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The cephalosporin antibiotics  

Microsoft Academic Search

This article reviews the cephalosporin antibiotics in the practice of obstetrics and gynecology. Available cephalosporins are classified as limited-, intermediate-, and broad-spectrum agents. This group of ?-lactam drugs has a mechanism of action similar to penicillin but a broader range of activity due to increased resistance to ?-lactamases. The biochemistry and pharmacology of the cephalosporins are briefly reviewed, with emphasis

Stefanie S. Christian; Jeffrey S. Christian



Third-generation cephalosporins as antibiotic prophylaxis in neurosurgery: what's the evidence?  


To analyze the role of third-generation cephalosporins as prophylactic antibiotics in neurosurgery. We reviewed the literature for data from randomized controlled trials (RCTs) on third-generation cephalosporins compared to other antibiotic regimen in neurosurgery. End point of the RCTs was the occurrence of surgical site infections (SSIs)--data were pooled in a fixed-effects meta-analysis. Five randomized controlled trials enrolling a total of 2209 patients were identified. The pooled odds ratio for SSIs (overall) with third-generation cephalosporins prophylaxis in the five RCTs was 0.94 (95% CI, 0.59-1.52; P=0.81). No significant difference between third-generation cephalosporins and alternative regimen was identified. When analyzing organ SSIs (osteomyelitis, meningitis, and others intracranial infections) in data derived from four RCTs (1596 patients), third-generation cephalosporins failed to show superiority (pooled odds ratio 0.88; 95% CI 0.45-1.74; P=0.72). Third-generation cephalosporin antibiotic prophylaxis fails to show superiority over conventional regimens regarding both incisional and organ related SSIs in neurosurgery. PMID:24269048

Liu, Weiming; Neidert, Marian Christoph; Groen, Rob J M; Woernle, Christoph Michael; Grundmann, Hajo



Resistance to Third-Generation Cephalosporins and Other Antibiotics by Enterobacteriaceae in Western Nigeria  

Microsoft Academic Search

Problem statement: The emergence and spread of resistance to third-gen eration cephalosporins are threatening to create species re sistant to all currently available agents. The most common cause of bacterial resistance to beta-lactam antibiotics is the production of beta-lactamases and many of the 2nd and 3rd-generation penicillins and cephalosporins were specifically designed to resist the hydrolytic action of major ?-lactamases.

A. O. Okesola; O. Makanjuola




Technology Transfer Automated Retrieval System (TEKTRAN)

Background: Extended-spectrum *-lactamases (ESBLs) are important resistance mechanisms which affect *-lactam antibiotics, including cephalosporins. Extended-spectrum 3rd generation cephalosporins are considered drugs of choice for serious Salmonella infections. The emergence of ESBL-producing orga...


Third generation cephalosporin resistant Enterobacteriaceae and multidrug resistant gram-negative bacteria causing bacteremia in febrile neutropenia adult cancer patients in Lebanon, broad spectrum antibiotics use as a major risk factor, and correlation with poor prognosis  

PubMed Central

Introduction: Bacteremia remains a major cause of life-threatening complications in patients receiving anticancer chemotherapy. The spectrum and susceptibility profiles of causative microorganisms differ with time and place. Data from Lebanon are scarce. We aim at evaluating the epidemiology of bacteremia in cancer patients in a university hospital in Lebanon, emphasizing antibiotic resistance and risk factors of multi-drug resistant organism (MDRO)-associated bacteremia. Materials and Methods: This is a retrospective study of 75 episodes of bacteremia occurring in febrile neutropenic patients admitted to the hematology-oncology unit at Makassed General Hospital, Lebanon, from October 2009-January 2012. It corresponds to epidemiological data on bacteremia episodes in febrile neutropenic cancer patients including antimicrobial resistance and identification of risk factors associated with third generation cephalosporin resistance (3GCR) and MDRO-associated bacteremia. Results: Out of 75 bacteremias, 42.7% were gram-positive (GP), and 57.3% were gram-negative (GN). GP bacteremias were mostly due to methicillin-resistant coagulase negative staphylococci (28% of total bacteremias and 66% of GP bacteremias). Among the GN bacteremias, Escherichia coli (22.7% of total, 39.5% of GN organisms) and Klebsiella pneumoniae(13.3% of total, 23.3% of GN organisms) were the most important causative agents. GN bacteremia due to 3GC sensitive (3GCS) bacteria represented 28% of total bacteremias, while 29% were due to 3GCR bacteria and 9% were due to carbapenem-resistant organisms. There was a significant correlation between bacteremia with MDRO and subsequent intubation, sepsis and mortality. Among potential risk factors, only broad spectrum antibiotic intake >4 days before bacteremia was found to be statistically significant for acquisition of 3GCR bacteria. Using carbapenems or piperacillin/tazobactam>4 days before bacteremia was significantly associated with the emergence of MDRO (p < 0.05). Conclusion: Our findings have major implications for the management of febrile neutropenia, especially in breakthrough bacteremia and fever when patients are already on broadspectrum antibiotics. Emergence of resistance to 3GCs and, to a lesser extent, to carbapenems in GN isolates has to be considered seriously in our local guidelines for empiric treatment of febrile neutropenia, especially given that their occurrence was proven to be associated with poorer outcomes. PMID:25729741

Moghnieh, Rima; Estaitieh, Nour; Mugharbil, Anas; Jisr, Tamima; Abdallah, Dania I.; Ziade, Fouad; Sinno, Loubna; Ibrahim, Ahmad



Genome Sequence and Annotation of Acremonium chrysogenum, Producer of the ?-Lactam Antibiotic Cephalosporin C  

PubMed Central

The filamentous fungus Acremonium chrysogenum is the industrial producer of the ?-lactam antibiotic cephalosporin C. Here, we present the genome sequence of strain ATCC 11550, which contains genes for 8,901 proteins, 127 tRNAs, and 22 rRNAs. Genome annotation led to the prediction of 42 gene clusters for secondary metabolites. PMID:25291769

Terfehr, Dominik; Dahlmann, Tim A.; Specht, Thomas; Zadra, Ivo; Kürnsteiner, Hubert



Gastric emptying and the pharmacokinetics of the cephalosporin antibiotic, cefpodoxime proxetil.  


The effects of gastric motility on the pharmacokinetics of cefpodoxime proxetil, an oral, broad spectrum, third-generation cephalosporin antibiotic were evaluated in 12 healthy subjects. In this open-label, crossover trial, each subject took a 200 mg dose (two 100 mg film-coated tablets) in each study period. There was an initial fasting period followed by a control period and then either a propantheline or metoclopramide period. Gastric motility was measured using [99mTc]-labeled sulfur colloid in oatmeal in the control, propantheline and metoclopramide periods. Treatment with propantheline or metoclopramide was given 30 min before dosing with the antibiotic and the radioisotope. Serial images with a gamma counter were made every 15 min for 2 h. Gastric emptying time was faster than control with metoclopramide, but generally slower with propantheline than control. The mean peak plasma concentration, mean area under plasma concentration time curve and mean half-life of cefpodoxime proxetil were similar in all groups as compared to control. The mean time to peak plasma concentration was delayed in the propantheline period and peak plasma concentrations were greater at all sampling times at six hours after dosing. This study utilized the gastric nuclear scan with modification of gastric motility by metoclopramide and propantheline and with simultaneous determination of the disposition of cefpodoxime proxetil to understand the absorption of the drug. PMID:2352449

Hughes, G S; Heald, D L; Patel, R; Spillers, C R; Batts, D H; Euler, A R



Case report: Long-standing complex regional pain syndrome relieved by a cephalosporin antibiotic.  


We describe a young woman who had had treatment-refractory complex regional pain syndrome (CRPS) for 6 years before receiving antibiotic treatment with cefadroxil (a cephalosporin derivative) for a minor infection. Cefadroxil reduced the patient's pain and motor dysfunction (dystonia and impaired voluntary movement) within days; the pain and motor disorder returned when cefadroxil was discontinued; and both again abated when cefadroxil was re-instituted. The patient has now had symptom relief for more than 3 years on continuing cefadroxil therapy. We discuss this case in the context of previous reports of antibiotic treatment relieving neuropathic pain in experimental animals. PMID:24667741

Ware, Mark A; Bennett, Gary J



Ceftriaxone, an FDA-approved cephalosporin antibiotic, suppresses lung cancer growth by targeting Aurora B  

PubMed Central

Ceftriaxone, an FDA-approved third-generation cephalosporin antibiotic, has antimicrobial activity against both gram-positive and gram-negative organisms. Generally, ceftriaxone is used for a variety of infections such as community-acquired pneumonia, meningitis and gonorrhea. Its primary molecular targets are the penicillin-binding proteins. However, other activities of ceftriaxone remain unknown. Herein, we report for the first time that ceftriaxone has antitumor activity in vitro and in vivo. Kinase profiling results predicted that Aurora B might be a potential ‘off’ target of ceftriaxone. Pull-down assay data confirmed that ceftriaxone could bind with Aurora B in vitro and in A549 cells. Furthermore, ceftriaxone (500 µM) suppressed anchorage-independent cell growth by targeting Aurora B in A549, H520 and H1650 lung cancer cells. Importantly, in vivo xenograft animal model results showed that ceftriaxone effectively suppressed A549 and H520 lung tumor growth by inhibiting Aurora B. These data suggest the anticancer efficacy of ceftriaxone for the treatment of lung cancers through its inhibition of Aurora B. PMID:22962305

Li, Xiang; Li, Haitao; Li, Shengqing; Zhu, Feng; Dong, Zigang



Feasibility and impact of an intensified antibiotic stewardship programme targeting cephalosporin and fluoroquinolone use in a tertiary care university medical center  

PubMed Central

Background Restricted use of third-generation cephalosporins and fluoroquinolones has been linked to a reduced incidence of hospital-acquired infections with multidrug-resistant bacteria. We implemented an intensified antibiotic stewardship (ABS) programme in the medical service of a university hospital center aiming at a reduction by at least 30% in the use of these two drug classes. Methods The ABS programme was focused on the 300-bed medical service. Prescription of third-generation cephalosporins was discouraged, whereas the use of penicillins was encouraged. Monthly drug use density was measured in WHO-ATC defined and locally recommended daily doses (DDD and RDD) per 100 patient days, to evaluate trends before (01/2008 to 10/2011) and after starting the intervention (1/2012 to 3/2013). The effect was analysed using interrupted time-series analysis with six non-intervention departments as controls. Results Following initiation of the ABS intervention, overall antibiotic use in the medical service declined (p?cephalosporins and fluoroquinolones (p?cephalosporin use reductions (p?cephalosporins from 16.3 to 10.3 (?37%) and for fluoroquinolones from 17.7 to 10.1 (?43%), respectively. During the same period, the use of penicillins increased (15.4 to 18.2; 18%). The changes in expenditures for antibiotics in the medical service compared to control services minus programme costs indicated initial net cost savings likely to be associated with the programme. Conclusion An intensified ABS programme targeting cephalosporin und fluoroquinolone use in the setting of a large academic hospital is feasible and effective. The intervention may serve as a model for other services and hospitals with a similar structure and baseline situation. PMID:24731220



Possible transfer of plasmid mediated third generation cephalosporin resistance between Escherichia coli and Shigella sonnei in the human gut.  


Choice of antibiotic for treatment of serious bacterial infection is rapidly diminishing by plasmid mediated transfer of antibiotic resistance. Here, we report a possible horizontal transfer of plasmid carrying third-generation-cephalosporin (TGC) resistance between Escherichia coli and Shigella sonnei. Two different types of colonies were identified in MacConkey agar plate from a faecal specimen collected from a patient with shigellosis. The colonies were identified as E. coli and S. sonnei. Both of the isolates were resistant to ampicillin, chloramphenicol, co-trimoxazole, erythromycin, azithromycin, nalidixic acid, ceftriaxone, cefixime, ceftazidime, cefotaxime and susceptible to co-amoxiclave, amikacin, imipenam, astreonam, levofloxacin, moxifloxacin, mecillinam. These two strains were positive for extended spectrum ?-lactamase. We were able to transfer ESBL producing property from both ceftriaxone-resistant isolates to the ceftriaxone susceptible recipient E. coli K12 and S. sonnei. Plasmid profile analysis revealed that the first-generation E. coli K12 and S. sonnei transconjugants harbored a 50MDa R plasmid, as two-parent ESBL-producing S. sonnei and E. coli strains. Similar patterns of ESBL producing plasmid and transferable antimicrobial phenotype suggests that the ESBL producing plasmid might transferred between E. coli and S. sonnei through conjugation in the human gut. PMID:25461693

Rashid, Harunur; Rahman, Mahbubur



In Vitro Activity of TD-1792, a Multivalent Glycopeptide-Cephalosporin Antibiotic, against 377 Strains of Anaerobic Bacteria and 34 Strains of Corynebacterium Species  

PubMed Central

TD-1792 is a multivalent glycopeptide-cephalosporin heterodimer antibiotic with potent activity against Gram-positive bacteria. We tested TD-1792 against 377 anaerobes and 34 strains of Corynebacterium species. Against nearly all Gram-positive strains, TD-1792 had an MIC90 of 0.25 ?g/ml and was typically 3 to 7 dilutions more active than vancomycin and daptomycin. PMID:22290981

Citron, Diane M.; Warren, Yumi A.; Goldstein, Ellie J. C.



Infective endocarditis due to Enterobacter cloacae resistant to third- and fourth-generation cephalosporins.  


We report the case of using a long-term combination of meropenem and amikacin to treat infective endocarditis caused by Enterobacter cloacae resistant to third- and fourth-generation cephalosporins. Multi-drug resistant Gram-negative bacilli, such as the E. cloacae in our study, may become possible pathogens of infective endocarditis. Our experience with this case indicates that long-term use of a combination of ?-lactam and aminoglycosides might represent a suitable management option for future infective endocarditis cases due to non-Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella spp. (HACEK group) Gram-negative bacilli such as ours. PMID:23017689

Yoshino, Yusuke; Okugawa, Shu; Kimura, Satoshi; Makita, Eiko; Seo, Kazunori; Koga, Ichiro; Matsunaga, Naohisa; Kitazawa, Takatoshi; Ota, Yasuo



Evaluation of the ?Lacta Test, a Rapid Test Detecting Resistance to Third-Generation Cephalosporins in Clinical Strains of Enterobacteriaceae  

PubMed Central

For decades, third-generation cephalosporins (3GC) have been major drugs used to treat infections due to Enterobacteriaceae; growing resistance to these antibiotics makes the rapid detection of such resistance important. The ?Lacta test is a chromogenic test developed for detecting 3GC-resistant isolates from cultures on solid media within 15 min. A multicenter prospective study conducted in 5 French and Belgian hospitals evaluated the performance of this test on clinical isolates. Based on antibiotic susceptibility testing, strains resistant or intermediate to cefotaxime or ceftazidime were classified as 3GC resistant, and molecular characterization of this resistance was performed. The rates of 3GC resistance were 13.9% (332/2,387) globally, 9.4% in Escherichia coli (132/1,403), 25.6% in Klebsiella pneumoniae (84/328), 30.3% in species naturally producing inducible AmpC beta-lactamases (109/360), and 5.6% in Klebsiella oxytoca and Citrobacter koseri (7/124). The sensitivities and specificities of the ?Lacta test were, respectively, 87.7% and 99.6% overall, 96% and 100% for E. coli and K. pneumoniae, and 67.4% and 99.6% for species naturally producing inducible AmpC beta-lactamase. False-negative results were mainly related to 3GC-resistant strains producing AmpC beta-lactamase. Interestingly, the test was positive for all 3GC-resistant extended-spectrum beta-lactamase-producing isolates (n = 241). The positive predictive value was 97% and remained at ?96% for prevalences of 3GC resistance ranging between 10 and 30%. The negative predictive values were 99% for E. coli and K. pneumoniae and 89% for the species producing inducible AmpC beta-lactamase. In conclusion, the ?Lacta test was found to be easy to use and efficient for the prediction of resistance to third-generation cephalosporins, particularly in extended-spectrum beta-lactamase-producing strains. PMID:24068012

Renvoisé, Aurélie; Decré, Dominique; Amarsy-Guerle, Rishma; Huang, Te-Din; Jost, Christelle; Podglajen, Isabelle; Raskine, Laurent; Genel, Nathalie; Bogaerts, Pierre; Jarlier, Vincent



Microbial production of 7-amino-cephalosporanic acid and new generation cephalosporins (cephalothin) by different processing strategies.  


The development of beta-lactam antibiotics has been a continuous battle of the design of new compounds to withstand inactivation by the ever-increasing diversity of beta-lactamases. Semisynthetic cephalosporins like cephalothin were synthesized from 7-amino-cephalosporanic acid (7-ACA), and thiophene-2-acetic acid using cephalosporin-C acylase enzyme was studied. The production of cephalosporin-C acylase by Pseudomonas diminuta was used and the growth kinetics studied. The optimum condition of enzyme activity was determined by using response surface methodology. A 2(3) full-factorial composite design was employed for experimental design and the result analyzed. The pH value and temperature for optimum activity were 6.5 and 32 degrees C, respectively. The structural analog compound similar to the side-chain of semisynthetic cephalosporins, e.g., thiophene-2-acetic acid, was added. HPLC data analysis indicate that the concentration of cephalothin was 1.6 mg/mL. PMID:17701482

Gaurav, Kumar; Kundu, Kanika; Kundu, Subir



Gonococcal Resistance: Are Cephalosporins Next?  

Microsoft Academic Search

The development of resistance to multiple antibiotics has limited treatment options for gonorrhea in many countries. Currently,\\u000a the Centers for Disease Control and Prevention only recommend cephalosporin antibiotics for treatment of uncomplicated gonorrhea.\\u000a Although the cephalosporins remain effective, the demonstrated ability of Neisseria gonorrhoeae to develop resistance has raised concerns about the possibility of multidrug-resistant N. gonorrhoeae strains, which include

Robert D. Kirkcaldy; Ronald C. Ballard; Deborah Dowell



Cephalosporin C acylase: dream and(/or) reality.  


Cephalosporins currently constitute the most widely prescribed class of antibiotics and are used to treat diseases caused by both Gram-positive and Gram-negative bacteria. Cephalosporins contain a 7-aminocephalosporanic acid (7-ACA) nucleus which is derived from cephalosporin C (CephC). The 7-ACA nucleus is not sufficiently potent for clinical use; however, a series of highly effective antibiotic agents could be produced by modifying the side chains linked to the 7-ACA nucleus. The industrial production of higher-generation semi-synthetic cephalosporins starts from 7-ACA, which is obtained by deacylation of the naturally occurring antibiotic CephC. CephC can be converted to 7-ACA either chemically or enzymatically using D-amino acid oxidase and glutaryl-7-aminocephalosporanic acid acylase. Both these methods show limitation, including the production of toxic waste products (chemical process) and the expense (the enzymatic one). In order to circumvent these problems, attempts have been undertaken to design a single-step means of enzymatically converting CephC to 7-ACA in the course of the past 10 years. The most suitable approach is represented by engineering the activity of a known glutaryl-7-aminocephalosporanic acid acylase such that it will bind and deacylate CephC more preferentially over glutaryl-7-aminocephalosporanic acid. Here, we describe the state of the art in the production of an effective and specific CephC acylase. PMID:23417342

Pollegioni, Loredano; Rosini, Elena; Molla, Gianluca



Degradation kinetics in aqueous solution of cefotaxime sodium, a third-generation cephalosporin.  


The degradation kinetics of a 3- acetoxymethylcephalosporin , cefotaxime sodium salt, in aqueous solution investigated by HPLC under different conditions (pH, ionic strength, temperature) and using different buffers. The scheme of degradation involves a cleavage of the beta-lactam nucleus and the deacetylation of the side chain. In highly acidic medium, the deacetylated derivative is easily converted to the lactone. The degradation rate constants were calculated at three pH values (1.9, 4.0, and 9.0) by measuring the residual cephalosporin and the main decomposition products. The degradation pathway is both supported by the results of a primary salt effect and by the agreement between the theoretical pH-rate profile and the experimental values. In the pH range from 3.0 to 7.0, the main process is a slow water-catalyzed or spontaneous cleavage of the beta-lactam nucleus with intramolecular participation of the side chain amido fraction in the 7-position. In alkaline or strongly acidic medium, the hydrolysis is a base- or acid-catalyzed reaction. Of the buffer systems investigated, carbonate buffer (pH 8.5) and borate buffers (pH 9.5 and 10.0) are found to increase the degradation rates, while acetate buffer decreases the degradation rates. The apparent activation energies determined at different pH values are compatible with a solvolysis mechanism and similar to those previously given in the literature for other cephalosporins. Cefotaxime in aqueous solution is slightly less stable than the main cephalosporin derivatives, despite its high resistance to the beta-lactamases and its remarkable biological activity. PMID:6330342

Fabre, H; Eddine, N H; Berge, G



Prevalence of lactose fermenting coliforms resistant to third generation cephalosporins in cattle feedlot throughout a production cycle and molecular characterization of resistant isolates  

Technology Transfer Automated Retrieval System (TEKTRAN)

Introduction: Increases in incidence of human infections caused by Enterobacteriaceae resistant to 3rd generation cephalosporins (3GC) have become a public health concern. The 3GC ceftiofur is commonly used for the therapeutic treatment of feedlot cattle but the impact this practice has on public h...


Nonconvulsive Status epilepticus during Cephalosporin Therapy  

Microsoft Academic Search

Cephalosporins may induce nonconvulsive status epilepticus (NCSE), a potentially reversible condition. Despite the wide use of these antibiotics, there are only few reported cases, because this condition is probably underestimated. We report two new cases of NCSE occurring during treatment with cefepime and ceftazidime, and emphasize the utility of emergent electroencephalogram in patients with an acute altered state of consciousness

Alberto Primavera; Leonardo Cocito; Daniela Audenino



Advanced-generation macrolides: tissue-directed antibiotics  

Microsoft Academic Search

The azalide antibiotic azithromycin and the newer macrolides, such as clarithromycin, dirithromycin and roxithromycin, can be regarded as ‘advanced-generation’ macrolides compared with erythromycin, the first macrolide used clinically as an antibiotic. Their pharmacokinetics are characterized by a combination of low serum concentrations, high tissue concentrations and, in the case of azithromycin, an extended tissue elimination half-life. Azithromycin is particularly noted

G. W Amsden



Reciprocal Regulation of Cephalosporin Resistance in Enterococcus faecalis  

PubMed Central

ABSTRACT Antibiotic-resistant enterococci are major causes of hospital-acquired infections and therefore represent a serious public health problem. One well-known risk factor for the acquisition of hospital-acquired enterococcal infections is prior therapy with broad-spectrum cephalosporin antibiotics. Enterococci can proliferate in patients undergoing cephalosporin therapy due to intrinsic cephalosporin resistance, a characteristic of the genus Enterococcus. However, the molecular basis for cephalosporin resistance in E. faecalis has yet to be adequately elucidated. Previously we determined that a putative Ser/Thr kinase, IreK (formerly PrkC), is required for intrinsic cephalosporin resistance in E. faecalis. Here we show that kinase activity is required for cephalosporin resistance and, further, that resistance in E. faecalis is reciprocally regulated by IreK and IreP, a PP2C-type protein phosphatase encoded immediately upstream of IreK. Mutants of two divergent lineages of E. faecalis lacking IreP exhibit remarkable hyperresistance to cephalosporins but not to antibiotics targeting other cellular processes. Further genetic analyses indicate that hyperresistance of the IreP mutant is mediated by the IreK kinase. Additionally, competition experiments reveal that hyperresistant ?ireP mutants exhibit a substantial fitness defect in the absence of antibiotics, providing an evolutionary rationale for the use of a complex signaling system to control intrinsic cephalosporin resistance. These results support a model in which IreK and IreP act antagonistically via protein phosphorylation and dephosphorylation as part of a signal transduction circuit to regulate cellular adaptation to cephalosporin-induced stress. PMID:22045988

Kristich, Christopher J.; Little, Jaime L.; Hall, Cherisse L.; Hoff, Jessica S.



Catalytically impaired fluorescent class C ?-lactamase enables rapid and sensitive cephalosporin detection by stabilizing fluorescence signals: implications for biosensor design.  


Biosensors have found applications in many sectors including the food industry, where cephalosporin detection has played an important role in reducing the incidence of cephalosporin contamination, ensuring food safety, and reducing the spread of antibiotic resistance. Taking advantage of the specific interaction between ?-lactamase and its cephalosporin substrates/inhibitors, we previously constructed a biosensor based on a fluorescein-labeled class C ?-lactamase mutant, V211Cf, for specific and reagentless detection of cephalosporins and class C ?-lactamase inhibitors (Anal. Chem. 2011, 83, 1996-2004). Upon the addition of substrate/ inhibitor (i.e. the biosensor's analyte), the analyte induced a change in the local environment of the fluorescein molecule that was covalently tethered to a site close to the enzyme's active site (the 211 position), triggering a fluorescence enhancement of V211Cf. To improve the performance of V211Cf for better cephalosporin detection of the biosensor, we have developed Y150S/V211Cf, a derivative of V211Cf constructed by introducing the Y150S mutation to suppress the hydrolytic activity of V211Cf thereby improving the stability of the fluorescence signal. From our results, Y150S/V211Cf not only demonstrated improved fluorescence signal sustainability over V211Cf, but also showed a rapid response towards cephalothin (a first generation cephalosporin). These features make it feasible to of use Y150S/V211Cf for the rapid and specific detection of cephalosporins, and illustrate the possibilities for rational biosensor design of catalytically impaired fluorescent enzymes for rapid and sensitive analyte detection purposes. PMID:25181520

Tsang, Man-Wah; So, Pui-Kin; Liu, Sze-Yan; Tsang, Chun-Wai; Chan, Pak-Ho; Wong, Kwok-Yin; Leung, Yun-Chung



Analysis of Salmonella enterica with reduced susceptibility to the 3rd generation cephalosporin, ceftriaxone, isolated from US cattle during 2000-2004  

Technology Transfer Automated Retrieval System (TEKTRAN)

Over the past decade enteric bacteria in Europe, Africa and Asia have become increasingly resistant to cephalosporin antimicrobials. This is largely due to the spread of genes encoding extended-spectrum ß-lactamase (ESBL) enzymes which can inactivate many cephalosporins. Recently these resistance me...




Antibiotics are powerful medicines that fight bacterial infections. Used properly, antibiotics can save lives. They either kill bacteria or ... natural defenses can usually take it from there. Antibiotics do not fight infections caused by viruses, such ...


Spectrophotometric Determination of Cephalosporins in Pure Form and in Pharmaceutical Preparations  

Microsoft Academic Search

A spectrophotometric determination is described for cephalosporins, offering adequate sensitivity and good precision. The procedure applies successfully to a wide variety of cephalosporins, also in pharmaceutical preparations: cephalothin, cefacetrile, cephapirin, cefotaxime, ceftizoxime, cephaloridine, cefazolin, cefamandole nafate, cephalexin, cefadroxil, cefoxitin and cefuroxime. The method employs a reaction with ammonium molybdate in sulphuric acid medium. The antibiotic is heated at 91.5°C for

Basilio Morelli; Pasquale Peluso



An azido-oxazolidinone antibiotic for live bacterial cell imaging and generation of antibiotic variants  

PubMed Central

An azide-functionalised analogue of the oxazolidinone antibiotic linezolid was synthesised and shown to retain antimicrobial activity. Using facile ‘click’ chemistry, this versatile intermediate can be further functionalised to explore antimicrobial structure–activity relationships or conjugated to fluorophores to generate fluorescent probes. Such probes can report bacteria and their location in a sample in real time. Modelling of the structures bound to the cognate 50S ribosome target demonstrates binding to the same site as linezolid is possible. The fluorescent probes were successfully used to image Gram-positive bacteria using confocal microscopy. PMID:25023540

Phetsang, Wanida; Blaskovich, Mark A.T.; Butler, Mark S.; Huang, Johnny X.; Zuegg, Johannes; Mamidyala, Sreeman K.; Ramu, Soumya; Kavanagh, Angela M.; Cooper, Matthew A.



Dissemination of Cephalosporin Resistance Genes between Escherichia coli Strains from Farm Animals and Humans by Specific Plasmid Lineages  

PubMed Central

Third-generation cephalosporins are a class of ?-lactam antibiotics that are often used for the treatment of human infections caused by Gram-negative bacteria, especially Escherichia coli. Worryingly, the incidence of human infections caused by third-generation cephalosporin-resistant E. coli is increasing worldwide. Recent studies have suggested that these E. coli strains, and their antibiotic resistance genes, can spread from food-producing animals, via the food-chain, to humans. However, these studies used traditional typing methods, which may not have provided sufficient resolution to reliably assess the relatedness of these strains. We therefore used whole-genome sequencing (WGS) to study the relatedness of cephalosporin-resistant E. coli from humans, chicken meat, poultry and pigs. One strain collection included pairs of human and poultry-associated strains that had previously been considered to be identical based on Multi-Locus Sequence Typing, plasmid typing and antibiotic resistance gene sequencing. The second collection included isolates from farmers and their pigs. WGS analysis revealed considerable heterogeneity between human and poultry-associated isolates. The most closely related pairs of strains from both sources carried 1263 Single-Nucleotide Polymorphisms (SNPs) per Mbp core genome. In contrast, epidemiologically linked strains from humans and pigs differed by only 1.8 SNPs per Mbp core genome. WGS-based plasmid reconstructions revealed three distinct plasmid lineages (IncI1- and IncK-type) that carried cephalosporin resistance genes of the Extended-Spectrum Beta-Lactamase (ESBL)- and AmpC-types. The plasmid backbones within each lineage were virtually identical and were shared by genetically unrelated human and animal isolates. Plasmid reconstructions from short-read sequencing data were validated by long-read DNA sequencing for two strains. Our findings failed to demonstrate evidence for recent clonal transmission of cephalosporin-resistant E. coli strains from poultry to humans, as has been suggested based on traditional, low-resolution typing methods. Instead, our data suggest that cephalosporin resistance genes are mainly disseminated in animals and humans via distinct plasmids. PMID:25522320

de Toro, María; Scharringa, Jelle; Dohmen, Wietske; Du, Yu; Hu, Juan; Lei, Ying; Li, Ning; Tooming-Klunderud, Ave; Heederik, Dick J. J.; Fluit, Ad C.; Bonten, Marc J. M.; Willems, Rob J. L.; de la Cruz, Fernando; van Schaik, Willem



National Ambulatory Antibiotic Prescribing Patterns for Pediatric Urinary Tract Infection, 1998–2007  

PubMed Central

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. PMID:21555502

Shapiro, Daniel J.; Hersh, Adam L.



Surveillance of antibiotic resistance in Neisseria gonorrhoeae in the WHO Western Pacifi c Region, 2005  

Microsoft Academic Search

The World Health Organization Western Pacifi c Region Gonococcal Antimicrobial Surveillance Programme examined about 8,700 isolates of Neisseria gonorrhoeae from 15 countries for resistance to antibiotics in 2005. High to very high rates of resistance to penicillins and quinolones persisted in most centres. Increasing numbers of gonococci with decreased susceptibility to third generation cephalosporins were found in several countries. There

John Tapsall



Mutations in the ? Subunit of RNA Polymerase Alter Intrinsic Cephalosporin Resistance in Enterococci  

PubMed Central

As major causes of hospital-acquired infections, antibiotic-resistant enterococci are a serious public health concern. Enterococci are intrinsically resistant to many cephalosporin antibiotics, a trait that enables proliferation in patients undergoing cephalosporin therapy. Although a few genetic determinants of cephalosporin resistance in enterococci have been described, overall, many questions remain about the underlying genetic and biochemical basis for cephalosporin resistance. Here we describe an unexpected effect of specific mutations in the ? subunit of RNA polymerase (RNAP) on intrinsic cephalosporin resistance in enterococci. We found that RNAP mutants, selected initially on the basis of their ability to provide resistance to rifampin, resulted in allele-specific alterations of the intrinsic resistance of enterococci toward expanded- and broad-spectrum cephalosporins. These mutations did not affect resistance toward a diverse collection of other antibiotics that target a range of alternative cellular processes. We propose that the RNAP mutations identified here lead to alterations in transcription of as-yet-unknown genes that are critical for cellular adaption to cephalosporin stress. PMID:22290974

Little, Jaime L.



Effects of reducing beta-lactam antibiotic pressure on intestinal colonization of antibiotic-resistant gram-negative bacteria  

Microsoft Academic Search

Background  We determined the effects of two antibiotic policies (predominance of either ?-lactam antibiotics or fluroquinolones) on acquisition\\u000a with third-generation cephalosporin-resistant Enterobacteriaceae (CRE) and fluoroquinolone-resistant CRE (FCRE) in two ICUs,\\u000a with monitoring of other variables that may influence acquisition.\\u000a \\u000a \\u000a \\u000a Methods  After an 8-month baseline period, units were randomized to a predominant ?-lactam antibiotic regimen (weekly cycling of ceftriaxone,\\u000a amoxicillin–clavulanic acid and fluroquinolones)

Saskia Nijssen; Ad Fluit; David van de Vijver; Janetta Top; R. J. L. Willems; Marc J. M. Bonten



Cephalosporin Induced Disulfiram-Like Reaction: A Retrospective Review of 78 Cases  

PubMed Central

Concomitant ingestion of alcohol and cephalosporin may cause a disulfiram-like reaction; however its fatal outcomes are not commonly known. We retrospectively reviewed 78 patients who had cephalosporin induced disulfiram-like reaction (CIDLR). The patients who had a negative skin test to cephalosporin prior to intravenous antibiotics were included, and those who were allergic to either alcohol or antibiotics were excluded. The average age of 78 patients was 37.8±12.2 (21–60) years. Of the 78 patients, 93.58% of the patients were males, 70.51% of the patients consumed alcohol after use of antibiotics, and 29.49% patients consumed alcohol initially, followed by intravenous antibiotics; however, no significant difference of morbidity was observed in these two groups. All patients were administered antibiotics intravenously. Five of 78 patients (6.41%) developed severe CIDLR too urgently to be rescued successfully. In conclusion, it is important for clinicians to educate patients that no alcohol should be used if one is taking cephalosporin. Also, clinicians should keep in mind that cephalosporin should not be prescribed for any alcoholics. PMID:24670024

Ren, Shiyan; Cao, Yuxia; Zhang, Xiuwei; Jiao, Shichen; Qian, Songyi; Liu, Peng



Surveillance of antibiotic resistance in Neisseria gonorrhoeae in the WHO Western Pacific Region, 2001 The WHO Western Pacific Gonococcal Antimicrobial Surveillance Programme  

Microsoft Academic Search

A long-term program of surveillance of antimicrobial resistance in Neisseria gonorrhoeae isolated in the World Health Organization's Western Pacific Region (WHO WPR GASP) continued in 2001. Seventeen focal points contributed data on about 10,000 gonococci. Resistance to quinolone and penicillin antibiotics remained widely dispersed and at high levels. Gonococci with decreased suscep- tibility to third generation cephalosporins were again observed

John Tapsall



Outcome of Cephalosporin Treatment for Serious Infections Due to Apparently Susceptible Organisms Producing Extended-Spectrum  -Lactamases: Implications for the Clinical Microbiology Laboratory  

Microsoft Academic Search

Although extended-spectrum beta-lactamases (ESBLs) hydrolyze cephalosporin antibiotics, some ESBL- producing organisms are not resistant to all cephalosporins when tested in vitro. Some authors have suggested that screening klebsiellae or Escherichia coli for ESBL production is not clinically necessary, and when most recently surveyed the majority of American clinical microbiology laboratories did not make efforts to detect ESBLs. We performed a




Comparative activity of ampicillin and seven cephalosporins against group D streptococci  

PubMed Central

Minimum inhibitory concentrations have been determined for ampicillin and seven cephalosporins against 93 strains of group D streptococci isolated recently from clinical material. Ampicillin was much the most active compound (modal MIC = 1·6 ?g/ml); cephaloridine, cephacetrile, and cefazolin had a modal MIC of 25 ?g/ml, while corresponding figures for cephalothin, cephradine, cephalexin, and cefoxitin were 50, 100, 200, and 800 ?g/ml, respectively. Thus, none of the newer cephalosporins is an improvement in respect to activity against enterococci over existing compounds, and ampicillin remains overwhelmingly the ?-lactam antibiotic of choice for the treatment of infections by such organisms. Pharmacokinetic considerations, however, indicate that certain cephalosporins, for instance, cephaloridine, cefazolin, and cephanone, may be worthy of further study in view of possible synergy with aminoglycoside antibiotics. PMID:4214839

Hamilton-Miller, J. M. T.



Expedient antibiotics production: Final report  

Microsoft Academic Search

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

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



Industrial production of ß-lactam antibiotics  

Microsoft Academic Search

The industrial production of ?-lactam antibiotics by fermentation over the past 50 years is one of the outstanding examples of biotechnology. Today, the ?-lactam antibiotics, particularly penicillins and cephalosporins, represent the world's major biotechnology products with worldwide dosage form sales of ~US$ 15 billion or ~65% of the total world market for antibiotics. Over the past five decades, major improvements in the

R. P. Elander



Adherence to perioperative antibiotic prophylaxis among orthopedic trauma patients  

PubMed Central

Background The goal of this study was to assess whether patients receive their antibiotic prophylaxis as prescribed. We also investigated what doses and durations of antibiotics are typically ordered, which patients actually receive antibiotics and factors causing the ordered antibiotic regimen to be altered. Methods We performed a retrospective review of 205 patient charts and sent a national survey to all surgeon members of the Canadian Orthopaedic Trauma Society (COTS) about antibiotic prophylaxis in the setting of surgical treatment for closed fractures. Results In all, 93% (179 of 193) of patients received an appropriate preoperative dose of antibiotics, whereas less than 32% (58 of 181) of patients received their postoperative antibiotics as ordered. The most commonly stated reason for patients not receiving their postoperative antibiotics as ordered was patients being discharged before completing 3 postoperative doses. There was a 70% (39 of 56) response rate to the survey sent to COTS surgeons. A single dose of a first-generation cephalosporin preoperatively followed by 3 doses postoperatively is the most common practice among orthopedic trauma surgeons across Canada, but several surgeons give only preoperative prophylaxis. Conclusion Adherence to multidose postoperative antibiotic regimens is poor. Meta-analyses have failed to demonstrate the superiority of multidose regimens over single-dose prophylaxis. Single-dose preoperative antibiotic prophylaxis may be a reasonable choice for most orthopedic trauma patients with closed fractures. PMID:21092428

Lundine, Kristopher M.; Nelson, Susan; Buckley, Richard; Putnis, Sven; Duffy, Paul J.



Identifying Genetic Susceptibility to Sensitization to Cephalosporins in Health Care Workers  

PubMed Central

Exposure to cephalosporins could cause occupational allergic diseases in health care workers (HCWs). We evaluated the prevalence of serum specific IgE and IgG antibodies to cephalosporin-human serum albumin (HSA) conjugate and to identify potential genetic risk factors associated with sensitization to cephalosporins in exposed HCWs. The study population consisted of 153 HCWs who had been exposed to antibiotics in a single university hospital and 86 unexposed healthy controls. A questionnaire survey of work-related symptoms (WRS) was administered. A skin-prick test (SPT) was performed, and serum-specific IgE and IgG antibodies to 3 commonly prescribed cephalosporins were measured by ELISA. Four single-nucleotide polymorphisms of the candidate genes related to IgE sensitization were genotyped. The prevalence of WRS to cephalosporins was 2.6%. The prevalence rates of serum-specific IgE and IgG antibodies to cephalosporins were 20.3% and 14.7%, respectively. The Fc?R1?-109T > C polymorphism was significantly associated with IgE sensitization to cephalosporins in HCWs (P = 0.036, OR = 3.553; CI, 1.324-9.532). The in vitro functional assay demonstrated that the T allele of Fc?R1?-109T had greater promoter activity than did the C allele (P < 0.001). The Fc?R1?-109T > C polymorphism may be a potential genetic risk factor for increased IgE sensitization to cephalosporins. PMID:23166408

Nam, Young-Hee; Kim, Jeong-Eun; Kim, Seung-Hyun; Jin, Hyun Jung; Hwang, Eui-Kyung; Shin, Yoo-Seob; Ye, Young-Min



Recent trends on bacterial resistance to antibiotics.  


