines recommend a combination for specific pathogens and for infections commonly caused by these pathogens. Avoiding unnecessary antibiotic use and optimizing the administration of antimicrobial agents will improve patient outcomes while minimizing risks for the development of bacterial resistance. It is important to note that each intensive care unit should have a program in place which monitors antibiotic utilisation and its effectiveness. Only in this way can the impact of interventions aimed at improving antibiotic use be evaluated at the local level.

Nanoengineered drug delivery systems for enhancing antibiotic therapy.

PubMed

Kalhapure, Rahul S; Suleman, Nadia; Mocktar, Chunderika; Seedat, Nasreen; Govender, Thirumala

2015-03-01

Formulation scientists are recognizing nanoengineered drug delivery systems as an effective strategy to overcome limitations associated with antibiotic drug therapy. Antibiotics encapsulated into nanodelivery systems will contribute to improved management of patients with various infectious diseases and to overcoming the serious global burden of antibiotic resistance. An extensive review of several antibiotic-loaded nanocarriers that have been formulated to target drugs to infectious sites, achieve controlled drug release profiles, and address formulation challenges, such as low-drug entrapment efficiencies, poor solubility and stability is presented in this paper. The physicochemical properties and the in vitro/in vivo performances of various antibiotic-loaded delivery systems, such as polymeric nanoparticles, micelles, dendrimers, liposomes, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, nanohybirds, nanofibers/scaffolds, nanosheets, nanoplexes, and nanotubes/horn/rods and nanoemulsions, are highlighted and evaluated. Future studies that will be essential to optimize formulation and commercialization of these antibiotic-loaded nanosystems are also identified. The review presented emphasizes the significant formulation progress achieved and potential that novel nanoengineered antibiotic drug delivery systems have for enhancing the treatment of patients with a range of infections. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Chemical Genetic Analysis and Functional Characterization of Staphylococcal Wall Teichoic Acid 2-Epimerases Reveals Unconventional Antibiotic Drug Targets.

PubMed

Mann, Paul A; Müller, Anna; Wolff, Kerstin A; Fischmann, Thierry; Wang, Hao; Reed, Patricia; Hou, Yan; Li, Wenjin; Müller, Christa E; Xiao, Jianying; Murgolo, Nicholas; Sher, Xinwei; Mayhood, Todd; Sheth, Payal R; Mirza, Asra; Labroli, Marc; Xiao, Li; McCoy, Mark; Gill, Charles J; Pinho, Mariana G; Schneider, Tanja; Roemer, Terry

2016-05-01

Here we describe a chemical biology strategy performed in Staphylococcus aureus and Staphylococcus epidermidis to identify MnaA, a 2-epimerase that we demonstrate interconverts UDP-GlcNAc and UDP-ManNAc to modulate substrate levels of TarO and TarA wall teichoic acid (WTA) biosynthesis enzymes. Genetic inactivation of mnaA results in complete loss of WTA and dramatic in vitro β-lactam hypersensitivity in methicillin-resistant S. aureus (MRSA) and S. epidermidis (MRSE). Likewise, the β-lactam antibiotic imipenem exhibits restored bactericidal activity against mnaA mutants in vitro and concomitant efficacy against 2-epimerase defective strains in a mouse thigh model of MRSA and MRSE infection. Interestingly, whereas MnaA serves as the sole 2-epimerase required for WTA biosynthesis in S. epidermidis, MnaA and Cap5P provide compensatory WTA functional roles in S. aureus. We also demonstrate that MnaA and other enzymes of WTA biosynthesis are required for biofilm formation in MRSA and MRSE. We further determine the 1.9Å crystal structure of S. aureus MnaA and identify critical residues for enzymatic dimerization, stability, and substrate binding. Finally, the natural product antibiotic tunicamycin is shown to physically bind MnaA and Cap5P and inhibit 2-epimerase activity, demonstrating that it inhibits a previously unanticipated step in WTA biosynthesis. In summary, MnaA serves as a new Staphylococcal antibiotic target with cognate inhibitors predicted to possess dual therapeutic benefit: as combination agents to restore β-lactam efficacy against MRSA and MRSE and as non-bioactive prophylactic agents to prevent Staphylococcal biofilm formation.

Antibiotics and Facial Fractures: Evidence-Based Recommendations Compared with Experience-Based Practice

PubMed Central

Mundinger, Gerhard S.; Borsuk, Daniel E.; Okhah, Zachary; Christy, Michael R.; Bojovic, Branko; Dorafshar, Amir H.; Rodriguez, Eduardo D.

2014-01-01

Efficacy of prophylactic antibiotics in craniofacial fracture management is controversial. The purpose of this study was to compare evidence-based literature recommendations regarding antibiotic prophylaxis in facial fracture management with expert-based practice. A systematic review of the literature was performed to identify published studies evaluating pre-, peri-, and postoperative efficacy of antibiotics in facial fracture management by facial third. Study level of evidence was assessed according to the American Society of Plastic Surgery criteria, and graded practice recommendations were made based on these assessments. Expert opinions were garnered during the Advanced Orbital Surgery Symposium in the form of surveys evaluating senior surgeon clinical antibiotic prescribing practices by time point and facial third. A total of 44 studies addressing antibiotic prophylaxis and facial fracture management were identified. Overall, studies were of poor quality, precluding formal quantitative analysis. Studies supported the use of perioperative antibiotics in all facial thirds, and preoperative antibiotics in comminuted mandible fractures. Postoperative antibiotics were not supported in any facial third. Survey respondents (n = 17) cumulatively reported their antibiotic prescribing practices over 286 practice years and 24,012 facial fracture cases. Percentages of prescribers administering pre-, intra-, and postoperative antibiotics, respectively, by facial third were as follows: upper face 47.1, 94.1, 70.6; midface 47.1, 100, 70.6%; and mandible 68.8, 94.1, 64.7%. Preoperative but not postoperative antibiotic use is recommended for comminuted mandible fractures. Frequent use of pre- and postoperative antibiotics in upper and midface fractures is not supported by literature recommendations, but with low-level evidence. Higher level studies may better guide clinical antibiotic prescribing practices. PMID:25709755

Thiopeptide antibiotics stimulate biofilm formation in Bacillus subtilis.

PubMed

Bleich, Rachel; Watrous, Jeramie D; Dorrestein, Pieter C; Bowers, Albert A; Shank, Elizabeth A

2015-03-10

Bacteria have evolved the ability to produce a wide range of structurally complex natural products historically called "secondary" metabolites. Although some of these compounds have been identified as bacterial communication cues, more frequently natural products are scrutinized for antibiotic activities that are relevant to human health. However, there has been little regard for how these compounds might otherwise impact the physiology of neighboring microbes present in complex communities. Bacillus cereus secretes molecules that activate expression of biofilm genes in Bacillus subtilis. Here, we use imaging mass spectrometry to identify the thiocillins, a group of thiazolyl peptide antibiotics, as biofilm matrix-inducing compounds produced by B. cereus. We found that thiocillin increased the population of matrix-producing B. subtilis cells and that this activity could be abolished by multiple structural alterations. Importantly, a mutation that eliminated thiocillin's antibiotic activity did not affect its ability to induce biofilm gene expression in B. subtilis. We go on to show that biofilm induction appears to be a general phenomenon of multiple structurally diverse thiazolyl peptides and use this activity to confirm the presence of thiazolyl peptide gene clusters in other bacterial species. Our results indicate that the roles of secondary metabolites initially identified as antibiotics may have more complex effects--acting not only as killing agents, but also as specific modulators of microbial cellular phenotypes.

Thiopeptide antibiotics stimulate biofilm formation in Bacillus subtilis

PubMed Central

Bleich, Rachel; Watrous, Jeramie D.; Dorrestein, Pieter C.; Bowers, Albert A.; Shank, Elizabeth A.

2015-01-01

Bacteria have evolved the ability to produce a wide range of structurally complex natural products historically called “secondary” metabolites. Although some of these compounds have been identified as bacterial communication cues, more frequently natural products are scrutinized for antibiotic activities that are relevant to human health. However, there has been little regard for how these compounds might otherwise impact the physiology of neighboring microbes present in complex communities. Bacillus cereus secretes molecules that activate expression of biofilm genes in Bacillus subtilis. Here, we use imaging mass spectrometry to identify the thiocillins, a group of thiazolyl peptide antibiotics, as biofilm matrix-inducing compounds produced by B. cereus. We found that thiocillin increased the population of matrix-producing B. subtilis cells and that this activity could be abolished by multiple structural alterations. Importantly, a mutation that eliminated thiocillin’s antibiotic activity did not affect its ability to induce biofilm gene expression in B. subtilis. We go on to show that biofilm induction appears to be a general phenomenon of multiple structurally diverse thiazolyl peptides and use this activity to confirm the presence of thiazolyl peptide gene clusters in other bacterial species. Our results indicate that the roles of secondary metabolites initially identified as antibiotics may have more complex effects—acting not only as killing agents, but also as specific modulators of microbial cellular phenotypes. PMID:25713360

Abscess of residual lobe after pulmonary resection for lung cancer.