Antimicrobial resistance has become a major medical and public health problem. The main factor responsible for development and spread of bacterial resistance is injudicious use of antimicrobial agents which has resulted in most gram positive and gram negative bacteria continuously developing resistance to the antimicrobials in regular use at different time periods. In East Africa, among E. coli in urinary tract infections, more than 80% are currently resistant to ampicillin, cotrimoxazole and tetracycline while more than 80% of the isolates are still susceptible to nitrofurantoin, gentamicin and third generation cephalosporins. Penicillin G resistant strains of pneumococci were first reported in 1967 but had gradually increased to about 20% in 1991. Among group A streptococci, all natural strains are still sensitive to penicillin G while resistance to tetracycline has reached alarming proportions. In Tanzania, more than 65% of N. gonorrhoeae isolates are beta-lactamase producers, however, spectinomycin, second and third generation cephalosporins and ciprofloxacin are effective against most strains. Vibrio cholerae 01 strains resistant to multiple antibiotics are widely spread globally, however, there are recent reports indicating that withdrawal of the drugs can lead to loss of the antibiotic resistance factors. Despite varied susceptibility of N. meningitidis strains world wide, isolates in Tanzania are still susceptible to commonly available drugs including penicillin G and chloramphenicol. Available methods for control of spread of bacterial resistance include rational use of antimicrobial agents including control in animal husbandry, change to newer antimicrobials, rotational use of drugs and constant surveillance for emerging bacterial resistance. PMID:9185405

Urassa, W; Lyamuya, E; Mhalu, F



In Vitro selection of Neisseria gonorrhoeae mutants with elevated MIC values and increased resistance to cephalosporins.  


Strains of Neisseria gonorrhoeae with mosaic penA genes bearing novel point mutations in penA have been isolated from ceftriaxone treatment failures. Such isolates exhibit significantly higher MIC values to third-generation cephalosporins. Here we report the in vitro isolation of two mutants with elevated MICs to cephalosporins. The first possesses a point mutation in the transpeptidase region of the mosaic penA gene, and the second contains an insertion mutation in pilQ. PMID:25199775

Johnson, Steven R; Grad, Yonatan; Ganakammal, Satishkumar Ranganathan; Burroughs, Mark; Frace, Mike; Lipsitch, Marc; Weil, Ryan; Trees, David



[Perioperative antibiotic prophylaxis practice of French anesthesiologists and resuscitators: results of a national survey].  


Antibiotics are the most prescribed drugs in French hospitals in one third of cases they are used for antiobiotic prophylaxis in surgery. In spite of the guidelines for antibioprophylaxis produced in the last years, their prescription patterns remain still often inappropriate. This survey aimed to assess whether the prescription of antibiotics for prophylaxis by French anaesthetits complied with the French recommendations for antibioprophylaxis in surgery. It focused on the recommended agents, the time of the first injection, the duration of treatment. A sample of 1,473 anaesthetists participated in the survey. In 93% of cases, the first injection of the antibiotic took place at anaesthesia induction, as specified by the recommendations. Cephalosporins of the first and second generation were often administered, as well as the association amoxicillin-clavulanic acid. In contradiction with the recommendations, the cephalosporins of the third generation were widely prescribed in digestive and urological surgery, and the quinolones in urology and ophtalmology. The duration of treatment was restricted to 48 hours by 94% of anaesthetists. However there was a strong tendency to prolonge it in immunodepressed patients and in case of major surgery. This survey showed disparities between the French recommendations for antibioprophylaxis in surgery and the prescription patterns of anaesthetists. The lack of compliance occurred mainly for recent cephalosporins and treatment duration of over 48 hours. It is concluded that a stronger adherence to the principles of antibioprophylaxis is required in surgical patients. PMID:9750623

Martin, C; Pourriat, J L



Clinical Pharmacokinetics of Penicillins, Cephalosporins and Aminoglycosides in the Neonate: A Review  

PubMed Central

Bacterial infections are common in the neonates and are a major cause of morbidity and mortality. Sixty percent of preterm infants admitted to neonatal intensive care units received at least one antibiotic during the first week of life. Penicillins, aminoglycosides and cephalosporins comprised 53, 43 and 16%, respectively. Kinetic parameters such as the half-life (t1/2), clearance (Cl), and volume of distribution (Vd) change with development, so the kinetics of penicillins, cephalosporins and aminoglycosides need to be studied in order to optimise therapy with these drugs. The aim of this study is to review the pharmacokinetics of penicillins, cephalosporins and aminoglycosides in the neonate in a single article in order to provide a critical analysis of the literature and thus provide a useful tool in the hands of physicians. The bibliographic search was performed electronically using PubMed, as the search engine, until February 2nd, 2010. Medline search terms were as follows: pharmacokinetics AND (penicillins OR cephalosporins OR aminoglycosides) AND infant, newborn, limiting to humans. Penicillins, cephalosporins and aminoglycosides are fairly water soluble and are mainly eliminated by the kidneys. The maturation of the kidneys governs the pharmacokinetics of penicillins, cephalosporins and aminoglycosides in the neonate. The renal excretory function is reduced in preterms compared to term infants and Cl of these drugs is reduced in premature infants. Gestational and postnatal ages are important factors in the maturation of the neonate and, as these ages proceed, Cl of penicillins, cephalosporins and aminoglycosides increases. Cl and t1/2 are influenced by development and this must be taken into consideration when planning a dosage regimen with these drugs. More pharmacokinetic studies are required to ensure that the dose recommended for the treatment of sepsis in the neonate is evidence based.

Pacifici, Gian Maria



?-Lactam formation by a non-ribosomal peptide synthetase during antibiotic biosynthesis.  


Non-ribosomal peptide synthetases are giant enzymes composed of modules that house repeated sets of functional domains, which select, activate and couple amino acids drawn from a pool of nearly 500 potential building blocks. The structurally and stereochemically diverse peptides generated in this manner underlie the biosynthesis of a large sector of natural products. Many of their derived metabolites are bioactive such as the antibiotics vancomycin, bacitracin, daptomycin and the ?-lactam-containing penicillins, cephalosporins and nocardicins. Penicillins and cephalosporins are synthesized from a classically derived non-ribosomal peptide synthetase tripeptide (from ?-(L-?-aminoadipyl)-L-cysteinyl-D-valine synthetase). Here we report an unprecedented non-ribosomal peptide synthetase activity that both assembles a serine-containing peptide and mediates its cyclization to the critical ?-lactam ring of the nocardicin family of antibiotics. A histidine-rich condensation domain, which typically performs peptide bond formation during product assembly, also synthesizes the embedded four-membered ring. We propose a mechanism, and describe supporting experiments, that is distinct from the pathways that have evolved to the three other ?-lactam antibiotic families: penicillin/cephalosporins, clavams and carbapenems. These findings raise the possibility that ?-lactam rings can be regio- and stereospecifically integrated into engineered peptides for application as, for example, targeted protease inactivators. PMID:25624104

Gaudelli, Nicole M; Long, Darcie H; Townsend, Craig A



Susceptibility of cutaneous propionibacteria to newer antibiotics.  


The minimal inhibitory concentrations of 18 newer antibiotics were determined for 33 strains of cutaneous propionibacteria, i. e., P. acnes, P. granulosum and P. avidum. All the strains showed high sensitivity to the penicillin and cephalosporin antibiotics tested. They were mostly resistant to aminoglycosides in therapeutically achievable concentrations, and nitroimidazole compounds were completely ineffective. PMID:7353441

Höffler, U; Niederau, W; Pulverer, G



Susceptibility of Cutaneous Propionibacteria to Newer Antibiotics  

Microsoft Academic Search

The minimal inhibitory concentrations of 18 newer antibiotics were determined for 33 strains of cutaneous propionibacteria, i.e., P.acnes, P. granulosum and P. avidum. All the strains showed high sensitivity to the penicillin and cephalosporin antibiotics tested. They were mostly resistant to aminoglycosides in therapeutically achievable concentrations, and nitroimidazole compounds were completely ineffective.Copyright © 1980 S. Karger AG, Basel

Ulrich Höffler; Walter Niederau; Gerhard Pulverer



Beta-lactam antibiotics  

Microsoft Academic Search

The large family of ?-lactams comprises penicillins, cephalosporins, cephamycins, monobactams, carbacephems and carbapenems\\u000a and are so named since they all containing the ?-lactam moiety.\\u000a \\u000a \\u000a Penicillin was the first ?-lactam antibiotic and was discovered in 1928 by Sir Alexander Fleming at St. Mary’s Hospital, London [1].\\u000a The ?-lactam chemical structure for penicillin was first proposed by Abraham and Chain in 1943

Constantin Cojocel


Influence of inorganic phosphate and organic buffers on cephalosporin production by Streptomyces clavuligerus  

Microsoft Academic Search

A high concentration of potassium phosphate (75–100 mM) stabilized pH and supported extensive growth of Streptomyces clavuligerus in a chemically defined medium; such a concentration also inhibited cephalosporin production. Although Tris buffer was found to have detrimental effects on growth and antibiotic production, 3-(N-morpholino)-propane sulfonate (MOPS) or 2-(N-morpholino)-ethane sulfonate (MES) buffer provided a nontoxic buffering system. In the presence of

Yair Aharonowitz; Arnold L. Demain



Evaluation of separation and purification processes in the antibiotic industry  

Microsoft Academic Search

The different separation and purification processes for three major types of antibiotics, Penicillins, Cephalosporins and Tetracyclines will be discussed. All antibiotic, processing plants contain two majors sections, a relatively small and highly specialized fermentation section and a very large (60-80% of the plant) separation and purification section. The fermentation sections for the different antibiotics are essentially identical, except for differences

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



A novel cephalosporin deacetylating acetyl xylan esterase from Bacillus subtilis with high activity toward cephalosporin C and 7-aminocephalosporanic acid.  


A cephalosporin deacetylating acetyl xylan esterase was cloned from the genomic DNA of Bacillus subtilis CICC 20034 and functionally expressed in Escherichia coli. Its gene contained an open reading frame of 957 bp encoding 318 amino acids with a calculated mass of 35,607 Da, and it displayed significant identity to acetyl xylan esterases from Bacillus sp. 916, B. subtilis 168, and Bacillus pumilus Cect5072. The enzyme was a native homohexamer but a trimer under the condition of 1% sodium dodecyl sulfate (SDS); both forms were active and could transit to each other by incubating in or removing SDS. The enzyme belongs to carbohydrate esterase family 7 and had a double specificity on both the acetylated oligosaccharide and cephalosporin C (CPC) and 7-aminocephalosporanic acid (7-ACA). The activity of this purified enzyme toward CPC and 7-ACA was highest among all the acetyl xylan esterase from CE family 7, which were 484 and 888 U/mg, respectively, and endowed itself with great industrial interest on semi-synthetic ?-lactam antibiotics. The optimum pH of the purified enzyme was 8.0, and the optimum temperature was 50 °C, and the enzyme had high thermal stability, broad range of pH tolerance, and extremely organic solvent tolerance. PMID:23828600

Tian, Qianqian; Song, Ping; Jiang, Ling; Li, Shuang; Huang, He



Azithromycin resistance is coevolving with reduced susceptibility to cephalosporins in Neisseria gonorrhoeae in Ontario, Canada.  


Azithromycin (AZM) is routinely recommended as a component of dual therapy for gonorrhea in combination with third-generation cephalosporins (3GC). In this study, we examined the prevalence of AZM-resistant (AZM(r)) Neisseria gonorrhoeae from July 2010 to February 2013, assessed the rate of concurrent cephalosporin resistance under the current treatment recommendations, and analyzed the clonal distribution of AZM(r) isolates in Ontario, Canada. Nineteen AZM(r) clinical isolates (one per patient; MIC, ?2 ?g/ml) were included in the study. Susceptibility profiles of these isolates to 11 antibiotics, molecular typing, characterization of macrolide resistance mechanisms, and penicillin-binding protein 2 (PBP2) patterns were determined for all the isolates. Two groups were defined based on AZM(r) level; group A isolates displayed high-level resistance (MIC, ?2,048 ?g/ml) due to mutations (A2143G) in the four copies of the 23S rRNA rrl gene, and group B isolates had moderate resistance to AZM (MICs, 2 to 8 ?g/ml, C2599T mutation in the rrl gene), with a subgroup belonging to sequence type 3158 (ST3158) (n = 8), which also showed reduced susceptibility to 3GC (MICs, 0.12 to 0.25 ?g/ml, PBP2 pattern XXXIV). This AZM(r) phenotype was not observed in previous provincial surveillance in 2008 (the ST3158 clone was found, with AZM MICs of 0.25 to 0.5 ?g/ml associated with mtrR mutations). We hypothesized that the AZM mutant prevention concentration (MPC) in the ST3158 subpopulation we found in 2008 was higher than the MPC in wild-type isolates (AZM MIC, ?0.031 ?g/ml), increasing the chances of additional selection of AZM(r) mutations. Full AZM resistance is now emerging in this clone together with reduced susceptibility to 3GC, threatening the future efficacy of these antibiotics as therapeutic options for treatment of gonorrhea. PMID:24514092

Allen, Vanessa G; Seah, Christine; Martin, Irene; Melano, Roberto G



Antibiotic therapy for acute uncomplicated pyelonephritis in women. Take resistance into account.  


Acute uncomplicated pyelonephritis is a bacterial infection of the renal parenchyma, common in women. The bacterium responsible is usually Escherichia coli. Empirical antibiotic therapy should be initiated promptly to prevent serious complications. As of 2014, which empirical antibiotic regimen should be offered to non-pregnant adult women with acute uncomplicated pyelonephritis, while awaiting the results of antimicrobial susceptibility testing? We reviewed the available evidence using the standard Prescrire methodology. Certain oral fluoroquinolones were effective in a few clinical trials in the 2000s and 2010s: ciprofloxacin and levofloxacin, an isomer of ofloxacin. Symptoms resolved within 5 to 7 days in about 96% of the women. In France, in 2011, about 10% of E. coli isolated in community laboratories from outpatients with urinary tract infections were resistant to ciprofloxacin. Resistance is mainly a problem in patients treated with a quinolone during the preceding months and in recently hospitalised patients. In hospital laboratories, the fluoroquinolone resistance rate was about 18% in 2012 in France, and even higher in some other European countries. The main harms of fluoroquinolones are neuropsychiatric disorders, photosensitivity, tendon disorders, arrhythmia and cardiac conduction disorders, and Clostridium difficile infection. Injectable "third-generation" cephalosporins, such as ceftriaxone, are often effective against enterobacteria, in particular E. coli, and have good kidney penetration. The prevalence of E. coli resistance to third-generation cephalosporins is rising rapidly in France, particularly in hospitals: 1% in 2005 versus 10% in 2012. The main harms of cephalosporins are hypersensitivity reactions and C. difficile infection. Monotherapy with an aminoglycoside is an alternative that has not been evaluated in this clinical situation. Due to the serious irreversible adverse effects of aminoglycosides (nephrotoxicity, ototoxicity), they should only be used when the other options are unacceptable. In practice, as of 2014, the first-choice empirical antibiotic treatment for acute uncomplicated pyelonephritis remains an oral fluoroquinolone (ciprofloxacin or ofloxacin) or, in certain cases, the injectable third-generation cephalosporin ceftriaxone. Given the rapid development of bacterial resistance, broader-spectrum antibiotics should not be used as empirical therapy, to preserve their efficacy in serious infections. The empirical treatment should be adjusted as soon as the results of antimicrobial susceptibility testing are known. Whenever possible, it is preferable to avoid the use of fluoroquinolones and third-generation cephalosporins in non-serious infections such as cystitis. PMID:25629148



Differences in the changes in resistance patterns to third- and fourth-generation cephalosporins and piperacillin\\/tazobactam among Klebsiella pneumoniae and Escherichia coli clinical isolates following a restriction policy in a Greek tertiary care hospital  

Microsoft Academic Search

The aim of the present study was to investigate whether replacement of broad-spectrum cephalosporins (CEPs) by piperacillin\\/tazobactam (TZP) as first-line empirical therapy may have an effect on ?-lactam resistance among Klebsiella pneumoniae and Escherichia coli in a tertiary care hospital. Data regarding CEP and TZP consumption and resistance were collected on a bimonthly basis during an open-label 2-year (1 year

George Petrikkos; Antonios Markogiannakis; Joseph Papapareskevas; George L. Daikos; George Stefanakos; Nicholas P Zissis; Athina Avlamis



Antibiotic Susceptibilities of Bacteria Isolated within the Oral Flora of Florida Blacktip Sharks: Guidance for Empiric Antibiotic Therapy  

PubMed Central

Sharks possess a variety of pathogenic bacteria in their oral cavity that may potentially be transferred into humans during a bite. The aim of the presented study focused on the identification of the bacteria present in the mouths of live blacktip sharks, Carcharhinus limbatus, and the extent that these bacteria possess multi-drug resistance. Swabs were taken from the oral cavity of nineteen live blacktip sharks, which were subsequently released. The average fork length was 146 cm (±11), suggesting the blacktip sharks were mature adults at least 8 years old. All swabs underwent standard microbiological work-up with identification of organisms and reporting of antibiotic susceptibilities using an automated microbiology system. The oral samples revealed an average of 2.72 (±1.4) bacterial isolates per shark. Gram-negative bacteria, making up 61% of all bacterial isolates, were significantly (p<0.001) more common than gram-positive bacteria (39%). The most common organisms were Vibrio spp. (28%), various coagulase-negative Staphylococcus spp. (16%), and Pasteurella spp. (12%). The overall resistance rate was 12% for all antibiotics tested with nearly 43% of bacteria resistant to at least one antibiotic. Multi-drug resistance was seen in 4% of bacteria. No association between shark gender or fork length with bacterial density or antibiotic resistance was observed. Antibiotics with the highest overall susceptibility rates included fluoroquinolones, 3rd generation cephalosporins and sulfamethoxazole/trimethoprim. Recommended empiric antimicrobial therapy for adult blacktip shark bites should encompass either a fluoroquinolone or combination of a 3rd generation cephalosporin plus doxycycline. PMID:25110948

Unger, Nathan R.; Ritter, Erich; Borrego, Robert; Goodman, Jay; Osiyemi, Olayemi O.



Targeted Inactivation of the mecB Gene, Encoding Cystathionine-?-Lyase, Shows that the Reverse Transsulfuration Pathway Is Required for High-Level Cephalosporin Biosynthesis in Acremonium chrysogenum C10 but Not for Methionine Induction of the Cephalosporin Genes  

PubMed Central

Targeted gene disruption efficiency in Acremonium chrysogenum was increased 10-fold by applying the double-marker enrichment technique to this filamentous fungus. Disruption of the mecB gene by the double-marker technique was achieved in 5% of the transformants screened. Mutants T6 and T24, obtained by gene replacement, showed an inactive mecB gene by Southern blot analysis and no cystathionine-?-lyase activity. These mutants exhibited lower cephalosporin production than that of the control strain, A. chrysogenum C10, in MDFA medium supplemented with methionine. However, there was no difference in cephalosporin production between parental strain A. chrysogenum C10 and the mutants T6 and T24 in Shen's defined fermentation medium (MDFA) without methionine. These results indicate that the supply of cysteine through the transsulfuration pathway is required for high-level cephalosporin biosynthesis but not for low-level production of this antibiotic in methionine-unsupplemented medium. Therefore, cysteine for cephalosporin biosynthesis in A. chrysogenum derives from the autotrophic (SH2) and the reverse transsulfuration pathways. Levels of methionine induction of the cephalosporin biosynthesis gene pcbC were identical in the parental strain and the mecB mutants, indicating that the induction effect is not mediated by cystathionine-?-lyase. PMID:11160109

Liu, Gang; Casqueiro, Javier; Bañuelos, Oscar; Cardoza, Rosa E.; Gutiérrez, Santiago; Martín, Juan F.



Strategic alliance between the infectious diseases specialist and intensive care unit physician for change in antibiotic use.  


There is a general consensus that antimicrobial use in intensive care units (ICU) is greater than that in general wards. By implementing a strategy of systematic infectious disease consultations in agreement with the ICU chief, we have modified the antibiotic prescription habits of the ICU physician. A reduction was observed in the use of selected antibiotics (third-generation cephalosporins, vancomycin, carbapenems and piperacillin-tazobactam), with a significant reduction in the length of hospital stay for ICU patients and lower antibiotic costs without negative impact on patient mortality. Leadership by the infectious diseases consultant in combination with commitment by ICU physicians is a simple and effective method to change antibiotic prescription habits in the ICU. PMID:15828447

Curcio, D; Belloni, R



Ready for a world without antibiotics? The Pensières Antibiotic Resistance Call to Action  

PubMed Central

Resistance to antibiotics has increased dramatically over the past few years and has now reached a level that places future patients in real danger. Microorganisms such as Escherichia coli and Klebsiella pneumoniae, which are commensals and pathogens for humans and animals, have become increasingly resistant to third-generation cephalosporins. Moreover, in certain countries, they are also resistant to carbapenems and therefore susceptible only to tigecycline and colistin. Resistance is primarily attributed to the production of beta-lactamase genes located on mobile genetic elements, which facilitate their transfer between different species. In some rare cases, Gram-negative rods are resistant to virtually all known antibiotics. The causes are numerous, but the role of the overuse of antibiotics in both humans and animals is essential, as well as the transmission of these bacteria in both the hospital and the community, notably via the food chain, contaminated hands, and between animals and humans. In addition, there are very few new antibiotics in the pipeline, particularly for Gram-negative bacilli. The situation is slightly better for Gram-positive cocci as some potent and novel antibiotics have been made available in recent years. A strong and coordinated international programme is urgently needed. To meet this challenge, 70 internationally recognized experts met for a two-day meeting in June 2011 in Annecy (France) and endorsed a global call to action ("The Pensières Antibiotic Resistance Call to Action"). Bundles of measures that must be implemented simultaneously and worldwide are presented in this document. In particular, antibiotics, which represent a treasure for humanity, must be protected and considered as a special class of drugs. PMID:22958833



Magnetic separation of antibiotics by electrochemical magnetic seeding  

NASA Astrophysics Data System (ADS)

Magnetic separation of several classes of antibiotics was investigated using electrochemical magnetic seeding. Electrocoagulation with a sacrificial anode followed by addition of magnetite particles was applied for the magnetic seeding of antibiotics. With electrochemical magnetic seeding using an iron anode, tetracycline antibiotics (oxytetracycline, chlortetracycline, doxycycline and tetracycline) and cephalosporin antibiotic (cefdinir) were rapidly removed from synthetic wastewater by magnetic separation using a neodymium magnet. Iron and aluminium anodes were suitable for magnetic seeding of the antibiotics. The results indicated that the ability of antibiotics to form strong complex with iron and aluminium allowed the higher removal by magnetic separation. This method would be appropriate for rapid treatment of antibiotics in wastewater.

Ihara, I.; Toyoda, K.; Beneragama, N.; Umetsu, K.



[Emerging and important antibiotic resistance in Gram negative bacteria: epidemiology, theory and practice].  


Emerging and clinically-relevant antibiotic resistance mechanisms among Gram-negative rods are the extended-spectrum beta-lactamases (ESBL), carbapenemases, and 16S RNA methylases conferring resistance to aminoglycosides. Those resistance determinants do confer multiresistance to antibiotics. They are found in Enterobacteriaceae (especially community-acquired isolates, Pseudomonas aeruginosa and Acinetobacter baumannii). Detection of ESBL-producing and carbapenemase-producing isolates rely on the use of rapid diagnostic techniques that have to be performed when a reduced susceptibility to 3rd/4th generation cephalosporins or to carbapenems is observed, respectively. Only an early detection of those emerging resistance traits may contribute to limit their nosocomial spread and to optimize the antibiotic stewardship. PMID:24843986

Nordmann, P; Poirel, L



Inactivation of Antibiotics and the Dissemination of Resistance Genes  

Microsoft Academic Search

The emergence of multidrug-resistant bacteria is a phenomenon of concern to the clinician and the pharmaceutical industry, as it is the major cause of failure in the treatment of infectious diseases. The most common mechanism of resistance in pathogenic bacteria to antibiotics of the aminoglycoside, beta-lactam (penicillins and cephalosporins), and chloramphenicol types involves the enzymic inactivation of the antibiotic by

Julian Davies



Antibiotic allergy: Immunochemical and clinical considerations  

Microsoft Academic Search

Antibiotics are among the most widely and heavily prescribed drugs, but despite this, allergic reactions to most groups of\\u000a antibiotics are relatively uncommon—especially when compared with the number and frequency of type 1 hypersensitivity responses\\u000a to the ?-lactams (ie, penicillins, cephalosporins, and, to a lesser extent, carbopenems). Still, there remains a steady flow\\u000a of reports of allergic reactions to some

Brian A. Baldo; Zhenjun Zhao; Nghia H. Pham



Prospective Randomized Study for Antibiotic Prophylaxis in Spine Surgery: Choice of Drug, Dosage, and Timing  

PubMed Central

Study Design Prospective randomized study of antibiotic prophylaxis in elective spine surgery. Purpose The aim of this study was to compare the rate of postoperative surgical site infection for a single dose of two different generations of cephalosporin with different dosage and timing of the antibiotics. Overview of Literature Current recommendation for prophylaxis in elective spine surgery is up to 60 minutes prior to incision. No study has investigated between different generation of cephalosporin for prophylaxis in elective spine surgery with respect to choice, dosage and timing. Methods This study was a prospective randomized study of 90 patients, assessed for the occurrence of surgical site infection (defined by the Centers for Disease Control and Prevention criteria) and other infections for up to 6 months after surgery. Demographic, surgical and further data were collected on subsequent operations, including hardware removal. Results Mean age in our group was 47 years (range, 19-71 years). The male to female ratio was 49:41 and the average timing of administration of antibiotics was 77 minutes (range, 30-120 minutes). The average blood loss was 626 mL (range, 150-3,000 mL) with a mean duration of surgery for 3.2 hours (range, 1.5-6 hours). One case of superficial infection and one case of deep infection met the exclusion criteria. Conclusions Our results support the use of a single preoperative dose of antibiotics in instrumented and non-instrumented elective spine surgery up to one hour prior to incision. There was no difference in terms of occurrence of surgical site infection with respect to dosage, choice and timing of antibiotics. PMID:24066215

Kailash, Kannan Karthick; Vijayraghavan, P.V.



Use of a Heavy Inoculum in the In Vitro Evaluation of the Anti-Staphylococcal Activity of 19 Cephalosporins  

PubMed Central

The in vitro activity of 19 cephalosporins against 105 clinical isolates of Staphylococcus aureus and S. epidermidis was determined by using a heavy inoculum, i.e., 108 to 109 organisms per ml, to maximally challenge the antibiotics. The anti-staphylococcal activities of cephaloridine and 87/312 were consistently decreased by the use of a heavy inoculum when compared with the activity obtained with two less-concentrated inocula. The activity of most of the other compounds was also decreased with the use of a heavy inoculum, but this was observed only with selected isolates. Cephapirin, cephalothin, and cefazaflur were the most active drugs against the methicillin-susceptible isolates. Cephaloridine, cefamandole, cefazaflur, and 87/312 had substantial activity against methicillin-resistant staphylococci even with heavy inocula. With the exception of cefaclor against S. aureus, the orally absorbed cephalosporins were generally one-half to one-sixteenth as active as the parenterally administered cephalosporins. The median minimal inhibitory concentrations of five of the 12 parenteral cephalosporins were lower with the methicillin-susceptible S. aureus than with the methicillin-susceptible S. epidermidis strains. PMID:352261

Laverdiere, Michel; Welter, Diane; Sabath, L. D.



Validation of a microbiological method: the STAR protocol, a five-plate test, for the screening of antibiotic residues in milk  

Microsoft Academic Search

The results of an in-house laboratory validation of a microbiological method for the screening of antibiotic residues in milk are presented. The sensitivity of this five-plate test, called Screening Test for Antibiotic Residues (STAR), was established by the analysis of milk samples spiked with 66 antibiotics at eight different concentrations. Ten different groups of antibiotics were studied: macrolides, aminoglycosides, cephalosporins,

V. Gaudin; P. Maris; R. Fuselier; J.-L. Ribouchon; N. Cadieu; A. Rault



Strategic manipulation of an industrial biocatalyst--evolution of a cephalosporin C acylase.  


Semi-synthetic cephalosporins are synthesized from the 7-amino cephalosporanic acid (7-ACA) nucleus produced from the antibiotic cephalosporin C (CephC). In recent years, a single-step enzymatic process in which CephC is directly converted into 7-ACA by a cephalosporin C acylase (CA) has attracted industrial interest because of the prospects of simplifying the process and reducing costs. CAs are members of the glutaryl acylase family that specifically use CephC as their substrate; however, known natural glutaryl acylases show very low activity on the antibiotic. We previously enhanced the catalytic efficiency on CephC of a glutaryl acylase from Pseudomonas N176 (named VAC) by a protein engineering approach, and solved the structures of the VAC, thus providing insight into the substrate binding and catalytic activity of CAs. However, the properties of such enzymes are not sufficient to encourage 7-ACA manufacturers to shift to single-step enzymatic conversion of CephC. Here, we combine structural knowledge, semi-rational design, computational approaches and evolution analysis to isolate VAC variants with altered substrate specificity (i.e. with a > 11,000-fold increase in specificity constant for CephC versus glutaryl-7-amino cephalosporanic acid, compared to wild-type) and with the highest kinetic efficiency so far obtained for a CA. Indeed, the H57?S-H70?S-L154?Y VAC variant shows the highest conversion of CephC into 7-ACA under conditions resembling those used at industrial level because of its high kinetic efficiency and the absence of substrate or product inhibition effects, and may be suitable for industrial application of the mono-step process for CephC conversion. PMID:24684708

Conti, Gianluca; Pollegioni, Loredano; Molla, Gianluca; Rosini, Elena



“Affect of anaerobiosis on the antibiotic susceptibility of H. influenzae”  

PubMed Central

Background Haemophilus influenzae is a human-restricted facultative anaerobe which resides mostly in the oropharynx. The majority of isolates recovered from the throat are unencapsulated commensals (NTHi), but depending on host susceptibility they cause bronchitis, otitis media and on occasion bacteremia and meningitis. Because of the variable oxygen availability in the various niche permitting bacterium replication, the organism must thrive in well oxygenated surfaces, such as pharyngeal epithelium to anoxic environments like the bottom of a Biofilm and in airway mucus. Other reports indicate that H. influenzae use aerobic respiration, anaerobic respiration and fermentation to generate ATP. To gain insight in to the activity of several classes of antibiotics against five well-characterized unencapsulated H. influenzae in room air, in 5% CO2 and under strict anaerobiosis. We also tested for the role of oxidative killing by all cidal antibiotics. Results In comparison to room air, testing in 5% CO2 had minimal effects on the susceptibility to aminoglycosides, cephalosporins, tetracycline and chloramphenicol: the MIC of rifampin and ciprofloxacin increased eight fold with certain strains in 5% CO2. All antibiotics, except trimethoprim were cidal under both growth conditions. Aminoglycosides remained bactericidal in a strict anaerobic environment, while a reliable MBC was obtained with trimethoprim only under anaerobic conditions. Kinetic analysis of the cidal action of spectinomycin and tetracycline indicated slower killing anaerobically. An oxidative mechanism for aerobic killing could not be demonstrated. Conclusions We conclude that ?-lactams, cephalosporins, macrolides, tetracycline’s, aminoglycosides, chloramphenicol, rifampin and ciprofloxacin are bactericidal against five well-characterizes H. influenzae in an aerobic and anaerobic environment. The activity of trimethoprim was increased in anaerobic conditions. PMID:23803418



Surveillance of Antibiotic Consumption Using the “Focus of Infection” Approach in 2 Hospitals in Ujjain, India  

PubMed Central

Antibiotic surveillance initiatives are limited in resource-constrained settings. In the present study, a quantitative comparison of antibiotic use rates for suspected infections in 2 hospitals in India was performed using the “focus of infection” approach to identify targets for quality improvement in antibiotic prescription patterns in hospitalized patients. Methods This observational study was carried out in one teaching and one nonteaching hospital. All the patients with suspected bacterial etiology were included. Data on the prescribed antibiotics and the focus of infection were prospectively collected using a structured questionnaire. Each diagnosis was further reviewed and confirmed by an independent consultant. The prescribed antibiotics were coded according to the World Health Organization Anatomic Therapeutic Classification (ATC) index with the defined daily dose (DDD) methodology. Focus-specific DDDs were calculated per hundred patient days (DDD/HPD). Results A total of 6026 patients were included from 72 participating physicians out of available 75 physicians. Overall antibiotic prescribing was higher by 5 percentage points in the teaching hospital (95%) than in the nonteaching hospital (90%). Quinolones (ciprofloxacin constituting 86% of DDD/HPD) were the highest prescribed class in the teaching hospital, and third-generation cephalosporins (with ceftriaxone and ceftriaxone/sulbactam constituting 40% and 28% of the DDD/HPD, respectively), in the nonteaching hospital. The targets identified for improvement were the following: longer than recommended duration of prophylaxis and lack of distinction between prophylaxis and therapy among surgical patients; irrational antibiotic prescribing in gastroenteritis; overuse of quinolones and lack of use of penicillin in pneumonia; overuse of quinolones and lack of use of doxycycline and macrolides in genital infections; and overreliance on antibiotics for treating skin and soft tissue infections. Conclusions Providing a quantitative comparison of antibiotic use rates for suspected infections, using the “focus of infection” approach along with the ATC/DDD methodology, appears appropriate for identifying targets for quality improvement with regards to antibiotic prescribing. PMID:22715402

Pathak, Ashish; Mahadik, Kalpana; Dhaneria, Surya Prakesh; Sharma, Ashish; Eriksson, Bo; Lundborg, Cecilia Stålsby



The eradication of bacterial persisters with antibiotic-generated hydroxyl radical  

E-print Network

During Mycobacterium tuberculosis infection, a population of bacteria likely becomes refractory to antibiotic killing in the absence of genotypic resistance, making treatment challenging. We describe an in vitro model ...

Haseley, Nathan Scott


Influence of medium composition on the cephalosporin C production with a highly productive strain Cephalosporium acremonium.  


Cephalosporin production by a highly productive Cephalosporium acremonium strain was carried out and optimized by fed-batch operation in a 40 l stirred tank reactor using a complex medium containing 30-120 g l-1 peanut flour. The concentrations of cephalosporin C (CPC) and its precursors: penicillin N (PEN N), deacetoxy cephalosporin C (DAOC), and deacetyl cephalosporin C (DAC) were monitored with an on-line HPLC. The concentrations of amino acids valine (VAL), cysteine (CYS), alpha-amino adipic acid (alpha-AAA), the dipeptide alpha-amino-adipyl-cysteine (AC), and the tripeptide alpha-amino-adipyl-cysteinyl-valine (ACV), were determined off-line by HPLC. The RNA content and dry weight of the sediment as well as the oxygen transfer rate (OTR) and the CO2 production rate (CPR) were used to calculate the cell mass concentration (X). The influences of peanut flour (PF) and the on-line monitored and controlled medium components: glucose (GLU), phosphate, methionine (MET) as well as the dissolved oxygen (DOC) on the cell growth, the product formation, and the pathway of cephalosporin C biosynthesis were investigated and evaluated. When the glucose fed-batch cycle was optimized and oxygen transfer limitation was avoided (DOC greater than 20% of the saturation value), high process performance (103.5 g l-1 X, 11.84 g l-1 CPC, a maximum CPC productivity of 118 mg l-1 h-1, and the whole concentration of the beta-lactam antibiotics CPC, DAC, DAOC, PEN N 17.34 g l-1) was achieved by using 100 g l-1 PF in the medium with the optimum concentration of phosphate (260-270 mg l-1) and a low glucose concentration (less than 0.5 g l-1). The cultivations with different medium concentrations demonstrated that the product formation was directly proportional to the cell mass concentration. On the average, the cell mass-based yield coefficient of CPC: YCPC/X amounted to 0.115 g CPC per g cell mass. PMID:1368249

Zhou, W; Holzhauer-Rieger, K; Dors, M; Schügerl, K



Antimicrobial sensitivity patterns of cerebrospinal fluid (CSF) isolates in Namibia: implications for empirical antibiotic treatment of meningitis  

PubMed Central

Objective Bacterial meningitis is a medical emergency associated with high mortality rates. Cerebrospinal fluid (CSF) culture is the “gold standard” for diagnosis of meningitis and it is important to establish the susceptibility of the causative microorganism to rationalize treatment. The Namibia Standard Treatment Guidelines (STGs) recommends initiation of empirical antibiotic treatment in patients with signs and symptoms of meningitis after taking a CSF sample for culture and sensitivity. The objective of this study was to assess the antimicrobial sensitivity patterns of microorganisms isolated from CSF to antibiotics commonly used in the empirical treatment of suspected bacterial meningitis in Namibia. Methods This was a cross-sectional descriptive study of routinely collected antibiotic susceptibility data from the Namibia Institute of Pathology (NIP) database. Results of CSF culture and sensitivity from January 1, 2009 to May 31, 2012, from 33 state hospitals throughout Namibia were analysed. Results The most common pathogens isolated were Streptococcus species, Neisseria meningitidis, Haemophilus influenzae, Staphylococcus, and Escherichia coli. The common isolates from CSF showed high resistance (34.3% –73.5%) to penicillin. Over one third (34.3%) of Streptococcus were resistance to penicillin which was higher than 24.8% resistance in the United States. Meningococci were susceptible to several antimicrobial agents including penicillin. The sensitivity to cephalosporins remained high for Streptococcus, Neisseria, E. coli and Haemophilus. The highest percentage of resistance to cephalosporins was seen among ESBL K. pneumoniae (n?=?7, 71%–100%), other Klebsiella species (n?=?7, 28%–80%), and Staphylococcus (n?=?36, 25%–40%). Conclusions The common organisms isolated from CSF were Streptococcus Pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Staphylococcus, and E. coli. All common organisms isolated from CSF showed high sensitivity to cephalosporins used in the empirical treatment of meningitis. The resistance of the common isolates to penicillin is high. Most ESBL K. pneumoniae were isolated from CSF samples drawn from neonates and were found to be resistant to the antibiotics recommended in the Namibia STGs. Based on the above findings, it is recommended to use a combination of aminoglycoside and third-generation cephalosporin to treat non–ESBL Klebsiella isolates. Carbapenems (e.g., meropenem) and piperacillin/tazobactam should be considered for treating severely ill patients with suspected ESBL Klebsiella infection. Namibia should have a national antimicrobial resistance surveillance system for early detection of antibiotics that may no longer be effective in treating meningitis and other life-threatening infections due to resistance. PMID:24764539



In vitro activity of beta-lactam antibiotics to community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA).  


Community-associated (CA) MRSA often display low MIC values against oxacillin. The in vitro activity of various beta-lactam antibiotics against heterogeneous CA-MRSA (n?=?98) isolated in a low endemic area was determined by Etest, and Mueller-Hinton agar (MUHAP) was compared with Mueller-Hinton agar supplemented with 2% NaCl (MUHSP). In general, the CA-MRSA isolates showed higher MIC values for the various beta-lactam antibiotics on MUHSP compared with MUHAP. MIC values for oxacillin ranged from 1 to >256 mg/L on MUHSP. Cephalothin, representing the first generation of cephalosporins, showed MICs from 0.75 to 96 mg/L and the MIC(50) and MIC(90) for cefuroxime, cefotaxime and cefepime, representing the second, third and fourth generations, respectively, were rather high. However, the MIC(50) and MIC(90) for ceftobiprole (fifth generation) were 1.5 and 2 mg/L, respectively, on MUHSP. The MIC(50) and MIC(90) for imipenem were 0.75 and 2 mg/L, respectively, on MUHSP. Only 3/98 (3%) CA-MRSA isolates showed a MIC >4 mg/L. Consequently, low MIC values for imipenem, lower than those of the newly developed fifth generation cephalosporins, were found among CA-MRSA. These findings may be considered for further studies including clinical trials in order to evaluate carbapenems as a potential treatment option for infections caused by CA-MRSA. PMID:21932140

Germel, C; Haag, A; Söderquist, B



The use of cephalosporins for gonorrhea: The impending problem of resistance  

PubMed Central

Gonorrhea remains an important clinical and public health problem throughout the world. Gonococcal infections have historically been diagnosed by Gram stain and culture, but are increasingly diagnosed through nucleic acid tests thereby eliminating the opportunity for antimicrobial susceptibility testing. Gonococcal infections are typically treated with single-dose therapy with an agent found to cure >95% of cases. Unfortunately, the gonococcus has repeatedly developed resistance to antimicrobials including sulfonamides, penicillin, tetracyclines, and fluoroquinolones. This has left third-generation cephalosporins as the lone class of antimicrobials currently recommended as first line therapy for gonorrhea in some regions. However, resistance to oral third-generation cephalosporins has emerged and spread in Asia, Australia and elsewhere. The mechanism of this resistance seems to be associated with a mosaic penicillin binding protein (penA) in addition to other chromosomal mutations previously found to confer resistance to beta-lactam antimicrobials (ponA, mtrR, penB, pilQ). Few good options exist or are in development for treating cephalosporin resistant isolates as most have had multidrug resistance. Preventing the spread of resistant isolates will depend on ambitious antimicrobial management programs, strengthening and expanding surveillance networks, and through effective sexually transmitted disease control and prevention. PMID:19284360

Barry, Pennan M.; Klausner, Jeffrey D.



New Generation of Plasmid Backbones Devoid of Antibiotic Resistance Marker for Gene Therapy Trials  

Microsoft Academic Search

Since it has been established that the injection of plasmid DNA can lead to an efficient expression of a specific protein in vivo, nonviral gene therapy approaches have been considerably improved, allowing clinical trials. However, the use of antibiotic resistance genes as selection markers for plasmid production raises safety concerns which are often pointed out by the regulatory authorities. Indeed,

Gaëlle Vandermeulen; Corinne Marie; Daniel Scherman; Véronique Préat



Antibiotic Resistance  


... For Consumers Consumer Information by Audience For Women Antibiotic Resistance Print and Share (PDF 108KB) En Español Antibiotic ... these products really help. To Learn More about Antibiotic Resistance Get Smart About Antibiotics (Video) Fact Sheets and ...


Targeting metallo-carbapenemases via modulation of electronic properties of cephalosporins.  


The global proliferation of metallo-carbapenemase-producing Enterobacteriaceae has created an unmet need for inhibitors of these enzymes. The rational design of metallo-carbapenemase inhibitors requires detailed knowledge of their catalytic mechanisms. Nine cephalosporins, structurally identical except for the systematic substitution of electron-donating and withdrawing groups in the para position of the styrylbenzene ring, were synthesized and utilized to probe the catalytic mechanism of New Delhi metallo-?-lactamase (NDM-1). Under steady-state conditions, K(m) values were all in the micromolar range (1.5-8.1 ?M), whereas k(cat) values varied widely (17-220 s(-1)). There were large solvent deuterium isotope effects for all substrates under saturating conditions, suggesting a proton transfer is involved in the rate-limiting step. Pre-steady-state UV-visible scans demonstrated the formation of short-lived intermediates for all compounds. Hammett plots yielded reaction constants (?) of -0.34 ± 0.02 and -1.15 ± 0.08 for intermediate formation and breakdown, respectively. Temperature-dependence experiments yielded ?G(‡) values that were consistent with the Hammett results. These results establish the commonality of the formation of an azanide intermediate in the NDM-1-catalysed hydrolysis of a range cephalosporins with differing electronic properties. This intermediate is a promising target for judiciously designed ?-lactam antibiotics that are poor NDM-1 substrates and inhibitors with enhanced active-site residence times. PMID:25220027

Yang, Hao; Young, Heather; Yu, Sophia; Sutton, Larry; Crowder, Michael W



Enhancing the Antibiotic Antibacterial Effect by Sub Lethal Tellurite Concentrations: Tellurite and Cefotaxime Act Synergistically in Escherichia coli  

PubMed Central

The emergence of antibiotic-resistant pathogenic bacteria during the last decades has become a public health concern worldwide. Aiming to explore new alternatives to treat antibiotic-resistant bacteria and given that the tellurium oxyanion tellurite is highly toxic for most microorganisms, we evaluated the ability of sub lethal tellurite concentrations to strengthen the effect of several antibiotics. Tellurite, at nM or µM concentrations, increased importantly the toxicity of defined antibacterials. This was observed with both Gram negative and Gram positive bacteria, irrespective of the antibiotic or tellurite tolerance of the particular microorganism. The tellurite-mediated antibiotic-potentiating effect occurs in laboratory and clinical, uropathogenic Escherichia coli, especially with antibiotics disturbing the cell wall (ampicillin, cefotaxime) or protein synthesis (tetracycline, chloramphenicol, gentamicin). In particular, the effect of tellurite on the activity of the clinically-relevant, third-generation cephalosporin (cefotaxime), was evaluated. Cell viability assays showed that tellurite and cefotaxime act synergistically against E. coli. In conclusion, using tellurite like an adjuvant could be of great help to cope with several multi-resistant pathogens. PMID:22536386

Molina-Quiroz, Roberto C.; Muñoz-Villagrán, Claudia M.; de la Torre, Erick; Tantaleán, Juan C.; Vásquez, Claudio C.; Pérez-Donoso, José M.



QSAR Study of -Lactam Antibiotic Efflux by the Bacterial Multidrug Resistance Pump AcrB Mrcia Miguel Castro Ferreira (PQ) and Rudolf Kiralj (PQ)  

E-print Network

QSAR Study of -Lactam Antibiotic Efflux by the Bacterial Multidrug Resistance Pump AcrB Márcia antibiotics (penicillins and cephalosporins) as substrates of multidrug resistance efflux membrane pump Acr M. M. C., Kiralj R., "QSAR study of -lactam antibiotic efflux by the bacterial multidrug resistance

Ferreira, Márcia M. C.


Trends in antibiotic use among outpatients in New Delhi, India  

PubMed Central

Background The overall volume of antibiotic consumption in the community is one of the foremost causes of antimicrobial resistance. There is much ad-hoc information about the inappropriate consumption of antibiotics, over-the-counter availability, and inadequate dosage but there is very little actual evidence of community practices. Methods This study surveyed antibiotic use in the community (December 2007-November 2008) using the established methodology of patient exit interviews at three types of facilities: 20 private retail pharmacies, 10 public sector facilities, and 20 private clinics to obtain a complete picture of community antibiotic use over a year. The Anatomical Therapeutic Chemical (ATC) classification and the Defined Daily Dose (DDD) measurement units were assigned to the data. Antibiotic use was measured as DDD/1000 patients visiting the facility and also as percent of patients receiving an antibiotic. Results During the data collection period, 17995, 9205, and 5922 patients visiting private retail pharmacies, public facilities and private clinics, respectively, were included in our study. 39% of the patients attending private retail pharmacies and public facilities and 43% of patients visiting private clinics were prescribed at least one antibiotic. Consumption patterns of antibiotics were similar at private retail pharmacies and private clinics where fluoroquinolones, cephalosporins, and extended spectrum penicillins were the three most commonly prescribed groups of antibiotics. At public facilities, there was a more even use of all the major antibiotic groups including penicillins, fluoroquinolones, macrolides, cephalosporins, tetracyclines, and cotrimoxazole. Newer members from each class of antibiotics were prescribed. Not much seasonal variation was seen although slightly higher consumption of some antibiotics in winter and slightly higher consumption of fluoroquinolones during the rainy season were observed. Conclusions A very high consumption of antibiotics was observed in both public and private sector outpatients. There was a high use of broad spectrum and newer antibiotics in the community. Suitable and sustainable interventions should be implemented to promote rational use of antibiotics that will help in decreasing the menace of antibiotic resistance. PMID:21507212



De novo generation of histamine in sputum and the effect of antibiotics.  


We have performed experiments to test the hypothesis that bacteria may contribute to the presence of histamine in sputum. Sputum samples obtained from 7 patients with exacerbations of chronic bronchitis and 7 patients with cystic fibrosis were incubated at 37 degrees C for 72 hours. Serial sputum histamine estimations, performed by a recently-developed HPLC technique, showed large, progressive increases in both groups of samples. Both the pre-heating of samples at 100 degrees C prior to incubation and the addition of antibiotics to the incubates substantially reduced these increases. These findings strongly suggest that bacteria may contribute to sputum histamine in infective lung disease. PMID:3706048

Sheinman, B D; Devalia, J L; Crook, S J; Davies, R J



Expedient antibiotics production: Final report  

SciTech Connect

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. 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.

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



A broadly applicable approach to prepare monoclonal anti-cephalosporin antibodies for immunochemical residue determination in milk.  


A simple, efficient and rapid method for the synthesis of cephalosporin-protein conjugates was established. These conjugates were used as immunogens to produce monoclonal antibodies (mAbs) and as solid phase antigens in competitive indirect enzyme immunoassays (EIAs). With this generic approach, a novel set of monoclonal antibodies for cephalosporins was prepared, including ceftiofur and cephalexin as well as, reported here for the first time, cefoperazone, cefquinome and cephapirin. All 5 EIAs were highly sensitive, with standard curve IC(50) values of 0.7 (ceftiofur), 1.1 (cefquinome), 5.2 (cephalexin), 13.8 (cefoperazone) and 40.3 ng mL(-1) (cephapirin). Detection limits (IC(30)) ranged from 0.3 (ceftiofur mAb 1D7) to 17.2 ng mL(-1) (cephapirin mAb 2F10). Specificity studies revealed that cephalosporin-antibody binding was strongly determined by the side chain residues of the cephem nucleus. Therefore all mAbs, to some extent, recognized other beta-lactam antibiotics with similar side chain residues. Within the group of cephalosporins approved for use in veterinary medicine, however, the final EIAs were highly selective for their respective antigen, except for the ceftiofur EIA which showed cross-reactions with cefquinome. The applicability of the five assays for drug residue testing in milk was demonstrated. In each EIA the target drug could be determined in milk with high accuracy and precision at concentrations far below the European Union maximum residue limits. PMID:22362272

Bremus, Anna; Dietrich, Richard; Dettmar, Lars; Usleber, Ewald; Märtlbauer, Erwin



Antibiotic Safety  


... not effectively treated with an antibiotic • Viral gastroenteritis Bacterial infections should be treated with antibiotics. Some examples of bacterial infections include: • Ear infections—Antibiotics are used for most, ...


In vitro activity of HR 810, a new cephalosporin.  

PubMed Central

The in vitro susceptibility of 409 clinical isolates to HR 810, a new cephalosporin, was evaluated and compared with their susceptibility to aztreonam, cefazolin, ceftazidime, imipenem, moxalactam, piperacillin, and gentamicin. On a weight basis, the activity of HR 810 against gram-negative bacilli was equivalent or superior to that of the other beta-lactam agents except imipenem. PMID:6593000

Bertram, M A; Bruckner, D A; Young, L S



RESEARCH Cephalosporin-resistant Pneumococci and Sickle Cell Disease  

E-print Network

Sickle cell anemia patients have 600 times the risk for invasive pneumococcal disease than their healthy peers. High-level cephalosporin resistance was described in the 1990s in healthy children from Tennessee, but its prevalence in sickle cell disease patients is unknown. Pneumococcal isolates

Martha L. Miller; Caroline A. Obert; Geli Gao; Najat C. Daw; Patricia Flynn; Elaine Tuomanen


A questionnaire-based survey to ascertain the views of clinicians regarding rational use of antibiotics in teaching hospitals of Kolkata  

PubMed Central

Objectives: The objective was to assess the views of clinicians in teaching hospitals of Kolkata regarding the use of antibiotics in their own hospitals, focusing on perceived misuse, reasons behind such misuse and feasible remedial measures. Materials and Methods: A total of 200 clinicians from core clinical disciplines was approached in six teaching hospitals of Kolkata through purposive sampling. A structured, validated questionnaire adopted from published studies and modified to suit the responding population was completed by consenting respondents through face-to-face interaction with a single interviewer. Respondents were free to leave out questions they did not wish to answer. Results: Among 130 participating clinicians (65% of approached), all felt that antibiotic misuse occurs in various hospital settings; 72 (55.4% of the respondents) felt it was a frequent occurrence and needed major rectification. Cough and cold (78.5%), fever (65.4%), and diarrhea (62.3%) were perceived to be the commonest conditions of antibiotic misuse. About half (50.76%) felt that oral preparations were more misused compared to injectable or topical ones. Among oral antibiotics, co-amoxiclav (66.9%) and cefpodoxime (63.07%) whereas among parenteral ones, ceftriaxone and other third generation cephalosporins (74.6%) followed by piperacillin-tazobactam (61.5%) were selected as the most misused ones. Deficient training in rational use of medicines (70.7%) and absence of institutional antibiotic policy (67.7%) were listed as the two most important predisposing factors. Training of medical students and interns in rational antibiotic use (78.5%), implementation of antibiotic policy (76.9%), improvement in microbiology support (70.7%), and regular surveillance on this issue (64.6%) were cited as the principal remedial measures. Conclusions: Clinicians acknowledge that the misuse of antibiotics is an important problem in their hospitals. A system of clinical audit of antibiotic usage, improved microbiology support and implementation of antibiotic policy can help to promote rational use of antimicrobial agents.

Chatterjee, Dattatreyo; Sen, Sukanta; Begum, Sabnam Ara; Adhikari, Anjan; Hazra, Avijit; Das, Anup Kumar



Improving the quality of antibiotic prescribing in the NHS by developing a new Antimicrobial Stewardship Programme: Start Smart--Then Focus.  


There has been dramatic change in antibiotic use in English hospitals. Data from 2004 and 2009 show that the focus on reducing fluoroquinolone and second- and third-generation cephalosporin use seems to have been heeded in NHS secondary care, and has been associated with a substantial decline in hospital Clostridium difficile rates. However, there has been a substantial increase in use of co-amoxiclav, carbapenems and piperacillin/tazobactam. In primary care, antibiotic prescribing fell markedly from 1995 to 2000, but has since risen steadily to levels seen in the early 1990s. There remains a 2-fold variation in antimicrobial prescribing among English General Practices. In 2010, the NHS Atlas of Variation documented a 3-fold variation in the prescription of quinolones and an 18-fold variation in cephalosporins by Primary Care Trusts across England. There is a clear need to improve antimicrobial prescribing. This paper describes the development of new antimicrobial stewardship programmes for primary care and hospitals by the Department of Health's Advisory Committee on Antimicrobial Resistance and Healthcare Associated Infection: Antimicrobial Stewardship in Primary Care Initiative. The secondary care programme promotes the rapid prescription of the right antibiotic at the right dose at the right time, followed by active review for all patients still on antibiotics 48 h after admission. The five options available are to stop, switch to oral, continue and review again, change (if possible to a narrower spectrum) or move to outpatient parenteral antibiotic therapy. A range of audit and outcome tools has been developed, but to maintain optimal antimicrobial usage, monitoring of local and national quantitative and qualitative data on prescribing and consumption is required, linked to the development of key performance indicators in primary, secondary and tertiary care. PMID:22855879

Ashiru-Oredope, Diane; Sharland, Mike; Charani, Esmita; McNulty, Cliodna; Cooke, Jonathan



Dissemination of cephalosporin-resistant Serratia marcescens strains producing a plasmidic SHV type beta-lactamase in Greek hospitals  

Microsoft Academic Search

The resistance to third generation cephalosporins in nineSerratia marcescens strains isolated in Greek hospitals was studied. Eight of the strains transferred resistance toEscherichia coli by means of large plasmids that encoded for an extended-spectrum ?-lactamase. Hybridization, isoelectric focusing and hydrolysis studies showed that the enzyme resembled the SHV-5 ?-lactamase. In the eight isolates that possessed the SHV type enzyme, cephalosporinase

D. Gianneli; E. Tzelepi; L. S. Tzouvelekis; A. F. Mentis; C. Nikolopoulou



Stenotrophomonas maltophilia endogenous endophthalmitis: clinical presentation, antibiotic susceptibility, and outcomes  

PubMed Central

Objective To describe clinical presentation, antibiotic susceptibility, and outcomes in patients with Stenotrophomonas maltophilia endogenous endophthalmitis. Design Retrospective case series. Participants Four eyes of four patients with S. maltophilia endogenous endophthalmitis. Methods Retrospective chart review of culture-positive S. maltophilia endogenous endophthalmitis treated at L V Prasad Eye Institute, Hyderabad, India, between January 2007 and December 2012, was done. Collected information included demographic, clinical, and microbiology data. Results These four patients with S. maltophilia endogenous endophthalmitis cases accounted for 0.47% (4/836) of total bacterial endophthalmitis cases treated in this period. All patients were from a rural setting and younger than 40 years. Two of the four patients had a history of immune compromise or hospitalization. The visual acuity at presentation was less than 20/320 in all patients. Common presenting features were severe anterior and posterior segment inflammation and hypopyon. All patients underwent vitrectomy with injection of intravitreal antibiotics and dexamethasone. Direct microscopy of the vitreous sample was positive in all cases. All isolates were sensitive to fluoroquinolones and chloramphenicol; sensitivity to aminoglycosides and third-generation cephalosporins was highly variable. The final visual acuity was 20/80 or more in three patients. The time to presentation did not seem to influence the visual or anatomical outcome. Conclusion S. maltophilia is a rare cause of endogenous endophthalmitis and usually occurs in young and apparently healthy individuals. Clinical presentation is moderate to severe, and recovery is variable. Fourth-generation fluoroquinolones and chloramphenicol were the most sensitive antibiotics against S. maltophilia in this series of patients. PMID:25170244

Chhablani, Jay; Sudhalkar, Aditya; Jindal, Animesh; Das, Taraprasad; Motukupally, Swapna R; Sharma, Savitri; Pathengay, Avinash; Flynn, Harry W



Antibiotic rotation strategies to reduce antimicrobial resistance in Gram-negative bacteria in European intensive care units: study protocol for a cluster-randomized crossover controlled trial  

PubMed Central

Background Intensive care units (ICU) are epicenters for the emergence of antibiotic-resistant Gram-negative bacteria (ARGNB) because of high rates of antibiotic usage, rapid patient turnover, immunological susceptibility of acutely ill patients, and frequent contact between healthcare workers and patients, facilitating cross-transmission. Antibiotic stewardship programs are considered important to reduce antibiotic resistance, but the effectiveness of strategies such as, for instance, antibiotic rotation, have not been determined rigorously. Interpretation of available studies on antibiotic rotation is hampered by heterogeneity in implemented strategies and suboptimal study designs. In this cluster-randomized, crossover trial the effects of two antibiotic rotation strategies, antibiotic mixing and cycling, on the prevalence of ARGNB in ICUs are determined. Antibiotic mixing aims to create maximum antibiotic heterogeneity, and cycling aims to create maximum antibiotic homogeneity during consecutive periods. Methods/Design This is an open cluster-randomized crossover study of mixing and cycling of antibiotics in eight ICUs in five European countries. During cycling (9 months) third- or fourth-generation cephalosporins, piperacillin-tazobactam and carbapenems will be rotated during consecutive 6-week periods as the primary empiric treatment in patients suspected of infection caused by Gram-negative bacteria. During mixing (9 months), the same antibiotics will be rotated for each consecutive antibiotic course. Both intervention periods will be preceded by a baseline period of 4 months. ICUs will be randomized to consecutively implement either the mixing and then cycling strategy, or vice versa. The primary outcome is the ICU prevalence of ARGNB, determined through monthly point-prevalence screening of oropharynx and perineum. Secondary outcomes are rates of acquisition of ARGNB, bacteremia and appropriateness of therapy, length of stay in the ICU and ICU mortality. Results will be adjusted for intracluster correlation, and patient- and ICU-level variables of case-mix and infection-prevention measures using advanced regression modeling. Discussion This trial will determine the effects of antibiotic mixing and cycling on the unit-wide prevalence of ARGNB in ICUs. Trial registration NCT01293071 December 2010. PMID:25011604



Hernia, Mesh, and Topical Antibiotics, Especially Gentamycin: Seeking the Evidence for the Perfect Outcome…  

PubMed Central

Inguinal hernia repair is a clean surgical procedure and surgical site infection (SSI) rate is generally below 2%. Antibiotic prophylaxis is not routinely recommended, but it may be a good choice for institutions with high rates of wound infection (>5%). Typical prophylaxis is the intravenous application of first or second-generation cephalosporins before the skin incision. However, SSI rate remains more than 2% in many centers in spite of intravenous antibiotic prophylaxis. Even a 1% SSI rate may be unacceptable for the surgeons who specifically deal with hernia surgery. A hernia center targets to be a center of excellence not only in respect of recurrence rate but also for other postoperative outcomes, therefore a further measure is required for an excellent result regarding infection control. Topical gentamycin application in combination with preoperative single-dose intravenous antibiotic may be a useful to obtain this perfect outcome. Data about this subject are not complete and high-grade evidence has not been cumulated yet. Prospective randomized controlled trials can make our knowledge more solid about this subject and help the surgeons who seek perfect outcome regarding infection control in inguinal hernia surgery. PMID:25699259

Kulacoglu, Hakan



Cephamycins, a New Family of ?-Lactam Antibiotics I. Production by Actinomycetes, Including Streptomyces lactamdurans sp. n1  

PubMed Central

A number of actinomycetes isolated from soil were found to produce one or more members of a new family of antibiotics, the cephamycins, which are structurally related to cephalosporin C. The cephamycins were produced in submerged fermentation in a wide variety of media by one or more of eight different species of Streptomyces, including a newly described species, S. lactamdurans. These antibiotics exhibit antibacterial activity against a broad spectrum of bacteria which includes many that are resistant to the cephalosporins and penicillins. PMID:4790552

Stapley, E. O.; Jackson, M.; Hernandez, S.; Zimmerman, S. B.; Currie, S. A.; Mochales, S.; Mata, J. M.; Woodruff, H. B.; Hendlin, D.



Cybernetic modeling of the cephalosporin C fermentation process by Cephalosporium acremonium.  


A cybernetic mathematical model has been developed to describe the production of cephalosporin C. In developing the model, diauxic behavior of substrate consumption, morphological differentiation of cells, and catabolite repression of cephalosporin C production by the preferred substrate, glucose, were considered. The proposed model was tested on the experimental data from the literature and could adequately describe the morphological differentiation of cells, the sequential utilization of carbon sources and the production of cephalosporin C. It could be a useful tool to optimize the production of cephalosporin C by Cephalosporium acremonium in batch, fed-batch or continuous operations. PMID:12882154

Kim, Byung Min; Kim, Seung Wook; Yang, Dae Ryook



Stability and Blood Level Determinations of Cefaclor, a New Oral Cephalosporin Antibiotic  

PubMed Central

Cefaclor solutions in pH 2.5 and 4.5 buffers contained at least 90% of their initial activity after 72 h at 4°C. Samples in pH 6.0, 7.0, and 8.0 buffers contained 70, 46, and 34%, respectively, of their initial activity after 72 h at 4°C. After 72 h at 25°C, samples prepared with pH 2.5, 4.5, 6.0, 7.0, and 8.0 buffers contained 95, 69, 16, 5, and 3%, respectively, of their initial activity. After 72 h at 37°C, cefaclor solutions in pH 2.5 buffer contained 80% of the initial activity, whereas samples prepared in pH 4.5, 6.0, 7.0, and 8.0 buffers contained less than 20%. Laboratory-prepared plasma and serum samples showed an 8% loss in activity when incubated for 6 h at 4°C, a 51% loss when incubated for 6 h at 25°C, and a 48% loss when incubated for 2 h at 37°C. Clinical samples demonstrated a similar stability pattern. Degradation rates for cefaclor in commercially prepared serum increased from 4- to 10-fold in comparison to rates obtained when samples were made in human serum freshly prepared in our laboratory. Consequently, serum standards should be made in freshly prepared human serum. PMID:24410

Foglesong, M. A.; Lamb, J. W.; Dietz, J. V.



Role of Ceftiofur in Selection and Dissemination of blaCMY-2-Mediated Cephalosporin Resistance in Salmonella enterica and Commensal Escherichia coli Isolates from Cattle?  

PubMed Central

Third-generation cephalosporin resistance of Salmonella and commensal Escherichia coli isolates from cattle in the United States is predominantly conferred by the cephamycinase CMY-2, which inactivates ?-lactam antimicrobial drugs used to treat a wide variety of infections, including pediatric salmonellosis. The emergence and dissemination of blaCMY-2--bearing plasmids followed and may in part be the result of selection pressure imposed by the widespread utilization of ceftiofur, a third-generation veterinary cephalosporin. This study assessed the potential effects of ceftiofur on blaCMY-2 transfer and dissemination by (i) an in vivo experimental study in which calves were inoculated with competent blaCMY-2-bearing plasmid donors and susceptible recipients and then subjected to ceftiofur selection and (ii) an observational study to determine whether ceftiofur use in dairy herds is associated with the occurrence and frequency of cephalosporin resistance in Salmonella and commensal E. coli. The first study revealed blaCMY-2 plasmid transfer in both ceftiofur-treated and untreated calves but detected no enhancement of plasmid transfer associated with ceftiofur treatment. The second study detected no association (P = 0.22) between ceftiofur use and either the occurrence of ceftiofur-resistant salmonellosis or the frequency of cephalosporin resistance in commensal E. coli. However, herds with a history of salmonellosis (including both ceftiofur-resistant and ceftiofur-susceptible Salmonella isolates) used more ceftiofur than herds with no history of salmonellosis (P = 0.03) These findings fail to support a major role for ceftiofur use in the maintenance and dissemination of blaCMY-2-bearing plasmid mediated cephalosporin resistance in commensal E. coli and in pathogenic Salmonella in these dairy cattle populations. PMID:19376926

Daniels, Joshua B.; Call, Douglas R.; Hancock, Dale; Sischo, William M.; Baker, Katherine; Besser, Thomas E.



Bactericidal Activity against Cephalosporin-ResistantStreptococcus pneumoniaein Cerebrospinal Fluid of Children with Acute Bacterial Meningitis  

Microsoft Academic Search

There are reports of failure of extended-spectrum cephalosporin treatment in pneumococcal meningitis. On the basis of in vitro and animal experimental studies, the addition of vancomycin or rifampin to an extended- spectrum cephalosporin has been recommended for empiric treatment of these patients. Cerebrospinal fluid (CSF) was taken from 31 children with bacterial meningitis randomized to receive ceftriaxone alone (n 511),



Antibiotic prescribing in women during and after delivery in a non-teaching, tertiary care hospital in Ujjain, India: a prospective cross-sectional study  

PubMed Central

Objectives Antibacterial drugs (hereafter referred to as antibiotics) are crucial to treat infections during delivery and postpartum period to reduce maternal mortality. Institutional deliveries have the potential to save lives of many women but extensive use of antibiotics, add to the development and spread of antibiotic resistance. The aim of this study was to present antibiotic prescribing among inpatients during and after delivery in a non-teaching, tertiary care hospital in the city of Ujjain, Madhya Pradesh, India. Methods A prospective cross-sectional study was conducted including women having had either a vaginal delivery or a cesarean section in the hospital. Trained nursing staff collected the data on daily bases, using a specific form attached to each patient file. Statistical analysis, including bivariate and multivariable logistic regression was conducted. Results Of the total 1077 women, 566 (53%) had a vaginal delivery and 511 (47%) had a cesarean section. Eighty-seven percent of the women that had a vaginal delivery and 98% of the women having a cesarean section were prescribed antibiotics. The mean number of days on antibiotics in hospital for the women with a vaginal delivery was 3.1 (±1.7) and for the women with cesarean section was 6.0 (±2.5). Twenty-eight percent of both the women with vaginal deliveries and the women with cesarean sections were prescribed antibiotics at discharge. The most commonly prescribed antibiotic group in the hospital for both the women that had a vaginal delivery and the women that had a cesarean section were third-generation cephalosporins (J01DD). The total number of defined daily doses (DDD) per100 bed days for women that had a vaginal delivery was 101, and 127 for women that had a cesarean section. Conclusions The high percentage of women having had a vaginal delivery that received antibiotics and the deviation from recommendation for cesarean section in the hospital is a cause of concern. Improved maternal health and rational use of antibiotics are intertwined. Specific policy and guidelines on how to prescribe antibiotics during delivery at health care facilities are needed. Additionally, monitoring system of antibiotic prescribing and resistance needs to be developed and implemented.



Animal antibiotic use has an early but important impact on the emergence of antibiotic resistance in human commensal bacteria  

Microsoft Academic Search

Antibiotic use is known to promote the development of antibiotic resistance, but substantial controversy exists about the impact of agricultural antibiotic use (AAU) on the subsequent emergence of antibiotic-resistant bacteria among humans. AAU for animal growth promotion or for treatment or control of animal diseases generates reservoirs of antibiotic-resistant (AR) bacteria that contaminate animal food products. Mathematical models are an

David L. Smith; Anthony D. Harris; Judith A. Johnson; Ellen K. Silbergeld; J. Glenn Morris Jr.



Cefatrizine Activity Compared with That of Other Cephalosporins  

PubMed Central

Cefatrizine, a new orally administered cephalosporin, was tested against 400 clinical isolates. Cefatrizine had excellent activity against gram-positive cocci, inhibiting all except enterococci at minimal inhibitory concentrations below 1 ?g/ml. Cefatrizine inhibited the majority of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Salmonella at concentrations below 12.5 ?g/ml. Although cefatrizine was not hydrolyzed by many ?-lactamases, it did not inhibit a number of strains of Enterobacter, Serratia, or indole-positive Proteus. Cefatrizine was more active than cephalothin or cephalexin against E. coli, Klebsiella, Enterobacter, Citrobacter, Salmonella, and Shigella. Its overall activity was less than that of cefoxitin against strains resistant to cephalothin, but its activity against cephalothin-susceptible strains was equivalent to that of cefamandole. PMID:426514

Neu, Harold C.; Fu, Kwung P.



Antibiotics Quiz  


... Antibiotic Use Respiratory Illnesses Sinus Infection Sore Throat Common Cold and Runny Nose Ear Infections Bronchitis (Chest Cold) ... Tips Appropriate Treatment Summary Cough Illness/Bronchitis The Common Cold Otitis Media Pharyngitis: Treat Only Proven GAS Online ...


Analysis of some common pathogens and their drug resistance to antibiotics  

PubMed Central

Objective: To investigate the common bacterial resistance of clinical isolates in our hospital in the second half of 2011. Methodology: Pathogens isolated from clinical samples in the second half of 2011 were analyzed and categorized to perform susceptibility tests. Results: In the gram-negative bacteria, Enterobacteriaceae and non-fermenting gram-negative bacilli accounted for 55.89% and 34.51%. In the gram-positive bacteria, Staphylococcus aureus, Coagulase-negative staphylococci, Enterococcus, Strptococcus pneumonia accounted for 32.85%, 40.39%, 12.41% and 10.22%, respectively. Other species accounted for 4.14%. Klebsiella pneumonia and Pseudomonas aeruginosa were sensitive to cepoperazon, cefepime and imipenem. However,Acinetobacter baumannii was more sensitive to carbapenems antibiotics, which was followed by fourth generation cephalosporins. Klebsiella pneumoniae was extremely sensitive to amikacin, cefepime and imipenem, but was resistant to ampicillin. The detection rates of the broad-spectrum Escherichia coli, Pseudomonasaeruginosa and Klebsiella pneumoniae were 54.51%, 52.08% and 38.65%. The gram negative bacilli were the prevalent clinical pathogens in our hospital in the second half of 2011. Conclusion: The drug resistance of pathogenic bacteria has increased significantly recently, thus the surveillance of antibacterial agents is necessary, and rational use of antibiotic will be urgently needed to reduce the production and dissemination of drug resistant strains. PMID:24353525

Bao, Lidao; Peng, Rui; Ren, Xianhua; Ma, Ruilian; Li, Junping; Wang, Yi



E-0702, a new cephalosporin, is incorporated into Escherichia coli cells via the tonB-dependent iron transport system.  

PubMed Central

E-0702, a new cephalosporin with a potent antipseudomonal action, was synthesized. In the study of the mode of action of this antibiotic in Escherichia coli, it was found that mutants which acquired resistance to E-0702 were isolated spontaneously and could be shown to be susceptible to its closely related derivatives, E-0702-060 and E-0702-061, and other representative beta-lactam antibiotics. In these mutants, no increased production of beta-lactamase was detectable. No apparent differences between the resistant mutants and the parental strains were observed in the affinity of E-0702 for penicillin-binding proteins. Furthermore, no significant reduction in or loss of both OmpF and OmpC porin proteins in the outer membrane was observed. The mutation was mapped to the tonB gene, which is known to be essential for the iron transport system of bacteria. The bactericidal action of E-0702 was rapidly expressed against iron-starved cells in which the iron transport system was induced, whereas the bactericidal action against iron-supplemented cells was ineffective. It is suggested that E-0702 is incorporated into bacterial cells as a chelator of iron via the tonB-dependent iron transport system, after which its strong and rapid bactericidal action is manifested. Images PMID:3037997

Watanabe, N A; Nagasu, T; Katsu, K; Kitoh, K



Retrospective analysis of antibiotic resistance pattern to urinary pathogens in a Tertiary Care Hospital in South India  

PubMed Central

Context: The distribution of uropathogens and their susceptibility pattern to antibiotics vary regionally and even in the same region, they change over time. Therefore, the knowledge on the frequency of the causative microorganisms and their susceptibility to various antibiotics are necessary for a better therapeutic outcome. Aim: The aim was to study the frequency and distribution of uropathogens and their resistance pattern to antibiotics in a tertiary care hospital. Settings and Design: Retrospective study for a period of 1 year from January 2011 to December 2011 in a tertiary care hospital. Materials and Methods: The culture and sensitivity data of the uropathogens from suspected cases of UTI were collected from the records of Microbiology Department for study period. Midstream urine samples were processed for microscopy and culture, and the organisms were identified by standard methods. Antibiotic susceptibility was carried out by Kirby-Bauer disk diffusion method according to Clinical and Laboratory Standards Institute guidelines. Descriptive statistics were used to analyze the data. Results: Of 896 urine samples, 348 (38.84%) samples were positive for urine culture. Escherichia coli (52.59%) was the most common organism followed by Klebsiella. E. coli was least resistant to imipenem (8%) and amikacin (16%) and was highly resistant to co-trimoxazole (69%) and ampicillin (86%). Klebsiella species were least resistant to amikacin (26%) and were highly resistant to ampicillin (92%). The overall resistance pattern of antibiotics to uropathogens was the highest to nalidixic acid (79%) followed by co-trimoxazole (75%) and ampicillin (72%). Good susceptibility was seen with imipenem and cephalosporins. Conclusion: E. coli is still the most common uropathogen. Nalidixic acid, ampicillin, co-trimoxazole, and first-generation fluoroquinolones have limited value for the treatment of UTI. Sensitivity to imipenem and amikacin are still retained and may be prescribed for complicated UTI. Routine monitoring of drug resistance pattern will help to identify the resistance trends regionally. This will help in the empirical treatment of UTIs to the clinicians. PMID:25316990

Somashekara, Saligrama Chikkannasetty; Deepalaxmi, Salmani; Jagannath, Narumalla; Ramesh, Bannaravuri; Laveesh, Madathil Ravindran; Govindadas, Damodaram



Prediction of plasma protein binding of cephalosporins using an artificial neural network.  


An artificial neural network model is developed to predict the fraction of cephalosporins bound to plasma proteins (f(b)) from their molecular structural parameters. These molecular structural parameters are the molecular weight (MW), the surface area occupied by oxygen and nitrogen atoms (S(O),N), and the surface area occupied by hydrogen atoms attached to oxygen or nitrogen atoms (S(H)). For a training set of 20 cephalosporins and a test set of 3 cephalosporins, root mean squared errors (RMSE) between experimental fb values and calculated/predicted fb values are 0.036 and 0.045, respectively. PMID:17341040

Fu, X C; Wang, G P; Gao, J Q; Zhan, S Y; Liang, W Q



Thin Layer Chromatographic Analysis of Beta-Lactam Antibiotics  

PubMed Central

Purpose: The paper describes some thin layer chromatographic procedures that allow simple and rapid separation and identification of penicillins and cephalosporins from complex mixtures. Methods: Using silicagel GF254 as stationary phase and selecting different mobile phases we succeeded in the separation of the studied beta-lactamins. Our aim was not only to develop a simple, rapid and efficient method for their separation but also the optimization of the analytical conditions. Results: No system will separate all the beta-lactams, but they could be identified when supplementary information is used from color reactions and/or by using additional chromatographic systems. Conclusion: The right combination of solvent system and detection method allows the identification of the studied penicillins and cephalosporins and can be successfully used in the preliminary analysis beta-lactam antibiotics. PMID:24312862

Hancu, Gabriel; Simon, Brigitta; Kelemen, Hajnal; Rusu, Aura; Mircia, Eleonora; Gyéresi, Árpád



Identification and Evaluation of Improved 4?-O-(Alkyl) 4,5-Disubstituted 2-Deoxystreptamines as Next-Generation Aminoglycoside Antibiotics  

PubMed Central

ABSTRACT The emerging epidemic of drug resistance places the development of efficacious and safe antibiotics in the spotlight of current research. Here, we report the design of next-generation aminoglycosides. Discovery efforts were driven by rational synthesis focusing on 4? alkylations of the aminoglycoside paromomycin, with the goal to alleviate the most severe and disabling side effect of aminoglycosides—irreversible hearing loss. Compounds were evaluated for target activity in in vitro ribosomal translation assays, antibacterial potency against selected pathogens, cytotoxicity against mammalian cells, and in vivo ototoxicity. The results of this study produced potent compounds with excellent selectivity at the ribosomal target, promising antibacterial activity, and little, if any, ototoxicity upon chronic administration. The favorable biocompatibility profile combined with the promising antibacterial activity emphasizes the potential of next-generation aminoglycosides in the treatment of infectious diseases without the risk of ototoxicity. PMID:25271289

Duscha, Stefan; Boukari, Heithem; Shcherbakov, Dimitri; Salian, Sumantha; Silva, Sandrina; Kendall, Ann; Kato, Takayuki; Akbergenov, Rashid; Perez-Fernandez, Deborah; Bernet, Bruno; Vaddi, Swapna; Thommes, Pia; Schacht, Jochen; Crich, David; Böttger, Erik C.



A Comprehensive Insight into Tetracycline Resistant Bacteria and Antibiotic Resistance Genes in Activated Sludge Using Next-Generation Sequencing  

PubMed Central

In order to comprehensively investigate tetracycline resistance in activated sludge of sewage treatment plants, 454 pyrosequencing and Illumina high-throughput sequencing were used to detect potential tetracycline resistant bacteria (TRB) and antibiotic resistance genes (ARGs) in sludge cultured with different concentrations of tetracycline. Pyrosequencing of 16S rRNA gene revealed that tetracycline treatment greatly affected the bacterial community structure of the sludge. Nine genera consisting of Sulfuritalea, Armatimonas, Prosthecobacter, Hyphomicrobium, Azonexus, Longilinea, Paracoccus, Novosphingobium and Rhodobacter were identified as potential TRB in the sludge. Results of qPCR, molecular cloning and metagenomic analysis consistently indicated that tetracycline treatment could increase both the abundance and diversity of the tet genes, but decreased the occurrence and diversity of non-tetracycline ARG, especially sulfonamide resistance gene sul2. Cluster analysis showed that tetracycline treatment at subinhibitory concentrations (5 mg/L) was found to pose greater effects on the bacterial community composition, which may be responsible for the variations of the ARGs abundance. This study indicated that joint use of 454 pyrosequencing and Illumina high-throughput sequencing can be effectively used to explore ARB and ARGs in the environment, and future studies should include an in-depth investigation of the relationship between microbial community, ARGs and antibiotics in sewage treatment plant (STP) sludge. PMID:24905407

Huang, Kailong; Tang, Junying; Zhang, Xu-Xiang; Xu, Ke; Ren, Hongqiang



FDA: Antibiotic Resistance  

NSDL National Science Digital Library

In the past few years, there have been more reports of bacteria that are increasingly resilient to antibiotics. Understandably, this antibiotic resistance is of great concern to the medical community in terms of public health, and is due largely to the increased use of antibiotics. With this in mind, the United States Food and Drug Administration has developed this Web site to inform the general public about this phenomenon, as well as to provide a number of documents generated by different government agencies about this problem and strategies for combating it. For those unacquainted with the situation, there are several helpful general fact sheets and overviews provided online from the Center for Disease Control and the University of Wisconsin. Additionally, the site contains several papers outlining some general recommendations about how the problem can be contained with the cooperation of doctors, hospitals, and increased awareness of the populace.