PubMed

Ligabue, Tommaso; Voltolini, Luca; Ghiribelli, Claudia; Luzzi, Luca; Rapicetta, Cristian; Gotti, Giuseppe

2008-04-01

Abscess of the residual lobe after lobectomy is a rare but potentially lethal complication. Between January 1975 and December 2006, 1,460 patients underwent elective pulmonary lobectomy for non-small-cell lung cancer at our institution. Abscess of the residual lung parenchyma occurred in 5 (0.3%) cases (4 bilobectomies and 1 lobectomy). Postoperative chest radiography showed incomplete expansion and consolidation of residual lung parenchyma. Flexible bronchoscopy revealed persistent bronchial occlusion from purulent secretions and/or bronchial collapse. Computed tomography in 3 patients demonstrated lung abscess foci. Surgical treatment included completion right pneumonectomy in 3 patients and a middle lobectomy in one. Complications after repeat thoracotomy comprised contralateral pneumonia and sepsis in 1 patient. Residual lobar abscess after lobectomy should be suspected in patients presenting with fever, leukocytosis, bronchial obstruction and lung consolidation despite antibiotic therapy, physiotherapy and bronchoscopy. Computed tomography is mandatory for early diagnosis. Surgical resection of the affected lobe is recommended.

Antibiotic-Induced Rash in Patients With Infectious Mononucleosis.

PubMed

Thompson, Dennis F; Ramos, Carroll L

2017-02-01

To provide an extensive review of case reports, epidemiological data, and the underlying mechanism of antibiotic-induced skin rash in patients with concurrent infectious mononucleosis (IM). A MEDLINE literature search inclusive of the dates 1946 to June 2016 was performed using the search terms anti-bacterial agents and infectious mononucleosis. EMBASE (1980 to June 2016) was searched using the terms mononucleosis and antibiotic agent and drug eruption. References of all relevant articles were reviewed for additional citations and information. We selected English-language, primary literature, review articles, and mechanistic articles that addressed antibiotic-induced skin rash in patients with concurrent IM. We assessed all case reports available for causality utilizing a modified Naranjo nomogram specifically designed for this subject. We assembled the available epidemiological data into tables to identify trends in incidence rates over the years. We identified 17 case reports of antibiotic-associated rash in patients with IM. The median Naranjo score was 6 (range = 1 to 8). The top 3 reported drugs were ampicillin, azithromycin, and amoxicillin. Incidence of this adverse effect was higher in the 1960s (55.6%, 45%, and 33%) than in 2013 (33% and 15%). The mechanism most commonly proposed is a transient virus-mediated immune alteration that sets the stage for loss of antigenic tolerance and the development of a reversible, delayed-type hypersensitivity reaction to the antibiotic. A reassessment of the long-held belief of the high incidence (80%-100%) of antibiotic-induced skin rash in patients with IM seems prudent. Additional studies will be necessary to clarify this issue.

The Culturable Soil Antibiotic Resistome: A Community of Multi-Drug Resistant Bacteria

PubMed Central

Walsh, Fiona; Duffy, Brion

2013-01-01

Understanding the soil bacterial resistome is essential to understanding the evolution and development of antibiotic resistance, and its spread between species and biomes. We have identified and characterized multi-drug resistance (MDR) mechanisms in the culturable soil antibiotic resistome and linked the resistance profiles to bacterial species. We isolated 412 antibiotic resistant bacteria from agricultural, urban and pristine soils. All isolates were multi-drug resistant, of which greater than 80% were resistant to 16–23 antibiotics, comprising almost all classes of antibiotic. The mobile resistance genes investigated, (ESBL, bla NDM-1, and plasmid mediated quinolone resistance (PMQR) resistance genes) were not responsible for the respective resistance phenotypes nor were they present in the extracted soil DNA. Efflux was demonstrated to play an important role in MDR and many resistance phenotypes. Clinically relevant Burkholderia species are intrinsically resistant to ciprofloxacin but the soil Burkholderia species were not intrinsically resistant to ciprofloxacin. Using a phenotypic enzyme assay we identified the antibiotic specific inactivation of trimethoprim in 21 bacteria from different soils. The results of this study identified the importance of the efflux mechanism in the soil resistome and variations between the intrinsic resistance profiles of clinical and soil bacteria of the same family. PMID:23776501

The culturable soil antibiotic resistome: a community of multi-drug resistant bacteria.

PubMed

Walsh, Fiona; Duffy, Brion

2013-01-01

Understanding the soil bacterial resistome is essential to understanding the evolution and development of antibiotic resistance, and its spread between species and biomes. We have identified and characterized multi-drug resistance (MDR) mechanisms in the culturable soil antibiotic resistome and linked the resistance profiles to bacterial species. We isolated 412 antibiotic resistant bacteria from agricultural, urban and pristine soils. All isolates were multi-drug resistant, of which greater than 80% were resistant to 16-23 antibiotics, comprising almost all classes of antibiotic. The mobile resistance genes investigated, (ESBL, bla NDM-1, and plasmid mediated quinolone resistance (PMQR) resistance genes) were not responsible for the respective resistance phenotypes nor were they present in the extracted soil DNA. Efflux was demonstrated to play an important role in MDR and many resistance phenotypes. Clinically relevant Burkholderia species are intrinsically resistant to ciprofloxacin but the soil Burkholderia species were not intrinsically resistant to ciprofloxacin. Using a phenotypic enzyme assay we identified the antibiotic specific inactivation of trimethoprim in 21 bacteria from different soils. The results of this study identified the importance of the efflux mechanism in the soil resistome and variations between the intrinsic resistance profiles of clinical and soil bacteria of the same family.

Nano-antibiotics in chronic lung infection therapy against Pseudomonas aeruginosa.

PubMed

Hadinoto, Kunn; Cheow, Wean Sin

2014-04-01

Antibiotic encapsulation into nanoparticle carriers has emerged as a promising inhaled antibiotic formulation for treatment of chronic Pseudomonas aeruginosa lung infection prevalent in chronic obstructive pulmonary diseases. Attributed to their prolonged lung retention, sustained antibiotic release, and mucus penetrating ability, antibiotic nanoparticles, or nano-antibiotics in short, can address the principal weakness of inhaled antibiotic solution, i.e. low antibiotic exposure in the vicinity of P. aeruginosa biofilm colonies resulting in diminished anti-pseudomonal efficacy after repeated uses. This review details the current state of development and limitations of the two most widely studied forms of nano-antibiotics, i.e. liposomes and polymer nanoparticles. Factors in their formulation that influence the anti-pseudomonal efficacy in vitro and in vivo, such as liposome's membrane rigidity, surface charge, size, and polymer hydrophobicity, are discussed. This review reveals that the superior anti-pseudomonal efficacy of liposomal antibiotics to free antibiotics has been clearly established when they are correctly formulated, with several liposomal antibiotic formulations are currently undergoing clinical trials. Liposomal antibiotics, nevertheless, are not without limitation due to their weak physicochemical stability. In contrast, only mucus penetrating ability of the more stable polymeric nano-antibiotics has been established, while their anti-pseudomonal efficacy has only been examined in vitro from which their superiority to free antibiotics has not been ascertained. Lastly, future research needs to bring liposome and polymer-based nano-antibiotics closer to their clinical realization are identified. Copyright © 2014 Elsevier B.V. All rights reserved.

National ambulatory antibiotic prescribing patterns for pediatric urinary tract infection, 1998-2007.

PubMed

Copp, Hillary L; Shapiro, Daniel J; Hersh, Adam L

2011-06-01

The goal of this study was to investigate patterns of ambulatory antibiotic use and to identify factors associated with broad-spectrum antibiotic prescribing for pediatric urinary tract infections (UTIs). We examined antibiotics prescribed for UTIs for children aged younger than 18 years from 1998 to 2007 using the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey. Amoxicillin-clavulanate, quinolones, macrolides, and second- and third-generation cephalosporins were classified as broad-spectrum antibiotics. We evaluated trends in broad-spectrum antibiotic prescribing patterns and performed multivariable logistic regression to identify factors associated with broad-spectrum antibiotic use. Antibiotics were prescribed for 70% of pediatric UTI visits. Trimethoprim-sulfamethoxazole was the most commonly prescribed antibiotic (49% of visits). Broad-spectrum antibiotics were prescribed one third of the time. There was no increase in overall use of broad-spectrum antibiotics (P = .67); however, third-generation cephalosporin use doubled from 12% to 25% (P = .02). Children younger than 2 years old (odds ratio: 6.4 [95% confidence interval: 2.2-18.7, compared with children 13-17 years old]), females (odds ratio: 3.6 [95% confidence interval: 1.6-8.5]), and temperature ≥ 100.4°F (odds ratio: 2.9 [95% confidence interval: 1.0-8.6]) were independent predictors of broad-spectrum antibiotic prescribing. Race, physician specialty, region, and insurance status were not associated with antibiotic selection. Ambulatory care physicians commonly prescribe broad-spectrum antibiotics for the treatment of pediatric UTIs, especially for febrile infants in whom complicated infections are more likely. The doubling in use of third-generation cephalosporins suggests that opportunities exist to promote more judicious antibiotic prescribing because most pediatric UTIs are susceptible to narrower alternatives.