Generation of a safety enhanced Salmonella Gallinarum ghost using antibiotic resistance free plasmid and its potential as an effective inactivated vaccine candidate against fowl typhoid.  


A safety enhanced Salmonella Gallinarum (SG) ghost was constructed using an antibiotic resistance gene free plasmid and evaluated its potential as fowl typhoid (FT) vaccine candidate. The antibiotic resistance free pYA3342 plasmid possesses aspartate semialdehyde dehydrogenase gene which is complimentary to the deletion of the chromosomal asd gene in the bacterial host. This plasmid was incorporated with a ghost cassette containing the bacteriophage PhiX174 lysis gene E, designated as pJHL101. The plasmid pJHL101 was transformed into a two virulence genes-deleted SG. The SG ghosts with tunnel formation and loss of cytoplasmic contents were observed by scanning electron microscopy and transmission electron microscopy. The cell viability of the culture solution was decreased to 0% at 24h after the induction of gene E expression by an increase in temperature from 37°C to 42°C. The safety and protective efficacy of the SG ghost vaccine was further examined in chickens which were divided into three groups: group A (non-immunized control), group B (orally immunized), and group C (intramuscularly immunized). The birds were immunized at 7d of age. No clinical symptoms associated with FT such as anorexia, depression and greenish diarrhea were observed in the immunized chickens. Upon challenge with a virulent SG strain at 3 week post-immunization, the chickens immunized with the SG ghost via various routes were efficiently protected, as shown by significantly lower mortality and post-mortem lesions in comparison with control group. In addition, all the immunized chickens showed significantly higher antibody responses accompanied by a potent antigen-specific lymphocyte proliferative response along with significantly increased numbers of CD4? and CD8? T lymphocytes. Overall, our results provide a promising approach of generating SG ghosts using the antibiotic resistance free plasmid in order to prepare a non-living bacterial vaccine candidate which could be environmentally safe yet efficient to prevent FT in chickens. PMID:24406393

Jawale, Chetan V; Chaudhari, Atul A; Lee, John Hwa



Penicillin and cephalosporin biosynthesis: Mechanism of carbon catabolite regulation of penicillin production  

Microsoft Academic Search

Penicillins and cephalosporins are synthesized by a series of enzymatic reactions that form the tripeptide d-(L-a-aminoadipyl)-L-cysteinyl-D-valine and convert this tripeptide into the final penicillin or cephalosporin molecules. One of the enzymes, isopenicillin N synthase has been crystallyzed and its active center identified. The three genes pcbAB, pcbC and penDE involved in penicillin biosynthesis are clustered in Penicillium chrysogenum, Aspergillus nidulans

Juan F. Martín; Javier Casqueiro; Katarina Kosalková; Ana T. Marcos



Seasonality and Physician-related Factors Associated with Antibiotic Prescribing: A Cross-sectional Study in Isfahan, Iran  

PubMed Central

Background: Irrational antibiotic prescribing as a global health problem has a major influence on medical care quality and healthcare expenditure. This study was aimed to determine the pattern of antibiotic use and to assess the seasonality and physician-related factors associated with variability in antibiotic prescribing in Isfahan province of Iran. Methods: This cross-sectional survey was conducted on all prescriptions issued by general physicians from rural and urban areas in 2011. Associations between season of prescribing and physician-related variables including gender, practice location and time since graduation with antibiotic prescriptions and also the pattern of antibiotic prescribing were assessed using Chi-square tests and multiple logistic regression models. Results: Of the 7439709 prescriptions issued by 3772 general practitioners, 51% contained at least one antibiotic. Penicillins were the most frequently prescribed antibiotics, followed by cephalosporins and macrolides. Over-prescription of penicillins was associated with female gender (odds ratio [OR], 2.61; 95% confidence interval [CI] 2.13–3.19) and with moderate duration of time in practice (10–20 years) (OR, 1.42; 95% CI 1.14–1.76). Higher rates of cephalosporins prescription were observed in urban areas than rural areas and by male physicians. Seasonal peak was detected for penicillins and cephalosporins prescriptions in autumn. Conclusions: These findings showed the widespread use of antibiotics by general practitioners that was associated with the physicians’ gender, time since graduation and practice location and also season of prescribing. More researches are needed on other factors related to the overprescribing of antibiotics and they could be used to project educational programs for improvement of antibiotic prescribing quality in our country. PMID:25789136

Safaeian, Leila; Mahdanian, Ali-Reza; Salami, Solmaz; Pakmehr, Farzaneh; Mansourian, Marjan



Human Pharmacology of Cefotaxime (HR 756), a New Cephalosporin  

PubMed Central

Cefotaxime (HR 756) is a new semisynthetic parenteral cephalosporin with exceptional activity against gram-negative organisms and considerable stability against their ?-lactamases. To study its pharmacokinetic properties, 0.5-, 1-, and 2-g doses were administered to each of six volunteers intravenously over 15 min, followed by a sustaining infusions of 0.5, 1, and 2 g/h, respectively, for 3 consecutive hours. The loading doses produced mean peak levels of 41, 93, and 160 ?g/ml, and mean steady-state serum concentrations were 27, 64, and 138 ?g/ml, respectively. The mean terminal half-life was 75 ± 7 min. The total volume of distribution averaged 0.22 ± 0.03 liters/kg of body weight. Total body and renal clearances were 232 ± 30 and 145 ± 24 ml/min per 1.73 m2, respectively; 63 ± 9% of the administered dose was excreted through the kidneys in 24 h. To determine the effect of cefotaxime on the renal tubules, urinary alanine aminopeptidase excretion was measured before, during, and after the infusions. It remained within the normal range in all instances; however, 48 ± 14% of the total daily alanine aminopeptidase output was recovered during the infusion period. Side effects were dose related and included fatigue, loose stools, and night sweats. No significant changes in hematology, serum chemistry, or urinalysis were recorded. PMID:485125

Lüthy, Ruedi; Münch, Reiner; Blaser, Jürg; Bhend, Hansjörg; Siegenthaler, Walter



TCA Cycle-Mediated Generation of ROS Is a Key Mediator for HeR-MRSA Survival under ?-Lactam Antibiotic Exposure  

PubMed Central

Methicillin-resistant Staphylococcus aureus (MRSA) is a major multidrug resistant pathogen responsible for several difficult-to-treat infections in humans. Clinical Hetero-resistant (HeR) MRSA strains, mostly associated with persistent infections, are composed of mixed cell populations that contain organisms with low levels of resistance (hetero-resistant HeR) and those that display high levels of drug resistance (homo-resistant HoR). However, the full understanding of ?-lactam-mediated HeR/HoR selection remains to be completed. In previous studies we demonstrated that acquisition of the HoR phenotype during exposure to ?-lactam antibiotics depended on two key elements: (1) activation of the SOS response, a conserved regulatory network in bacteria that is induced in response to DNA damage, resulting in increased mutation rates, and (2) adaptive metabolic changes redirecting HeR-MRSA metabolism to the tricarboxylic acid (TCA) cycle in order to increase the energy supply for cell-wall synthesis. In the present work, we identified that both main mechanistic components are associated through TCA cycle-mediated reactive oxygen species (ROS) production, which temporally affects DNA integrity and triggers activation of the SOS response resulting in enhanced mutagenesis. The present work brings new insights into a role of ROS generation on the development of resistance to ?-lactam antibiotics in a model of natural occurrence, emphasizing the cytoprotective role in HeR-MRSA survival mechanism. PMID:24932751

Rosato, Roberto R.; Fernandez, Regina; Paz, Liliana I.; Singh, Christopher R.; Rosato, Adriana E.



A fluoroquinolone antibiotic with a methoxy group at the 8 position yields reduced generation of 8-oxo-7,8-dihydro-2'-deoxyguanosine after ultraviolet-A irradiation.  


We have previously reported that two fluoroquinolone antibiotics gave rise to 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) in DNA of cells concurrently exposed to UV-A and that this correlated with clinical phototoxicity. To determine the structural basis for generation of oxidative damage, the ability of two synthetic fluoroquinolone candidate antibiotics, Bayer 12-8039 (12-8039) and Bayer Y3118 (Y3118), to give rise to 8-oxo-dG in cultured liver epithelial cells was compared. 12-8039 contains a methoxy group at the 8 position of the quinolone nucleus, whereas Y3118 contains a chlorine group at the same position. Y3118 produced dose-dependent increases in 8-oxo-dG formation in cultured cells after UVA irradiation, whereas the 8-OCH3-substituted 12-8039 produced no increase. Also, after exposure to 20 J/cm2 UVA, UV spectral scans of both compounds revealed that Y3118 underwent photodegradation whereas 12-8039 was stable. These results demonstrate that the presence of an 8-OCH3 group on the quinolone nucleus is important for the reduction of photogeneration of oxidative DNA damage and photodegradation in the presence of UVA irradiation. From this, we suggest that 12-8039 has little phototoxic potential. PMID:9266812

Rosen, J E; Chen, D; Prahalad, A K; Spratt, T E; Schluter, G; Williams, G M



Improving known classes of antibiotics: an optimistic approach for the future.  


New antibiotic agents are desperately needed to treat the multidrug-resistant pathogens that continue to emerge at alarming rates. Many of the agents that have entered full clinical development since 1995 have been members of previously accepted classes of antibiotics. Among these are a new aminoglycoside (plazomicin), anti-MRSA cephalosporins (ceftobiprole and ceftaroline), a monocyclic ?-lactam (BAL30072), the ?-lactamase inhibitor combination of tazobactam with the anti-pseudomonal cephalosporin ceftolozane, ?-lactam combinations with new non-?-lactam inhibitors (MK-7655 with imipenem, and avibactam with ceftazidime and ceftaroline), new macrolides (cethromycin and solithromycin), oxazolidinones (tedizolid phosphate and radezolid), and quinolones (delafloxacin, nemonoxacin and JNJ-Q2). Resistance and safety issues have been circumvented by some of these new agents that have well-established mechanisms of action and defined pathways leading toward regulatory approval. PMID:22748801

Bush, Karen



Total Synthesis of the Antitumor Antibiotic (±)-Streptonigrin: First- and Second-Generation Routes for de Novo Pyridine Formation Using Ring-Closing Metathesis  

PubMed Central

The total synthesis of (±)-streptonigrin, a potent tetracyclic aminoquinoline-5,8-dione antitumor antibiotic that reached phase II clinical trials in the 1970s, is described. Two routes to construct a key pentasubstituted pyridine fragment are depicted, both relying on ring-closing metathesis but differing in the substitution and complexity of the precursor to cyclization. Both routes are short and high yielding, with the second-generation approach ultimately furnishing (±)-streptonigrin in 14 linear steps and 11% overall yield from inexpensive ethyl glyoxalate. This synthesis will allow for the design and creation of druglike late-stage natural product analogues to address pharmacological limitations. Furthermore, assessment of a number of chiral ligands in a challenging asymmetric Suzuki–Miyaura cross-coupling reaction has enabled enantioenriched (up to 42% ee) synthetic streptonigrin intermediates to be prepared for the first time. PMID:24328139



Risk factors and treatment outcomes of bloodstream infection caused by extended-spectrum cephalosporin-resistant Enterobacter species in adults with cancer.  


Treatment of Enterobacter infection is complicated due to its intrinsic resistance to cephalosporins. Medical records of 192 adults with cancer who had Enterobacter bacteremia were analyzed retrospectively to evaluate the risk factors for and the treatment outcomes in extended-spectrum cephalosporin (ESC)-resistant Enterobacter bacteremia in adults with cancer. The main outcome measure was 30-day mortality. Of the 192 patients, 53 (27.6%) had bloodstream infections caused by ESC-resistant Enterobacter species. Recent use of a third-generation cephalosporin, older age, tumor progression at last evaluation, recent surgery, and nosocomial acquisition were associated with ESC-resistant Enterobacter bacteremia. The 30-day mortality rate was significantly higher in the resistant group. Multivariate analysis showed that respiratory tract infection, tumor progression, septic shock at presentation, Enterobacter aerogenes as the culprit pathogen, and diabetes mellitus were independent risk factors for mortality. ESC resistance was significantly associated with mortality in patients with E. aerogenes bacteremia, although not in the overall patient population. PMID:24321352

Huh, Kyungmin; Kang, Cheol-In; Kim, Jungok; Cho, Sun Young; Ha, Young Eun; Joo, Eun-Jeong; Chung, Doo Ryeon; Lee, Nam Yong; Peck, Kyong Ran; Song, Jae-Hoon



Ceftobiprole: a new cephalosporin for the treatment of skin and skin structure infections.  


Ceftobiprole is among the first of a new generation of cephalosporins with activity against aerobic Gram-negative bacilli, which extends to cefepime-sensitive Pseudomonas aeruginosa, and activity against Gram-positive organisms, which includes methicillin-resistant Staphylococcus aureus. Ceftobiprole is currently undergoing evaluation by the US FDA for the treatment of complicated skin and skin structure infections, with a decision pending further evaluation of study site monitoring. It is also being evaluated for the treatment of community-acquired and healthcare-associated pneumonia. Two Phase III multicenter trials have demonstrated noninferiority in complicated skin and skin structure infections when tested against vancomycin in primarily Gram-positive bacterial infections, and when tested against vancomycin plus ceftazidime in Gram-positive and Gram-negative bacterial infections. It is well tolerated, with the most common side effects being nausea and dysgeusia. Ceftobiprole is likely to prove useful as an empiric as well as directed monotherapy in patients with complicated skin and skin structure infections, in which both Gram-positive pathogens including methicillin-resistant S. aureus and Gram-negative pathogens including cefepime-sensitive P. aeruginosa may be involved. PMID:19735220

Schirmer, Patricia L; Deresinski, Stanley C



Antibiotic-Resistant Fecal Bacteria, Antibiotics, and Mercury in Surface Waters of Oakland County, Michigan, 2005-2006  

USGS Publications Warehouse

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

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



Characterization of Novel Mycobacterium tuberculosis and Mycobacterium smegmatis Mutants Hypersusceptible to  Lactam Antibiotics  

Microsoft Academic Search

with deletions in the genes for their major -lactamases, BlaC and BlaS, respectively, and showed that the mutants have increased susceptibilities to most -lactam antibiotics, particularly the penicillins. However, there is still a basal level of resistance in the mutants to certain penicillins, and the susceptibilities of the mutants to some cephalosporin-based -lactams are essentially the same as those of

Anthony R. Flores; Linda M. Parsons; Martin S. Pavelka



Identification of a ferritin-like protein of Listeria monocytogenes as a mediator of ?-lactam tolerance and innate resistance to cephalosporins  

PubMed Central

Background The food-borne pathogen Listeria monocytogenes is the causative agent of listeriosis. The ?-lactam antibiotics penicillin G and ampicillin are the current drugs of choice for the treatment of listerial infections. While isolates of L. monocytogenes are susceptible to these antibiotics, their action is only bacteriostatic and consequently, this bacterium is regarded as tolerant to ?-lactams. In addition, L. monocytogenes has a high level of innate resistance to the cephalosporin family of ?-lactams frequently used to treat sepsis of unknown etiology. Given the high mortality rate of listeriosis despite rational antibiotic therapy, it is important to identify genes that play a role in the susceptibility and tolerance of L. monocytogenes to ?-lactams. Results The hly-based promoter trap system was applied to identify penicillin G-inducible genes of L. monocytogenes. The results of reporter system studies, verified by transcriptional analysis, identified ten penicillin G-inducible genes. The contribution of three of these genes, encoding a ferritin-like protein (fri), a two-component phosphate-response regulator (phoP) and an AraC/XylS family transcriptional regulator (axyR), to the susceptibility and tolerance of L. monocytogenes to ?-lactams was examined by analysis of nonpolar deletion mutants. The absence of PhoP or AxyR resulted in more rapid growth of the strains in the presence of sublethal concentration of ?-lactams, but had no effect on the MIC values or the ability to survive a lethal dose of these antibiotics. However, the ?fri strain showed impaired growth in the presence of sublethal concentrations of penicillin G and ampicillin and a significantly reduced ability to survive lethal concentrations of these ?-lactams. A lack of Fri also caused a 2-fold increase in the sensitivity of L. monocytogenes to cefalotin and cephradine. Conclusions The present study has identified Fri as an important mediator of ?-lactam tolerance and innate resistance to cephalosporins in L. monocytogenes. PhoP and AxyR are probably involved in transmitting signals to adjust the rate of growth of L. monocytogenes under ?-lactam pressure, but these regulators do not play a significant role in susceptibility and tolerance to this class of antibiotics. PMID:23176286



Antibiotics Use and Mis-use Antibiotics -  

E-print Network

Antibiotics ­ Use and Mis-use Antibiotics - Use and Misuse Karen Macsween #12;Risk factors for C.difficile · Antibiotics · age · Prolonged hospital stay · GI surgery · ITU · Enteral feeding · Immunosuppressant drugs%) Kissule et al 2008 J Hosp Med 3: 64 #12;In-patient antibiotic misuse · Nature of patients ­ acutely ill

Glasgow, University of


How Antibiotics Work  

NSDL National Science Digital Library

Students are introduced to a challenge question. Towards answering the question, they generate ideas for what they need to know about medicines and how they move through our bodies, watch a few short videos to gain multiple perspectives, and then learn lecture material to obtain a basic understanding of how antibiotics kill bacteria in the human body. They learn why different forms of medicine (pill, liquid or shot) get into the blood stream at different speeds.

VU Bioengineering RET Program,


Nutritional Control of Antibiotic Resistance via an Interface between the Phosphotransferase System and a Two-Component Signaling System  

PubMed Central

Enterococci are ubiquitous inhabitants of the gastrointestinal (GI) tract. However, antibiotic-resistant enterococci are also major causes of hospital-acquired infections. Enterococci are intrinsically resistant to cephalosporins, enabling growth to abnormally high densities in the GI tract in patients during cephalosporin therapy, thereby promoting dissemination to other sites where they cause infection. Despite its importance, many questions about the underlying basis for cephalosporin resistance remain. A specific two-component signaling system, composed of the CroS sensor kinase and its cognate response regulator (CroR), is required for cephalosporin resistance in Enterococcus faecalis, but little is known about the factors that control this signaling system to modulate resistance. To explore the signaling network in which CroR participates to influence cephalosporin resistance, we employed a protein fragment complementation assay to detect protein-protein interactions in E. faecalis cells, revealing a previously unknown association of CroR with the HPr protein of the phosphotransferase system (PTS) responsible for carbohydrate uptake and catabolite control of gene expression. Genetic and physiological analyses indicate that association with HPr restricts the ability of CroR to promote cephalosporin resistance and gene expression in a nutrient-dependent manner. Mutational analysis suggests that the interface used by HPr to associate with CroR is distinct from the interface used to associate with other cellular partners. Our results define a physical and functional connection between a critical nutrient-responsive signaling system (the PTS) and a two-component signaling system that drives antibiotic resistance in E. faecalis, and they suggest a general strategy by which bacteria can integrate their nutritional status with diverse environmental stimuli. PMID:24277024

Snyder, Holly; Kellogg, Stephanie L.; Skarda, Laura M.; Little, Jaime L.



Antibiotic Resistance Questions and Answers  


... Get Smart: Know When Antibiotics Work Share Compartir Antibiotic Resistance Questions & Answers On this Page Questions about Bacteria, ... of antibiotic resistance. Top of Page Questions about Antibiotic Resistance Q: What is antibiotic resistance? A: Antibiotic resistance ...


Porin Involvement in Cephalosporin and Carbapenem Resistance of Burkholderia pseudomallei  

PubMed Central

Background Burkholderia pseudomallei (Bps) is a Gram-negative bacterium that causes frequently lethal melioidosis, with a particularly high prevalence in the north and northeast of Thailand. Bps is highly resistant to many antimicrobial agents and this resistance may result from the low drug permeability of outer membrane proteins, known as porins. Principal Findings Microbiological assays showed that the clinical Bps strain was resistant to most antimicrobial agents and sensitive only to ceftazidime and meropenem. An E. coli strain defective in most porins, but expressing BpsOmp38, exhibited considerably lower antimicrobial susceptibility than the control strain. In addition, mutation of Tyr119, the most prominent pore-lining residue in BpsOmp38, markedly altered membrane permeability, substitution with Ala (mutant BpsOmp38Y119A) enhanced uptake of the antimicrobial agents, while substitution with Phe (mutant BpsOmp38Y119F) inhibited uptake. Channel recordings of BpsOmp38 reconstituted in a planar black lipid membrane (BLM) suggested that the higher permeability of BpsOmp38Y119A was caused by widening of the pore interior through removal of the bulky side chain. In contrast, the lower permeability of BpsOmp38Y119F was caused by introduction of the hydrophobic side chain (Phe), increasing the ‘greasiness’ of the pore lumen. Significantly, liposome swelling assays showed no permeation through the BpsOmp38 channel by antimicrobial agents to which Bps is resistant (cefoxitin, cefepime, and doripenem). In contrast, high permeability to ceftazidime and meropenem was observed, these being agents to which Bps is sensitive. Conclusion/Significance Our results, from both in vivo and in vitro studies, demonstrate that membrane permeability associated with BpsOmp38 expression correlates well with the antimicrobial susceptibility of the virulent bacterium B. pseudomallei, especially to carbapenems and cephalosporins. In addition, substitution of the residue Tyr119 affects the permeability of the BpsOmp38 channel to neutral sugars and antimicrobial agents. PMID:24788109

Aunkham, Anuwat; Schulte, Albert; Winterhalter, Mathias; Suginta, Wipa



Intracerebroventricular injection of the antibiotic cefoselis produces convulsion in mice via inhibition of GABA receptors  

Microsoft Academic Search

A majority of ?-lactam antibiotics (e.g., cephalosporins and penicillins) have convulsive activity to a greater or lesser extent. (6R,7R)-3-{[3-Amino-2-(2-hydroxyethyl)-2H-pyrazol-1-ium-1-yl]methyl}-7-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetylamino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate monosulfate (cefoselis), a newly developed injectable ?-lactam antibiotic with activity against methicillin-resistant Staphylococcus aureus (MRSA), might induce convulsions if cerebral concentrations become highly elevated. In the present study, we examined whether or not cefoselis had convulsive activity after direct brain administration,

Shunji Yamazaki; Yoshitaka Mochizuki; Takao Terai; Masahiro Sugimoto; Ichiro Uchida; Nobuya Matsuoka; Seitaro Mutoh



Non-Phenotypic Tests to Detect and Characterize Antibiotic Resistance Mechanisms in Enterobacteriaceae  

PubMed Central

In the past two decades, we have observed a rapid increase of infections due to multidrug-resistant Enterobacteriaceae. Regrettably, these isolates possess genes encoding for extended-spectrum ?-lactamases (e.g., blaCTX-M, blaTEM, blaSHV) or plasmid-mediated AmpCs (e.g., blaCMY) that confer resistance to last-generation cephalosporins. Furthermore, other resistance traits against quinolones (e.g., mutations in gyrA and parC, qnr elements) and aminoglycosides (e.g., aminoglycosides modifying enzymes and 16S rRNA methylases) are also frequently co-associated. Even more concerning is the rapid increase of Enterobacteriaceae carrying genes conferring resistance to carbapenems (e.g., blaKPC, blaNDM). Therefore, the spread of these pathogens puts in peril our antibiotic options. Unfortunately, standard microbiological procedures require several days to isolate the responsible pathogen and to provide correct antimicrobial susceptibility test results. This delay impacts the rapid implementation of adequate antimicrobial treatment and infection control countermeasures. Thus, there is emerging interest in the early and more sensitive detection of resistance mechanisms. Modern non-phenotypic tests are promising in this respect, and hence, can influence both clinical outcome and healthcare costs. In this review, we present a summary of the most advanced methods (e.g., next-generation DNA sequencing, multiplex PCRs, real-time PCRs, microarrays, MALDITOF MS, and PCR/ESI MS) presently available for the rapid detection of antibiotic resistance genes in Enterobacteriaceae. Taking into account speed, manageability, accuracy, versatility, and costs, the possible settings of application (research, clinic, and epidemiology) of these methods and their superiority against standard phenotypic methods are discussed. PMID:24091103

Lupo, Agnese; Papp-Wallace, Krisztina M.; Sendi, Parham; Bonomo, Robert A.; Endimiani, Andrea



Non-phenotypic tests to detect and characterize antibiotic resistance mechanisms in Enterobacteriaceae.  


In the past 2 decades, we have observed a rapid increase of infections due to multidrug-resistant Enterobacteriaceae. Regrettably, these isolates possess genes encoding for extended-spectrum ?-lactamases (e.g., blaCTX-M, blaTEM, blaSHV) or plasmid-mediated AmpCs (e.g., blaCMY) that confer resistance to last-generation cephalosporins. Furthermore, other resistance traits against quinolones (e.g., mutations in gyrA and parC, qnr elements) and aminoglycosides (e.g., aminoglycosides modifying enzymes and 16S rRNA methylases) are also frequently co-associated. Even more concerning is the rapid increase of Enterobacteriaceae carrying genes conferring resistance to carbapenems (e.g., blaKPC, blaNDM). Therefore, the spread of these pathogens puts in peril our antibiotic options. Unfortunately, standard microbiological procedures require several days to isolate the responsible pathogen and to provide correct antimicrobial susceptibility test results. This delay impacts the rapid implementation of adequate antimicrobial treatment and infection control countermeasures. Thus, there is emerging interest in the early and more sensitive detection of resistance mechanisms. Modern non-phenotypic tests are promising in this respect, and hence, can influence both clinical outcome and healthcare costs. In this review, we present a summary of the most advanced methods (e.g., next-generation DNA sequencing, multiplex PCRs, real-time PCRs, microarrays, MALDI-TOF MS, and PCR/ESI MS) presently available for the rapid detection of antibiotic resistance genes in Enterobacteriaceae. Taking into account speed, manageability, accuracy, versatility, and costs, the possible settings of application (research, clinic, and epidemiology) of these methods and their superiority against standard phenotypic methods are discussed. PMID:24091103

Lupo, Agnese; Papp-Wallace, Krisztina M; Sendi, Parham; Bonomo, Robert A; Endimiani, Andrea



Increased Expression Levels of Chromosomal AmpC ?-Lactamase in Clinical Escherichia coli Isolates and Their Effect on Susceptibility to Extended-Spectrum Cephalosporins.  


Forty-nine clinical Escherichia coli isolates, both extended-spectrum ?-lactamase (ESBL) negative and ESBL positive, were studied to investigate whether increased AmpC expression is a mechanism involved in cefoxitin resistance and if this influences the third-generation cephalosporin activity. Nine of 33 (27.2%) cefoxitin-resistant (minimum inhibitory concentration [MIC] >8?mg/L) isolates showed hyperproduction of chromosomal AmpC (c-AmpC) based on (1) at least two positive tests using AmpC inhibitors, (2) mutations in the promoter/attenuator regions, and (3) a 6.1- to 163-fold increase in c-ampC expression by quantitative reverse transcription-polymerase chain reaction. In ESBL-negative isolates, MICs of ceftazidime and cefotaxime were mostly above the wild-type (WT) level, but below the S/I breakpoint (EUCAST guideline), except for one isolate with MICs of 4?mg/L. No plasmid-mediated AmpCs were found. Periplasmic extracts of nine c-AmpC hyperproducers were preincubated with or without cefuroxime or ceftazidime and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Cefuroxime and ceftazidime were stable to hydrolysis but acted as inhibitors of the enzyme. None of these isolates showed loss of porins. Thus, cefoxitin resistance has low specificity for detecting upregulated c-AmpC production. c-AmpC hyperproducing E. coli is mostly still susceptible to third-generation cephalosporins but less than WT E. coli. Surveillance of cefoxitin-resistant E. coli to monitor developments in the activity of third-generation cephalosporins against c-AmpC hyperproducers is warranted. PMID:25188329

Paltansing, Sunita; Kraakman, Margriet; van Boxtel, Ria; Kors, Ivo; Wessels, Els; Goessens, Wil; Tommassen, Jan; Bernards, Alexandra



Antibiotic sensitivity pattern and cost-effectiveness analysis of antibiotic therapy in an Indian tertiary care teaching hospital  

PubMed Central

Objective: The purpose of this study is to analyze the antibiotic sensitivity pattern of microorganisms, to study the antibiotic usage pattern, and to conduct a cost-effectiveness analysis (CEA) for the antibiotics prescribed in a tertiary care teaching hospital in south India. Methods: This prospective study was carried out in the General Medicine and Pulmonology departments of the hospital for a period of 6 months. The study was carried out in three phases: A prospective analysis to check the sensitivity pattern of microorganisms to various antibiotics, data extraction and determining the cost of antibiotics and finally evaluation of the sensitivity pattern of microorganisms and the antibiotic usage. A total of 796 documented records were analyzed. Findings: It was found that Escherichia coli was the major organism identified in 36.4% of the isolated specimens, followed by Klebsiella sp. (18.9%), Streptococcus pneumoniae (15.8%), Staphylococcus aureus (12.4%), and Pseudomonas (9.3%). The sensitivity pattern data of the prospective study revealed that E. coli was highly sensitive to Amikacin (99.3%), Klebsiella to Amikacin (93.8%), Pseudomonas to Meropenem (97.6%), and S. pneumoniae to Ofloxacin (93.8%). In the prescribing pattern study, it was found that the most common disease (21.2%) was found to be lower respiratory tract infection in 51 patients. Cephalosporins (73%), in particular Ceftriaxone (63.5%) was highly prescribed, followed by fluoroquinolones (53.9%). In the CEA, it was revealed that Ceftriaxone was the cost-effective antibiotic with a cost-effectiveness ratio (CER) of 78.27 compared to Levofloxacin, which had a CER of 95.13. Conclusion: Continuous surveillance of susceptibility testing is necessary for cost-effective customization of empiric antibiotic therapy. Furthermore, reliable statistics on antibiotic resistance and policies should be made available. PMID:24991607

Sriram, Shamungum; Aiswaria, Varghese; Cijo, Annie Eapen; Mohankumar, Thekkinkattil



Antibiotic usage in 2013 on a dairy CAFO in NY State, USA  

PubMed Central

Antimicrobial resistance is threatening humans and animals worldwide. Biosecurity and 1-year usage of antibiotics on a dairy concentrated animal feeding operation (CAFO) in NY State, USA, were mapped: how much antibiotics were used, for what purpose, and whether any decrease could be warranted. Approximately 493 kg antibiotics was used, of which 376 kg was ionophores (monensin and lasalocides), 79 kg penicillin, 16.5 kg lincosamides, 8.0 kg aminoglycosides, 7.7 kg sulfamides, 3.4 kg cephalosporin, 2 kg macrolides, 0.7 kg amphenicols, and 0.1 kg fluoroquinolones. Usage reduction by 84% was realistic without compromising the animal welfare. Further reduction could be possible by improving the biosecurity and by utilizing antibiotic sensitivity testing. PMID:24891936

Doane, Marie; Sarenbo, Sirkku



In Vitro Antibiotic Susceptibilities of Yersinia pestis Determined by Broth Microdilution following CLSI Methods.  


In vitro susceptibilities to 45 antibiotics were determined for 30 genetically and geographically diverse strains of Yersinia pestis by the broth microdilution method at two temperatures, 28°C and 35°C, following Clinical and Laboratory Standards Institute (CLSI) methods. The Y. pestis strains demonstrated susceptibility to aminoglycosides, quinolones, tetracyclines, ?-lactams, cephalosporins, and carbapenems. Only a 1-well shift was observed for the majority of antibiotics between the two temperatures. Establishing and comparing antibiotic susceptibilities of a diverse but specific set of Y. pestis strains by standardized methods and establishing population ranges and MIC50 and MIC90 values provide reference information for assessing new antibiotic agents and also provide a baseline for use in monitoring any future emergence of resistance. PMID:25583720

Heine, Henry S; Hershfield, Jeremy; Marchand, Charles; Miller, Lynda; Halasohoris, Stephanie; Purcell, Bret K; Worsham, Patricia L




Technology Transfer Automated Retrieval System (TEKTRAN)

We examined a group of cephalosporin resistant isolates from various swine sources submitted to the National Antimicrobial Resistance Monitoring System (NARMS). A total of 50 isolates were obtained between the years 1997 and 1999. Each of the isolates had MIC's to Ceftriaxone, Ceftiofur, and Cephalo...


New cephalosporins cefotaxime, cefpimizole, BMY 28142, and HR 810 in experimental pneumococcal meningitis in rabbits.  

PubMed Central

Four new cephalosporins, cefotaxime, cefpimizole (U 63196E), BMY 28142, and HR 810 were evaluated in experimental pneumococcal meningitis. Cefotaxime penetrated only moderately into the cerebrospinal fluid of rabbits with meningitis, whereas cefpimizole, BMY 28142, and HR 810 all exhibited unusually good penetration. The bactericidal activity in infected cerebrospinal fluid was comparable for the four drugs. PMID:3838872

Täuber, M G; Hackbarth, C J; Scott, K G; Rusnak, M G; Sande, M A



Effect of incubation temperature and time on the precision of data generated by antibiotic disc diffusion assays.  


The influence on the precision of disc diffusion data of the conditions under which the tests were performed was examined by analysing multilaboratory data sets generated after incubation at 35 °C for 18 h, at 28 °C for 24 h and 22 °C for 24 h and 48 h. Analyses of these data sets demonstrated that precision was significantly and progressively decreased as the test temperature was reduced from 35 to 22 °C. Analysis of the data obtained at 22 °C also showed the precision was inversely related to the time of incubation. Temperature and time related decreases in precision were not related to differences in the mean zone sizes of the data sets obtained under these test conditions. Analysis of the zone data obtained at 28 and 22 °C as single laboratory sets demonstrated that reductions of incubation temperature resulted in significant increases in both intralaboratory and interlaboratory variation. Increases in incubation time at 22 °C were, however, associated with statistically significant increases in interlaboratory variation but not with any significant increase in intralaboratory variation. The significance of these observations for the establishment of the acceptable limits of precision of data sets that can be used for the setting of valid epidemiological cut-off values is discussed. PMID:25074782

Smith, P; Kronvall, G



Evaluation of separation and purification processes in the antibiotic industry  

SciTech Connect

The different separation and purification processes for three major types of antibiotics, Penicillins, Cephalosporins and Tetracyclines will be discussed. All antibiotic, processing plants contain two majors sections, a relatively small and highly specialized fermentation section and a very large (60-80% of the plant) separation and purification section. The fermentation sections for the different antibiotics are essentially identical, except for differences in growth media and operating variables, but there are vast differences in the separation and purification sections. Several different separation methods are used including filtration, ultrafiltration, centrifugation, precipitation, extraction, chromatography and various membrane methods. Variables affecting the specific separation and purification configurations include final fermentation broth concentration, by-product formed during fermentation, the physical properties and molecular structure of the various antibiotics and special purification requirements. Necessary reductions in the separation and purification processes required for rebuilding the antibiotic industry after a national emergency are discussed along with several relatively new separation/purification methods that hold great promise for effecting these reductions, chromatography, supercritical fluid extraction (SCF), and membranes. 35 refs., 10 figs., 2 tabs.

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



Sample preservation for the analysis of antibiotics in water.  


This paper describes a stability study performed for 56 antibiotics belonging to 9 different groups--macrolides, tetracyclines, fluoroquinolones, quinolones, penicillins, cephalosporines, lincosamides, sulfonamides and nitroimidazole antibiotics--in purified water samples fortified with the selected compounds at 10 ng/ml. For this purpose, three different sample preservation modes were tested with the aim of avoiding biotic and abiotic degradation: (i) storage at -20°C, (ii) storage at -20°C with 0.1% of EDTA and (iii) pre-concentration in a solid phase extraction cartridge (SPE), which was afterwards stored at -20°C. Concentrations of antibiotics in the samples preserved using the different protocols were monitored after 0, 1, 2 and 12 weeks. The results showed that, for the accurate determination of all compounds they should be analyzed right after sampling. However, if this is not possible, most of the antibiotics can be analyzed within the 1st week after sampling and preservation at -20°C (with or without EDTA) or in a SPE cartridges at -20°C. Nonetheless, some antibiotics found extensively in the environment, such as sulfamethoxazole, ciprofloxacin, ofloxacin, erythromycin, azithromycin and clarithromycin exhibited low stability after 1 week preservation and, therefore, they should be analyzed within this time. PMID:25441070

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



Antibiotic resistance in microbes  

Microsoft Academic Search

The treatment of infectious disease is compromised by the development of antibiotic-resistant strains of microbial pathogens. A variety of biochemical processes are involved that may keep antibiotics out of the cell, alter the target of the drug, or disable the antibiotic. Studies have shown that resistance determinants arise by either of two genetic mechanisms: mutation and acquisition. Antibiotic resistance genes

D. Mazel; J. Davies



Chemistry & Biology Acyldepsipeptide Antibiotics Induce the Formation  

E-print Network

Chemistry & Biology Article Acyldepsipeptide Antibiotics Induce the Formation of a Structured AxialP requires the ATPases to degrade folded or unfolded substrates, but binding of acyldepsipeptide antibiotics-terminal loops of ClpP in a b-hairpin conformation, generating a stable pore through which extended polypeptides

Guarne, Alba


Ceftolozane/tazobactam: a novel cephalosporin/?-lactamase inhibitor combination with activity against multidrug-resistant gram-negative bacilli.  


Ceftolozane is a novel cephalosporin currently being developed with the ?-lactamase inhibitor tazobactam for the treatment of complicated urinary tract infections (cUTIs), complicated intra-abdominal infections (cIAIs), and ventilator-associated bacterial pneumonia (VABP). The chemical structure of ceftolozane is similar to that of ceftazidime, with the exception of a modified side-chain at the 3-position of the cephem nucleus, which confers potent antipseudomonal activity. As a ?-lactam, its mechanism of action is the inhibition of penicillin-binding proteins (PBPs). Ceftolozane displays increased activity against Gram-negative bacilli, including those that harbor classical ?-lactamases (e.g., TEM-1 and SHV-1), but, similar to other oxyimino-cephalosporins such as ceftazidime and ceftriaxone, it is compromised by extended-spectrum ?-lactamases (ESBLs) and carbapenemases. The addition of tazobactam extends the activity of ceftolozane to include most ESBL producers as well as some anaerobic species. Ceftolozane is distinguished from other cephalosporins by its potent activity versus Pseudomonas aeruginosa, including various drug-resistant phenotypes such as carbapenem, piperacillin/tazobactam, and ceftazidime-resistant isolates, as well as those strains that are multidrug-resistant (MDR). Its antipseudomonal activity is attributed to its ability to evade the multitude of resistance mechanisms employed by P. aeruginosa, including efflux pumps, reduced uptake through porins and modification of PBPs. Ceftolozane demonstrates linear pharmacokinetics unaffected by the coadministration of tazobactam; specifically, it follows a two-compartmental model with linear elimination. Following single doses, ranging from 250 to 2,000 mg, over a 1-h intravenous infusion, ceftolozane displays a mean plasma half-life of 2.3 h (range 1.9-2.6 h), a steady-state volume of distribution that ranges from 13.1 to 17.6 L, and a mean clearance of 102.4 mL/min. It demonstrates low plasma protein binding (20 %), is primarily eliminated via urinary excretion (?92 %), and may require dose adjustments in patients with a creatinine clearance <50 mL/min. Time-kill experiments and animal infection models have demonstrated that the pharmacokinetic-pharmacodynamic index that is best correlated with ceftolozane's in vivo efficacy is the percentage of time in which free plasma drug concentrations exceed the minimum inhibitory concentration of a given pathogen (%fT >MIC), as expected of ?-lactams. Two phase II clinical trials have been conducted to evaluate ceftolozane ± tazobactam in the settings of cUTIs and cIAIs. One trial compared ceftolozane 1,000 mg every 8 h (q8h) versus ceftazidime 1,000 mg q8h in the treatment of cUTI, including pyelonephritis, and demonstrated similar microbiologic and clinical outcomes, as well as a similar incidence of adverse effects after 7-10 days of treatment, respectively. A second trial has been conducted comparing ceftolozane/tazobactam 1,000/500 mg and metronidazole 500 mg q8h versus meropenem 1,000 mg q8h in the treatment of cIAI. A number of phase I and phase II studies have reported ceftolozane to possess a good safety and tolerability profile, one that is consistent with that of other cephalosporins. In conclusion, ceftolozane is a new cephalosporin with activity versus MDR organisms including P. aeruginosa. Tazobactam allows the broadening of the spectrum of ceftolozane versus ?-lactamase-producing Gram-negative bacilli including ESBLs. Potential roles for ceftolozane/tazobactam include empiric therapy where infection by a resistant Gram-negative organism (e.g., ESBL) is suspected, or as part of combination therapy (e.g., with metronidazole) where a polymicrobial infection is suspected. In addition, ceftolozane/tazobactam may represent alternative therapy to the third-generation cephalosporins after treatment failure or for documented infections due to Gram-negative bacilli producing ESBLs. Finally, the increased activity of ceftolozane/tazobactam versus P. aeruginosa, including MDR

Zhanel, George G; Chung, Phillip; Adam, Heather; Zelenitsky, Sheryl; Denisuik, Andrew; Schweizer, Frank; Lagacé-Wiens, Philippe R S; Rubinstein, Ethan; Gin, Alfred S; Walkty, Andrew; Hoban, Daryl J; Lynch, Joseph P; Karlowsky, James A



Mutation Frequencies and Antibiotic Resistance  

Microsoft Academic Search

MULTIPLE DIMENSIONS OF THE MUTATION RATE Antibiotic resistance can be achieved by horizontal acquisi- tion of resistance genes (carried by plasmids or transposons), by recombination of foreign DNA into the chromosome, or by mutations in different chromosomal loci (15). In studies of molecular evolutionary biology, the term mutation rate is ap- plied to estimations of the rate (per generation) of

J. L. Martinez; F. Baquero



Antibiotic Consumption and Healthcare-Associated Infections Caused by Multidrug-Resistant Gram-Negative Bacilli at a Large Medical Center in Taiwan from 2002 to 2009: Implicating the Importance of Antibiotic Stewardship  

PubMed Central

Background Better depicting the relationship between antibiotic consumption and evolutionary healthcare-associated infections (HAIs) caused by multidrug-resistant Gram-negative bacilli (MDR-GNB) may help highlight the importance of antibiotic stewardship. Methodology/Principal Findings The correlations between antibiotic consumption and MDR-GNB HAIs at a 2,700-bed primary care and tertiary referral center in Taiwan between 2002 and 2009 were assessed. MDR-GNB HAI referred to a HAI caused by MDR-Enterobacteriaceae, MDR-Pseudomonas aeruginosa or MDR-Acinetobacter spp. Consumptions of individual antibiotics and MDR-GNB HAI series were first evaluated for trend over time. When a trend was significant, the presence or absence of associations between the selected clinically meaningful antibiotic resistance and antibiotic consumption was further explored using cross-correlation analyses. Significant major findings included (i) increased consumptions of extended-spectrum cephalosporins, carbapenems, aminopenicillins/?-lactamase inhibitors, piperacillin/tazobactam, and fluoroquinolones, (ii) decreased consumptions of non-extended-spectrum cephalosporins, natural penicillins, aminopenicillins, ureidopenicillin and aminoglycosides, and (iii) decreasing trend in the incidence of the overall HAIs, stable trends in GNB HAIs and MDR-GNB HAIs throughout the study period, and increasing trend in HAIs caused by carbapenem-resistant (CR) Acinetobacter spp. since 2006. HAIs due to CR-Acinetobacter spp. was found to positively correlate with the consumptions of carbapenems, extended-spectrum cephalosporins, aminopenicillins/?-lactamase inhibitors, piperacillin/tazobactam and fluoroquinolones, and negatively correlate with the consumptions of non-extended-spectrum cephalosporins, penicillins and aminoglycosides. No significant association was found between the increased use of piperacilllin/tazobactam and increasing HAIs due to CR-Acinetobacter spp. Conclusions The trend in overall HAIs decreased and trends in GNB HAIs and MDR-GNB HAIs remained stable over time suggesting that the infection control practice was effective during the study period, and the escalating HAIs due to CR- Acinetobacter spp. were driven by consumptions of broad-spectrum antibiotics other than piperacillin/tazobactam. Our data underscore the importance of antibiotic stewardship in the improvement of the trend of HAIs caused by Acinetobacter spp. PMID:23738018

Su, Li-Hsiang; Tang, Ya-Feng; Chang, Shun-Jen; Liu, Jien-Wei



Influence of nine antibiotics on key secondary metabolites and physiological characteristics in Triticum aestivum: leaf volatiles as a promising new tool to assess toxicity.  


Extensive worldwide use of antibiotics has resulted in significant diffuse pollution of antibiotics in environment, but understanding the effects of many important antibiotics on plant physiological activity is still limited, especially at realistic environmental concentrations of antibiotics. To gain insight into influences of different antibiotics on plant performance and identify the most promising traits for fast assessment of toxicity, we studied impacts of nine antibiotics (amoxicillin, ampicillin, penicillin G, ceftazidime, ceftriaxone, tetracycline, doxycycline, ciprofloxacin and erythromycin) on foliage photosynthesis, photosynthetic pigment content and emissions of secondary volatile metabolites in wheat (Triticum aestivum L. cv. "Lovrin"). The antibiotics were applied at concentrations of 0.5 mg L?¹ or 1.5 mg L?¹ either by watering for one week (0.5 L solution) or for two weeks (1 L solution) with given solution. Net assimilation rate was inhibited most strongly by ciprofloxacin and cephalosporins, but the inhibition was mainly due to reductions in stomatal conductance. Photosynthetic electron transport rate was affected by penicillins, cephalosporins and tetracyclines. Contents of photosynthetic pigments, chlorophylls and carotenoids, were most strongly reduced in treatments with tetracyclines, ciprofloxacin and erythromycin. The magnitude of plant photosynthetic and pigment responses generally increased with increasing the antibiotics' dose, but the overall effects were moderate, 10-20 percent in most cases. Emissions of the lipoxygenase pathway products (LOX, green leaf volatiles) were most sensitive indicators of antibiotic treatments. LOX emissions were increased by five to six fold in response to antibiotic treatments and the emissions were quantitatively associated with the treatment dose. Monoterpene emissions were also strongly enhanced by antibiotic treatments, but the dose dependence was weaker. These data collectively suggest that analysis of leaf volatiles can provide a novel sensitive assay to gauge the toxicity of different antibiotics. PMID:23084040

Opri?, Ocsana; Copaciu, Florina; Loredana Soran, Maria; Ristoiu, Dumitru; Niinemets, Ulo; Copolovici, Lucian



Plasmid-Mediated Resistance to Expanded-Spectrum Cephalosporins among Enterobacter aerogenes Strains  

Microsoft Academic Search

Resistance to expanded-spectrum cephalosporins commonly develops in Enterobacter aerogenes during ther- apy due to selection of mutants producing high levels of the chromosomal Bush group 1 b-lactamase. Recently, resistant strains producing plasmid-mediated extended-spectrum b-lactamases (ESBLs) have been isolated as well. A study was designed to investigate ESBL production among 31 clinical isolates of E. aerogenes from Richmond, Va., with decreased




Batch production of deacetyl 7-aminocephalosporanic acid by immobilized cephalosporin-C deacetylase  

Microsoft Academic Search

Bacillus subtilis SHS0133 cephalosporin-C deacetylase (CAH) overexpressed in Escherichia coli was immobilized on an anion-exchange resin, KA-890, using glutaraldehyde. The activity yield of immobilized enzyme was approximately 55% of the free enzyme. The pH range for stability of the immobilized enzyme (pH 5–10) was broader than that for free enzyme. The K m app value of immobilized enzyme for 7-aminocephalosporanic

Akio Takimoto; Tomoaki Takakura; Hiroyoshi Tani; Shigeo Yagi; Kenji Mitsushima



Genetic Profiles of Fluoroquinolone-Nonsusceptible Klebsiella pneumoniae Among Cephalosporin-Resistant K. pneumoniae.  


The rate of fluoroquinolone (FQ) resistance among the cephalosporin-resistant Klebsiella pneumoniae is considerably high, however, their genetic profiles have not been well investigated. We selected 61 ciprofloxacin-nonsusceptible isolates from 102 K. pneumoniae isolates judged to be "resistant" to some cephalosporins during 2009 and 2012 throughout Japan. Pulsed-field gel electrophoresis excluded clonal isolates, and 29 isolates were subjected to multilocus sequence typing (MLST), detection of the amino acid substitutions in the quinolone resistance determining regions (QRDRs) of GyrA and ParC, ?-lactamase typing, and identification of plasmid-mediated quinolone resistance (PMQR) genes. PCR-based replicon typing was performed, after PMQR gene transfer. Four major sequence types (STs) or clonal complexes (CCs), that is, ST37, CC17 (consisting of ST17 and ST20), ST11, and CC528 (consisting of ST528 and ST1130), were found, and they accounted for 48.2% of the isolates tested. Amino acid substitutions in the QRDRs and the presence of PMQR genes were identified in 20 (68.9%) and 18 (62.0%) isolates, respectively. The replicon type of three PMQR-carrying plasmids was IncN, but others were nontypable. Fifteen (83.3%) of the 18 PMQR-harboring isolates coharbored blaCTX-M and/or blaDHA-1. Ciprofloxacin-nonsusceptible K. pneumoniae clinical isolates demonstrating cephalosporin resistance often belong to the global epidemic lineages and possess PMQR and/or QRDR substitutions. PMID:25419619

Nagasaka, Yukiko; Kimura, Kouji; Yamada, Keiko; Wachino, Jun-Ichi; Jin, Wanchun; Notake, Shigeyuki; Yanagisawa, Hideji; Arakawa, Yoshichika



Combating Antibiotic Resistance  


... for infectious diseases. back to top Antibiotics Fight Bacteria, Not Viruses Antibiotics are meant to be used ... treat strep throat, which is caused by streptococcal bacteria, and skin infections caused by staphylococcal bacteria. Although ...


Antibiotic Susceptibility of Streptococcus Pyogenes Isolated from Respiratory Tract Infections in Dakar, Senegal  

PubMed Central

Group A Streptococcus (GAS) is one of the major causes of respiratory tract infections. The objectives of this study were to identify isolates of S. pyogenes obtained from respiratory tract infections, and to assess their susceptibility to several antibiotics. A total of 40 strains were isolated and their susceptibility to 17 antibiotics was tested using a standard disk diffusion method. The minimum inhibitory concentrations (MICs) were determined using the E-test. All isolates were sensitive to ?-lactam antibiotics including penicillin, amoxicillin, and cephalosporins. Macrolides remain active with the exception of spiramycin, which showed reduced susceptibility. Out of the 40 isolates, 100% of the isolates were resistant to tetracycline. Interestingly, isolates were sensitive to chloramphenicol, teicoplanin, vancomycine, and levofloxacin, providing potential alternative choices of treatment against infections with S. pyogenes. PMID:24826076

Camara, Makhtar; Dieng, Assane; Boye, Cheikh Saad Bouh



Occupational Asthma in Antibiotic Manufacturing Workers: Case Reports and Systematic Review  

PubMed Central

Background. The risks of occupational asthma (OA) from antibiotics are uncertain. We report 4 new cases and a systematic review of the literature. Methods. Cases were identified through a specialist clinic, each underwent specific provocation testing (SPT). We subsequently reviewed the published literature. Results. The patients were employed in the manufacture of antibiotics; penicillins were implicated in three cases, in the fourth erythromycin, not previously reported to cause OA. In two, there was evidence of specific IgE sensitisation. At SPT each developed a late asthmatic reaction and increased bronchial hyperresponsiveness. 36 case reports have been previously published, 26 (citing penicillins or cephalosporins). Seven cross-sectional workplace-based surveys found prevalences of 5–8%. Conclusions. OA in antibiotic manufacturers may be more common than is generally recognised. Its pathogenesis remains unclear; immunological tests are of uncertain value and potential cases require confirmation with SPT. Further study of its frequency, mechanisms, and diagnosis is required. PMID:21603168

Díaz Angulo, Sara; Szram, Joanna; Welch, Jenny; Cannon, Julie; Cullinan, Paul



TB and Antibiotic Resistance  

NSDL National Science Digital Library

How does the development of antibiotic resistant strains of TB influence modern healthcare practices? We will consider genetic, environmental, epidemiological, and social perspectives of this renewed threat to public health. The TB simulation allows us to experiment with several TB strains and the antibiotics used to treat TB as we explore antibiotic resistance. * use sequence information to develop a protocol for treating antibiotic resistant TB

Marion Fass (Beloit College; Biology)



Experimental evolution of antibiotic resistance  

E-print Network

SUPERBUGS! Experimental evolution of antibiotic resistance #12;REVIEW Most bacteria;Susceptible + Antibiotic Antibiotic Resistant #12;QUESTION How can we cause bacteria to evolve antibiotic resistance? #12;HYPOTHESIS If bacteria are grown in the presence

Rose, Michael R.


Role of pleiotropy during adaptation of TEM-1 ?-lactamase to two novel antibiotics  

PubMed Central

Pleiotropy is a key feature of the genotype–phenotype map, and its form and extent have many evolutionary implications, including for the dynamics of adaptation and the evolution of specialization. Similarly, pleiotropic effects of antibiotic resistance mutations may affect the evolution of antibiotic resistance in the simultaneous or fluctuating presence of different antibiotics. Here, we study the role of pleiotropy during the in vitro adaptation of the enzyme TEM-1 ?-lactamase to two novel antibiotics, cefotaxime (CTX) and ceftazidime (CAZ). We subject replicate lines for four rounds of evolution to selection with CTX and CAZ alone, and in their combined and fluctuating presence. Evolved alleles show positive correlated responses when selecting with single antibiotics. Nevertheless, pleiotropic constraints are apparent from the effects of single mutations and from selected alleles showing smaller correlated than direct responses and smaller responses after simultaneous and fluctuating selection with both than with single antibiotics. We speculate that these constraints result from structural changes in the oxyanion pocket surrounding the active site, where accommodation of CTX and the larger CAZ is balanced against their positioning with respect to the active site. Our findings suggest limited benefits from the combined or fluctuating application of these related cephalosporins for containing antibiotic resistance.

Schenk, Martijn F; Witte, Sariette; Salverda, Merijn L M; Koopmanschap, Bertha; Krug, Joachim; de Visser, J Arjan G M



Antibiotic susceptibility of Clostridium difficile is similar worldwide over two decades despite widespread use of broad-spectrum antibiotics: an analysis done at the University Hospital of Zurich.  


Background Clostridium difficile infection (CDI) remains a major health problem worldwide. Antibiotic use, in general, and clindamycin and ciprofloxacin, in particular, have been implicated in the pathogenesis of CDI. Here, we hypothesized that antibiotics that are highly active in vitro against C. difficile are less frequently associated with CDI than others. The primary goals of our study were to determine if antibiotic susceptibility and CDI are associated and whether the antimicrobial susceptibility of C. difficile changed over the years.Methods and resultsWe examined a large panel of C. difficile strains collected in 2006¿2008 at the University Hospital of Zurich. We found that the antimicrobial susceptibilities to amoxicillin/clavulanate, piperacillin/tazobactam, meropenem, clindamycin, ciprofloxacin, ceftriaxone, metronidazole and vancomycin were similar to those reported in the literature and that they are similar to those reported in other populations over the last two decades. Antibiotic activity did not prevent CDI. For example, thre use of meropenem, which is highly active against all strains tested, was a clear risk factor for CDI. Most of the antibiotics tested also showed a higher minimum inhibitory concentration distribution than that of EUCAST. All strains were susceptible to metronidazole. One strain was resistant to vancomycin.ConclusionsAntibiotic susceptibilities of the collection of C. difficile from the University Hospital of Zurich are similar to those reported by others since the 1980. Patients treated with carbapenems and cephalosporins had the highest risk of developing CDI irrespective of the antimicrobial activity of carbapenems. PMID:25425433

Büchler, Andrea C; Rampini, Silvana K; Stelling, Simon; Ledergerber, Bruno; Peter, Silke; Schweiger, Alexander; Ruef, Christian; Zbinden, Reinhard; Speck, Roberto F



Antibiotic resistance in Chlamydiae  

PubMed Central

There are few documented reports of antibiotic resistance in Chlamydia and no examples of natural and stable antibiotic resistance in strains collected from humans. While there are several reports of clinical isolates exhibiting resistance to antibiotics, these strains either lost their resistance phenotype in vitro, or lost viability altogether. Differences in procedures for chlamydial culture in the laboratory, low recovery rates of clinical isolates and the unknown significance of heterotypic resistance observed in culture may interfere with the recognition and interpretation of antibiotic resistance. Although antibiotic resistance has not emerged in chlamydiae pathogenic to humans, several lines of evidence suggest they are capable of expressing significant resistant phenotypes. The adept ability of chlamydiae to evolve to antibiotic resistance in vitro is demonstrated by contemporary examples of mutagenesis, recombination and genetic transformation. The isolation of tetracycline-resistant Chlamydia suis strains from pigs also emphasizes their adaptive ability to acquire antibiotic resistance genes when exposed to significant selective pressure. PMID:20860486

Sandoz, Kelsi M; Rockey, Daniel D



Coping with antibiotic resistance: combining nanoparticles with antibiotics and other antimicrobial agents.  


The worldwide escalation of bacterial resistance to conventional medical antibiotics is a serious concern for modern medicine. High prevalence of multidrug-resistant bacteria among bacteria-based infections decreases effectiveness of current treatments and causes thousands of deaths. New improvements in present methods and novel strategies are urgently needed to cope with this problem. Owing to their antibacterial activities, metallic nanoparticles represent an effective solution for overcoming bacterial resistance. However, metallic nanoparticles are toxic, which causes restrictions in their use. Recent studies have shown that combining nanoparticles with antibiotics not only reduces the toxicity of both agents towards human cells by decreasing the requirement for high dosages but also enhances their bactericidal properties. Combining antibiotics with nanoparticles also restores their ability to destroy bacteria that have acquired resistance to them. Furthermore, nanoparticles tagged with antibiotics have been shown to increase the concentration of antibiotics at the site of bacterium-antibiotic interaction, and to facilitate binding of antibiotics to bacteria. Likewise, combining nanoparticles with antimicrobial peptides and essential oils generates genuine synergy against bacterial resistance. In this article, we aim to summarize recent studies on interactions between nanoparticles and antibiotics, as well as other antibacterial agents to formulate new prospects for future studies. Based on the promising data that demonstrated the synergistic effects of antimicrobial agents with nanoparticles, we believe that this combination is a potential candidate for more research into treatments for antibiotic-resistant bacteria. PMID:22029522

Allahverdiyev, Adil M; Kon, Kateryna Volodymyrivna; Abamor, Emrah Sefik; Bagirova, Malahat; Rafailovich, Miriam



Influence of dissolved oxygen concentration on the biosynthesis of cephalosporin C.  


Cephalosporin C was produced by a highly productive strain of Cephalosporium acremonium under industrial production conditions by fed-batch cultivation in a 40-l stirred-tank reactor using a complex medium containing 50 g l-1 peanut flour. The influence of dissolved oxygen concentration (pO2, DOC), which was maintained at different constant levels between 5 and 40% of its saturation value, during the production phase by means of a parameter-adaptive pO2-controller, on the cephalosporin C biosynthesis, was investigated. The concentrations of cephalosporin C (CPC) and its precursors penicillin N (PEN N), deacetoxycephalosporin C (DAOC), and deacetylcephalosporin C (DAC) were monitored by on-line HPLC. The concentrations of amino acids, valine (VAL), cysteine (CYS), alpha-amino-adipic acid (alpha-AAA), the dipeptide alpha-amino-adipyl-cysteine (AC), and the tripeptide alpha-amino-adipyl-cysteinyl-valine (ACV) were determined by off-line HPLC. By reducing the pO2 in the production phase from 40 to 5% of its saturation value, the CPC concentration diminished from 7.2 to 1.1 g l-1 and the PEN N concentration increased from 2.57 to 7.65 g l-1. The DAC concentration also dropped from 3.13 to 0.42 g l-1; however, the DAOC concentration was less influenced. The concentrations of AC and ACV were also less affected. The small DOC did not lead to an accumulation of the intermediate AC and ACV during the production phase. With increasing DOC in the range of 5-20%, the maximal specific production rate, the cell mass concentration-based and the substrate-based yield coefficients for CPC increased almost linearly, and fell back for PEN N.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1368971

Zhou, W; Holzhauer-Rieger, K; Dors, M; Schügerl, K



Comparative kinetic analysis on thermal degradation of some cephalosporins using TG and DSC data  

PubMed Central

Background The thermal decomposition of cephalexine, cefadroxil and cefoperazone under non-isothermal conditions using the TG, respectively DSC methods, was studied. In case of TG, a hyphenated technique, including EGA, was used. Results The kinetic analysis was performed using the TG and DSC data in air for the first step of cephalosporin’s decomposition at four heating rates. The both TG and DSC data were processed according to an appropriate strategy to the following kinetic methods: Kissinger-Akahira-Sunose, Friedman, and NPK, in order to obtain realistic kinetic parameters, even if the decomposition process is a complex one. The EGA data offer some valuable indications about a possible decomposition mechanism. The obtained data indicate a rather good agreement between the activation energy’s values obtained by different methods, whereas the EGA data and the chemical structures give a possible explanation of the observed differences on the thermal stability. A complete kinetic analysis needs a data processing strategy using two or more methods, but the kinetic methods must also be applied to the different types of experimental data (TG and DSC). Conclusion The simultaneous use of DSC and TG data for the kinetic analysis coupled with evolved gas analysis (EGA) provided us a more complete picture of the degradation of the three cephalosporins. It was possible to estimate kinetic parameters by using three different kinetic methods and this allowed us to compare the Ea values obtained from different experimental data, TG and DSC. The thermodegradation being a complex process, the both differential and integral methods based on the single step hypothesis are inadequate for obtaining believable kinetic parameters. Only the modified NPK method allowed an objective separation of the temperature, respective conversion influence on the reaction rate and in the same time to ascertain the existence of two simultaneous steps. PMID:23594763



Antibiotic susceptibility survey of Neisseria gonorrhoeae in Thailand.  


The antibiotic susceptibilities of Neisseria gonorrhoeae isolates obtained from patients attending sexually transmitted disease clinics in Cholburi and Bangkok, Thailand, were determined by agar dilution. Some 28.2% of isolates produced beta-lactamase. A total of 97.9% of beta-lactamase-positive and 51% of beta-lactamase-negative isolates tested were resistant to penicillin (MICs, greater than or equal to 2 micrograms/ml), 70% of isolates tested were resistant to tetracycline (MICs, greater than or equal to 2 micrograms/ml), and 91% of isolates tested were susceptible to spectinomycin (MICs, less than or equal to 64 micrograms/ml). The MICs for 90% of isolates for the other drugs tested were 2 micrograms/ml for erythromycin, 2 micrograms/ml for cefoxitin, 1 micrograms/ml for cefuroxime, 0.125 micrograms/ml for cefpodoxime, 0.06 micrograms/ml for cefotaxime, 0.25 micrograms/ml for ceftazidime, 0.03 micrograms/ml for ceftizoxime, 0.03 micrograms/ml for ceftriaxone, 0.03 micrograms/ml for cefixime, 0.06 micrograms/ml for aztreonam, 0.008 micrograms/ml for ciprofloxacin, 0.125 micrograms/ml for norfloxacin, and 0.075 micrograms/ml for ofloxacin. Fewer than 1.5% of isolates were resistant to the extended-spectrum cephalosporins tested. Some 0.3% or fewer isolates were resistant to broad-spectrum cephalosporins, fluoroquinolones, or the monobactam aztreonam. Antibiotic resistance among N. gonorrhoeae isolates from Cholburi and Bangkok in May 1990 appeared to be primarily limited to penicillin and tetracycline, which are no longer used to control gonorrhea. Spectinomycin, which has been in general use against gonorrhea in Thailand since 1983, has dwindling utility, with resistance at a level of 8.9%. PMID:1416851

Clendennen, T E; Echeverria, P; Saengeur, S; Kees, E S; Boslego, J W; Wignall, F S



[Mouth diseases and antibiotic therapy practices in Yaounde].  


Based on 309 patients (171 women and 138 men), consulted by 15 dental surgeons of Yaounde during one year, the aim of this study was the evaluation of bringing into use an antibiotherapy in daily practice. A questionnaire on the subject was distributed to practitioners. We registered 10 most frequent mouth dental diseases that needed curative antibiotherapy, being 87% of prescriptions. A prophylactic antibiotherapy has been prescripted in three per cent of cases to patients carriers of general pathologies (cardiopathies, diabete...) or mandibular fractures. In 10% of cases, a covering antibiotherapy has been established during simple extractions of teeth without infections, from healthy patients. In 48% of cases the duration of antibiotherapy was short (less than eight days) and in 32% of cases, the quantities were infratherapeutic. There were three per cent of prescriptions concerning antibiotics (sulfonamides, phenicoles...) unsuited to usual germs of mouth cavity. Generics drugs have been prescribed in 12% of cases. The more prescribed antibiotics were amoxicillins, macrolides and cephalosporines. Only a best knowledge of antibiotics' families and their indications are able to avoid clumsiness. At last generic drugs prescription in our difficult economical environment should be common. PMID:16704021

Onana, J; Bengondo, M C; Bengono, G



Management of meningitis due to antibiotic-resistant Acinetobacter species.  


Acinetobacter meningitis is becoming an increasingly common clinical entity, especially in the postneurosurgical setting, with mortality from this infection exceeding 15%. Infectious Diseases Society of America guidelines for therapy of postneurosurgical meningitis recommend either ceftazidime or cefepime as empirical coverage against Gram-negative pathogens. However, assessment of the pharmacodynamics of these cephalosporins in cerebrospinal fluid suggests that recommended doses will achieve pharmacodynamic targets against fewer than 10% of contemporary acinetobacter isolates. Thus, these antibiotics are poor options for suspected acinetobacter meningitis. From in vitro and pharmacodynamic perspectives, intravenous meropenem plus intraventricular administration of an aminoglycoside may represent a superior, albeit imperfect, regimen for suspected acinetobacter meningitis. For cases of meningitis due to carbapenem-resistant acinetobacter, use of tigecycline is not recommended on pharmacodynamic grounds. The greatest clinical experience rests with use of polymyxins, although an intravenous polymyxin alone is inadvisable. Combination with an intraventricularly administered antibiotic plus removal of infected neurosurgical hardware appears the therapeutic strategy most likely to succeed in this situation. Unfortunately, limited development of new antibiotics plus the growing threat of multidrug-resistant acinetobacter is likely to increase the problems posed by acinetobacter meningitis in the future. PMID:19324297

Kim, Baek-Nam; Peleg, Anton Y; Lodise, Thomas P; Lipman, Jeffrey; Li, Jian; Nation, Roger; Paterson, David L



Structures of the class D Carbapenemases OXA-23 and OXA-146: mechanistic basis of activity against carbapenems, extended-spectrum cephalosporins, and aztreonam.  


Class D ?-lactamases that hydrolyze carbapenems such as imipenem and doripenem are a recognized danger to the efficacy of these "last-resort" ?-lactam antibiotics. Like all known class D carbapenemases, OXA-23 cannot hydrolyze the expanded-spectrum cephalosporin ceftazidime. OXA-146 is an OXA-23 subfamily clinical variant that differs from the parent enzyme by a single alanine (A220) inserted in the loop connecting ?-strands ?5 and ?6. We discovered that this insertion enables OXA-146 to bind and hydrolyze ceftazidime with an efficiency comparable to those of other extended-spectrum class D ?-lactamases. OXA-146 also binds and hydrolyzes aztreonam, cefotaxime, ceftriaxone, and ampicillin with higher efficiency than OXA-23 and preserves activity against doripenem. In this study, we report the X-ray crystal structures of both the OXA-23 and OXA-146 enzymes at 1.6-? and 1.2-? resolution. A comparison of the two structures shows that the extra alanine moves a methionine (M221) out of its normal position, where it forms a bridge over the top of the active site. This single amino acid insertion also lengthens the ?5-?6 loop, moving the entire backbone of this region further away from the active site. A model of ceftazidime bound in the active site reveals that these two structural alterations are both likely to relieve steric clashes between the bulky R1 side chain of ceftazidime and OXA-23. With activity against all four classes of ?-lactam antibiotics, OXA-146 represents an alarming new threat to the treatment of infections caused by Acinetobacter spp. PMID:23877677

Kaitany, Kip-Chumba J; Klinger, Neil V; June, Cynthia M; Ramey, Maddison E; Bonomo, Robert A; Powers, Rachel A; Leonard, David A



Biotic acts of antibiotics  

PubMed Central

Biological functions of antibiotics are not limited to killing. The most likely function of antibiotics in natural microbial ecosystems is signaling. Does this signaling function of antibiotics also extend to the eukaryotic – in particular mammalian – cells? In this review, the host modulating properties of three classes of antibiotics (macrolides, tetracyclines, and ?-lactams) will be briefly discussed. Antibiotics can be effective in treatment of a broad spectrum of diseases and pathological conditions other than those of infectious etiology and, in this capacity, may find widespread applications beyond the intended antimicrobial use. This use, however, should not compromise the primary function antibiotics are used for. The biological background for this inter-kingdom signaling is also discussed. PMID:23966991

Aminov, Rustam I.



On the use of antibiotics to reduce rhizoplane microbial populations in root physiology and ecology investigations  

NASA Technical Reports Server (NTRS)

No straightforward method exists for separating the proportion of ion exchange and respiration due to rhizoplane microbial organisms from that of root ion exchange and respiration. We examined several antibiotics that might be used for the temporary elimination of rhizoplane bacteria from hydroponically grown wheat roots (Triticum aestivum cv. Veery 10). Each antibiotic was tested for herbicidal activity and plate counts were used to enumerate bacteria and evaluate antibiotic kinetics. Only lactam antibiotics (penicillins and cephalosporins) did not reduce wheat growth rates. Aminoglycosides, the pyrimidine trimethoprim, colistin and rifampicin reduced growth rates substantially. Antibiotics acted slowly, with maximum reductions in rhizoplane bacteria occurring after more than 48 h of exposure. Combinations of nonphytotoxic antibiotics reduced platable rhizoplane bacteria by as much as 98%; however, this was generally a reduction from about 10(9) to 10(6) colony forming units per gram of dry root mass, so that many viable bacteria remained on root surfaces. We present evidence which suggests that insufficient bacterial biomass exists on root surfaces of nonstressed plants grown under well-aerated conditions to quantitatively interfere with root nitrogen absorption measurements.

Smart, D. R.; Ferro, A.; Ritchie, K.; Bugbee, B. G.



Sideromycins: tools and antibiotics  

Microsoft Academic Search

Sideromycins are antibiotics covalently linked to siderophores. They are actively transported into gram-positive and gram-negative\\u000a bacteria. Energy-coupled transport across the outer membrane and the cytoplasmic membrane strongly increases their antibiotic\\u000a efficiency; their minimal inhibitory concentration is at least 100-fold lower than that of antibiotics that enter cells by\\u000a diffusion. This is particularly relevant for gram-negative bacteria because the outer membrane,

Volkmar Braun; Avijit Pramanik; Thomas Gwinner; Martin Köberle; Erwin Bohn



Turning the tide or riding the waves? Impacts of antibiotic stewardship and infection control on MRSA strain dynamics in a Scottish region over 16?years: non-linear time series analysis  

PubMed Central

Objectives To explore temporal associations between planned antibiotic stewardship and infection control interventions and the molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA). Design Retrospective ecological study and time-series analysis integrating typing data from the Scottish MRSA reference laboratory. Setting Regional hospital and primary care in a Scottish Health Board. Participants General adult (N=1?051?993) or intensive care (18?235) admissions and primary care registrations (460?000 inhabitants) between January 1997 and December 2012. Interventions Hand-hygiene campaign; MRSA admission screening; antibiotic stewardship limiting use of macrolides and ‘4Cs’ (cephalosporins, coamoxiclav, clindamycin and fluoroquinolones). Outcome measures Prevalence density of MRSA clonal complexes CC22, CC30 and CC5/Other in hospital (isolates/1000 occupied bed days, OBDs) and community (isolates/10?000 inhabitant-days). Results 67% of all clinical MRSA isolates (10?707/15?947) were typed. Regional MRSA population structure was dominated by hospital epidemic strains CC30, CC22 and CC45. Following declines in overall MRSA prevalence density, CC5 and other strains of community origin became increasingly important. Reductions in use of ‘4Cs’ and macrolides anticipated declines in sublineages with higher levels of associated resistances. In multivariate time-series models (R2=0.63–0.94) introduction of the hand-hygiene campaign, reductions in mean length of stay (when >4?days) and bed occupancy (when >74 to 78%) predicted declines in CC22 and CC30, but not CC5/other strains. Lower importation pressures, expanded MRSA admission screening, and reductions in macrolide and third generation cephalosporin use (thresholds for association: 135–141, and 48–81 defined daily doses/1000 OBDs, respectively) were followed by declines in all clonal complexes. Strain-specific associations with fluoroquinolones and clindamycin reflected resistance phenotypes of clonal complexes. Conclusions Infection control measures and changes in population antibiotic use were important predictors of MRSA strain dynamics in our region. Strategies to control MRSA should consider thresholds for effects and strain-specific impacts. PMID:25814495

Lawes, Timothy; López-Lozano, José-María; Nebot, César; Macartney, Gillian; Subbarao-Sharma, Rashmi; Dare, Ceri R J; Edwards, Giles F S; Gould, Ian M



Novel Method for Detection of ?-Lactamases by Using a Chromogenic Cephalosporin Substrate  

PubMed Central

A new cephalosporin with a highly reactive ?-lactam ring was found to give an immediate color change in the presence of ?-lactamases from many bacteria, including staphylococci, Bacillus species, Enterobacteriaceae, and Pseudomonas. The reaction is confined to organisms producing ?-lactamases, but it is sufficiently sensitive to indicate the presence of this enzyme is small amounts in strains previously considered not to produce it. The compound has an unusual ultraviolet spectrum, and the color change can be followed quantitatively by measuring changes in absorption which occur in the 380- to 500-nm region, where cephalosporins normally have no absorption. The development of color is thought to be a consequence of the ?-lactam ring being unusually highly conjugated with the 3-substituent. Although in the bacteria only ?-lactamases produce this color change, it was found that serum and tissues from experimental animals also rapidly produced the colored breakdown product, which was then excreted in the urine. The mechanism of the mammalian breakdown was considered to be different from that found in bacteria. PMID:4208895

O'Callaghan, Cynthia H.; Morris, A.; Kirby, Susan M.; Shingler, A. H.



The Real Practice of Antibiotic Prophylaxis for Prostate Biopsy in Korea Where the Prevalence of Quinolone-Resistant Escherichia coli Is High  

PubMed Central

Purpose Transrectal ultrasonography-guided prostate biopsy (TRUS-Bx) is an essential procedure for diagnosing prostate cancer. The American Urological Association (AUA) Guideline recommends fluoroquinolone alone for 1 day during TRUS-Bx. However, this recommendation may not be appropriate in regions where the prevalence of quinolone-resistant Escherichia coli is high. We investigated the real practice of antibiotic prophylaxis for TRUS-Bx in Korea. Materials and Methods A total of 77 hospitals performing TRUS-Bx were identified and an e-mail was sent to the Urology Department of those hospitals. The questions in the e-mail included the choice of antibiotics before and after the procedure and the duration of antibiotic therapy after TRUS-Bx. Results A total of 54 hospitals (70.0%) responded to the e-mail. Before TRUS-Bx, all hospitals administered intravenous antibiotic prophylaxis. The percentage of hospitals that used quinolone, cephalosporin, and aminoglycoside alone was 48.1%, 20.4%, and 9.3%, respectively. The percentage of hospitals that used two or more antibiotics was 22.2%. After biopsy, all 54 hospitals prescribed oral antibiotics. The percentage of hospitals that prescribed quinolone alone, cephalosporin alone, or a combination of two or more antibiotics was 77.8%, 20.4%, and 1.8%, respectively. The duration of antibiotic use was more than 3 days in most hospitals (79.6%). Only four hospitals (7.4%) followed the AUA recommendation of a 1-day regimen. Conclusions The AUA recommendation was not followed by most hospitals in Korea. This clinical behavior might reflect the high quinolone resistance rate in Korea, and further studies on the most efficient prophylactic antibiotics after TRUS-Bx in Korea are warranted. PMID:25237461

Kim, Dae Hyun; Bae, Sang Rak; Choi, Woo Suk; Paick, Sung Hyun; Kim, Hyeong Gon; Loh, Yong Soo



Access to antibiotics in New Delhi, India: implications for antibiotic policy  

PubMed Central

Objective The present survey was conducted to investigate the price and availability of a basket of 24 essential antibiotics and eight high-end antibiotics at various levels of health care in public and private sector in National Capital Territory of Delhi, India using standardized WHO/HAI methodology. Methods Data on procurement price and availability was collected from three public healthcare providers in the state: the federal (central) government, state government and Municipal Corporation of Delhi (MCD). Overall a total of 83 public facilities, 68 primary care, 10 secondary cares and 5 tertiary care facilities were surveyed. Data was also collected from private retail (n?=?40) and chain pharmacies (n?=?40) of a leading corporate house. Prices were compared to an international reference price (expressed as median price ratio-MPR). Results Public sector: Delhi state government has its essential medicine list (Delhi state EML) and was using Delhi state EML 2007 for procurement; the other two agencies had their own procurement list. All the antibiotics procured including second and third generation antibiotics except for injections were available at primary care facilities. Antibiotic available were on the basis of supply rather than rationality or the Delhi state EML and none was 100% available. There was sub-optimal availability of some essential antibiotics while other non-essential ones were freely available. Availability of antibiotics at tertiary care facilities was also sub-optimal. Private sector: Availability of antibiotics was good. For most of the antibiotics the most expensive and popular trade names were often available. High-end antibiotics, meropenam, gemifloxacin, and moxifloxacin were commonly available. In retail pharmacies some newer generation non-essential antibiotics like gemifloxacin were priced lower than the highest-priced generic of amoxicillin?+?clavulanic acid, azithromycin, and cefuroxime aexitl. Conclusions Inappropriate availability and pricing of newer generation antibiotics, which may currently be bought without prescription, is likely to lead to their over-use and increased resistance. All providers should follow the EML of whichever of the three concerned Delhi public sector agencies that it is under and these EMLs should follow the essential medicine concept. The Indian regulatory authorities need to consider urgently, drug schedules and pricing policies that will curtail inappropriate access to new generation antibiotics. PMID:24764541



?-Lactams and Florfenicol Antibiotics Remain Bioactive in Soils while Ciprofloxacin, Neomycin, and Tetracycline Are Neutralized?  