Interspecific differences in growth response and tolerance to the antibiotic sulfadiazine in ten clonal wetland plants in South China.

PubMed

Chen, Jinfeng; Xu, Huilian; Sun, Yingbo; Huang, Lili; Zhang, Peixia; Zou, Chunping; Yu, Bo; Zhu, Genfa; Zhao, Chaoyi

2016-02-01

Pollution caused by residual antibiotics is a worldwide environmental issue. Antibiotic residues often occur in aquatic ecosystems, posing threats to the health of aquatic organisms. The effects of antibiotic residues on the growth of crop plants and on human health are reasonably well known. However, less is known about antibiotic effects on wetland plants. Therefore, we studied the response and tolerance of ten clonal wetland plants grown in soil spiked with sulfadiazine at 10 mg kg(-1) (an environmentally relevant concentration) and 100 mg kg(-1). At 10 mg kg(-1), ramet number was the least affected trait, while root number was the most affected among plant species. Plant shoot and total biomass were reduced in all species except in Cyperus malaccensis var. brevifolius and Panicum repens. Chlorophyll content was reduced in Alocasia macrorrhiza, Saururus chinensis, and Commelina diffusa. In general, Panicum paludosum and C. malaccensis var. brevifolius showed the least reduction of growth parameters, whereas growth of both A. macrorrhiza and S. chinensis was severely reduced. At 100 mg kg(-1), negative responses occurred in all species. Comprehensive tolerance analysis revealed that P. paludosum and C. malaccensis var. brevifolius were the species most resistant to sulfadiazine. These species are potential candidates for sulfadiazine polluted wetland restoration. A. macrorrhiza and S. chinensis were the most susceptible species and they should be protected from sulfadiazine pollution. Relative plant shoot biomass and height were the most useful indicators for evaluating plant tolerance to sulfadiazine. Plant tolerance to sulfadiazine was associated with the differences of plants in height and shoot biomass. Copyright © 2015 Elsevier B.V. All rights reserved.

Proposal of a pharmacokinetically optimized dosage regimen of antibiotics in patients receiving continuous hemodiafiltration.

PubMed

Yamamoto, Takehito; Yasuno, Nobuhiro; Katada, Shoichi; Hisaka, Akihiro; Hanafusa, Norio; Noiri, Eisei; Yahagi, Naoki; Fujita, Toshiro; Suzuki, Hiroshi

2011-12-01

The aim of the study was to quantitatively predict the clearance of three antibiotics, amikacin, vancomycin, and teicoplanin, during continuous hemodiafiltration (CHDF) and to propose their optimal dosage in patients receiving CHDF. For this goal, in vitro CHDF experiments with a polyacrylonitrile (PAN) membrane were first performed using these antibiotics, and then the clearances were compared with in vivo CHDF situations determined in 16 critically ill patients. The in vitro CHDF clearances were described as the product of the outflow rate of a drain (Q(outflow)) and the drug unbound fraction in artificial plasma, indicating that drug adsorption to the PAN membrane has minor effect on drug clearance in our settings. The observed in vivo clearances also agreed very well with the predicted values, with a product of Q(outflow) and plasma unbound fraction, when residual creatinine clearance (CL(CR)) was taken into account (within a range of 0.67- to 1.5-fold for 15 of 16 patients). Based on these results, a nomogram of the optimized dosages of amikacin, vancomycin, and teicoplanin was proposed, and it was evident that Q(outflow) and residual CL(CR) are major determinants of the dosage and dosing interval for these antibiotics. Although the applicability needs to be confirmed with another type of membrane or higher Q(outflow), our nomogram can help determine the dosage setting in critically ill patients receiving CHDF.

6-Iso-chlortetracycline or keto form of chlortetracycline? Need for clarification for relevant monitoring of chlortetracycline residues in food.

PubMed

Gaugain, Murielle; Gautier, Sophie; Bourcier, Sophie; Jacques, Anne-Marie; Laurentie, Michel; Abjean, Jean-Pierre; Hurtaud-Pessel, Dominique; Verdon, Eric

2015-01-01

Chlortetracycline (CTC) is a broad-spectrum antibiotic used in veterinary medicine for pulmonary or digestive infections and having a regulatory maximum residue limit (MRL) necessitating an official analytical control method. The purpose of this study was to clarify the identification of different forms of CTC observed in standard solution, in spiked muscle samples and in naturally incurred muscle samples of pigs analysed by LC-MS/MS and to demonstrate the in vivo formation of 6-iso-chlortetracycline and 4-epi-6-iso-CTC as a metabolite of CTC and 4-epi-CTC in muscle. The six following forms were identified, all being isobaric with a protonated molecule at m/z 479 (precursor ion): the keto-enol forms of CTC and the keto-enol forms of 4-epi-chlortetracycline (4-epi-CTC), 6-iso-chlortetracycline (6-iso-CTC) and 4-epi-6-iso-chlortetracycline (4-epi-6-iso-CTC). The 6-iso-CTC and 4-epi-6-iso-CTC were observed only in incurred pig samples so were identified for the first time as metabolites of CTC and 4-epi-CTC. Identification of the different forms was obtained by comparing incurred muscle samples with standard solutions and with spiked samples. Then the differences between the features of the chromatograms obtained by LC-TQ-MS and the fragmentation study of the different forms of CTC obtained by LC-Q-TOF-MS helped us to support this identification. The extraction steps and the LC-MS/MS conditions developed to analyse muscle tissue samples are described. This clarification concerning the rigorous identification of chromatographic peaks allowed us to evaluate the relevance of our monitoring method with regard to the regulations in place in the European Union and could be of help to laboratories involved in official control of antibiotic residues in food of animal origin. Additional results are also presented highlighting the transformation of the CTC when prepared in a mixture with other antibiotics.

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

On the feasibility of a CENTA-based biosensor to measure antibiotics concentration in milk

NASA Astrophysics Data System (ADS)

Ferrari, Luca; Rovati, Luigi; Costi, Maria Paola; Venturelli, Alberto; Luciani, Rosaria; Cattini, Stefano

2017-07-01

In veterinary practice antibiotics are used and abused all over the world both to treat diseases and prevent infections and, to increase feed efficiency thus promoting growth in food producing animals. With more than 30 years history, β-lactam antibiotics are nowadays one of the most important group of antibiotics in veterinary medicine. In this paper we investigate the possibility to realize a measurement method suitable for field testing and we propose a competitive biosensor based on a relatively low-cost chromogenic cephalosporin (CENTA) for the quantitative analysis of β-lactams concentration in milk. In particular, the reported preliminary study has been focused on cloxacillin and the reported results indicates that the method is potentially able to detect cloxacillin at a concentration of about one order of magnitude lower than the maximal residue limits (MRL) set by the European Commission.

Human Health Risk Assessment (HHRA) for environmental development and transfer of antibiotic resistance.

PubMed

Ashbolt, Nicholas J; Amézquita, Alejandro; Backhaus, Thomas; Borriello, Peter; Brandt, Kristian K; Collignon, Peter; Coors, Anja; Finley, Rita; Gaze, William H; Heberer, Thomas; Lawrence, John R; Larsson, D G Joakim; McEwen, Scott A; Ryan, James J; Schönfeld, Jens; Silley, Peter; Snape, Jason R; Van den Eede, Christel; Topp, Edward

2013-09-01

Only recently has the environment been clearly implicated in the risk of antibiotic resistance to clinical outcome, but to date there have been few documented approaches to formally assess these risks. We examined possible approaches and sought to identify research needs to enable human health risk assessments (HHRA) that focus on the role of the environment in the failure of antibiotic treatment caused by antibiotic-resistant pathogens. The authors participated in a workshop held 4-8 March 2012 in Québec, Canada, to define the scope and objectives of an environmental assessment of antibiotic-resistance risks to human health. We focused on key elements of environmental-resistance-development "hot spots," exposure assessment (unrelated to food), and dose response to characterize risks that may improve antibiotic-resistance management options. Various novel aspects to traditional risk assessments were identified to enable an assessment of environmental antibiotic resistance. These include a) accounting for an added selective pressure on the environmental resistome that, over time, allows for development of antibiotic-resistant bacteria (ARB); b) identifying and describing rates of horizontal gene transfer (HGT) in the relevant environmental "hot spot" compartments; and c) modifying traditional dose-response approaches to address doses of ARB for various health outcomes and pathways. We propose that environmental aspects of antibiotic-resistance development be included in the processes of any HHRA addressing ARB. Because of limited available data, a multicriteria decision analysis approach would be a useful way to undertake an HHRA of environmental antibiotic resistance that informs risk managers.

Cardiac surgery antibiotic prophylaxis and calculated empiric antibiotic therapy.

PubMed

Gorski, Armin; Hamouda, Khaled; Özkur, Mehmet; Leistner, Markus; Sommer, Sebastian-Patrick; Leyh, Rainer; Schimmer, Christoph

2015-03-01

Ongoing debate exists concerning the optimal choice and duration of antibiotic prophylaxis as well as the reasonable calculated empiric antibiotic therapy for hospital-acquired infections in critically ill cardiac surgery patients. A nationwide questionnaire was distributed to all German heart surgery centers concerning antibiotic prophylaxis and the calculated empiric antibiotic therapy. The response to the questionnaire was 87.3%. All clinics that responded use antibiotic prophylaxis, 79% perform it not longer than 24 h (single-shot: 23%; 2 doses: 29%; 3 doses: 27%; 4 doses: 13%; and >5 doses: 8%). Cephalosporin was used in 89% of clinics (46% second-generation, 43% first-generation cephalosporin). If sepsis is suspected, the following diagnostics are performed routinely: wound inspection 100%; white blood cell count 100%; radiography 99%; C-reactive protein 97%; microbiological testing of urine 91%, blood 81%, and bronchial secretion 81%; procalcitonin 74%; and echocardiography 75%. The calculated empiric antibiotic therapy (depending on the suspected focus) consists of a multidrug combination with broad-spectrum agents. This survey shows that existing national guidelines and recommendations concerning perioperative antibiotic prophylaxis and calculated empiric antibiotic therapy are well applied in almost all German heart centers. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Use of phages against antibiotic-resistant Staphylococcus aureus isolated from bovine mastitis.

PubMed

Dias, R S; Eller, M R; Duarte, V S; Pereira, Â L; Silva, C C; Mantovani, H C; Oliveira, L L; Silva, E de A M; De Paula, S O

2013-08-01

Bovine mastitis is the primary disease of dairy cattle worldwide and it causes large economic losses. Among several microorganisms that are the causative agents of this disease, Staphylococcus aureus is the most prevalent. Although antibiotic therapy is still the most widely used procedure for the treatment of bovine mastitis, alternative means of treatment are necessary due to the presence of antibiotic residues in milk, which is a growing concern because of its interference with the production of milk derivatives and the selection of resistant bacterial strains. The use of bacteriophages as a tool for the control of pathogens is an alternative treatment to antibiotic therapy. In this work, to obtain phages with the potential for use in phage therapy as a treatment for mastitis, we isolated and identified the bacteria from the milk of mastitis-positive cows. A total of 19% of the animals from small and medium farms of the Zona da Mata Mineira, Brazil, was positive for bovine mastitis, and bacteria of the genus Staphylococcus were the most prevalent pathogens. The majority of the S. aureus isolates tested was resistant to penicillin and ampicillin. In parallel, we isolated 10 bacteriophages able to infect some of these S. aureus isolates. We determined that these phages contained DNA genomes of approximately 175 kb in length, and the protein profiles indicated the presence of 4 major proteins. Electron microscopy revealed that the phages are caudate and belong to the Myoviridae family. The isolates exhibited interesting features for their use in phage therapy such as a high lytic potential, a wide range of hosts, and thermostability, all of which favor their use in the field.

Physicians' knowledge, expectations, and practice regarding antibiotic use in primary health care.

PubMed

Al-Homaidan, Homaidan T; Barrimah, Issam E

2018-01-01

Physicians' knowledge of antibiotics, their attitudes, expectations, and practices regarding antibiotic prescription is fundamental for controlling the irrational antibiotic use. This study evaluates primary health care (PHC) physicians' knowledge, expectation, and practices regarding antibiotics use in upper respiratory tract infections. A cross-sectional study conducted in the Qassim region where 32 PHC centers were selected randomly. A total of 294 PHC physicians were surveyed. A pre-tested questionnaire was used after an orientation of participating physicians. Response rate was 80.3%. There is a significant belief among participants that the use of antibiotics leads to relief of symptoms in the case of viral disease and that taking antibiotics without rational indication increases the side effects. Participants identified that inadequate prescription, use without prescription, and non-compliance of patients are the most important factors contributing to the development of bacterial resistance. Participants often blamed the pharmacist for contributing mostly to the development of the problem of antibiotic resistance. Most physicians identified that they feel under pressure if patients expect an antibiotic prescription. In the absence of laboratory confirmation, most physicians selected high fever as the symptom that makes them prescribe antibiotics. Although having practice guidelines, participants demonstrated that these guidelines do not consider individual variations of patients' need. They do not support a regulation to prohibit antibiotic prescription without laboratory confirmation. The distribution of PHC physicians' knowledge, attitudes, and practices did not significantly vary between urban and rural centers. Therefore, whichever measures will be taken to improve the antibiotics practices can be applied to any PHC setting.

Antibiotics for preventing recurrent sore throat.

PubMed

Ng, Gareth J Y; Tan, Stephanie; Vu, Anh N; Del Mar, Chris B; van Driel, Mieke L

2015-07-14

Antibiotics are sometimes used to prevent recurrent sore throat, despite concern about resistance. However, there is conflicting primary evidence regarding their effectiveness. To assess the effects of antibiotics in patients with recurrent sore throat. The Cochrane Ear, Nose and Throat Disorders Group (CENTDG) Trials Search Co-ordinator searched the CENTDG Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 5); PubMed; EMBASE; CINAHL; Web of Science; Clinicaltrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 25 June 2015. Randomised controlled trials (RCTs) of antibiotics in adults and children suffering from pre-existing recurrent sore throat, defined as three or more sore throats in a year, examining the incidence of sore throat recurrence, with follow-up of at least 12 months post-antibiotic therapy. Two authors independently assessed trial quality and extracted data. Multiple attempts to contact the authors of one study yielded no response. We identified no trials that met the inclusion criteria for the review. We discarded the majority of the references retrieved from our search following screening of the title and abstract. We formally excluded four studies following review of the full-text report. There is insufficient evidence to determine the effectiveness of antibiotics for preventing recurrent sore throat. This finding must be balanced against the known adverse effects and cost of antibiotic therapy, when considering antibiotics for this purpose. There is a need for high quality RCTs that compare the effects of antibiotics versus placebo in adults and children with pre-existing recurrent sore throat on the following outcomes: incidence of sore throat recurrence, adverse effects, days off work and absence from school, and the incidence of complications. Future studies should be conducted and reported according to the CONSORT statement.

Antibiotics for acute otitis media in children.

PubMed

Venekamp, Roderick P; Sanders, Sharon; Glasziou, Paul P; Del Mar, Chris B; Rovers, Maroeska M

2013-01-31

Acute otitis media (AOM) is one of the most common diseases in early infancy and childhood. Antibiotic use for AOM varies from 56% in the Netherlands to 95% in the USA, Canada and Australia. To assess the effects of antibiotics for children with AOM. We searched CENTRAL (2012, Issue 10), MEDLINE (1966 to October week 4, 2012), OLDMEDLINE (1958 to 1965), EMBASE (January 1990 to November 2012), Current Contents (1966 to November 2012), CINAHL (2008 to November 2012) and LILACS (2008 to November 2012). Randomised controlled trials (RCTs) comparing 1) antimicrobial drugs with placebo and 2) immediate antibiotic treatment with expectant observation (including delayed antibiotic prescribing) in children with AOM. Two review authors independently assessed trial quality and extracted data. For the review of antibiotics against placebo, 12 RCTs (3317 children and 3854 AOM episodes) from high-income countries were eligible. However, one trial did not report patient-relevant outcomes, leaving 11 trials with generally low risk of bias. Pain was not reduced by antibiotics at 24 hours (risk ratio (RR) 0.89; 95% confidence interval (CI) 0.78 to 1.01) but almost a third fewer had residual pain at two to three days (RR 0.70; 95% CI 0.57 to 0.86; number needed to treat for an additional beneficial outcome (NNTB) 20) and fewer had pain at four to seven days (RR 0.79; 95% CI 0.66 to 0.95; NNTB 20). When compared with placebo, antibiotics did not alter the number of abnormal tympanometry findings at either four to six weeks (RR 0.92; 95% CI 0.83 to 1.01) or at three months (RR 0.97; 95% CI 0.76 to 1.24), or the number of AOM recurrences (RR 0.93; 95% CI 0.78 to 1.10). However, antibiotic treatment did lead to a statistically significant reduction of tympanic membrane perforations (RR 0.37; 95% CI 0.18 to 0.76; NNTB 33) and halved contralateral AOM episodes (RR 0.49; 95% CI 0.25 to 0.95; NNTB 11) as compared with placebo. Severe complications were rare and did not differ between

Antibiotics and Resistance: Glossary

MedlinePlus

... R S T U V W X Y Z Antibacterials (see Antibacterial agents ) Antibiotics (see About bacteria and antibiotics ) Antibiotic ... antibiotic resistance? When and how to take antibiotics Antibacterial agents Bioterrorism & stockpiling antibiotics The Cost of Resistance ...

Paper-based and web-based intervention modeling experiments identified the same predictors of general practitioners' antibiotic-prescribing behavior.