PubMed Central

It is generally assumed that antibiotic residues in soils select for antibiotic-resistant bacteria. This assumption was tested by separately adding 10 different antibiotics (?200 ppm) to three soil-water slurries (silt-loam, sand-loam, and sand; 20% soil [wt/vol]) and incubating mixtures for 24 h at room temperature. The antibiotic activity of the resultant supernatant was assessed by culturing a sensitive Escherichia coli strain in the filter-sterilized supernatant augmented with Luria-Bertani broth. We found striking differences in the abilities of supernatants to suppress growth of the indicator E. coli. Ampicillin, cephalothin, cefoxitin, ceftiofur, and florfenicol supernatants completely inhibited growth while bacterial growth was uninhibited in the presence of neomycin, tetracycline, and ciprofloxacin supernatants. High-performance liquid chromatography (HPLC) analysis demonstrated that cefoxitin and florfenicol were almost completely retained in the supernatants, whereas tetracycline and ciprofloxacin were mostly removed. Antibiotic dissipation in soil, presumably dominated by adsorption mechanisms, was sufficient to neutralize 200 ppm of tetracycline; this concentration is considerably higher than reported contamination levels. Soil pellets from the tetracycline slurries were resuspended in a minimal volume of medium to maximize the interaction between bacteria and soil particles, but sensitive bacteria were still unaffected by tetracycline (P = 0.6). Thus, residual antibiotics in soil do not necessarily exert a selective pressure, and the degree to which the pharmaceutical remains bioactive depends on the antibiotic. Efforts to control antibiotic contamination would be better directed toward compounds that retain biological activity in soils (e.g., cephalosporins and florfenicol) because these are the antibiotics that could exert a selective pressure in the environment. PMID:21856822

Subbiah, Murugan; Mitchell, Shannon M.; Ullman, Jeffrey L.; Call, Douglas R.



Tackling antibiotic resistance  

Microsoft Academic Search

The development and spread of antibiotic resistance in bacteria is a universal threat to both humans and animals that is generally not preventable but can nevertheless be controlled, and it must be tackled in the most effective ways possible. To explore how the problem of antibiotic resistance might best be addressed, a group of 30 scientists from academia and industry

Karen Bush; Patrice Courvalin; Gautam Dantas; Barry Eisenstein; Pentti Huovinen; George A. Jacoby; Roy Kishony; Barry N. Kreiswirth; Elizabeth Kutter; Stephen A. Lerner; Stuart Levy; Kim Lewis; Olga Lomovskaya; Jeffrey H. Miller; Shahriar Mobashery; Laura J. V. Piddock; Steven Projan; Christopher M. Thomas; Alexander Tomasz; Paul M. Tulkens; Timothy R. Walsh; James D. Watson; Jan Witkowski; Wolfgang Witte; Gerry Wright; Pamela Yeh; Helen I. Zgurskaya; Julian Davies



Antibiotic resistance in animals  

Microsoft Academic Search

There is currently no systematic surveillance or monitoring of antibiotic resistance in Australian animals. Registration of antibiotics for use in animals is tightly controlled and has been very conservative. Fluoroquinolones have not been registered for use in food producing animals and other products have been removed from the market because of human health concerns. In the late 1970s, the Animal

Mary D Barton; Rachael Pratt; Wendy S Hart


Antibiotic Resistance in Poultry  

Microsoft Academic Search

The worldwide increase in the use of antibiotics as an integral part of the poultry and livestock production industry to treat and prevent infectious bacterial diseases and as growth promoters at sub - therapeutic levels in feeds has led to the problem of the development of bacterial antibiotic resistance during the past years. Recent scientific evidence has shown that resistance

D. F. Apata



Evolution of an Antibiotic Resistance Enzyme Constrained by Stability and Activity Trade-offs  

SciTech Connect

Pressured by antibiotic use, resistance enzymes have been evolving new activities. Does such evolution have a cost? To investigate this question at the molecular level, clinically isolated mutants of the {beta}-lactamase TEM-1 were studied. When purified, mutant enzymes had increased activity against cephalosporin antibiotics but lost both thermodynamic stability and kinetic activity against their ancestral targets, penicillins. The X-ray crystallographic structures of three mutant enzymes were determined. These structures suggest that activity gain and stability loss is related to an enlarged active site cavity in the mutant enzymes. In several clinically isolated mutant enzymes, a secondary substitution is observed far from the active site (Met182 {yields} Thr). This substitution had little effect on enzyme activity but restored stability lost by substitutions near the active site. This regained stability conferred an advantage in vivo. This pattern of stability loss and restoration may be common in the evolution of new enzyme activity.

Wang, Xiaojun; Minasov, George; Shoichet, Brian K. (NWU)



Methicillin-resistant Staphylococcus aureus Bacterial Nitric-oxide Synthase Affects Antibiotic Sensitivity  

E-print Network

Methicillin-resistant Staphylococcus aureus Bacterial Nitric-oxide Synthase Affects Antibiotic of Medicine, New York, New York 10016 Background: Methicillin-resistant Staphylococcus aureus (MRSA) generates activities to reduce MRSA pathology and increase antibiotic effectiveness. Staphylococcus aureus infections

Nizet, Victor


Impact of the Use of ?-Lactam Antimicrobials on the Emergence of Escherichia coli Isolates Resistant to Cephalosporins under Standard Pig-Rearing Conditions.  


The aim of this study was to evaluate if the treatments with ceftiofur and amoxicillin are risk factors for the emergence of cephalosporin resistant (CR) E. coli in a pig farm during the rearing period. One hundred 7-day-old piglets were divided into two groups, a control (n = 50) group and a group parenterally treated with ceftiofur (n = 50). During the fattening period, both groups were subdivided in two. A second treatment with amoxicillin was administered in feed to two of the four groups, as follows: group 1 (untreated, n = 20), group 2 (treated with amoxicillin, n = 26), group 3 (treated with ceftiofur, n = 20), and group 4 (treated with ceftiofur and amoxicillin, n = 26). During treatment with ceftiofur, fecal samples were collected before treatment (day 0) and at days 2, 7, 14, 21, and 42 posttreatment, whereas with amoxicillin, the sampling was extended 73 days posttreatment. CR E. coli bacteria were selected on MacConkey agar with ceftriaxone (1 mg/liter). Pulsed-field gel electrophoresis (PFGE), MICs of 14 antimicrobials, the presence of cephalosporin resistance genes, and replicon typing of plasmids were analyzed. Both treatments generated an increase in the prevalence of CR E. coli, which was statistically significant in the treated groups. Resistance diminished after treatment. A total of 47 CR E. coli isolates were recovered during the study period; of these, 15 contained blaCTX-M-1, 10 contained blaCTX-M-14, 4 contained blaCTX-M-9, 2 contained blaCTX-M-15, and 5 contained blaSHV-12. The treatment with ceftiofur and amoxicillin was associated with the emergence of CR E. coli during the course of the treatment. However, by the time of finishing, CR E. coli bacteria were not recovered from the animals. PMID:25548055

Cameron-Veas, Karla; Solà-Ginés, Marc; Moreno, Miguel A; Fraile, Lorenzo; Migura-Garcia, Lourdes



Sorption Mechanisms of Antibiotic Cephapirin onto Quartz and Feldspar by Raman Spectroscopy  

SciTech Connect

Raman spectroscopy was used to investigate the sorption mechanisms of cephapirin (CHP), a veterinary antibiotic, onto quartz (SiO2) and feldspar (KAlSi3O8) at different pH values. Depending on the charge and surface properties of the mineral, different reaction mechanisms including electrostatic attraction, monodentate and bidentate complexation were found to be responsible for CHP sorption. The zwitterion (CHPo) adsorbs to a quartz(+) surface by electrostatic attraction of the carboxylate anion group ( COO-) at a low pH, but adsorbs to a quartz(-) surface through electrostatic attraction of the pyridinium cation and possibly COO- bridge complexes at relatively higher pH conditions. CHP- bonds to a quartz(-) surface by bidentate complexation between one oxygen of COO- and oxygen from the carbonyl (C=O) of the acetoxymethyl group. On a feldspar surface of mixed charge, CHPo forms monodentate complexes between C=O as well as COO- bridging complexes or electrostatically attached to localized edge (hydr)oxy-Al surfaces. CHP- adsorbs to feldspar(-) through monodentate C=O complexation, and similar mechanisms may operate for the sorption of other cephalosporins. This research demonstrates, for the first time, that Raman spectroscopic techniques can be effective for evaluating the sorption processes and mechanisms of cephalosporin antibiotics even at relatively low sorbed concentrations (97-120 ?mol/kg).

Peterson, Jonathan [Hope College; Wang, Wei [ORNL; Gu, Baohua [ORNL



[Monitoring of level of antibiotic resistance of microbial strains, isolated in cases of surgical infections in period from 2003 to 2005 years].  


Microbial structure of surgical infections and level of antibiotic resistance of microbial strains isolated in period from 2003 to 2005 years was investigated. As a result of performed investigation, 871 strains of different microbial species were isolated. It occurred that, in microbial structure of wound infections isolation of gram-positive microflora (509 strains) was 1,5 times higher than gram-negative (362 strains). Quantitative analisation has shown, that microorganisms were isolated in high amount, COU=10(5)-10(8). In 49% of cases microorganisms were isolated as microbial associations. In 37% of isolated microorganisms they had Nosocomial features. Investigation of sensitivity of microorganisms to antibiotics of all known group has shown tendency of rise of level of resistance even to modern antibiotics. It was found out Cephalosporins, Phtorhinolons and Karbapenems are showing good result. Basing on performed investigations could be recommended--strictening of strategy and control in use of antibiotics. PMID:16575149

Chikviladze, D P; Metreveli, D A; Mikeladze, M L; Gachechiladze, Kh E; Iosebashvili, T S



Biosensors, antibiotics and food.  


Antibiotics are medicine's leading asset for fighting microbial infection, which is one of the leading causes of death worldwide. However, the misuse of antibiotics has led to the rapid spread of antibiotic resistance among bacteria and the development of multiple resistant pathogens. Therefore, antibiotics are rapidly losing their antimicrobial value. The use of antibiotics in food production animals is strictly controlled by the European Union (EU). Veterinary use is regulated to prevent the spread of resistance. EU legislation establishes maximum residue limits for veterinary medicinal products in foodstuffs of animal origin and enforces the establishment and execution of national monitoring plans. Among samples selected for monitoring, suspected noncompliant samples are screened and then subjected to confirmatory analysis to establish the identity and concentration of the contaminant. Screening methods for antibiotic residues are typically based on microbiological growth inhibition, whereas physico-chemical methods are used for confirmatory analysis. This chapter discusses biosensors, especially whole-cell based biosensors, as emerging screening methods for antibiotic residues. Whole-cell biosensors can offer highly sensitive and specific detection of residues. Applications demonstrating quantitative analysis and specific analyte identification further improve their potential as screening methods. PMID:25216955

Virolainen, Nina; Karp, Matti



Cephalosporin Resistance among Non-Typhi Salmonella from Humans, Retail Meats and Food Animals in the United States  

Technology Transfer Automated Retrieval System (TEKTRAN)

Background: The National Antimicrobial Resistance Monitoring System (NARMS) is a collaboration among the Food and Drug Administration (FDA), U.S. Department of Agriculture (USDA), and the Centers for Disease Control and Prevention (CDC). Here we report on decreased susceptibility to cephalosporins ...


Selective Pharmacologic Inhibition of a PASTA Kinase Increases Listeria monocytogenes Susceptibility to ?-Lactam Antibiotics  

PubMed Central

While ?-lactam antibiotics are a critical part of the antimicrobial arsenal, they are frequently compromised by various resistance mechanisms, including changes in penicillin binding proteins of the bacterial cell wall. Genetic deletion of the penicillin binding protein and serine/threonine kinase-associated protein (PASTA) kinase in methicillin-resistant Staphylococcus aureus (MRSA) has been shown to restore ?-lactam susceptibility. However, the mechanism remains unclear, and whether pharmacologic inhibition would have the same effect is unknown. In this study, we found that deletion or pharmacologic inhibition of the PASTA kinase in Listeria monocytogenes by the nonselective kinase inhibitor staurosporine results in enhanced susceptibility to both aminopenicillin and cephalosporin antibiotics. Resistance to vancomycin, another class of cell wall synthesis inhibitors, or antibiotics that inhibit protein synthesis was unaffected by staurosporine treatment. Phosphorylation assays with purified kinases revealed that staurosporine selectively inhibited the PASTA kinase of L. monocytogenes (PrkA). Importantly, staurosporine did not inhibit a L. monocytogenes kinase without a PASTA domain (Lmo0618) or the PASTA kinase from MRSA (Stk1). Finally, inhibition of PrkA with a more selective kinase inhibitor, AZD5438, similarly led to sensitization of L. monocytogenes to ?-lactam antibiotics. Overall, these results suggest that pharmacologic targeting of PASTA kinases can increase the efficacy of ?-lactam antibiotics. PMID:24867981

Pensinger, Daniel A.; Aliota, Matthew T.; Schaenzer, Adam J.; Boldon, Kyle M.; Ansari, Israr-ul H.; Vincent, William J. B.; Knight, Benjamin; Reniere, Michelle L.; Striker, Rob



Environmental pollution by antibiotics and by antibiotic resistance determinants  

Microsoft Academic Search

Antibiotics are among the most successful drugs used for human therapy. However, since they can challenge microbial populations, they must be considered as important pollutants as well. Besides being used for human therapy, antibiotics are extensively used for animal farming and for agricultural purposes. Residues from human environments and from farms may contain antibiotics and antibiotic resistance genes that can

Jose Luis Martinez



Previous antibiotic exposure and evolution of antibiotic resistance in mechanically ventilated patients with  

E-print Network

Previous antibiotic exposure and evolution of antibiotic resistance in mechanically ventilated, Taichung, Taiwan Keywords: Antibiotic resistance; Antibiotic exposure; Antibiotic selection pressure of antibiotic-resistant infections. Methods: We retrospectively analyzed 167 mechanically ventilated patients

Cochran-Stafira, D. Liane


Structural features of cephalosporin acylase reveal the basis of autocatalytic activation.  


Cephalosporin acylase (CA), a member of the N-terminal nucleophile hydrolase family, is activated through two steps of intramolecular autoproteolysis, the first mediated by a serine residue, and the second by a glutamate, which releases the pro-segment and produces an active enzyme. In this study, we have determined the crystal structures of mutants which could affect primary or secondary auto-cleavage and of sequential intermediates of a slow-processing mutant at 2.0-2.5A resolutions. The pro-segments of the mutants undergo dynamic conformational changes during activation and adopt surprisingly different loop conformations from one another. However, the autoproteolytic site was found to form a catalytically competent conformation with a solvent water molecule, which was essentially conserved in the CA mutants. PMID:19800869

Cho, Ki Joon; Kim, Jin Kwang; Lee, Ji-Hye; Shin, Hye Jeong; Park, Sung Soo; Kim, Kyung Hyun



Fighting antibiotic resistance in the intensive care unit using antibiotics.  


ABSTRACT? 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. PMID:25812462

Plantinga, Nienke L; Wittekamp, Bastiaan Hj; van Duijn, Pleun J; Bonten, Marc Jm



Aspergillomarasmine A overcomes metallo-?-lactamase antibiotic resistance.  


The emergence and spread of carbapenem-resistant Gram-negative pathogens is a global public health problem. The acquisition of metallo-?-lactamases (MBLs) such as NDM-1 is a principle contributor to the emergence of carbapenem-resistant Gram-negative pathogens that threatens the use of penicillin, cephalosporin and carbapenem antibiotics to treat infections. To date, a clinical inhibitor of MBLs that could reverse resistance and re-sensitize resistant Gram-negative pathogens to carbapenems has not been found. Here we have identified a fungal natural product, aspergillomarasmine A (AMA), that is a rapid and potent inhibitor of the NDM-1 enzyme and another clinically relevant MBL, VIM-2. AMA also fully restored the activity of meropenem against Enterobacteriaceae, Acinetobacter spp. and Pseudomonas spp. possessing either VIM or NDM-type alleles. In mice infected with NDM-1-expressing Klebsiella pneumoniae, AMA efficiently restored meropenem activity, demonstrating that a combination of AMA and a carbapenem antibiotic has therapeutic potential to address the clinical challenge of MBL-positive carbapenem-resistant Gram-negative pathogens. PMID:24965651

King, Andrew M; Reid-Yu, Sarah A; Wang, Wenliang; King, Dustin T; De Pascale, Gianfranco; Strynadka, Natalie C; Walsh, Timothy R; Coombes, Brian K; Wright, Gerard D



Eight More Ways To Deal with Antibiotic Resistance  

PubMed Central

The fight against antibiotic resistance must be strengthened. We propose actions that U.S. government agencies and private sector entities can take to build a more comprehensive effort. These actions can increase the viability of investing in new antibiotics, ensure the quality and stewardship of all antibiotics, and make responses to emerging resistance more informed. Success requires the thoughtful exercise of federal authority and a firm commitment to share data and reward developers for the value generated with new, life-saving antibiotics. PMID:24867992

Shlaes, David M.



Antibiotic Resistant Bacteria  

NSDL National Science Digital Library

This week's Topic In Depth is about antibiotic resistant bacteria.The first site is a recent news report from BBC news (1) that describes some recent research on resistant strains of two "of the world's most dangerous bacteria. Next is a Centers for Disease Control (CDC) page (2) with a brief background on antibiotic resistance and how to prevent it. A much more in-depth report is provided by the Select Committee on Science and Technology of the British House of Lords (3). There has been some public concern over the use of antibiotic resistant bacteria strains as markers in genetically modified food crops. The next two resources present information specific to this topic. The first is from the European Federation of Biotechnology (4), and the second is a shorter report from the Council for Biotechnology Information (5). The Alliance for the Prudent Use of Antibiotics (6) has a consumer and patient information section that explains what individuals can do to help prevent the problem from increasing. Readers who need a brief primer on antibiotics may appreciate this Web site from the University of Edinburgh (7). The last site is a "bugs in the news" feature from the University of Kansas (8), which is an easy-to-read explanation of "what the heck" antibiotic resistance is.

Lee, Amy.



Strategies to Minimize Antibiotic Resistance  

PubMed Central

Antibiotic resistance can be reduced by using antibiotics prudently based on guidelines of antimicrobial stewardship programs (ASPs) and various data such as pharmacokinetic (PK) and pharmacodynamic (PD) properties of antibiotics, diagnostic testing, antimicrobial susceptibility testing (AST), clinical response, and effects on the microbiota, as well as by new antibiotic developments. The controlled use of antibiotics in food animals is another cornerstone among efforts to reduce antibiotic resistance. All major resistance-control strategies recommend education for patients, children (e.g., through schools and day care), the public, and relevant healthcare professionals (e.g., primary-care physicians, pharmacists, and medical students) regarding unique features of bacterial infections and antibiotics, prudent antibiotic prescribing as a positive construct, and personal hygiene (e.g., handwashing). The problem of antibiotic resistance can be minimized only by concerted efforts of all members of society for ensuring the continued efficiency of antibiotics. PMID:24036486

Lee, Chang-Ro; Cho, Ill Hwan; Jeong, Byeong Chul; Lee, Sang Hee



Strain improvement studies on production of cephalosporin C from Acremonium chrysogenum ATCC 48272.  


Strain development for antibiotic production has been an essential prerequistie for efficient production process. Studies were carried out to produce high antibiotic yield strain by using UV and N-methyl-N1-nitro-nitrosoguanidine (NTG) as mutagens. A superior mutant (PNTG-22) with a productivity of 2.4 time (810-1995 microg/ml higher than, the parent strain was produced. PMID:16281823

Ellaiah, P; Kumar, J Prem; Saisha, V; Sumitra, J J; Vaishali, P


Aminoglycoside Kinases and Antibiotic Resistance  

Microsoft Academic Search

The evolution of antibiotic-resistant bacteria represents a serious public health concern. The appearance of strains with\\u000a resistance to multiple antibiotics threatens to render some infections untreatable by existing drugs. As a result, there is\\u000a considerable interest in understanding the mechanisms of antibiotic resistance and in identifying ways in which antibiotic\\u000a resistance can be overcome. Aminoglycoside antibiotics are broad-spectrum bactericidal compounds

D. H. Fong; D. Burk; A. Berghuis


Antibiotic therapy for ocular infection.  

PubMed Central

Infections of the eye can rapidly damage important functional structures and lead to permanent vision loss or blindness. Broad-spectrum antibiotics should be administered to the appropriate site of infection as soon as a diagnosis is made. Topical drops are preferred for corneal and conjunctival infections. Intravitreal antibiotics, and possibly subconjunctival and parenteral antibiotics, are preferred for endophthalmitis. Parenteral antibiotics are recommended for infection in deep adnexal structures. We review specific aspects of antibiotic therapy for ocular and periocular infection. PMID:7856158

Snyder, R W; Glasser, D B



Antibiotic Prescriptions in Critically-Ill Patients: A Latin American Experience  

PubMed Central

Background: It is widely acknowledged that the presence of infection is an important outcome determinant for intensive care unit (ICU) patients. In fact, antibiotics are one of the most common therapies administered in the ICU settings. Aim: To evaluate the current usage of antibiotics in Latin American ICUs. Subjects and Methods: A one-day p-oint prevalence study to investigate the patterns of antibiotic was undertaken in 72 Latin American (LA) ICUs. Data was analyzed using the Statistix 8 statistical software, version 2.0 (USA). Results were expressed as proportions. When applicable, two tailed hypothesis testing for difference in proportions was used (Proportion Test); a P value of <0.05 was considered significant. Results: Of 704 patients admitted, 359 received antibiotic treatment on the day of the study (51%), of which 167/359 cases (46.5%) were due to hospital-acquired infections. The most frequent infection reorted was nosocomial pneumonia (74/359, 21%). Only in 264/359 patients (73.5%), cultures before starting antibiotic treatment were performed. Thirty-eight percent of the isolated microorganisms were Enterobacteriaceae extended-spectrum ?-lactamase-producing, 11% methicillin-resistant Staphylococcus aureus and 10% carbapenems-resistant non-fermentative Gram-negatives. The antibiotics most frequently prescribed were carbapenems (125/359, 35%), alone or in combination with vancomycin or other antibiotic. There were no significant differences in the “restricted” antibiotic prescription (carbapenems, vancomycin, piperacillin–tazobactam, broad-spectrum cephalosporins, fluoroquinolones, tigecycline and linezolid) between patients with APACHE II score at the beginning of the antibiotic treatment <15 [83/114 (72.5%)] and ?15 [179/245 (73%)] (P = 0.96). Only 29% of the antibiotic treatments were cultured directed (104/359). Conclusion: Carbapenems (alone or in combination) were the most frequently prescribed antibiotics in LA ICUs. However, the problem of carbapenem resistance in LA requires that physicians improve the use of this class of antibiotics. Our findings show that our web-based method for collection of one-day point prevalence was implemented successfully. However, based on the limitations of the model used, the results of this study must be taken with caution. PMID:23919194

Curcio, D



Outpatient Antibiotic Use and the Incidence of Acute Appendicitis in Finland: A Nationwide Study from 1990–2008  

PubMed Central

Abstract Background The incidence of acute appendicitis (AA) has decreased in Finland. We hypothesized that changing trends in outpatient antibiotic use might explain at least part of this declining incidence of AA. Methods The number of all patients with AA in Finland was extracted from the national data base from 1990 to 2008. For comparison, the incidence of acute diverticulitis of the colon (AD) was also recorded. All outpatient prescriptions of antibiotics belonging to the major groups of these drugs were also recorded. We used unit root and co-integration analyses for statistical analysis of the data in the study. Results The incidence of AA in Finland declined from 14.5 to 9.8 per 10,000 inhabitants (32%) and the incidence of AD increased by 47% between 1993 and 2007. The total outpatient use of antibiotics did not increase during this same period, but the use of antibiotics effective widely against colonic pathogens (macrolides, fluoroquinolones, and cephalosporins) increased significantly. No correlation was found between the incidence of AA, that of AD, and the use of different groups of antibiotics. Conclusions Our nationwide registry study indicated that changes in outpatient antibiotic use do not explain the decreasing trend in AA in Finland. Other factors, such as improved diagnosis of AA, may have some role in the decreasing incidence of AA. PMID:23859685

Miettinen, Pekka; Huovinen, Pentti; Herzig, Karl H.; Alajääski, Jennyl; Salminen, Paulina; Paajanen, Hannu



The multifaceted roles of antibiotics and antibiotic resistance in nature  

PubMed Central

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 in nature. PMID:23487476

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



Antibiotic activity in space.  


Environmental factors in space exert an influence on the behaviour of bacteria, particularly on their sensitivity to antibiotics. Thus, G. Taylor and S. Zaloguev observed that bacterial samples collected on the crew during flight in the Apollo-Soyouz Test Project Mission presented higher antibiotic resistance than controls. This paper presents the results of two experiments performed in 1982 and 1985 (Cytos 2 during the French-Soviet Mission and "Antibio" in the Biorack programme of the European Space Agency). The results show an increase of antibiotic resistance in bacteria growth in flight and a modification in the structure of the cell wall. All these modifications are transitory. Two hypotheses are put forward to explain the phenomenon. PMID:3569006

Lapchine, L; Moatti, N; Gasset, G; Richoilley, G; Templier, J; Tixador, R



Characterization of Novel Mycobacterium tuberculosis and Mycobacterium smegmatis Mutants Hypersusceptible to ?-Lactam Antibiotics  

PubMed Central

Our laboratory previously constructed mutants of Mycobacterium tuberculosis and Mycobacterium smegmatis with deletions in the genes for their major ?-lactamases, BlaC and BlaS, respectively, and showed that the mutants have increased susceptibilities to most ?-lactam antibiotics, particularly the penicillins. However, there is still a basal level of resistance in the mutants to certain penicillins, and the susceptibilities of the mutants to some cephalosporin-based ?-lactams are essentially the same as those of the wild types. We hypothesized that characterizing additional mutants (derived from ?-lactamase deletion mutants) that are hypersusceptible to ?-lactam antibiotics might reveal novel genes involved with other mechanisms of ?-lactam resistance, peptidoglycan assembly, and cell envelope physiology. We report here the isolation and characterization of nine ?-lactam antibiotic-hypersusceptible transposon mutants, two of which have insertions in genes known to be involved with peptidoglycan biosynthesis (ponA2 and dapB); the other seven mutants have insertions which affect novel genes. These genes can be classified into three groups: those involved with peptidoglycan biosynthesis, cell division, and other cell envelope processes. Two of the peptidoglycan-biosynthetic genes (ponA2 and pbpX) may encode ?-lactam antibiotic-resistant enzymes proposed to be involved with the synthesis of the unusual diaminopimelyl linkages within the mycobacterial peptidoglycan. PMID:15743935

Flores, Anthony R.; Parsons, Linda M.; Pavelka, Martin S.



Bile tolerance and its effect on antibiotic susceptibility of probiotic Lactobacillus candidates.  


Before use in practice, it is necessary to precisely identify and characterize a new probiotic candidate. Eight animal lactobacilli and collection strain Lactobacillus reuteri CCM 3625 were studied from the point of saccharide fermentation profiles, bile salt resistance, antibiogram profiles, and influence of bile on sensitivity to antibiotics. Studied lactobacilli differed in their sugar fermentation ability determined by API 50CHL and their identification based on these profiles did not correspond with molecular-biological one in most cases. Survival of strains Lactobacillus murinus C and L. reuteri KO4b was not affected by presence of bile. The resistance of genus Lactobacillus to vancomycin and quinolones (ofloxacin, ciprofloxacin) was confirmed in all strains tested. This study provides the new information about oxgall (0.5 and 1 %) effect on the lactobacilli antibiotic susceptibility. Antibiotic profiles were not noticeably affected, and both bile concentrations tested had comparable impact on the lactobacilli antibiotic sensitivity. Interesting change was noticed in L. murinus C, where the resistance to cephalosporins was reverted to susceptibility. Similarly, susceptibility of L. reuteri E to ceftazidime arose after incubation in both concentration of bile. After influence of 1 % bile, Lactobacillus mucosae D lost its resistance to gentamicin. On the base of gained outcomes, the best probiotic properties manifested L. reuteri KO4b, Lactobacillus plantarum KG4, and L. reuteri E due to their survival in the presence of bile. PMID:25413644

Hyacinta, Májeková; Hana, Ki?ová Sepová; Andrea, Bilková; Barbora, ?isárová



b-Lactamases Responsible for Resistance to Expanded-Spectrum Cephalosporins in Klebsiella pneumoniae, Escherichia coli, and Proteus mirabilis Isolates Recovered in South Africa  

Microsoft Academic Search

Although resistance to the expanded-spectrum cephalosporins among members of the family Enterobacteria- ceae lacking inducible b-lactamases occurs virtually worldwide, little is known about this problem among iso- lates recovered in South Africa. Isolates of Klebsiella pneumoniae, Escherichia coli, and Proteus mirabilis resistant to expanded-spectrum cephalosporins recovered from patients in various parts of South Africa over a 3-month period were investigated




Incidence of extended-spectrum-?-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolates that test susceptible to cephalosporins and aztreonam by the revised CLSI breakpoints.  


The incidence of aztreonam and cephalosporin susceptibility, determined using the revised CLSI breakpoints, for extended-spectrum-?-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae isolates was evaluated. Our analysis showed that results for aztreonam and/or ?1 cephalosporin were reported as susceptible or intermediate for 89.2% of ESBL-producing E coli isolates (569/638 isolates) and 67.7% of ESBL-producing K. pneumoniae isolates (155/229 isolates). PMID:24789185

McWilliams, Carla S; Condon, Susan; Schwartz, Rebecca M; Ginocchio, Christine C



Antibiotic bonding to polytetrafluoroethylene with tridodecylmethylammonium chloride  

SciTech Connect

Polytetrafluoroethylene (PTFE) treated with the cationic surfactant, triodecylmethylammonium chloride (TDMAC), binds /sup 14/C-penicillin (1.5 to 2 mg antibiotic/cm graft), whereas untreated PTFE or PTFE treated with anionic detergents shows little binding of antibiotic. TDMAC-treated PTFE concomitantly binds penicillin and heparin, generating a surface that potentially can resist both infection and thrombosis. The retention of these biologically active molecules is not due to passive entrapment in the PTFE but reflects an ionic interaction between the anionic ligands and surface-bound TDMAC. Penicillin bound to PTFE is not removed by exhaustive washing in aqueous buffers but is slowly released in the presence of plasma or when the PTFE is placed in a muscle pouch in the rat. Muscle tissue adjacent to the treated PTFE shows elevated levels of antibiotic following implantation. PTFE treated with TDMAC and placed in a muscle pouch binds /sup 14/C-penicillin when it is locally irrigated with antibiotic or when penicillin is administered intravenously. Thus, the TDMAC surface treated either in vitro or in vivo with penicillin provides an effective in situ source for the timed release of antibiotic.

Harvey, R.A.; Alcid, D.V.; Greco, R.S.



Rapid detection of ?-lactamase-hydrolyzing extended-spectrum cephalosporins in Enterobacteriaceae by use of the new chromogenic ?Lacta test.  


The chromogenic ?Lacta test developed for the rapid detection of ?-lactamase-hydrolyzing extended-spectrum cephalosporins in Enterobacteriaceae revealed good performance with extended-spectrum ?-lactamase (ESBL) producers (97.5% true-positive results). However, false-negative results occurred with chromosomal AmpC hyperproducers and plasmid AmpC producers, whereas uninterpretable results were mostly due to VIM-1 carbapenemase producers and possibly low levels of expressed ESBLs. PMID:24574293

Morosini, María Isabel; García-Castillo, María; Tato, Marta; Gijón, Desirèe; Valverde, Aránzazu; Ruiz-Garbajosa, Patricia; Cantón, Rafael



Rapid Detection of ?-Lactamase-Hydrolyzing Extended-Spectrum Cephalosporins in Enterobacteriaceae by Use of the New Chromogenic ?Lacta Test  

PubMed Central

The chromogenic ?Lacta test developed for the rapid detection of ?-lactamase-hydrolyzing extended-spectrum cephalosporins in Enterobacteriaceae revealed good performance with extended-spectrum ?-lactamase (ESBL) producers (97.5% true-positive results). However, false-negative results occurred with chromosomal AmpC hyperproducers and plasmid AmpC producers, whereas uninterpretable results were mostly due to VIM-1 carbapenemase producers and possibly low levels of expressed ESBLs. PMID:24574293

Morosini, María Isabel; García-Castillo, María; Tato, Marta; Gijón, Desirèe; Valverde, Aránzazu; Ruiz-Garbajosa, Patricia



Tackling antibiotic resistance  

PubMed Central

The development and spread of antibiotic resistance in bacteria is a universal threat to both humans and animals that is generally not preventable, but can nevertheless be controlled and must be tackled in the most effective ways possible. To explore how the problem of antibiotic resistance might best be addressed, a group of thirty scientists from academia and industry gathered at the Banbury Conference Centre in Cold Spring Harbor, New York, May 16-18, 2011. From these discussions emerged a priority list of steps that need to be taken to resolve this global crisis. PMID:22048738

Bush, Karen; Courvalin, Patrice; Dantas, Gautam; Davies, Julian; Eisenstein, Barry; Huovinen, Pentti; Jacoby, George A.; Kishony, Roy; Kreiswirth, Barry N.; Kutter, Elizabeth; Lerner, Stephen A.; Levy, Stuart; Lewis, Kim; Lomovskaya, Olga; Miller, Jeffrey H.; Mobashery, Shahriar; Piddock, Laura J. V.; Projan, Steven; Thomas, Christopher M.; Tomasz, Alexander; Tulkens, Paul M.; Walsh, Timothy R.; Watson, James D.; Witkowski, Jan; Witte, Wolfgang; Wright, Gerry; Yeh, Pamela; Zgurskaya, Helen I.



Antibiotic-related nephrotoxicity.  


The toxicity of aminoglycosides is related to their concentrative uptake by proximal tubular cells and their capacity to interact with critical intracellular targets. Concentrative uptake is mediated by adsorptive endocytosis across the apical membrane followed by sequestration within lysosomes. The fundamental mechanism underlying the toxicity of these organic polycations is their capacity to interact electrostatically with and disrupt the metabolism of anionic phospholipids, especially the phosphoinositides. Polyaspartic acid, a polyanionic peptide, protects against aminoglycoside nephrotoxicity by forming electrostatic complexes with these drugs and inhibiting their interaction with critical intracellular targets. The selective toxicity of beta-lactams towards renal proximal tubular cells is related to their concentrative uptake via the organic anion transport system. Lipid peroxidation appears to play a major role in the toxicity of cephaloridine. Depressed mitochondrial respiration secondary to acylation of the mitochondrial transporter for succinate has been implicated in the pathogenesis of toxicity caused by other cephalosporins and carbapenems. The predilection of the kidney for amphotericin B toxicity is unclear as little drug is excreted by the kidneys. Toxicity is manifested by increased renal vascular resistance, depression of RBF and GFR, and altered tubular function that reflects the capacity of this drug to interact with cholesterol-containing membranes and increase membrane permeability to ions including potassium, hydrogen, calcium, and magnesium. PMID:7800246

Kaloyanides, G J



Cephalosporin-resistant Escherichia coli among Summer Camp Attendees with Salmonellosis  

PubMed Central

Investigation of an acute gastroenteritis outbreak involving >100 persons at a summer camp in Girona, Spain, in June 2002 led to the detection of Salmonella and extended-spectrum cephalosporin-resistant Escherichia coli (ESCREC). Stool cultures were performed for 22 symptomatic campers, three asymptomatic food handlers, and 10 healthy household members. Of the 22 campers, 19 had Salmonella enterica, 9 had an ESCREC strain carrying an extended-spectrum ?-lactamase, and 2 had a second ESCREC strain carrying a plasmidic cephamycinase. Related ESCREC were detected in two (salmonella-negative) asymptomatic food handlers and in none of the healthy household members. Fecal ESCREC and its ?-lactamases and plasmids were extensively characterized. Three of the five ESCREC clones were recovered from multiple hosts. The apparent dissemination of ESCREC suggests a food or water vehicle. The observed distribution of resistance plasmids and ?-lactamase genes in several clones indicates a high degree of horizontal transfer. Heightened vigilance and increased efforts must be made to discover the reservoirs and vehicles for community dissemination of ESCREC. PMID:14609463

Mirelis, Beatriz; Miró, Elisenda; Navarro, Ferran; Llovet, Teresa; Johnson, James R.; Camps, Neus; Domínguez, Ángela; Salleras, Lluis



Bacterial cheating limits antibiotic resistance  

NASA Astrophysics Data System (ADS)

The widespread use of antibiotics has led to the evolution of resistance in bacteria. Bacteria can gain resistance to the antibiotic ampicillin by acquiring a plasmid carrying the gene beta-lactamase, which inactivates the antibiotic. This inactivation may represent a cooperative behavior, as the entire bacterial population benefits from removing the antibiotic. The cooperative nature of this growth suggests that a cheater strain---which does not contribute to breaking down the antibiotic---may be able to take advantage of cells cooperatively inactivating the antibiotic. Here we find experimentally that a ``sensitive'' bacterial strain lacking the plasmid conferring resistance can invade a population of resistant bacteria, even in antibiotic concentrations that should kill the sensitive strain. We observe stable coexistence between the two strains and find that a simple model successfully explains the behavior as a function of antibiotic concentration and cell density. We anticipate that our results will provide insight into the evolutionary origin of phenotypic diversity and cooperative behaviors.

Xiao Chao, Hui; Yurtsev, Eugene; Datta, Manoshi; Artemova, Tanya; Gore, Jeff



Antibiotic-Resistant Gonorrhea (ARG)  


... please visit this page: About . Gonorrhea Antibiotic Resistance Basic Information Laboratory Information Resources & References Facts & Brochures ... Surveillance Trends Challenges Laboratory Issues The development of antibiotic resistance in Neisseria gonorrhoeae is an urgent public health ...


Antibiotic therapy of cholera*  

PubMed Central

Recent clinical trials having established the value of tetracycline as an adjunct to fluid and electrolyte replacement in cholera treatment, a controlled trial of antibiotic therapy was conducted in Dacca on 318 adults hospitalized for cholera. The effects of 4 antibiotics orally administered in varying dosage schedules were studied. Cholera therapy with tetracycline or chloramphenicol caused a highly significant reduction in the duration of diarrhoea and of positive culture, in stool volume, and in intravenous fluid requirement as compared with the results in controls who received intravenous fluid therapy only. Streptomycin was also effective, but to a lesser degree; paromomycin was of little value. The severity of dehydration on admission was significantly related to subsequent duration of diarrhoea regardless of whether antibiotics were given. Increasing age was associated with more prolonged purging in patients receiving antibiotics. Increasing the dose of tetracycline to 2 to 3 times that usually administered, or prolonging treatment from 2 to 4 days, did not enhance the therapeutic results. The effect of tetracycline was apparent within a few hours of administration. Bacteriological relapses were seen after discontinuation of therapy in all treatment groups, but were not due to the development of resistant bacteria. PMID:4865453

Lindenbaum, John; Greenough, William B.; Islam, M. R.



Resistance-resistant antibiotics.  