PubMed

Treweek, Shaun; Bonetti, Debbie; Maclennan, Graeme; Barnett, Karen; Eccles, Martin P; Jones, Claire; Pitts, Nigel B; Ricketts, Ian W; Sullivan, Frank; Weal, Mark; Francis, Jill J

2014-03-01

To evaluate the robustness of the intervention modeling experiment (IME) methodology as a way of developing and testing behavioral change interventions before a full-scale trial by replicating an earlier paper-based IME. Web-based questionnaire and clinical scenario study. General practitioners across Scotland were invited to complete the questionnaire and scenarios, which were then used to identify predictors of antibiotic-prescribing behavior. These predictors were compared with the predictors identified in an earlier paper-based IME and used to develop a new intervention. Two hundred seventy general practitioners completed the questionnaires and scenarios. The constructs that predicted simulated behavior and intention were attitude, perceived behavioral control, risk perception/anticipated consequences, and self-efficacy, which match the targets identified in the earlier paper-based IME. The choice of persuasive communication as an intervention in the earlier IME was also confirmed. Additionally, a new intervention, an action plan, was developed. A web-based IME replicated the findings of an earlier paper-based IME, which provides confidence in the IME methodology. The interventions will now be evaluated in the next stage of the IME, a web-based randomized controlled trial. Copyright © 2014 Elsevier Inc. All rights reserved.

Antibiotic prophylaxis in permanent pacemaker implantation: a prospective randomised trial.

PubMed Central

Mounsey, J P; Griffith, M J; Tynan, M; Gould, F K; MacDermott, A F; Gold, R G; Bexton, R S

1994-01-01

BACKGROUND--Pacemaker pocket infection is a potentially serious problem after permanent pacemaker implantation. Antibiotic prophylaxis is commonly prescribed to reduce the incidence of this complication, but current trial evidence of its efficacy is conflicting. A large prospective randomised trial was therefore performed of antibiotic prophylaxis in permanent pacemaker implantation. The intention was firstly to determine whether antibiotic prophylaxis is efficacious in these patients and secondly to identify which patients are at the highest risk of infection. METHODS--A prospective randomised open trial of flucloxacillin (clindamycin if the patient was allergic to penicillin) v no antibiotic was performed in a cohort of patients undergoing first implantation of a permanent pacing system over a 17 month period. Intravenous antibiotics were started at the time of implantation and continued for 48 hours. The trial endpoint was a repeat operation for an infective complication. RESULTS--473 patients were entered into a randomised trial. 224 received antibiotic prophylaxis and 249 received no antibiotics. A further 183 patients were not randomised but were treated according to the operator's preference (64 antibiotics, 119 no antibiotics); these patients are included only in the analysis of predictors of infection. Patients were followed up for a mean (SD) of 19(5) months. Among the patients in the randomised group there were nine infections requiring a repeat operation, all in the group not receiving antibiotic (P = 0.003). In the total patient cohort there were 13 infections, all but one in the non-antibiotic group (P = 0.006). Nine of the infections presented as erosion of the pulse generator or electrode, three as septicaemia secondary to Staphylococcus aureus, and one as a pocket abscess secondary to Staphylococcus epidermidis. Infections were significantly more common when the operator was inexperienced (< or = 100 previous patients), the operation was prolonged

Occurrence and distribution of antibiotics in mariculture farms, estuaries and the coast of the Beibu Gulf, China: Bioconcentration and diet safety of seafood.

PubMed

Zhang, Ruiling; Pei, Jiying; Zhang, Ruijie; Wang, Shaopeng; Zeng, Weibin; Huang, Dali; Wang, Yi; Zhang, Yuanyuan; Wang, Yinghui; Yu, Kefu

2018-06-15

The occurrence, distribution, bioconcentration and diet safety via seafood consumption of 19 antibiotics were investigated in eight closed mariculture ponds, four estuaries, two nearshore areas and one offshore area from the Beibu Gulf. Seventeen, 16, 15 and 7 antibiotics were detected at total concentrations of 43.2 - 885 ng L -1 , 22.4 - 118 ng L -1 , 22.7 - 24.5 ng L -1 , and 1.81-3.23 ng L -1 in the water of the above different areas, respectively. This indicates that the mariculture ponds are important sources of antibiotic pollution on the coast of the Beibu Gulf. Ten antibiotics were detected in feed samples with concentrations ranging from 0.03 to 95.4 ng g -1 , demonstrating the presence of antibiotics in the feed and/or residual antibiotics in the raw material of the feed. The field bioconcentration factors (BCFs) of the antibiotics calculated in different culture organisms ranged from 0.55 to 10,774 L kg -1 . The estimated daily intakes (EDIs) of sulphonamides, fluoroquinolones, macrolides and chloramphenicols via aquatic products were 19.8-105, 33.7-178, 34.9-186 and 6.9-37.1 ng d -1 , respectively. According to the acceptable daily intakes (ADIs) and maximum residue limits (MRLs) proposed by different organisations, these aquatic products (shrimp, crab and oyster) reached the standard of safe consumption and could not pose a health risk to humans. However, a potential elevated risk to humans may remain because of the occurrence of multiple antibiotics in the cultured organisms, particularly for sensitive populations, such as pregnant women, the elderly and children. Copyright © 2018 Elsevier Inc. All rights reserved.

Australian consumer perspectives, attitudes and behaviours on antibiotic use and antibiotic resistance: a qualitative study with implications for public health policy and practice.

PubMed

Lum, Elaine P M; Page, Katie; Nissen, Lisa; Doust, Jenny; Graves, Nicholas

2017-10-10

Consumers receive over 27 million antibiotic prescriptions annually in Australian primary healthcare. Hence, consumers are a key group to engage in the fight against antibiotic resistance. There is a paucity of research pertaining to consumers in the Australian healthcare environment. This study aimed to investigate the perspectives, attitudes and behaviours of Australian consumers on antibiotic use and antibiotic resistance, to inform national programs for reducing inappropriate antibiotic consumption. Semi-structured interviews with 32 consumers recruited via convenience and snowball sampling from a university population in South East Queensland. Interview transcripts were deductively and inductively coded. Main themes were identified using iterative thematic analysis. Three themes emerged from the analysis, to elucidate factors affecting antibiotic use: (a) prescription type; (b) consumer attitudes, behaviours, skills and knowledge; and (c) consumer engagement with antibiotic resistance. Consumers held mixed views regarding the use of delayed antibiotic prescriptions, and were often not made aware of the use of repeat antibiotic prescriptions. Consumers with regular general practitioners were more likely to have shared expectations regarding minimising the use of antibiotics. Even so, advice or information mediated by general practitioners was influential with all consumers; and helped to prevent inappropriate antibiotic use behaviours. Consumers were not aware of the free Return of Unwanted Medicines service offered by pharmacies and disposed of leftover antibiotics through household waste. To engage with mitigating antibiotic resistance, consumers required specific information. Previous public health campaigns raising awareness of antibiotics were largely not seen by this sample of consumers. Australian consumers have specific information needs regarding prescribed antibiotics to enable appropriate antibiotic use behaviours. Consumers also have expectations

Antibiotics for acute bronchitis.

PubMed

Smith, Susan M; Fahey, Tom; Smucny, John; Becker, Lorne A

2017-06-19

The benefits and risks of antibiotics for acute bronchitis remain unclear despite it being one of the most common illnesses seen in primary care. To assess the effects of antibiotics in improving outcomes and to assess adverse effects of antibiotic therapy for people with a clinical diagnosis of acute bronchitis. We searched CENTRAL 2016, Issue 11 (accessed 13 January 2017), MEDLINE (1966 to January week 1, 2017), Embase (1974 to 13 January 2017), and LILACS (1982 to 13 January 2017). We searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov on 5 April 2017. Randomised controlled trials comparing any antibiotic therapy with placebo or no treatment in acute bronchitis or acute productive cough, in people without underlying pulmonary disease. At least two review authors extracted data and assessed trial quality. We did not identify any new trials for inclusion in this 2017 update. We included 17 trials with 5099 participants in the primary analysis. The quality of trials was generally good. At follow-up there was no difference in participants described as being clinically improved between the antibiotic and placebo groups (11 studies with 3841 participants, risk ratio (RR) 1.07, 95% confidence interval (CI) 0.99 to 1.15). Participants given antibiotics were less likely to have a cough (4 studies with 275 participants, RR 0.64, 95% CI 0.49 to 0.85; number needed to treat for an additional beneficial outcome (NNTB) 6) and a night cough (4 studies with 538 participants, RR 0.67, 95% CI 0.54 to 0.83; NNTB 7). Participants given antibiotics had a shorter mean cough duration (7 studies with 2776 participants, mean difference (MD) -0.46 days, 95% CI -0.87 to -0.04). The differences in presence of a productive cough at follow-up and MD of productive cough did not reach statistical significance.Antibiotic-treated participants were more likely to be improved according to clinician's global assessment (6 studies

Prophylactic antibiotics and anticonvulsants in neurosurgery.

PubMed

Ratilal, B; Sampaio, C

2011-01-01

The prophylactic administration of antibiotics to prevent infection and the prophylactic administration of anticonvulsants to prevent first seizure episodes are common practice in neurosurgery. If prophylactic medication therapy is not indicated, the patient not only incurs the discomfort and the inconvenience resulting from drug treatment but is also unnecessarily exposed to adverse drug reactions, and incurs extra costs. The main situations in which prophylactic anticonvulsants and antibiotics are used are described and those situations we found controversial in the literature and lack further investigation are identified: anticonvulsants for preventing seizures in patients with chronic subdural hematomas, antiepileptic drugs for preventing seizures in those suffering from brain tumors, antibiotic prophylaxis for preventing meningitis in patients with basilar skull fractures, and antibiotic prophylaxis for the surgical introduction of intracranial ventricular shunts.In the following we present systematic reviews of the literature in accordance with the standard protocol of The Cochrane Collaboration to evaluate the effectiveness of the use of these prophylactic medications in the situations mentioned. Our goal was to efficiently integrate valid information and provide a basis for rational decision-making.

Thermus Thermophilus as a Model System for the Study of Ribosomal Antibiotic Resistance

NASA Astrophysics Data System (ADS)

Gregory, Steven T.

2018-03-01

Ribosomes are the intracellular ribonucleoprotein machines responsible for the translation of mRNA sequence into protein sequence. As an essential cell component, the ribosome is the target of numerous antibiotics that bind to critical functional sites to impair protein synthesis. Mutations causing resistance to antibiotics arise in antibiotic binding sites, and an understanding of the basis of resistance will be an essential component of efforts to develop new antibiotics by rational drug design. We have identified a number of antibiotic-resistance mutations in ribosomal genes of the thermophilic bacterium Thermus thermophilus. This species offers two primary advantages for examining the structural basis of antibiotic-resistance, in particular, its potential for genetic manipulation and the suitability of its ribosomes for analysis by X-ray crystallography. Mutations we have identified in this organism are in many instances identical to those found in other bacterial species, including important pathogens, a result of the extreme conservation of ribosome functional sites. Here I summarize the advantages of this organism as a model system to study antibiotic-resistance mechanisms at the molecular level.

Antibiotic-resistant genes and antibiotic-resistant bacteria in the effluent of urban residential areas, hospitals, and a municipal wastewater treatment plant system.

PubMed

Li, Jianan; Cheng, Weixiao; Xu, Like; Strong, P J; Chen, Hong

2015-03-01

In this study, we determined the abundance of 8 antibiotics (3 tetracyclines, 4 sulfonamides, and 1 trimethoprim), 12 antibiotic-resistant genes (10 tet, 2 sul), 4 antibiotic-resistant bacteria (tetracycline, sulfamethoxazole, and combined resistance), and class 1 integron integrase gene (intI1) in the effluent of residential areas, hospitals, and municipal wastewater treatment plant (WWTP) systems. The concentrations of total/individual targets (antibiotics, genes, and bacteria) varied remarkably among different samples, but the hospital samples generally had a lower abundance than the residential area samples. The WWTP demonstrated removal efficiencies of 50.8% tetracyclines, 66.8% sulfonamides, 0.5 logs to 2.5 logs tet genes, and less than 1 log of sul and intI1 genes, as well as 0.5 log to 1 log removal for target bacteria. Except for the total tetracycline concentration and the proportion of tetracycline-resistant bacteria (R (2) = 0.330, P < 0.05), there was no significant correlation between antibiotics and the corresponding resistant bacteria (P > 0.05). In contrast, various relationships were identified between antibiotics and antibiotic resistance genes (P < 0.05). Tet (A) and tet (B) displayed noticeable relationships with both tetracycline and combined antibiotic-resistant bacteria (P < 0.01).

The expression of antibiotic resistance genes in antibiotic-producing bacteria.

PubMed

Mak, Stefanie; Xu, Ye; Nodwell, Justin R

2014-08-01

Antibiotic-producing bacteria encode antibiotic resistance genes that protect them from the biologically active molecules that they produce. The expression of these genes needs to occur in a timely manner: either in advance of or concomitantly with biosynthesis. It appears that there have been at least two general solutions to this problem. In many cases, the expression of resistance genes is tightly linked to that of antibiotic biosynthetic genes. In others, the resistance genes can be induced by their cognate antibiotics or by intermediate molecules from their biosynthetic pathways. The regulatory mechanisms that couple resistance to antibiotic biosynthesis are mechanistically diverse and potentially relevant to the origins of clinical antibiotic resistance. © 2014 John Wiley & Sons Ltd.

IDENTIFYING CRITICAL CYSTEINE RESIDUES IN ARSENIC (+3 OXIDATION STATE) METHYLTRANSFERASE

EPA Science Inventory

Arsenic (+3 oxidation state) methyltransferase (AS3MT) catalyzes methylation of inorganic arsenic to mono, di, and trimethylated arsenicals. Orthologous AS3MT genes in genomes ranging from simple echinoderm to human predict a protein with five conserved cysteine (C) residues. In ...

Impact of Rapid Susceptibility Testing and Antibiotic Selection Strategy on the Emergence and Spread of Antibiotic Resistance in Gonorrhea

PubMed Central

Tuite, Ashleigh R; Gift, Thomas L; Chesson, Harrell W; Hsu, Katherine; Salomon, Joshua A; Grad, Yonatan H

2017-01-01

Abstract Background Increasing antibiotic resistance limits treatment options for gonorrhea. We examined the impact of a hypothetical point-of-care (POC) test reporting antibiotic susceptibility profiles on slowing resistance spread. Methods A mathematical model describing gonorrhea transmission incorporated resistance emergence probabilities and fitness costs associated with resistance based on characteristics of ciprofloxacin (A), azithromycin (B), and ceftriaxone (C). We evaluated time to 1% and 5% prevalence of resistant strains among all isolates with the following: (1) empiric treatment (B and C), and treatment guided by POC tests determining susceptibility to (2) A only and (3) all 3 antibiotics. Results Continued empiric treatment without POC testing was projected to result in >5% of isolates being resistant to both B and C within 15 years. Use of either POC test in 10% of identified cases delayed this by 5 years. The 3 antibiotic POC test delayed the time to reach 1% prevalence of triply-resistant strains by 6 years, whereas the A-only test resulted in no delay. Results were less sensitive to assumptions about fitness costs and test characteristics with increasing test uptake. Conclusions Rapid diagnostics reporting antibiotic susceptibility may extend the usefulness of existing antibiotics for gonorrhea treatment, but ongoing monitoring of resistance patterns will be critical. PMID:28968710

The antibiotic resistome.

PubMed

Wright, Gerard D

2010-08-01

Antibiotics are essential for the treatment of bacterial infections and are among our most important drugs. Resistance has emerged to all classes of antibiotics in clinical use. Antibiotic resistance has, proven inevitable and very often it emerges rapidly after the introduction of a drug into the clinic. There is, therefore, a great interest in understanding the origins, scope and evolution of antibiotic resistance. The review discusses the concept of the antibiotic resistome, which is the collection of all genes that directly or indirectly contribute to antibiotic resistance. The review seeks to assemble current knowledge of the resistome concept as a means of understanding the totality of resistance and not just resistance in pathogenic bacteria. The concept of the antibiotic resistome provides a framework for the study and understanding of how resistance emerges and evolves. Furthermore, the study of the resistome reveals strategies that can be applied in new antibiotic discoveries.

Dispensing of non-prescribed antibiotics in Jordan

PubMed Central

Almaaytah, Ammar; Mukattash, Tareq L; Hajaj, Julia

2015-01-01

Objective Current regulations in Jordan state that antibiotics cannot be sold without a medical prescription. This study aimed to assess the percentage of pharmacies that dispense antibiotics without a medical prescription in the Kingdom of Jordan and identify and highlight the extent and seriousness of such practices among Jordanian pharmacies. Methods A prospective study was performed, and five different clinical scenarios were simulated at pharmacies investigated including sore throat, otitis media, acute sinusitis, diarrhea, and urinary tract infection in childbearing-aged women. Three levels of demand were used to convince the pharmacists to sell an antibiotic. Results A total of 202 total pharmacies in Jordan were visited in the present study. The majority of pharmacies (74.3%) dispensed antibiotics without prescription with three different levels of demand. The percentage of pharmacies dispensing antibiotics without a prescription for the sore throat scenario was 97.6%, followed by urinary tract infection (83.3%), diarrhea (83%), and otitis media (68.4%). The lowest percentage of antibiotic dispensing was for the acute sinusitis simulation at 48.5%. Among the pharmacies that dispensed antibiotics, the pharmacists provided an explanation as the number of times per day the drug should be taken in 95.3% of the cases, explained the duration of treatment in 25.7%, and inquired about allergies prior to the sale of the antibiotic in only 17.3%. Only 52 pharmacies (25.7%) refused to dispense any kind of antibiotics, the majority (61.5%) of this refusal response came from acute sinusitis cases, while the minority (2.4%) came from the sore throat cases. Conclusion The results of this study demonstrate that antibiotics continue to be dispensed without prescription in Jordan in violation with national regulations regarding this practice. The findings of this study could provide a layout for governmental health authorities to implement strict enfrorcment of national

Fluorescent Antibiotics: New Research Tools to Fight Antibiotic Resistance.