New antibiotics are needed because drug resistance is increasing while the introduction of new antibiotics is decreasing. We discuss here six possible approaches to develop 'resistance-resistant' antibiotics. First, multitarget inhibitors in which a single compound inhibits more than one target may be easier to develop than conventional combination therapies with two new drugs. Second, inhibiting multiple targets in the same metabolic pathway is expected to be an effective strategy owing to synergy. Third, discovering multiple-target inhibitors should be possible by using sequential virtual screening. Fourth, repurposing existing drugs can lead to combinations of multitarget therapeutics. Fifth, targets need not be proteins. Sixth, inhibiting virulence factor formation and boosting innate immunity may also lead to decreased susceptibility to resistance. Although it is not possible to eliminate resistance, the approaches reviewed here offer several possibilities for reducing the effects of mutations and, in some cases, suggest that sensitivity to existing antibiotics may be restored in otherwise drug-resistant organisms. PMID:25458541

Oldfield, Eric; Feng, Xinxin



Analysis of macrolide antibiotics  

Microsoft Academic Search

The following macrolide antibiotics have been covered in this review: erythromycin and its related substances, azithromycin, clarithromycin, dirithromycin, roxithromycin, flurithromycin, josamycin, rokitamycin, kitasamycin, mycinamycin, mirosamycin, oleandomycin, rosaramicin, spiramycin and tylosin. The application of various thin-layer chromatography, paper chromatography, gas chromatography, high-performance liquid chromatography and capillary zone electrophoresis procedures for their analysis are described. These techniques have been applied to the

Isadore Kanfer; Michael F. Skinner; Roderick B. Walker



Minocycline: far beyond an antibiotic  

PubMed Central

Minocycline is a second-generation, semi-synthetic tetracycline that has been in therapeutic use for over 30 years because of its antibiotic properties against both gram-positive and gram-negative bacteria. It is mainly used in the treatment of acne vulgaris and some sexually transmitted diseases. Recently, it has been reported that tetracyclines can exert a variety of biological actions that are independent of their anti-microbial activity, including anti-inflammatory and anti-apoptotic activities, and inhibition of proteolysis, angiogenesis and tumour metastasis. These findings specifically concern to minocycline as it has recently been found to have multiple non-antibiotic biological effects that are beneficial in experimental models of various diseases with an inflammatory basis, including dermatitis, periodontitis, atherosclerosis and autoimmune disorders such as rheumatoid arthritis and inflammatory bowel disease. Of note, minocycline has also emerged as the most effective tetracycline derivative at providing neuroprotection. This effect has been confirmed in experimental models of ischaemia, traumatic brain injury and neuropathic pain, and of several neurodegenerative conditions including Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Alzheimer's disease, multiple sclerosis and spinal cord injury. Moreover, other pre-clinical studies have shown its ability to inhibit malignant cell growth and activation and replication of human immunodeficiency virus, and to prevent bone resorption. Considering the above-mentioned findings, this review will cover the most important topics in the pharmacology of minocycline to date, supporting its evaluation as a new therapeutic approach for many of the diseases described herein. PMID:23441623

Garrido-Mesa, N; Zarzuelo, A; Gálvez, J



Antibiotic use for common cold  

Microsoft Academic Search

Antibiotics do not help patients with an uncomplicated common cold. Antibiotics can have side effects for the individual taking\\u000a them that range from unpleasant to serious, even lethal. Antibiotic use also contributes to communal harm by encouraging antibiotic\\u000a resistance. If there can be no benefit, but there can be harm, why is the common cold the commonest reason for doctors

Timothy W. Kenealy; Bruce Arroll


Antibiotic Production by Soil Actinomycetes  

NSDL National Science Digital Library

Students attempt to identify Streptomycetes with antibiotic properties in local soil samples. The purpose of this investigation is to try to discover Actinomycetes from local soil samples that have antibiotic properties. The use of known species of Streptomycetes that produce antibiotics can be easily seen as they produce zones of inhibition on a lawn of bacteria; the antibiotic activity from local soil samples is variable and takes many samples to find a few that produce zones of inhibition.

John William Goudie (Kalamazoo Area Math and Science Center REV)



Danger of Antibiotic Overuse (For Parents)  


... antibiotic treatment. This is called bacterial resistance or antibiotic resistance. Treating these resistant bacteria requires higher doses of ... some of the most powerful antibiotics available today. Antibiotic resistance is a widespread problem, and one that the ...


Immobilization of microbial cells in crosslinked, prepolymerized, linear polyacrylamide gels: antibiotic production by immobilized Streptomyces clavuligerus cells  

SciTech Connect

A mild method for the immobilization of whole microbial cells has been developed. Cells were suspended in a solution of preformed, linear, water-soluble polyacrylamide chains, partially substituted with acylhydrazide groups. The prepolymerized backbone polymer was crosslinked, in the presence of viable cells, by stoichiometric amounts of dialdehydes such as glyoxal, glutardialdehyde, and periodate-oxidized polyvinyl alcohol. The crosslinking reaction, carried out in cold, neutral physiological conditions resulted in cells entrapped in gels with physical properties similar to those of the common polyacrylamide gels. However, cell damage generally caused by the acrylamide monomer was avoided. Resting Streptomyces clavuligerus cells, possessing a high capacity for antibiotic production, were entrapped according to this procedure. These immobilized cells produced cephalosporins continuously for 96 hours with yields similar to those of free resting cells. The same cells, when immobilized by direct polymerization of acrylamide monomers, yielded significantly lower amounts of antibiotics. (Refs. 19).

Freeman, A.; Aharonowitz, Y.



Antibiotics acting on the translational  

E-print Network

Antibiotics acting on the translational machinery Jörg M. Harms1,*, Heike Bartels1, Frank Schlünzen antibiotics, including vancomycin (the `last resort'), development of new antimicrobial agents has slowed during recent decades. To aid design of new antibiotics, we must develop a detailed understanding

Yonath, Ada E.


Antibiotic Use in the Community  

Microsoft Academic Search

Sufficient data on antibiotic use in the community is lacking in most countries. Few countries can show antibiotic use data over time, to analyse trends in prescribing. All countries have an important role to ensure that validated national and regional, data on antibiotic prescribing and sales are made publicly available. The collection of DID data in the ESAC project is

Sigvard Mölstad; Otto Cars


Investigating the Antibiotic Resistance Problem.  

ERIC Educational Resources Information Center

Seeks to give teachers useful information on the extent of the problem of antibiotic-resistant bacteria, mechanisms bacteria use to resist antibiotics, the causes of the emergence of antibiotic-resistant organisms, and practices that can prevent or reverse this trend. Contains 19 references. (DDR)

Lawson, Michael; Lawson, Amy L.



Economics of antibiotic resistance  

Microsoft Academic Search

Antibiotics are developed to kill microorganisms; however, microorganisms develop and disseminate resistance as a reaction to antimicrobials in accordance with the laws of evolution and natural selection. Resistant and multidrug-resistant bacterial infections comprise a great problem in both the community and hospital setting. Increasing values of health expenditures, including antibiotics, is a global problem. Antibiotic resistance is not always, but

Oguz Resat Sipahi



Antibiotic resistance spread in food  

Microsoft Academic Search

Nutritive and therapeutic treatment of farm animals with antibiotics, amounting to half of the world's antibiotic output, has selected for resistant bacteria that may contaminate the food produced. Antibiotic-resistant enterococci and staphylococci from animals are found in food when they survive the production processes, as in raw cured sausages and raw milk cheeses. The broad host ranges of some plasmids

Vincent Perreten; Franziska Schwarz; Luana Cresta; Marianne Boeglin; Gottfried Dasen; Michael Teuber



The role and types of antibiotics, depending on the injuries of soldiers of IX and X Polish military contingent in Afghanistan.  


The frequency of external wounds sustained by soldiers on the modern battlefield is not declining. In particular, this concerns participants in humanitarian and stabilization missions in the third world countries, almost daily attacked with improvised booby-traps and firing missiles or multi-caliber weapons. The wound infection rate is high, which requires often the empirical use of antibiotics, both in local dressings, as well as the overall dose. The knowledge of the probable causative agent of a wound infection, its theoretical susceptibility to the antibiotic and spectrum antibiotics that are currently available, is a factor which is conditional in the success of treatment. In order to investigate, how the supply of PKW Afghanistan in antibiotics and chemotherapeutic drugs is presented and whether this supply range is suitable for medical problems, we analyzed the consumption of these drugs. Data for the years: 2010-2011 were available. The supply structure was dominated by antibiotics penicillin, cephalosporin, amino glycoside and macrolide. It was stated that each year the supply and consumption of antibiotics increased by 127.9%, with a stable number of serving people and a stable number of sustained injuries. Compared to 2010, in 2011 there were purchases of antibiotics used in severe, complicated infections caused by opportunistic multi-drug-resistant pathogens. This proves that the epidemiological situation was deteriorating on the area of PKW Afghanistan service mission. PMID:23285678

Ziemba, Rados?aw




NSDL National Science Digital Library

This page contains an article from The Science Creative Quarterly on acquired antibiotic resistance in bacteria. Topics covered include the discovery of antibiotics, the history and scope of antibiotic use and antibiotic resistance, mechanisms of antibiotic activity and antibiotic resistance, molecular biology of acquiring antibiotic resistance, and possible solutions to the antibiotic resistance problem. This article would be accessible to middle school or higher level students and teachers.

Grace Yim


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

PubMed Central

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?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?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 regions so efforts at reducing antibiotic consumption may need to be strengthened in this area. Increased consumption of antibiotics may not only produce greater resistance at the individual patient level but may also produce greater resistance at the community, country, and regional levels, which can harm individual patients. PMID:24405683



Selection of antibiotic resistance at very low antibiotic concentrations  

PubMed Central

Human use of antibiotics has driven the selective enrichment of pathogenic bacteria resistant to clinically used drugs. Traditionally, the selection of resistance has been considered to occur mainly at high, therapeutic levels of antibiotics, but we are now beginning to understand better the importance of selection of resistance at low levels of antibiotics. The concentration of an antibiotic varies in different body compartments during treatment, and low concentrations of antibiotics are found in sewage water, soils, and many water environments due to natural production and contamination from human activities. Selection of resistance at non-lethal antibiotic concentrations (below the wild-type minimum inhibitory concentration) occurs due to differences in growth rate at the particular antibiotic concentration between cells with different tolerance levels to the antibiotic. The minimum selective concentration for a particular antibiotic is reached when its reducing effect on growth of the susceptible strain balances the reducing effect (fitness cost) of the resistance determinant in the resistant strain. Recent studies have shown that resistant bacteria can be selected at concentrations several hundred-fold below the lethal concentrations for susceptible cells. Resistant mutants selected at low antibiotic concentrations are generally more fit than those selected at high concentrations but can still be highly resistant. The characteristics of selection at low antibiotic concentrations, the potential clinical problems of this mode of selection, and potential solutions will be discussed. PMID:24694026



Antibiotic alternatives: the substitution of antibiotics in animal husbandry?  

PubMed Central

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

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



Concurrent Use of Warfarin and Antibiotics and the Risk of Bleeding in Older Adults  

PubMed Central

Background Antibiotic medications are associated with an increased risk of bleeding among patients receiving warfarin. The recent availability of data from the Medicare Part D prescription drug program provides an opportunity to assess the association of antibiotic medications and the risk of bleeding in a national population of older adults receiving warfarin. Methods We conducted a case-control study nested within a cohort of 38,762 patients aged 65 years and older who were continuous warfarin users, using enrollment and claims data for a 5% national sample of Medicare beneficiaries with Part D benefits. Cases were defined as persons hospitalized for a primary diagnosis of bleeding and were matched with three control subjects on age, race, gender, and indication for warfarin. Logistic regression analysis was used to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the risk of bleeding associated with prior exposure to antibiotic medications. Results Exposure to any antibiotic agent within the 15 days of the event/index date was associated with an increased risk of bleeding (aOR 2.01; 95% CI, 1.62-2.50). All six specific antibiotic drug classes examined [azole antifungals (aOR, 4.57; 95% CI, 1.90-11.03), macrolides (aOR, 1.86; 95% CI, 1.08-3.21), quinolones (aOR, 1.69; 95% CI, 1.09-2.62), cotrimoxazole (aOR, 2.70; 95% CI, 1.46-5.05), penicillins (aOR, 1.92; 95% CI, 1.21-2.07) and cephalosporins (aOR, 2.45; 95% CI, 1.52-3.95) were associated with an increased risk of bleeding. Conclusion Among older continuous warfarin users, exposure to antibiotic agents—particularly azole antifungals—was associated with an increased risk of bleeding. PMID:22269622

Baillargeon, Jacques; Holmes, Holly M.; Lin, Yu-li; Raji, Mukaila A.; Sharma, Gulshan; Kuo, Yong-Fang



Method of physician remuneration and rates of antibiotic prescription  

PubMed Central

BACKGROUND: Rates of antibiotic prescription in Canada far exceed generally accepted rates of bacterial infection, which led the authors to postulate that rates of antibiotic prescription depend to some extent on factors unrelated to medical indication. The associations between antibiotic prescription rates and physician characteristics, in particular, method of remuneration and patient volume, were explored. METHODS: The authors evaluated all 153,047 antibiotic prescriptions generated by 476 Newfoundland general practitioners and paid for by the Newfoundland Drug Plan over the 1-year period ending Aug. 31 1996, and calculated rates of antibiotic prescription. Linear and logistic regression models controlling for several physician characteristics, specifically age, place of education (Canada or elsewhere), location of practice (urban or rural) and proportion of elderly patients seen, were used to analyse rates of antibiotic prescription. RESULTS: Fee-for-service payment (rather than salary) and greater volume of patients were strongly associated with higher antibiotic prescription rates. Fee-for-service physicians were much more likely than their salaried counterparts to prescribe at rates above the median value of 1.51 antibiotic prescriptions per unique patient per year. The association between rate of antibiotic prescription and patient volume (as measured by number of unique patients prescribed to) was evident for all physicians. However, the association was much stronger for fee-for-service physicians. Physicians with higher patient volumes prescribed antibiotics at higher rates. INTERPRETATION: In this study factors other than medical indication, in particular method of physician remuneration and patient volume, played a major role in determining antibiotic prescribing practices. PMID:10207340

Hutchinson, J M; Foley, R N



Co-occurrence of antibiotic and heavy metal resistance in K?z?l?rmak River isolates.  


Contamination of surface waters with antimicrobials has become an increasing public health concern because of the emergence of multi-resistant pathogens. For this reason, water samples collected from the K?z?l?rmak River-K?r?kkale, Turkey were analysed to learn more about the co-occurrence of heavy metal and antibiotic resistance in bacteria. Resistant profiles were determined by using 26 antibiotics and 17 heavy metals. Out of 290, 24 isolates with both heavy metal and antibiotic resistance were determined. Resistance to heavy metals including lead, tin, nickel, barium, aliminum, strontium, silver and lithium varied between 50 and 92 %. More than 50 % of the isolates showed resistance to cephalosporin, quinolone, sulfonamide and aminoglycoside type of antibiotics. The discharge of antimicrobials to water bodies may cause a combined effect of selection and co-selection towards resistant bacteria. Therefore, surface waters may be potential hot spots of the evolution of heavy metal- and antibiotic-resistant bacteria and require special scientific consideration. PMID:25257221

Icgen, Bulent; Yilmaz, Fadime



The effect of storage at 4 degrees C on antibiotic residues in kidney and meat tissues of dairy cows.  


A method is described for the quantitative assay of antibiotic residues in the body of slaughtered farm animals by means of 3 types of agar media and 3 test organisms. With the help of programmed calculation procedures, data from large-scale tests for antibiotic residues could be analyzed accurately and rapidly. The concentrations of penicillin G, ampicillin, amoxycillin, cloxacillin, cephapirin, cephacetrile, neomycin, kanamycin, and oxytetracycline in the kidney, and also of tylosin in meat from the diaphragm muscle of cattle treated parenterally with these antibiotics were measured periodically in samples kept at 4 degrees C for up to 7 days after slaughter. The concentrations of penicillin G, ampicillin, amoxycillin and the cephalosporins in the kidney decreased rapidly upon storage whereas the levels of the other antibiotics remained essentially unchanged. Antibiotic stability in the meat was considerably greater than in the kidney upon storage for 4 days, and neomycin meat tissue levels were not reduced during storage for up to 144 hours. Results are discussed in relation to the conduct of the official qualitative Sarcina lutea Kidney Test and the most desirable procedure for preparing meat samples for assay. PMID:1013973

Nouws, J F; Ziv, G



Molecular mechanisms of antibiotic resistance.  


Antibiotic-resistant bacteria that are difficult or impossible to treat are becoming increasingly common and are causing a global health crisis. Antibiotic resistance is encoded by several genes, many of which can transfer between bacteria. New resistance mechanisms are constantly being described, and new genes and vectors of transmission are identified on a regular basis. This article reviews recent advances in our understanding of the mechanisms by which bacteria are either intrinsically resistant or acquire resistance to antibiotics, including the prevention of access to drug targets, changes in the structure and protection of antibiotic targets and the direct modification or inactivation of antibiotics. PMID:25435309

Blair, Jessica M A; Webber, Mark A; Baylay, Alison J; Ogbolu, David O; Piddock, Laura J V



Generic antibiotics in Japan.  


Generic drugs have been used extensively in many developed countries, although their use in Japan has been limited. Generic drugs reduce drug expenses and thereby national medical expenditure. Because generic drugs provide advantages for both public administration and consumers, it is expected that they will be more widely used in the future. However, the diffusion rate of generic drugs in Japan is quite low compared with that of other developed countries. An investigation on generic drugs conducted by the Ministry of Health, Labour and Welfare in Japan revealed that 17.2 % of doctors and 37.2 % of patients had not used generic drugs. The major reasons for this low use rate included distrust of off-patent products and lower drug price margin compared with the brand name drug. The generic drugs available in the market include external drugs such as wet packs, antihypertensive agents, analgesics, anticancer drugs, and antibiotics. Among them, antibiotics are frequently used in cases of acute infectious diseases. When the treatment of these infections is delayed, the infection might be aggravated rapidly. The pharmacokinetics-pharmacodynamics (PK-PD) theory has been adopted in recent chemotherapy, and in many cases, the most appropriate dosage and administration of antibiotics are determined for individual patients considering renal function; high-dosage antibiotics are used preferably for a short duration. Therefore, a highly detailed antimicrobial agent is necessary. However, some of the generic antibiotics have less antibacterial potency or solubility than the brand name products. We showed that the potency of the generic products of vancomycin and teicoplanin is lower than that of the branded drugs by 14.6 % and 17.3 %, respectively. Furthermore, we confirmed that a generic meropenem drug for injection required about 82 s to solubilize in saline, whereas the brand product required only about 21 s. It was thought that the cause may be the difference in size of bulk particle and amount of solubilizer. The Japanese government hopes to increase the diffusion rate of generic drugs (in terms of quantity) from 20.2 % in 2010 to 30 % or more in 2012, and therefore it will be necessary to clarify the advantages of generic antibiotics in terms of expenditure and equivalency with the branded drugs. PMID:22684334

Fujimura, Shigeru; Watanabe, Akira



The Comprehensive Antibiotic Resistance Database  

PubMed Central

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; 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

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



When antibiotics are unnecessary.  


Dermatologists can decrease unnecessary use of antimicrobial agents by avoiding them in situations wherein good evidence indicates that they are ineffective. Controlled trials indicate that antimicrobial agents are unhelpful in treating cutaneous abscesses, inflamed epidermal cysts, uninfected atopic eczema, and cutaneous ulcers caused by venous insufficiency or diabetes in the absence of significant contiguous soft-tissue inflammation. Prophylactic antibiotics are rarely appropriate for routine dermatologic surgery and are not indicated for patients who have prosthetic joints or vascular grafts. They are recommended only for a small group of patients who have abnormal cardiac valves, and then only with surgery involving clearly infected skin or soft-tissue. Topical antibiotics are no better than white petrolatum in covering sutured wounds, and with moist occlusive dressings, no ointment is necessary. PMID:18984370

Hirschmann, J V



Pneumococcal resistance to antibiotics.  

PubMed Central

The geographic distribution of pneumococci resistant to one or more of the antibiotics penicillin, erythromycin, trimethoprim-sulfamethoxazole, and tetracycline appears to be expanding, and there exist foci of resistance to chloramphenicol and rifampin. Multiply resistant pneumococci are being encountered more commonly and are more often community acquired. Factors associated with infection caused by resistant pneumococci include young age, duration of hospitalization, infection with a pneumococcus of serogroup 6, 19, or 23 or serotype 14, and exposure to antibiotics to which the strain is resistant. At present, the most useful drugs for the management of resistant pneumococcal infections are cefotaxime, ceftriaxone, vancomycin, and rifampin. If the strains are susceptible, chloramphenicol may be useful as an alternative, less expensive agent. Appropriate interventions for the control of resistant pneumococcal outbreaks include investigation of the prevalence of resistant strains, isolation of patients, possible treatment of carriers, and reduction of usage of antibiotics to which the strain is resistant. The molecular mechanisms of penicillin resistance are related to the structure and function of penicillin-binding proteins, and the mechanisms of resistance to other agents involved in multiple resistance are being elucidated. Recognition is increasing of the standard screening procedure for penicillin resistance, using a 1-microgram oxacillin disk. PMID:2187594

Klugman, K P



Role of prophylactic antibiotics in cirrhotic patients with variceal bleeding  

PubMed Central

Bacterial infections are common in cirrhotic patients with acute variceal bleeding, occurring in 20% within 48 h. Outcomes including early rebleeding and failure to control bleeding are strongly associated with bacterial infection. However, mortality from variceal bleeding is largely determined by the severity of liver disease. Besides a higher Child-Pugh score, patients with hepatocellular carcinoma are particularly susceptible to infections. Despite several hypotheses that include increased use of instruments, greater risk of aspiration pneumonia and higher bacterial translocation, it remains debatable whether variceal bleeding results in infection or vice versa but studies suggest that antibiotic prophylaxis prior to endoscopy and up to 8 h is useful in reducing bacteremia and spontaneous bacterial peritonitis. Aerobic gram negative bacilli of enteric origin are most commonly isolated from cultures, but more recently, gram positives and quinolone-resistant organisms are increasingly seen, even though their clinical significance is unclear. Fluoroquinolones (including ciprofloxacin and norfloxacin) used for short term (7 d) have the most robust evidence and are recommended in most expert guidelines. Short term intravenous cephalosporin (especially ceftriaxone), given in a hospital setting with prevalent quinolone-resistant organisms, has been shown in studies to be beneficial, particularly in high risk patients with advanced cirrhosis. PMID:24587656

Lee, Yeong Yeh; Tee, Hoi-Poh; Mahadeva, Sanjiv



Developments in liquid membrane separation of beta-lactam antibiotics.  


This paper presents an overview on the developments in liquid membrane separation and purification of commercially important beta-lactam antibiotics. Reactive extraction via liquid-liquid ion exchange or ion-pair extraction mechanism can be exploited to develop liquid membrane processes for separation and concentration of penicillins and cephalosporins. Because of high selectivity and flux, liquid membrane processes can be adopted for direct extraction of beta-lactams from fermentation broth. Other advantages of liquid membrane technologies are low capital and operating costs, compact unit installation in commercial plants, low material inventory, etc. Both emulsion liquid membrane and supported liquid membrane techniques can be effective under the reactive extraction conditions. However, the stability problems of liquid membrane should be resolved before commercial application can be established. Alternately, reactive extraction in non-dispersive mode with hollow fiber membranes can be an attractive and viable strategy for practical application. Applicability of the liquid membrane processes has been discussed from process engineering and design considerations. PMID:8818264

Ghosh, A C; Bora, M M; Dutta, N N



Rapid screening of multiple antibiotic residues in milk using disposable amperometric magnetosensors.  


Disposable amperometric magnetosensors, involving a mixture of modified-magnetic beads (MBs), for the multiplex screening of cephalosporins (CPHs), sulfonamides (SAs) and tetracyclines (TCs) antibiotic residues in milk are reported for the first time in this work. The multiplexed detection relies on the use of a mixture of target specific modified magnetic beads (MBs) and application of direct competitive assays using horseradish peroxidase (HRP)-labeled tracers. The amperometric responses measured at -0.20 V vs. the Ag pseudo-reference electrode of screen-printed carbon electrodes (SPCE) upon the addition of H2O2 in the presence of hydroquinone (HQ) as redox mediator, were used to monitor the extent of the different affinity reactions. The developed methodology, involving a simple and short pretreatment, allowed discrimination between no contaminated UHT and raw milk samples and samples containing antibiotic residues at the maximum residue limits (MRLs). The usefulness of the multiplexed magnetosensor was demonstrated by analyzing spiked milk samples in only 5 min. The results demonstrated that a clear discrimination of milk samples contaminated with antibiotics at their MRL level or their mixtures, allowing the identification of milk not complying with current legislation. These features make the developed methodology a promising alternative in the development of user-friendly devices for on-site analysis to ensure quality control for dairy products. PMID:24745735

Conzuelo, F; Ruiz-Valdepeñas Montiel, V; Campuzano, S; Gamella, M; Torrente-Rodríguez, R M; Reviejo, A J; Pingarrón, J M



Determination of an inoculum effect with various cephalosporins among clinical isolates of methicillin-susceptible Staphylococcus aureus.  


Using 98 clinical methicillin-susceptible Staphylococcus aureus isolates of known beta-lactamase (Bla) type, we found a pronounced inoculum effect for cephalexin (mostly Bla type A and C strains), a mild inoculum effect for cephalothin (especially types B and C), and no inoculum effects for ceftriaxone and cefuroxime. Ceftobiprole showed the lowest MICs at a high inoculum but with a slight increase for Bla-positive versus Bla-negative strains. Since a potential therapeutic effect associated with a cephalosporin inoculum effect has been described, further studies are warranted. PMID:20211890

Nannini, Esteban C; Stryjewski, Martin E; Singh, Kavindra V; Rude, Tom H; Corey, G Ralph; Fowler, Vance G; Murray, Barbara E



Degradation kinetics and mechanism of ?-lactam antibiotics by the activation of H2O2 and Na2S2O8 under UV-254nm irradiation.  


The extensive production and usage of antibiotics have led to an increasing occurrence of antibiotic residuals in various aquatic compartments, presenting a significant threat to both ecosystem and human health. This study investigated the degradation of selected ?-lactam antibiotics (penicillins: ampicillin, penicillin V, and piperacillin; cephalosporin: cephalothin) by UV-254nm activated H2O2 and S2O8(2-) photochemical processes. The UV irradiation alone resulted in various degrees of direct photolysis of the antibiotics; while the addition of the oxidants improved significantly the removal efficiency. The steady-state radical concentrations were estimated, revealing a non-negligible contribution of hydroxyl radicals in the UV/S2O8(2-) system. Mineralization of the ?-lactams could be achieved at high UV fluence, with a slow formation of SO4(2-) and a much lower elimination of total organic carbon (TOC). The transformation mechanisms were also investigated showing the main reaction pathways of hydroxylation (+16Da) at the aromatic ring and/or the sulfur atom, hydrolysis (+18Da) at the ?-lactam ring and decarboxylation (-44Da) for the three penicillins. Oxidation of amine group was also observed for ampicillin. This study suggests that UV/H2O2 and UV/S2O8(2-) advanced oxidation processes (AOPs) are capable of degrading ?-lactam antibiotics decreasing consequently the antibiotic activity of treated waters. PMID:25086235

He, Xuexiang; Mezyk, Stephen P; Michael, Irene; Fatta-Kassinos, Despo; Dionysiou, Dionysios D



Combined administration of antibiotics and direct oral anticoagulants: a renewed indication for laboratory monitoring?  


The recent development and marketing of novel direct oral anticoagulants (DOACs) represents a paradigm shift in the management of patients requiring long-term anticoagulation. The advantages of these compounds over traditional therapy with vitamin K antagonists include a reportedly lower risk of severe hemorrhages and the limited need for laboratory measurements. However, there are several scenarios in which testing should be applied. The potential for drug-to-drug interaction is one plausible but currently underrecognized indication for laboratory assessment of the anticoagulant effect of DOACs. In particular, substantial concern has been raised during Phase I studies regarding the potential interaction of these drugs with some antibiotics, especially those that interplay with permeability glycoprotein (P-gp) and cytochrome 3A4 (CYP3A4). A specific electronic search on clinical trials published so far confirms that clarithromycin and rifampicin significantly impair the bioavailability of dabigatran, whereas clarithromycin, erythromycin, fluconazole, and ketoconazole alter the metabolism of rivaroxaban in vivo. Because of their more recent development, no published data were found for apixaban and edoxaban, or for potential interactions of DOACs with other and widely used antibiotics. It is noteworthy, however, that an online resource based on Food and Drug Administration and social media information, reports several hemorrhagic and thrombotic events in patients simultaneously taking dabigatran and some commonly used antibiotics such as amoxicillin, cephalosporin, and metronidazole. According to these reports, the administration of antibiotics in patients undergoing therapy with DOACs would seem to require accurate evaluation as to whether dose adjustments (personalized or antibiotic class driven) of the anticoagulant drug may be advisable. This might be facilitated by direct laboratory assessments of their anticoagulant effect ex vivo. PMID:24919144

Lippi, Giuseppe; Favaloro, Emmanuel J; Mattiuzzi, Camilla



De novo Comparative Transcriptome Analysis of Acremonium chrysogenum: High-Yield and Wild-Type Strains of Cephalosporin C Producer  

PubMed Central

?-lactam antibiotics are widely used in clinic. Filamentous fungus Acremonium chrysogenum is an important industrial fungus for the production of CPC, one of the major precursors of ?-lactam antibiotics. Although its fermentation yield has been bred significantly over the past decades, little is known regarding molecular changes between the industrial strain and the wild type strain. This limits the possibility to improve CPC production further by molecular breeding. Comparative transcriptome is a powerful tool to understand the molecular mechanisms of CPC industrial high yield producer compared to wild type. A total of 57 million clean sequencing reads with an average length of 100 bp were generated from Illumina sequencing platform. 22,878 sequences were assembled. Among the assembled unigenes, 9502 were annotated and 1989 annotated sequences were assigned to 121 pathways by searching against the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) database. Furthermore, we compared the transcriptome differences between a high-yield and a wild-type strain during fermentation. A total of 4329 unigenes with significantly different transcription level were identified, among which 1737 were up-regulated and 2592 were down-regulated. 24 pathways were subsequently determined which involve glycerolipid metabolism, galactose metabolism, and pyrimidine metabolism. We also examined the transcription levels of 18 identified genes, including 11 up-regulated genes and 7 down-regulated genes using reverse transcription quantitative -PCR (RT-qPCR). The results of RT-qPCR were consistent with the Illumina sequencing. In this study, the Illumina sequencing provides the most comprehensive sequences for gene expression profile of Acremonium chrysogenum and allows de novo transcriptome assembly while lacking genome information. Comparative analysis of RNA-seq data reveals the complexity of the transcriptome in the fermentation of different yield strains. This is an important public information platform which could be used to accelerate the research to improve CPC production in Acremonium chrysogenum. PMID:25118715

Liu, Yan; Xie, Liping; Gong, Guihua; Zhang, Wei; Zhu, Baoquan; Hu, Youjia



A Response Regulator from a Soil Metagenome Enhances Resistance to the ?-Lactam Antibiotic Carbenicillin in Escherichia coli  

PubMed Central

Functional metagenomic analysis of soil metagenomes is a method for uncovering as-yet unidentified mechanisms for antibiotic resistance. Here we report an unconventional mode by which a response regulator derived from a soil metagenome confers resistance to the ?-lactam antibiotic carbenicillin in Escherichia coli. A recombinant clone (?lr16) harboring a 5,169 bp DNA insert was selected from a metagenomic library previously constructed from a remote Alaskan soil. The ?lr16 clone conferred specific resistance to carbenicillin, with limited increases in resistance to other tested antibiotics, including other ?-lactams (penicillins and cephalosporins), rifampin, ciprofloxacin, erythromycin, chloramphenicol, nalidixic acid, fusidic acid, and gentamicin. Resistance was more pronounced at 24°C than at 37°C. Zone-of-inhibition assays suggested that the mechanism of carbenicillin resistance was not due to antibiotic inactivation. The DNA insert did not encode any genes known to confer antibiotic resistance, but did have two putative open reading frames (ORFs) that were annotated as a metallopeptidase and a two-component response regulator. Transposon mutagenesis and subcloning of the two ORFs followed by phenotypic assays showed that the response regulator gene was necessary and sufficient to confer the resistance phenotype. Quantitative reverse transcriptase PCR showed that the response regulator suppressed expression of the ompF porin gene, independently of the small RNA regulator micF, and enhanced expression of the acrD, mdtA, and mdtB efflux pump genes. This work demonstrates that antibiotic resistance can be achieved by the modulation of gene regulation by heterologous DNA. Functional analyses such as these can be important for making discoveries in antibiotic resistance gene biology and ecology. PMID:25782011

Allen, Heather K.; An, Ran; Handelsman, Jo; Moe, Luke A.



The Role of Antibiotic Prophylaxis in Prevention of Wound Infection After Lichtenstein Open Mesh Repair of Primary Inguinal Hernia  

PubMed Central

Objective: To determine whether the use of prophylactic antibiotics is effective in the prevention of postoperative wound infection after Lichtenstein open mesh inguinal hernia repair. Summary Background Data: A recent Cochrane meta-analysis (2003) concluded that “antibiotic prophylaxis for elective inguinal hernia repair cannot be firmly recommended or discarded.” Methods: Patients with a primary inguinal hernia scheduled for Lichtenstein repair were randomized to a preoperative single dose of 1.5 g intravenous cephalosporin or a placebo. Patients with recurrent hernias, immunosuppressive diseases, or allergies for the given antibiotic were excluded. Infection was defined using the Centers for Disease Control and Prevention criteria. Results: We included 1040 patients in the study between November 1998 and May 2003. According to the intention-to-treat principle, 1008 patients were analyzed. There were 8 infections (1.6%) in the antibiotic prophylaxis group and 9 (1.8%) in the placebo group (P = 0.82). There was 1 deep infection in the antibiotic prophylaxis group and 2 in the placebo group (P = 0.57). Statistical analysis showed an absolute risk reduction of 0.19% (95% confidence interval, ?1.78%–1.40%) and a number needed to treat of 520 for the total number of infections. For deep infection, the absolute risk reduction is 0.20% (95% confidence interval, ?0.87%–0.48%) with a number needed to treat of 508. Conclusions: A low percentage (1.7%) of wound infection after Lichtenstein open mesh inguinal (primary) hernia repair was found, and there was no difference between the antibiotic prophylaxis or placebo group. The results show that, in Lichtenstein inguinal primary hernia repair, antibiotic prophylaxis is not indicated in low-risk patients. PMID:15570201

Aufenacker, Theo J.; van Geldere, Dirk; van Mesdag, Taco; Bossers, Astrid N.; Dekker, Benno; Scheijde, Edo; van Nieuwenhuizen, Roos; Hiemstra, Esther; Maduro, John H.; Juttmann, Jan-Willem; Hofstede, Diederik; van Der Linden, Cunera T. M.; Gouma, Dirk J.; Simons, Maarten P.



A Response Regulator from a Soil Metagenome Enhances Resistance to the ?-Lactam Antibiotic Carbenicillin in Escherichia coli.  


Functional metagenomic analysis of soil metagenomes is a method for uncovering as-yet unidentified mechanisms for antibiotic resistance. Here we report an unconventional mode by which a response regulator derived from a soil metagenome confers resistance to the ?-lactam antibiotic carbenicillin in Escherichia coli. A recombinant clone (?lr16) harboring a 5,169 bp DNA insert was selected from a metagenomic library previously constructed from a remote Alaskan soil. The ?lr16 clone conferred specific resistance to carbenicillin, with limited increases in resistance to other tested antibiotics, including other ?-lactams (penicillins and cephalosporins), rifampin, ciprofloxacin, erythromycin, chloramphenicol, nalidixic acid, fusidic acid, and gentamicin. Resistance was more pronounced at 24°C than at 37°C. Zone-of-inhibition assays suggested that the mechanism of carbenicillin resistance was not due to antibiotic inactivation. The DNA insert did not encode any genes known to confer antibiotic resistance, but did have two putative open reading frames (ORFs) that were annotated as a metallopeptidase and a two-component response regulator. Transposon mutagenesis and subcloning of the two ORFs followed by phenotypic assays showed that the response regulator gene was necessary and sufficient to confer the resistance phenotype. Quantitative reverse transcriptase PCR showed that the response regulator suppressed expression of the ompF porin gene, independently of the small RNA regulator micF, and enhanced expression of the acrD, mdtA, and mdtB efflux pump genes. This work demonstrates that antibiotic resistance can be achieved by the modulation of gene regulation by heterologous DNA. Functional analyses such as these can be important for making discoveries in antibiotic resistance gene biology and ecology. PMID:25782011

Allen, Heather K; An, Ran; Handelsman, Jo; Moe, Luke A



Commonly Used Antibiotics on Dairies  

Microsoft Academic Search

A recent survey 1 of dairymen in Minnesota, Michigan, Wisconsin and New York studied the antibiotic use strategies used on nearly 100 conventional and 30 organic dairies. They found that 71% of the dairies kept antibiotic treatment records for lactating dairy cows. Slightly over half of the dairies kept records of treatment of dry-cows and only a third kept records

John H. Kirk; Extension Veterinarian


Chemistry of Antibiotics from Micromonospora  

PubMed Central

The isolation of everninomicin D and everninomicin B, two closely related antibiotics produced by Micromonospora carbonacea, is described. The structures of everninomicin D and B are shown to parallel closely that of curamycin, a polysaccharidic antibiotic with a low molecular weight and a dichloroisoeverninic acid end group. PMID:14346980

Herzog, H. L.; Meseck, E.; Delorenzo, S.; Murawski, A.; Charney, W.; Rosselet, J. P.



Biotherapeutics as alternatives to antibiotics  

Technology Transfer Automated Retrieval System (TEKTRAN)

Increasing pressure to limit antibiotic use in agriculture is heightening the need for alternative methods to reduce the adverse effects of clinical and subclinical disease on livestock performance that are currently managed by in-feed antibiotic usage. Immunomodulators have long been sought as such...


Macrolide antibiotics and pulmonary inflammation  

Microsoft Academic Search

Many clinically effective therapeutic agents can exhibit localized and systemic effects that are manifestly different from their intended primary pharmacological mode of action. Macrolide antibiotics such as erythromycin and its derivatives are no exception. In addition to their antibacterial action, this class of antibiotics exhibits anti-inflammatory activity in a variety of airway diseases such as asthma and diffuse panbronchiolitis that

Jeffrey C Hoyt; Richard A Robbins



Microbes: Too Smart for Antibiotics?  

NSDL National Science Digital Library

This lesson focuses on examining why microbes become resistant to antibiotics, as well as their roles in human health and the environment. Students can produce public-awareness campaigns on antibiotic use, create yogurt recipe cards, develop a commercial bioremediation product, experiment with simulated germs and more!

Peggy Deichstetter (St. Edward High School; )



Multiple antibiotic resistance and efflux  

Microsoft Academic Search

Multiple antibiotic resistance in bacteria was at first thought to be caused exclusively by the combination of several resistance genes, each coding for resistance to a single drug. More recently, it became clear that such phenotypes are often achieved by the activity of drug efflux pumps. Some of these efflux pumps exhibit an extremely wide specificity covering practically all antibiotics,

Hiroshi Nikaido



Veterinary use and antibiotic resistance  

Microsoft Academic Search

Globally, an estimated 50% of all antimicrobials serve veterinary purposes. Bacteria that inevitably develop antibiotic resistance in animals comprise food-borne pathogens, opportunistic pathogens and commensal bacteria. The same antibiotic resistance genes and gene transfer mechanisms can be found in the microfloras of animals and humans. Direct contact, food and water link animal and human habitats. The accumulation of resistant bacteria

Michael Teuber



The Antibiotic Resistance Problem Revisited  

ERIC Educational Resources Information Center

The term "antibiotic" was first proposed by Vuillemin in 1889 but was first used in the current sense by Walksman in 1941. An antibiotic is defined as a "derivative produced by the metabolism of microorganisms that possess antibacterial activity at low concentrations and is not toxic to the host." In this article, the author describes how…

Lawson, Michael A.



Essential oils, a new horizon in combating bacterial antibiotic resistance.  