PubMed

Stone, M Rhia L; Butler, Mark S; Phetsang, Wanida; Cooper, Matthew A; Blaskovich, Mark A T

2018-05-01

Better understanding how multidrug-resistant (MDR) bacteria can evade current and novel antibiotics requires a better understanding of the chemical biology of antibiotic action. This necessitates using new tools and techniques to advance our knowledge of bacterial responses to antibiotics, ideally in live cells in real time, to selectively investigate bacterial growth, division, metabolism, and resistance in response to antibiotic challenge. In this review, we discuss the preparation and biological evaluation of fluorescent antibiotics, focussing on how these reporters and assay methods can help elucidate resistance mechanisms. We also examine the potential utility of such probes for real-time in vivo diagnosis of infections. Copyright © 2018 Elsevier Ltd. All rights reserved.

Antibiotic distribution, risk assessment, and microbial diversity in river water and sediment in Hong Kong.

PubMed

Deng, Wen-Jing; Li, Na; Ying, Guang-Guo

2018-03-29

For the past fewer years, environment antibiotic residues have got more and more attention. The occurrence and distribution of eight common antibiotics, belonging to five classes, were determined in both water and sediment of eleven rivers of Hong Kong. The target antibiotics were found to be widely distributed. Sulfamethoxazole (n.d.-79.9 ng/L), sulfadimidine (n.d.-29.9 ng/L), and ofloxacin (n.d.-75.5 ng/L) were the dominant antibiotics in river water, with detection rates of 84.6, 76.9, and 69.2%, respectively. Tetracycline (n.d.-9.8 ng/g) was the dominant antibiotic in sediment, with a detection rate of 60%. The concentrations of all antibiotics in river water of Hong Kong were lower than which in various rivers of Europe, North America and Australia, as well as the Pearl River Basin of China. All sediment sites exhibited significant bacterial diversity. Gammaproteobacteria (0.08-12.7%) and Flavobacteria (0.14-14.1%) were the dominant bacterial classes in all sediments. The bacterial compositions varied between sites; areas polluted with high levels of antibiotics had rich and highly diverse bacterial communities. The environmental risk assessment determined that the antibiotics in 73.1% of the samples posed ecological risks to algae, and two samples posed low risks to invertebrates. Ofloxacin was the main contributor of risk to aquatic organisms, while the antibiotics in 11.5% of the samples posed resistance selection risks. The occurrence and distribution of eight common antibiotics, belonging to five classes, were widely distributed in Hong Kong. Sulfamethoxazole, sulfadimidine, and ofloxacin were the dominant antibiotics in river waters, Tetracycline was the dominant antibiotic in sediment. Areas polluted with high levels of antibiotics had rich and highly diverse bacterial communities. Antibiotics in 73.1% of the samples posed ecological risks, while the antibiotics in 11.5% of the samples posed resistance selection risks.

Knowledge of antibiotics and antibiotic resistance in patients followed by family physicians.

PubMed

Robert, A; Nguyen, Y; Bajolet, O; Vuillemin, B; Defoin, B; Vernet-Garnier, V; Drame, M; Bani-Sadr, F

2017-03-01

We aimed to evaluate factors associated with knowledge of antibiotics and drug resistance. A questionnaire was handed out by 14 family physicians to their patients between December 20, 2014 and April 20, 2015 in Rethel (North-East of France). We conducted a cross-sectional study using a logistical regression model to assess factors associated with antibiotic knowledge. Three criteria were used to assess that knowledge. Overall, 293 questionnaires were analysed; 48% of patients had received antibiotics in the previous 12 months. Only 44% and 26% gave a correct answer for the statements "Antibiotics are effective against bacteria and ineffective against viruses" and "Antibiotic resistance decreases if the antibiotic use decreases", respectively. Characteristics such as female sex, age>30 years, high level of education, high professional categories, and having received antibiotic information by the media were associated with high level of knowledge about antibiotics and/or antibiotic resistance. In contrast, having received antibiotic information from family physicians was not associated with good knowledge. Although media awareness campaigns had an independent impact on a higher public knowledge of antibiotics, the overall public knowledge remains low. It would be necessary to strengthen antibiotic campaigns with clearer information on the relation between the excessive use of antibiotics and the increased risk of antibiotic resistance. Family physicians should be more involved to improve antibiotic knowledge among target groups such as men, young patients, and people from a poor social and cultural background. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Distributed lags time series analysis versus linear correlation analysis (Pearson's r) in identifying the relationship between antipseudomonal antibiotic consumption and the susceptibility of Pseudomonas aeruginosa isolates in a single Intensive Care Unit of a tertiary hospital.

PubMed

Erdeljić, Viktorija; Francetić, Igor; Bošnjak, Zrinka; Budimir, Ana; Kalenić, Smilja; Bielen, Luka; Makar-Aušperger, Ksenija; Likić, Robert

2011-05-01

The relationship between antibiotic consumption and selection of resistant strains has been studied mainly by employing conventional statistical methods. A time delay in effect must be anticipated and this has rarely been taken into account in previous studies. Therefore, distributed lags time series analysis and simple linear correlation were compared in their ability to evaluate this relationship. Data on monthly antibiotic consumption for ciprofloxacin, piperacillin/tazobactam, carbapenems and cefepime as well as Pseudomonas aeruginosa susceptibility were retrospectively collected for the period April 2006 to July 2007. Using distributed lags analysis, a significant temporal relationship was identified between ciprofloxacin, meropenem and cefepime consumption and the resistance rates of P. aeruginosa isolates to these antibiotics. This effect was lagged for ciprofloxacin and cefepime [1 month (R=0.827, P=0.039) and 2 months (R=0.962, P=0.001), respectively] and was simultaneous for meropenem (lag 0, R=0.876, P=0.002). Furthermore, a significant concomitant effect of meropenem consumption on the appearance of multidrug-resistant P. aeruginosa strains (resistant to three or more representatives of classes of antibiotics) was identified (lag 0, R=0.992, P<0.001). This effect was not delayed and it was therefore identified both by distributed lags analysis and the Pearson's correlation coefficient. Correlation coefficient analysis was not able to identify relationships between antibiotic consumption and bacterial resistance when the effect was delayed. These results indicate that the use of diverse statistical methods can yield significantly different results, thus leading to the introduction of possibly inappropriate infection control measures. Copyright © 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Sustainability of water reclamation: long-term recharge with reclaimed wastewater does not enhance antibiotic resistance in sediment bacteria

USDA-ARS?s Scientific Manuscript database

Wastewater reclamation for municipal irrigation is an increasingly attractive option for extending water supplies. However, public health concerns include the potential for development of antibiotic resistance (AR) in soil bacteria after exposure to residual pharmaceuticals in reclaimed water. Thoug...

Fourier transform infrared and Raman spectroscopy studies on magnetite/Ag/antibiotic nanocomposites

NASA Astrophysics Data System (ADS)

Ivashchenko, Olena; Jurga-Stopa, Justyna; Coy, Emerson; Peplinska, Barbara; Pietralik, Zuzanna; Jurga, Stefan

2016-02-01

This article presents a study on the detection of antibiotics in magnetite/Ag/antibiotic nanocomposites using Fourier transform infrared (FTIR) and Raman spectroscopy. Antibiotics with different spectra of antimicrobial activities, including rifampicin, doxycycline, cefotaxime, and ceftriaxone, were studied. Mechanical mixtures of antibiotics and magnetite/Ag nanocomposites, as well as antibiotics and magnetite nanopowder, were investigated in order to identify the origin of FTIR bands. FTIR spectroscopy was found to be an appropriate technique for this task. The spectra of the magnetite/Ag/antibiotic nanocomposites exhibited very weak (for doxycycline, cefotaxime, and ceftriaxone) or even no (for rifampicin) antibiotic bands. This FTIR "invisibility" of antibiotics is ascribed to their adsorbed state. FTIR and Raman measurements show altered Csbnd O, Cdbnd O, and Csbnd S bonds, indicating adsorption of the antibiotic molecules on the magnetite/Ag nanocomposite structure. In addition, a potential mechanism through which antibiotic molecules interact with magnetite/Ag nanoparticle surfaces is proposed.

Fate and Effect of Antibiotics in Beef and Dairy Manure during Static and Turned Composting.

PubMed

Ray, Partha; Chen, Chaoqi; Knowlton, Katharine F; Pruden, Amy; Xia, Kang

2017-01-01

Manure composting has general benefits for production of soil amendment, but the effects of composting on antibiotic persistence and effects of antibiotics on the composting process are not well-characterized, especially for antibiotics commonly used in dairy cattle. This study provides a comprehensive, head-to-head, replicated comparison of the effect of static and turned composting on typical antibiotics used in beef and dairy cattle in their actual excreted form and corresponding influence on composting efficacy. Manure from steers (with or without chlortetracycline, sulfamethazine, and tylosin feeding) and dairy cows (with or without pirlimycin and cephapirin administration) were composted at small scale (wet mass: 20-22 kg) in triplicate under static and turned conditions adapted to represent US Food and Drug Administration guidelines. Thermophilic temperature (>55°C) was attained and maintained for 3 d in all composts, with no measureable effect of compost method on the pattern, rate, or extent of disappearance of the antibiotics examined, except tylosin. Disappearance of all antibiotics, except pirlimycin, followed bi-phasic first-order kinetics. However, individual antibiotics displayed different fate patterns in response to the treatments. Reduction in concentration of chlortetracycline (71-84%) and tetracycline (66-72%) was substantial, while near-complete removal of sulfamethazine (97-98%) and pirlimycin (100%) was achieved. Tylosin removal during composting was relatively poor. Both static and turned composting were generally effective for reducing most beef and dairy antibiotic residuals excreted in manure, with no apparent negative impact of antibiotics on the composting process, but with some antibiotics apparently more recalcitrant than others. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Antibiotics in dust originating from a pig-fattening farm: a new source of health hazard for farmers?

PubMed

Hamscher, Gerd; Pawelzick, Heike Theresia; Sczesny, Silke; Nau, Heinz; Hartung, Jörg

2003-10-01

Pig-house dust originates from feed, bedding, feces, and the animals themselves. If the animals receive drugs such as antibiotics, residues of these substances may occur in manure, in the air, or on surfaces of the respective animal house. In a retrospective study, we investigated dust samples collected during two decades from the same piggery for the occurrence of various antibiotics. In 90% of these samples, we detected up to five different antibiotics, including tylosin, various tetracyclines, sulfamethazine, and chloramphenicol, in total amounts up to 12.5 mg/kg dust. High dust exposure in animal confinement buildings is believed to be a respiratory health hazard because of the high content of microorganisms, endotoxins, and allergens. Further risks may arise from the inhalation of dust contaminated with a cocktail of antibiotics. Apart from that, our data provide first evidence for a new route of entry for veterinary drugs in the environment.

Restructuring of Enterococcus faecalis biofilm architecture in response to antibiotic-induced stress

DOE PAGES

Dale, Jennifer L.; Nilson, Jennifer L.; Barnes, Aaron M. T.; ...

2017-06-30

Bacterial biofilms are intrinsically resistant to antimicrobial treatment, which contributes to microbial persistence in clinical infections. Enterococcus faecalis is an opportunistic pathogen that readily forms biofilms and is the most prevalent enterococcal species identified in healthcare-associated infections. Since intrinsic resistance to multiple antibiotics is common for enterococci, and antibiotic resistance is elevated in biofilm populations, it is imperative to understand the mechanisms involved. Previously, we identified two glycosyltransferase genes whose disruption resulted in impaired nascent biofilm formation in the presence of antibiotic concentrations subinhibitory for parent growth and biofilm formation. The glycosyltransferases are involved in synthesis of the cell-wall-associated rhamnopolysaccharidemore » Epa. Here we examined the effect of epa mutations on the temporal development of E. faecalis biofilms, and on the effects of antibiotics on pre-formed biofilms using scanning electron microscopy. We show that ΔepaOX mutant cells arrange into complex multidimensional biofilms independent of antibiotic exposure, while parent cells form biofilms that are monolayers in the absence of antibiotics. Remarkably, upon exposure to antibiotics parent biofilm cells restructure into complex three-dimensional biofilms resembling those of the ΔepaOX mutant without antibiotics. All biofilms exhibiting complex cellular architectures were less structurally stable than monolayer biofilms, with the biofilm cells exhibiting increased detachment. Our results indicate that E. faecalis biofilms restructure in response to cellular stress whether induced by antibiotics in the case of parent cells, or by deficiencies in Epa composition for the ΔepaOX strain. The data demonstrate a link between cellular architecture and antibiotic resistance of E. faecalis biofilms.« less

Restructuring of Enterococcus faecalis biofilm architecture in response to antibiotic-induced stress

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

Dale, Jennifer L.; Nilson, Jennifer L.; Barnes, Aaron M. T.

Bacterial biofilms are intrinsically resistant to antimicrobial treatment, which contributes to microbial persistence in clinical infections. Enterococcus faecalis is an opportunistic pathogen that readily forms biofilms and is the most prevalent enterococcal species identified in healthcare-associated infections. Since intrinsic resistance to multiple antibiotics is common for enterococci, and antibiotic resistance is elevated in biofilm populations, it is imperative to understand the mechanisms involved. Previously, we identified two glycosyltransferase genes whose disruption resulted in impaired nascent biofilm formation in the presence of antibiotic concentrations subinhibitory for parent growth and biofilm formation. The glycosyltransferases are involved in synthesis of the cell-wall-associated rhamnopolysaccharidemore » Epa. Here we examined the effect of epa mutations on the temporal development of E. faecalis biofilms, and on the effects of antibiotics on pre-formed biofilms using scanning electron microscopy. We show that ΔepaOX mutant cells arrange into complex multidimensional biofilms independent of antibiotic exposure, while parent cells form biofilms that are monolayers in the absence of antibiotics. Remarkably, upon exposure to antibiotics parent biofilm cells restructure into complex three-dimensional biofilms resembling those of the ΔepaOX mutant without antibiotics. All biofilms exhibiting complex cellular architectures were less structurally stable than monolayer biofilms, with the biofilm cells exhibiting increased detachment. Our results indicate that E. faecalis biofilms restructure in response to cellular stress whether induced by antibiotics in the case of parent cells, or by deficiencies in Epa composition for the ΔepaOX strain. The data demonstrate a link between cellular architecture and antibiotic resistance of E. faecalis biofilms.« less

Diverse Antibiotic Resistance Genes in Dairy Cow Manure

PubMed Central

Wichmann, Fabienne; Udikovic-Kolic, Nikolina; Andrew, Sheila; Handelsman, Jo

2014-01-01

ABSTRACT Application of manure from antibiotic-treated animals to crops facilitates the dissemination of antibiotic resistance determinants into the environment. However, our knowledge of the identity, diversity, and patterns of distribution of these antibiotic resistance determinants remains limited. We used a new combination of methods to examine the resistome of dairy cow manure, a common soil amendment. Metagenomic libraries constructed with DNA extracted from manure were screened for resistance to beta-lactams, phenicols, aminoglycosides, and tetracyclines. Functional screening of fosmid and small-insert libraries identified 80 different antibiotic resistance genes whose deduced protein sequences were on average 50 to 60% identical to sequences deposited in GenBank. The resistance genes were frequently found in clusters and originated from a taxonomically diverse set of species, suggesting that some microorganisms in manure harbor multiple resistance genes. Furthermore, amid the great genetic diversity in manure, we discovered a novel clade of chloramphenicol acetyltransferases. Our study combined functional metagenomics with third-generation PacBio sequencing to significantly extend the roster of functional antibiotic resistance genes found in animal gut bacteria, providing a particularly broad resource for understanding the origins and dispersal of antibiotic resistance genes in agriculture and clinical settings. PMID:24757214

Global shortage of neonatal and paediatric antibiotic trials: rapid review

PubMed Central

Thompson, Georgina; Barker, Charlotte I; Folgori, Laura; Bielicki, Julia A; Bradley, John S; Lutsar, Irja; Sharland, Mike

2017-01-01

Objectives There have been few clinical trials (CTs) on antibiotics that inform neonatal and paediatric drug labelling. The rate of unlicensed and off-label prescribing in paediatrics remains high. It is unclear whether the current neonatal and paediatric antibiotic research pipeline is adequate to inform optimal drug dosing. Using the ClinicalTrials.gov registry, this review aims to establish the current global status of antibiotic CTs in children up to 18 years of age. Methods Studies were identified using key word searches of the ClinicalTrials.gov registry and were manually filtered using prespecified inclusion/exclusion criteria. Results 76 registered open CTs of antibiotics in children were identified globally; 23 (30%) were recruiting newborns (only 8 (11%) included preterm neonates), 52 (68%) infants and toddlers, 58 (76%) children and 54 (71%) adolescents. The majority of registered trials were late phase (10 (15%) phase 3 and 23 (35%) phase 4/pharmacovigilance). Two-thirds were sponsored by non-profit organisations, compared with pharmaceutical companies (50 (66%) vs 26 (34%), respectively). A greater proportion of non-profit funded trials were efficacy-based strategic trials (n=34, 68%), in comparison with industry-led trials, which were most often focused on safety or pharmacokinetic data (n=17, 65%). Only 2 of the 37 antibiotics listed on the May 2016 Pew Charitable Trusts antibiotic development pipeline, currently being studied in adults, appear to be currently recruiting in open paediatric CTs. Conclusions This review highlights that very few paediatric antibiotic CTs are being conducted globally, especially in neonates. There is a striking disparity noted between antibiotic drug development programmes in adults and children. PMID:29030411