For many years, the battle between humans and the multitudes of infection and disease causing pathogens continues. Emerging at the battlefield as some of the most significant challenges to human health are bacterial resistance and its rapid rise. These have become a major concern in global public health invigorating the need for new antimicrobial compounds. A rational approach to deal with antibiotic resistance problems requires detailed knowledge of the different biological and non-biological factors that affect the rate and extent of resistance development. Combination therapy combining conventional antibiotics and essential oils is currently blooming and represents a potential area for future investigations. This new generation of phytopharmaceuticals may shed light on the development of new pharmacological regimes in combating antibiotic resistance. This review consolidated and described the observed synergistic outcome between essential oils and antibiotics, and highlighted the possibilities of essential oils as the potential resistance modifying agent. PMID:24627729

Yap, Polly Soo Xi; Yiap, Beow Chin; Ping, Hu Cai; Lim, Swee Hua Erin



Essential Oils, A New Horizon in Combating Bacterial Antibiotic Resistance  

PubMed Central

For many years, the battle between humans and the multitudes of infection and disease causing pathogens continues. Emerging at the battlefield as some of the most significant challenges to human health are bacterial resistance and its rapid rise. These have become a major concern in global public health invigorating the need for new antimicrobial compounds. A rational approach to deal with antibiotic resistance problems requires detailed knowledge of the different biological and non-biological factors that affect the rate and extent of resistance development. Combination therapy combining conventional antibiotics and essential oils is currently blooming and represents a potential area for future investigations. This new generation of phytopharmaceuticals may shed light on the development of new pharmacological regimes in combating antibiotic resistance. This review consolidated and described the observed synergistic outcome between essential oils and antibiotics, and highlighted the possibilities of essential oils as the potential resistance modifying agent. PMID:24627729

Yap, Polly Soo Xi; Yiap, Beow Chin; Ping, Hu Cai; Lim, Swee Hua Erin



Antibiotic-resistant bacteria: a challenge for the food industry.  


Antibiotic-resistant bacteria were first described in the 1940s, but whereas new antibiotics were being discovered at a steady rate, the consequences of this phenomenon were slow to be appreciated. At present, the paucity of new antimicrobials coming into the market has led to the problem of antibiotic resistance fast escalating into a global health crisis. Although the selective pressure exerted by the use of antibiotics (particularly overuse or misuse) has been deemed the major factor in the emergence of bacterial resistance to these antimicrobials, concerns about the role of the food industry have been growing in recent years and have been raised at both national and international levels. The selective pressure exerted by the use of antibiotics (primary production) and biocides (e.g., disinfectants, food and feed preservatives, or decontaminants) is the main driving force behind the selection and spread of antimicrobial resistance throughout the food chain. Genetically modified (GM) crops with antibiotic resistance marker genes, microorganisms added intentionally to the food chain (probiotic or technological) with potentially transferable antimicrobial resistance genes, and food processing technologies used at sub-lethal doses (e.g., alternative non-thermal treatments) are also issues for concern. This paper presents the main trends in antibiotic resistance and antibiotic development in recent decades, as well as their economic and health consequences, current knowledge concerning the generation, dissemination, and mechanisms of antibacterial resistance, progress to date on the possible routes for emergence of resistance throughout the food chain and the role of foods as a vehicle for antibiotic-resistant bacteria. The main approaches to prevention and control of the development, selection, and spread of antibacterial resistance in the food industry are also addressed. PMID:23035919

Capita, Rosa; Alonso-Calleja, Carlos



Reducing fitness costs associated with antibiotic resistance  

E-print Network

Reducing fitness costs associated with antibiotic resistance Experimental evolution Reducing fitness costs associated with antibiotic resistance Experimental evolution in the filamentous;Schoustra, Sijmen Ecco Reducing fitness costs associated with antibiotic resistance ­ Experimental evolution

Kassen, Rees


A call for antibiotic alternatives research  

Technology Transfer Automated Retrieval System (TEKTRAN)

The persistence and spread of antibiotic resistance and decreased profitability of new antibiotics have created the dangerous prospect of ineffective therapies against bacterial diseases. The discovery, development, and application of effective antibiotic alternatives, especially in agriculture, sho...


[Antibiotic therapy in nephrology].  


The use of antibiotics in patients with kidney diseases is associated mainly with urinary tract infections (UTI) and urosepsis. Treatment of bacterial infections not related to UTI in patients with chronic renal failure is usually more complicated than in subjects with normal renal function. The high incidence of UTI, recurrent and chronic character of these disorders make them difficult to cure. In all these situations it is important to use effective drugs, without nephrotoxicity, with minimal risk of building up the resistance. Due to the increasing number of dialysis patients, especially treated with hemodialysis, it becomes essential to use effective antibacterial therapy in this group of patients, including infections specific for this kind of treatment. Proper mode of treatment adjusted to type of renal replacement therapy (hemodialysis, peritoneal dialysis or continuous renal replacement therapy) is very important. PMID:21675138

Niemczyk, Stanis?aw



Resistance to selected beta-lactam antibiotics.  


Susceptibility in vitro and trends in resistance to antimicrobials were determined by a dilution micromethod in a group of Actinobacillus pleuropneumoniae, Pasteurella multocida, Mannheimia haemolytica and Escherichia coli isolates from clinical cases of cattle and swine diseases in the Czech Republic from 2007 to 2011. A high susceptibility of pig and cattle respiratory pathogens to antimicrobials was found, with the exception of the moderate prevalence of M. haemolytica resistance to ampicillin. In contrast to respiratory pathogens, low susceptibility of E. coli of pig and cattle isolates to ampicillin and amoxicillin/clavulanic acid was noted. Regarding resistance trends, an increase in levels of resistance among E. coli isolates to ampicillin and amoxicillin/clavulanic acid was identified, but the resistance of respiratory isolates was low, with the exception of M. haemolytica. For the period of 2007-2011, there was a significant and almost continuous increase in sales (compared with population correction unit) of ceftiofur, cefquinome and other beta lactams for pigs. Consumption peaked in 2010. In the case of amoxicillin in combination with clavulanic acid, data showed a significant decrease in sales from 2007 to 2008, followed by a period of fluctuation. In cattle, within the groups of 3rd and 4th generation cephalosporins and for the whole group of other betalactams for the period of 2007-2011, there was a significant and almost continuous increase in sales (compared with population correction unit). Consumption peaked in 2010. In the case of ceftiofur, there was a huge increase noted from 2010. In the case of amoxicillin in combination with betalactamase inhibitor (clavulanic acid) data shows a significant decrease from 2007 to 2008, followed by a period of fluctuation in sales. PMID:24612952

Nedbalcova, K; Nechvatalova, K; Pokludova, L; Bures, J; Kucerova, Z; Koutecka, L; Hera, A



When and How to Take Antibiotics  


... antibiotics are a powerful medical tool to thwart bacterial diseases. Prudent use includes taking antibiotics only for diagnosed bacterial infections and following the precise directions on the prescription. ( ...


Enterobacteriaceae resistant to third-generation cephalosporins and quinolones in fresh culinary herbs imported from Southeast Asia.  


Since multidrug resistant bacteria are frequently reported from Southeast Asia, our study focused on the occurrence of ESBL-producing Enterobacteriaceae in fresh imported herbs from Thailand, Vietnam and Malaysia. Samples were collected from fresh culinary herbs imported from Southeast Asia in which ESBL-suspected isolates were obtained by selective culturing. Analysis included identification by MALDI-TOF mass spectrometry, susceptibility testing, XbaI-PFGE, microarray, PCR and sequencing of specific ESBL genes, PCR based replicon typing (PBRT) of plasmids and Southern blot hybridization. In addition, the quinolone resistance genotype was characterized by screening for plasmid mediated quinolone resistance (PMQR) genes and mutations in the quinolone resistance determining region (QRDR) of gyrA and parC. The study encompassed fifty samples of ten batches of culinary herbs (5 samples per batch) comprising nine different herb variants. The herbs originated from Thailand (Water morning glory, Acacia and Betel leaf), Vietnam (Parsley, Asian pennywort, Houttuynia leaf and Mint) and Malaysia (Holy basil and Parsley). By selective culturing 21 cefotaxime resistant Enterobacteriaceae were retrieved. Array analysis revealed 18 isolates with ESBL genes and one isolate with solely non-ESBL beta-lactamase genes. Mutations in the ampC promoter region were determined in two isolates with PCR and sequencing. The isolates were identified as Klebsiella pneumoniae (n=9), Escherichia coli (n=6), Enterobacter cloacae complex (n=5) and Enterobacter spp. (n=1). All isolates tested were multidrug resistant. Variants of CTX-M enzymes were predominantly found followed by SHV enzymes. PMQR genes (including aac(6')-1b-cr, qnrB and qnrS) were also frequently detected. In almost all cases ESBL and quinolone resistance genes were located on the same plasmid. Imported fresh culinary herbs from Southeast Asia are a potential source for contamination of food with multidrug resistant bacteria. Because these herbs are consumed without appropriate heating, transfer to human bacteria cannot be excluded. PMID:24607424

Veldman, Kees; Kant, Arie; Dierikx, Cindy; van Essen-Zandbergen, Alieda; Wit, Ben; Mevius, Dik



Public Knowledge, Attitudes, and Experience Regarding the Use of Antibiotics in Italy  

PubMed Central

Background The objectives of the study were to investigate the level of knowledge, attitudes, and behaviors regarding antibiotics of the general population in Italy, and to assess the correlates of these outcomes of interest. Methods A cross-sectional survey was conducted on a random sample of 630 parents of students attending nine randomly selected public primary and secondary schools. A self-administered questionnaire included questions on demographic characteristics, knowledge about antibiotic use and resistance, attitudes and behaviors towards antibiotic use, and sources of information. Results A total of 419 parents participated. Only 9.8% knew the definition of antibiotic resistance and 21.2% knew when it was appropriate to use antibiotics. Respondents with higher education, employed, with a family member working in the health care sector, and with no need for additional information on antibiotics were more likely to know the definition of antibiotic resistance. One third (32.7%) self-classified them as users of self-medication with antibiotics and those with a lower self-rated health status, who did not use the physician as source of information on antibiotics, and who have attended a physician in the last year were more likely to use self-medication. One-fourth (22.7%) of those who had never been self-medicated would be willing to take an antibiotic without a prescription of a physician. Respondents were more likely to be willing to take antibiotics without a prescription if they were under 40 years of age, if they had a lower self-rated health status, if they did not know that antibiotics are not indicated for treating flu and sore throat, and if they knew that antibiotics are not indicated for treating colds. Conclusions The survey has generated information about knowledge, attitudes, and behaviors regarding antibiotics in the general population and effective public education initiative should provide practical and appropriate means to change their behavior. PMID:24376793

Napolitano, Francesco; Izzo, Maria Teresa; Di Giuseppe, Gabriella; Angelillo, Italo F.



Mortality and Hospital Stay Associated with Resistant Staphylococcus aureus and Escherichia coli Bacteremia: Estimating the Burden of Antibiotic Resistance in Europe  

PubMed Central

Background The relative importance of human diseases is conventionally assessed by cause-specific mortality, morbidity, and economic impact. Current estimates for infections caused by antibiotic-resistant bacteria are not sufficiently supported by quantitative empirical data. This study determined the excess number of deaths, bed-days, and hospital costs associated with blood stream infections (BSIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) and third-generation cephalosporin-resistant Escherichia coli (G3CREC) in 31 countries that participated in the European Antimicrobial Resistance Surveillance System (EARSS). Methods and Findings The number of BSIs caused by MRSA and G3CREC was extrapolated from EARSS prevalence data and national health care statistics. Prospective cohort studies, carried out in hospitals participating in EARSS in 2007, provided the parameters for estimating the excess 30-d mortality and hospital stay associated with BSIs caused by either MRSA or G3CREC. Hospital expenditure was derived from a publicly available cost model. Trends established by EARSS were used to determine the trajectories for MRSA and G3CREC prevalence until 2015. In 2007, 27,711 episodes of MRSA BSIs were associated with 5,503 excess deaths and 255,683 excess hospital days in the participating countries, whereas 15,183 episodes of G3CREC BSIs were associated with 2,712 excess deaths and 120,065 extra hospital days. The total costs attributable to excess hospital stays for MRSA and G3CREC BSIs were 44.0 and 18.1 million Euros (63.1 and 29.7 million international dollars), respectively. Based on prevailing trends, the number of BSIs caused by G3CREC is likely to rapidly increase, outnumbering the number of MRSA BSIs in the near future. Conclusions Excess mortality associated with BSIs caused by MRSA and G3CREC is significant, and the prolongation of hospital stay imposes a considerable burden on health care systems. A foreseeable shift in the burden of antibiotic resistance from Gram-positive to Gram-negative infections will exacerbate this situation and is reason for concern. Please see later in the article for the Editors' Summary PMID:22022233

de Kraker, Marlieke E. A.; Davey, Peter G.; Grundmann, Hajo



A longitudinal field trial assesing the impact of feeding waste milk containing antibiotic residues on the prevalence of ESBL-producing Escherichia coli in calves.  


A longitudinal field trial was carried out on a farm known to harbour cefotaximase (CTX-M)-positive Escherichia coli, in order to assess the impact of feeding waste milk containing antibiotic residues (WM+AR) on the prevalence of these bacteria in the faeces of calves. Fifty calves were alternately assigned to one of two groups at birth and fed either milk replacer (control group) or WM+AR (treatment group). Faecal samples were collected from all calves daily for the first week after enrolment, twice weekly until weaning, then weekly for a further six weeks. Environmental samples from the calf housing were collected weekly. WM+AR and powdered milk samples were examined for antibiotic residues and CTX-M-positive E. coli. Total E. coli and CTX-M-positive E. coli in faecal samples were enumerated using selective media. Regression analyses were performed on the bacterial count data using a population-averaged approach based on generalised estimating equations (GEE) to account for repeated measurements on individual calves over time. Cefquinome, a fourth generation cephalosporin, was detected in 87% of WM+AR samples at a mean concentration of 0.746 mg/l. All environmental sampling locations yielded CTX-M-positive E. coli. Significantly more pen floor samples were positive in the treatment group. Calves in the treatment group shed greater numbers of CTX-M-positive E. coli than calves in the control group throughout the study, and shedding decreased at a slower rate in the treatment group. CTX-M-positive E. coli persisted in a larger number of calves fed WM+AR compared with calves fed milk replacer where the prevalence in the treatment group declined significantly slower over time. There was no difference between calves fed WM+AR or calves fed milk replacer in the proportion of E. coli isolates that were CTX-M-positive. These findings indicate that feeding WM+AR increased the amount of resistant bacteria shed in the faeces. Shedding of CTX-M-positive E. coli persisted for longer in calves fed WM+AR, and persisted after weaning. PMID:25172121

Brunton, L A; Reeves, H E; Snow, L C; Jones, J R



Systemic antibiotic therapy in periodontics  

PubMed Central

Systemic antibiotics in conjunction with scaling and root planing (SRP), can offer an additional benefit over SRP alone in the treatment of periodontitis, in terms of clinical attachment loss (CAL) and pocket depth change, and reduced risk of additional CAL loss. However, antibiotics are not innocuous drugs. Their use should be justified on the basis of a clearly established need and should not be substituted for adequate local treatment. The aim of this review is to discuss the rationale, proper selection, dosage and duration for antibiotic therapy so as to optimize the usefulness of drug therapy. PMID:23559912

Kapoor, Anoop; Malhotra, Ranjan; Grover, Vishakha; Grover, Deepak



[Antibiotic prophylaxis and endoluminal tubes].  


Surgical site infections are one of the most common complications after surgical procedures. The use of perioperative antibiotic prophylaxis can successfully reduce the number of wound infections. The indications, timing and choice of antibiotics are discussed critically. Taken together antibiotic prophylaxis should be evaluated depending on wound contamination, the type of operation and patient-specific risk factors. In the second part of this work the current literature on the effectiveness of endoluminal tubes in abdominal surgery is analyzed. While many surgeons use these tubes regularly in elective abdominal surgery, only few data are available on this topic. The use of nasogastric tubes in elective surgery should be avoided. PMID:22008844

Justinger, C; Schilling, M K



Antibiotic resistance in wild birds  

PubMed Central

Wild birds have been postulated as sentinels, reservoirs, and potential spreaders of antibiotic resistance. Antibiotic-resistant bacteria have been isolated from a multitude of wild bird species. Several studies strongly indicate transmission of resistant bacteria from human rest products to wild birds. There is evidence suggesting that wild birds can spread resistant bacteria through migration and that resistant bacteria can be transmitted from birds to humans and vice versa. Through further studies of the spatial and temporal distribution of resistant bacteria in wild birds, we can better assess their role and thereby help to mitigate the increasing global problem of antibiotic resistance. PMID:24697355

Bonnedahl, Jonas



Validation of a microbiological method: the STAR protocol, a five-plate test, for the screening of antibiotic residues in milk.  


The results of an in-house laboratory validation of a microbiological method for the screening of antibiotic residues in milk are presented. The sensitivity of this five-plate test, called Screening Test for Antibiotic Residues (STAR), was established by the analysis of milk samples spiked with 66 antibiotics at eight different concentrations. Ten different groups of antibiotics were studied: macrolides, aminoglycosides, cephalosporins, penicillins, quinolones, tetracyclines, sulphonamides, lincosamides, phenicolated and miscellaneous drugs. It was shown that 21 antibiotics were detected by the STAR protocol at or below the maximum residue limit (MRL), and that a further 27 drugs could be detected at levels from the MRL up to four times the MRL. The sensitivity of the STAR protocol was at or below the MRL for three macrolides, one tetracycline, two aminoglycosides, some sulphonamides, half of the beta-lactams, quinolones, lincosamides, trimethoprim and baquiloprim. Moreover, the STAR protocol was at least twice as sensitive as conventional methods for macrolides, quinolones and tetracyclines. The other antibiotics had limits of detection between four and 150 times the MRL. Each plate was preferentially sensitive for one or two families of antibacterials: the plate Bacillus cereus for tetracyclines, the plate Escherichia coli for quinolones, the plate Basillus subtilis for aminoglycosides, the plate Kocuria varians for macrolides, and the plate Bacillus stearothermophilus for sulphonamides and beta-lactams. This method has been used routinely on a day-to-day basis to direct the physicochemical confirmation towards one or two families of antibiotics. Considering the high cost of liquid chromatography coupled with tandem mass spectrometry detection analyses, the reduction of the range of antibiotics to test for confirmation is a significant gain in time and money. PMID:15204543

Gaudin, V; Maris, P; Fuselier, R; Ribouchon, J-L; Cadieu, N; Rault, A



The Double Life of Antibiotics  

PubMed Central

Antibiotic resistance is a persistent health care problem worldwide. Evidence for the negative consequences of subtherapeutic feeding in livestock production has been mounting while the antibiotic pipeline is drying up. In recent years, there has been a paradigm shift in our perception of antibiotics. Apart from its roles in self-defense, antibiotics also serve as inter-microbial signaling molecules, regulators of gene expression, microbial food sources, and as mediators of host immune response. “The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily under-dose himself and by exposing his microbes to nonlethal quantities of the drug make them resistant.”~Alexander Fleming PMID:24003650

Yap, Mee-Ngan F.



The determinants of the antibiotic resistance process  

PubMed Central

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

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



Antibiotic-Resistant Klebsiella pneumoniae and Escherichia coli High-Risk Clones and an IncFIIk Mosaic Plasmid Hosting Tn1 (blaTEM-4) in Isolates from 1990 to 2004.  


We describe the genetic background of blaTEM-4 and the complete sequence of pRYC11::blaTEM-4, a mosaic plasmid that is highly similar to pKpQIL-like variants, predominant among TEM-4 producers in a Spanish hospital (1990 to 2004), which belong to Klebsiella pneumoniae and Escherichia coli high-risk clones responsible for the current spread of different antibiotic resistance genes. Predominant populations of plasmids and host adapted clonal lineages seem to have greatly contributed to the spread of resistance to extended-spectrum cephalosporins. PMID:25691645

Rodríguez, Irene; Novais, Ângela; Lira, Felipe; Valverde, Aránzazu; Curião, Tânia; Martínez, José Luis; Baquero, Fernando; Cantón, Rafael; Coque, Teresa M



Antibiotic prophylaxis for arthroscopic surgery.  


Because the incidence of infection in arthroscopic surgery is very low, one can argue both for and against the use of prophylactic antibiotics. Administering antibiotics adds expense and introduces the potential for both exposure to allergic reactions and selection of resistant organisms. Antibiotics are given to prevent deep infection; such treatment may require further surgery, prolonged use of intravenous antibiotics, high costs, and outcomes that may be less than satisfactory. An answer to this controversial issue would require a study that includes large numbers of patients to make it adequately statistically powered because the incidence of infection is so low. No such research has yet been performed, and the American Academy of Orthopaedic Surgeons (AAOS) has not produced an advisory statement addressing this issue. It is the opinion of this author that antibiotic prophylaxis is indicated for arthroscopic surgery. Despite surgical team best practices, mistakes can occur. This has led the AAOS to issue an advisory statement to prevent wrong-site surgery. Similarly, complacency with repetition may produce breaks in sterility that may occasionally go undetected. Antibiotic usage may help to reduce infection in such circumstances. Arthroscopic procedures are not always performed in healthy patients. The risk of infection in "high-risk" patients, such as those with diabetes, immune problems, and skin disorders, may be reduced by prophylactic antibiotics. How one defines a case as arthroscopic can be debated. If small incisions are made, or if the scope is used for only a portion of the procedure, many would still consider the case to be arthroscopic. Surgeries are becoming more complex, which adds to their duration. Some cases also involve the use of implants such as interference screws and suture anchors. It is my opinion that antibiotics should be used in these situations. The potential exists for litigation in cases of infection. Medicolegally, it is easier to argue that all measures were taken to prevent infection if prophylactic antibiotics were given, although patient care issues supersede defensive medicine. Risk of infection in arthroscopic surgery is multifactorial, and antibiotic prophylaxis is only one facet of the issue. Although it is my opinion that antibiotics are recommended, others could be justified in supporting the opposite opinion, pending appropriately designed and adequately powered future investigations. PMID:16581459

Kurzweil, Peter R



In vitro antibiotic susceptibilities of Neisseria gonorrhoeae isolates in the Philippines.  


Antibiotic susceptibility surveillance testing was performed on clinical isolates of Neisseria gonorrhoeae collected in September 1989 in the Philippines. beta-Lactamase was produced by 77 (55%) of 140 isolates. In vitro MIC testing revealed significant resistance to penicillin (MIC for 90% of isolates [MIC90], greater than 64 micrograms/ml), tetracycline (MIC90, 4 micrograms/ml), and cefmetazole (MIC90, 8 micrograms/ml). Spectinomycin resistance was rare (10 of 117), but the MIC90 was 32 micrograms/ml. Isolates were susceptible to fluoroquinolones and cephalosporins at the time of this survey, as evidenced by the MIC90s of ciprofloxacin (0.25 microgram/ml), norfloxacin (2.0 micrograms/ml), ofloxacin (0.625 microgram/ml), cefpodoxime (2.0 micrograms/ml), cefotaxime (1.0 microgram/ml), ceftazidime (0.25 microgram/ml), ceftizoxime (0.25 microgram/ml), and ceftriaxone (0.06 microgram/ml). To date, ceftriaxone resistance has not emerged, despite the widespread use of this antibiotic in the Philippines. PMID:1605592

Clendennen, T E; Hames, C S; Kees, E S; Price, F C; Rueppel, W J; Andrada, A B; Espinosa, G E; Kabrerra, G; Wignall, F S



[Resistance to "last resort" antibiotics in Gram-positive cocci: The post-vancomycin era].  


New therapeutic alternatives have been developed in the last years for the treatment of multidrug-resistant Gram-positive infections. Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) are considered a therapeutic challenge due to failures and lack of reliable antimicrobial options. Despite concerns related to the use of vancomycin in the treatment of severe MRSA infections in specific clinical scenarios, there is a paucity of solid clinical evidence that support the use of alternative agents (when compared to vancomycin). Linezolid, daptomycin and tigecycline are antibiotics approved in the last decade and newer cephalosporins (such as ceftaroline and ceftobiprole) and novel glycopeptides (dalvavancin, telavancin and oritavancin) have reached clinical approval or are in the late stages of clinical development. This review focuses on discussing these newer antibiotics used in the "post-vancomycin" era with emphasis on relevant chemical characteristics, spectrum of antimicrobial activity, mechanisms of action and resistance, as well as their clinical utility. PMID:24968051

Rincón, Sandra; Panesso, Diana; Díaz, Lorena; Carvajal, Lina P; Reyes, Jinnethe; Munita, José M; Arias, César A




Technology Transfer Automated Retrieval System (TEKTRAN)

Fluoroquinolone antibiotics are currently used in both medical and veterinary applications. Use of these antibiotics in food animals has generated concern as the presence of these residues in food may contribute to increased microbial resistance in humans. Effective methods for analysis of fluoroq...


Antibiotics in third molar surgery.  


The aim of this survey was to assess the knowledge and practice of Swiss dentists focusing on the use of antibiotics in prophylactic surgical removal of lower wisdom teeth. A postal survey was conducted among all 3288 dentists who are members of the Swiss Dental Society (SSO) representing nearly all dentists in Switzerland. The questionnaire consisted of 13 questions with mostly multiple-choice answers. Demographic profile, surgical experience, the use of antibiotics, and wound management, i.e. wound closure and the use of mouth rinse were assessed. A response rate of 55% was obtained. Most Swiss dentists perform surgical extractions in their practices. Of all dentists, 18.6% used antibiotics routinely, but a large variation was found comparing the three linguistic regions of Switzerland with the highest prescription rate of 48% in the French-speaking south-west of Switzerland. Fifty-two percent of dentists prescribed amoxicillin in a dose of 750 mg. Most often three daily doses were prescribed (47%). A postoperative regime was prescribed by 54.4% of dentists. French language (p=0.003), graduation from the university of Geneva (p=0.007), foreign diplomas (p<0.001), and dentists with diplomas awarded from 2001-2006 (p=0.004) showed a highly significant correlation with the use of antibiotics. In Switzerland, prophylactic antibiotics are used in third molar surgery. Antibiotic prescription however largely depends on geographical situation and dentist profiles. The assessment of antibiotic use in private practices is important in the light of growing evidence that antibiotic overuse may lead to development of multiresistant bacterial strains. In a second part results regarding wound management and mouth rinse will be presented. PMID:24671748

Vlcek, Daniel; Razavi, Amir; Kuttenberger, Johannes J



Antibiotic prophylaxis in pediatric urology  

PubMed Central

Urinary tract infection (UTI) is a common problem in infants and children. Children at risk for UTI such as vesicoureteric reflux (VUR) commonly receive prophylactic antibiotics to prevent renal scarring, which may lead to complications such as hypertension or end-stage renal disease. Recurrent UTI, with or without VUR, is the most common reason for long-term antibiotic prophylaxis in infants and children. However, the efficacy and importance of long-term antibiotic prophylaxis have not been assessed in well-controlled, prospective studies. Nitrofurantoin, trimethoprim/sulfamethoxazole have been used as prophylactic antibiotics for the prevention of UTI in children. Such medications are mostly safe in children for the long-term prophylactic therapy. Serious side effects are extremely rare and most are reversible with discontinuation of therapy. Although it is difficult to perform prospective studies in children and many factors are involved in the clinical course and prognosis of these patients, further studies are needed to evaluate the actual benefits of prophylactic antibiotics. Meanwhile, in infants and children with risk factors, long-term antibiotic prophylaxis should be considered, at least until there is evidence that these patients are not endangered by avoiding it. PMID:19468387

Song, Seung-Hun; Kim, Kun Suk



Genome-wide analysis captures the determinants of the antibiotic cross-resistance interaction network  

PubMed Central

Understanding how evolution of antimicrobial resistance increases resistance to other drugs is a challenge of profound importance. By combining experimental evolution and genome sequencing of 63 laboratory-evolved lines, we charted a map of cross-resistance interactions between antibiotics in Escherichia coli, and explored the driving evolutionary principles. Here, we show that (1) convergent molecular evolution is prevalent across antibiotic treatments, (2) resistance conferring mutations simultaneously enhance sensitivity to many other drugs and (3) 27% of the accumulated mutations generate proteins with compromised activities, suggesting that antibiotic adaptation can partly be achieved without gain of novel function. By using knowledge on antibiotic properties, we examined the determinants of cross-resistance and identified chemogenomic profile similarity between antibiotics as the strongest predictor. In contrast, cross-resistance between two antibiotics is independent of whether they show synergistic effects in combination. These results have important implications on the development of novel antimicrobial strategies. PMID:25000950

Lázár, Viktória; Nagy, István; Spohn, Réka; Csörg?, Bálint; Györkei, Ádám; Nyerges, Ákos; Horváth, Balázs; Vörös, Andrea; Busa-Fekete, Róbert; Hrtyan, Mónika; Bogos, Balázs; Méhi, Orsolya; Fekete, Gergely; Szappanos, Balázs; Kégl, Balázs; Papp, Balázs; Pál, Csaba



Heat inactivation of beta-lactam antibiotics in milk.  


The presence of residues of antimicrobial substances in milk is one of the main concerns of the milk industry, as it poses a risk of toxicity to public health, and can seriously influence the technological properties of milk and dairy products. Moreover, the information available on the thermostability characteristics of these residues, particularly regarding the heat treatments used in control laboratories and the dairy industry, is very scarce. The aim of the study was, therefore, to analyze the effect of different heat treatments (40 degrees C for 10 min, 60 degrees C for 30 min, 83 degrees C for 10 min, 120 degrees C for 20 min, and 140 degrees C for 10 s) on milk samples fortified with three concentrations of nine beta-lactam antibiotics (penicillin G: 3, 6, and 12 microg/liter; ampicillin: 4, 8, and 16 microg/liter; amoxicillin: 4, 8, and 16 microg/liter; cloxacillin: 60, 120, and 240 microg/liter; cefoperazone: 55, 110, and 220 microg/liter; cefquinome: 100, 200, and 400 microg/liter; cefuroxime: 65, 130, and 260 microg/liter; cephalexin: 80, 160, and 220 microg/ liter; and cephalonium: 15, 30, and 60 microg/liter). The method used was a bioassay based on the inhibition of Geobacillus stearothermophilus var. calidolactis. The results showed that heating milk samples at 40 degrees C for 10 min hardly produced any heat inactivation at all, while the treatment at 83 degrees C for 10 min caused a 20% loss in penicillin G, 27% in cephalexin, and 35% in cefuroxime. Of the three dairy industry heat treatments studied in this work, low pasteurization (60 degrees C for 30 min) and treatment at 140 degrees C for 10 s only caused a small loss of antimicrobial activity, whereas classic sterilization (120 degrees C for 20 min) showed a high level of heat inactivation of over 65% for penicillins and 90% for cephalosporins. PMID:18592745

Zorraquino, M A; Roca, M; Fernandez, N; Molina, M P; Althaus, R



Antibiotic Attack (Kinetic City)  

NSDL National Science Digital Library

This game is a part of the Tau Pack of the Kinetic City site (see description below). In this simulation, the patient's bodies are filled with bacteria. The object is to cure as many patients as possible. Learning concepts enforced here are that antibiotics are specific for the type of bacteria they treat, their strength, and that the bacteria may also become resistant to the bacteria by mutations.KINETIC CITY DESCRIPTION: "Kinetic City" ( is a fun, Web-based after-school science club for kids, ages 8 through 11. It combines exciting online animations and activities with boxes of hands-on science experiments. Children earn "Kinetic City" power points and collect stickers as they complete missions and learn standards-based science content. Here's how it works: The "Kinetic City" super crew (Keisha, Curtis, Megan and Max) needs the help of Earth kids to save their planet Vearth, from the science-distorting computer virus Deep Delete. Each of Deep Delete's 60 hideous strains attacks a different area of science with disastrous consequences. After each attack, teams of Earth kids fight back by viewing a short online animation describing the situation on Vearth; performing a series of activities to re-learn the lost science and going on a mission to Vearth during which they answer science questions and gobble up Deep Delete viruses. Their scores appear on their own Kinetic City Club Web page. "Kinetic City" is produced by the American Association for the Advancement of Science (AAAS), with a grant from the National Science Foundation. AAAS writes the "Project 2061 Benchmarks for Science Literacy," which forms the basis of most state science standards.

American Association for the Advancement of Science (; )



High resolution mass spectrometry in the identification of transformation products and metabolites from ?-lactam antibiotics in thermally treated milk.  


Antibiotics such as ?-lactam derivatives (penicillins and cephalosporins) are frequently used in veterinary medicine. The presence of these antibiotics together with their metabolites and/or products produced in subsequent treatments at which milk is submitted (sterilization, pasteurization), may be responsible for bacterial resistance, allergy and/or toxicity on sensitive individuals. In this study, liquid chromatography coupled with high resolution mass spectrometry (LC-HRMS) is used to identify transformation products (TPs) from four ?-lactam antibiotics (amoxicillin (AMOX), cephapirin (PIR), ceftiofur (TIO) and penicillin G (PENG)) in thermally treated cow milk. In addition, milk from cows medicated with PENG has also been analogously treated and studied. The detected TPs come mainly from hydrolysis and decarboxylation reactions. Products more strongly degraded respect to parent compounds (of lower molecular weight) were obtained after treating milk at higher temperatures. Products identified in milk from cows medicated with PENG have been classified as TPs when coming from chemical/thermal degradation, and metabolites when resulting from the biological drug metabolism. While TPs are the result of hydrolysis and decarboxylation processes, as already indicated, an enzymatic conjugation with amino acids is suggested to be involved in the formation of metabolites. PMID:25441345

Junza, A; Montané, A; Barbosa, J; Minguillón, C; Barrón, D



The effects of the morphological response of Enterobacteriaceae to cephalosporins on PAE and CERT.  


PAE and CERT values of cefaclor, loracarbef and cefuroxime (0.1-100 x MIC) were established for 8 E. coli, 3 K. pneumoniae and 2 P. mirabilis isolates. Cell enumeration was by impedance (IMP) monitoring in combination with either bioluminescence (BIOL) or viable counting (VC). Morphology was determined by interference contrast microscopy. After 2 h exposure to cefaclor, loracarbef and cefuroxime; concentration-dependent differences in counts were seen by BIOL and VC, varying from a mean value of 0.07 x log10 after exposing the P. mirabilis isolates to 0.1 x MIC cefaclor to a mean value of 2.24 x log10 after exposing the E. coli strains to 100 x MIC cefuroxime. Higher concentrations gave rise to fragile morphological forms including spheroplasts and lower concentrations to less fragile forms such as long bacilli. The longest PAE and CERT values were obtained after exposing the E. coli strains to 100 x MIC cefaclor with mean values of 4.07 and 4.87 h, respectively. Corresponding values were PAE and CERT values of 2.17 and 2.60 h for 100 x cefuroxime and 3.45 and 2.91 h for 100 x MIC loracarbef. By the Student's t-test, PAE values determined by IMP/BIOL and IMP/VC were found to be significantly different, whereas CERT values were found not to be significantly different. PAE and CERT are concentration dependent and vary with specific antibiotic/organism combinations. PMID:9817524

Mackenzie, F M; Milne, K E; Gould, I M



Structural basis of emerging antibiotic resistance Enzyme structural plasticity and emergence of broad spectrum antibiotic  

E-print Network

Structural basis of emerging antibiotic resistance 1 Enzyme structural plasticity and emergence of broad spectrum antibiotic resistance Frédérique Maurice1 , Isabelle Broutin1 , Isabelle Podglajen2 25 Running title : Structural basis of emerging antibiotic resistance Keywords : acetyltransferase

Paris-Sud XI, Université de


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...


[Correlation of dose-antimicrobial effect in modeling in vitro pharmacokinetic profiles of normal and impaired elimination of antibiotics].  


Relationships between concentration and antimicrobial effect (AME) of sisomicin (SMN) and cefotaxime (CTX) were established by simulating their pharmacokinetic profiles in an in vitro dynamic model. The AME duration (TE, time shift between the curves of bacteria heat output in the presence and absence of the antibiotics) or intensity (IE, area between the above curves) for both the antibiotics depended in the same way on the area under the concentration/time curve (AUC, mimicing of intravenous administration of the antibiotics in various doses). At low and moderate values of the AUC the dependences of IE or TE vs the AUC (the bacteriostatic phase of the AME development) were of the sigmoid shape while at high values of the AUC there was a marked increase in IE or TE (the bactericidal phase). The patterns of the IE or TE vs AUC curves in impaired antibiotic elimination were analogous. At the same time the IE or TE vs AUC curves for both the antibiotics under simulation of normal elimination (T 1/2, SMN-2.1 h, T 1/2, CTX-1.2 h) and impaired one (T 1/2, SMN-8.3 h, T 1/2, CTX-4.6 h) did not match. In the first case the AMESMN was on the whole higher and the AMECTX was lower than in the second case. Therefore, in patients with renal failure the efficient concentration of the aminoglycoside in blood can be higher and that of the cephalosporin on the contrary can be lower than the normal. PMID:2662928

Firsov, A A



WAAR (World Alliance against Antibiotic Resistance): Safeguarding antibiotics  

PubMed Central

Summary Resistance to antibiotics has increased recently to a dramatic extend, and the pipeline of new antibiotics is almost dry for the five next years. Failures happen already for trivial community acquired infections, like pyelonephritis, or peritonitis, and this is likely to increase. Difficult surgical procedures, transplants, and other immunosuppressive therapies will become far more risky. Resistance is mainly due to an excessive usage of antibiotics, in all sectors, including the animal one. Action is urgently needed. Therefore, an alliance against MDRO has been recently created, which includes health care professionals, consumers, health managers, and politicians. The document highlights the different proposed measures, and represents a strong consensus between the different professionals, including general practicionners, and veterinarians. PMID:22958542



Community-Onset Escherichia coli Infection Resistant to Expanded-Spectrum Cephalosporins in Low-Prevalence Countries  

PubMed Central

By global standards, the prevalence of community-onset expanded-spectrum-cephalosporin-resistant (ESC-R) Escherichia coli remains low in Australia and New Zealand. Of concern, our countries are in a unique position, with high extramural resistance pressure from close population and trade links to Asia-Pacific neighbors with high ESC-R E. coli rates. We aimed to characterize the risks and dynamics of community-onset ESC-R E. coli infection in our low-prevalence region. A case-control methodology was used. Patients with ESC-R E. coli or ESC-susceptible E. coli isolated from blood or urine were recruited at six geographically dispersed tertiary care hospitals in Australia and New Zealand. Epidemiological data were prospectively collected, and bacteria were retained for analysis. In total, 182 patients (91 cases and 91 controls) were recruited. Multivariate logistic regression identified risk factors for ESC-R among E. coli strains, including birth on the Indian subcontinent (odds ratio [OR] = 11.13, 95% confidence interval [95% CI] = 2.17 to 56.98, P = 0.003), urinary tract infection in the past year (per-infection OR = 1.430, 95% CI = 1.13 to 1.82, P = 0.003), travel to southeast Asia, China, the Indian subcontinent, Africa, and the Middle East (OR = 3.089, 95% CI = 1.29 to 7.38, P = 0.011), prior exposure to trimethoprim with or without sulfamethoxazole and with or without an expanded-spectrum cephalosporin (OR = 3.665, 95% CI = 1.30 to 10.35, P = 0.014), and health care exposure in the previous 6 months (OR = 3.16, 95% CI = 1.54 to 6.46, P = 0.02). Among our ESC-R E. coli strains, the blaCTX-M ESBLs were dominant (83% of ESC-R E. coli strains), and the worldwide pandemic ST-131 clone was frequent (45% of ESC-R E. coli strains). In our low-prevalence setting, ESC-R among community-onset E. coli strains may be associated with both “export” from health care facilities into the community and direct “import” into the community from high-prevalence regions. PMID:24468775

Ingram, Paul R.; Runnegar, Naomi; Pitman, Matthew C.; Freeman, Joshua T.; Athan, Eugene; Havers, Sally M.; Sidjabat, Hanna E.; Jones, Mark; Gunning, Earleen; De Almeida, Mary; Styles, Kaylene; Paterson, David L.



Organic or antibiotic-free labeling does not impact the recovery of enteric pathogens and antimicrobial-resistant Escherichia coli from fresh retail chicken.  


We investigated the implied health benefits of retail chicken breast labeled as "organic" or "antibiotic-free" when compared to conventional products based on frequency of contamination by Salmonella spp., Campylobacter spp., and coliform bacteria resistant to fluoroquinolones, extended-spectrum cephalosporins, or carbapenems. We purchased 231 prepackaged chicken breasts from 99 grocery stores representing 17 retail chains in Ohio, Michigan, and Pennsylvania from June to September 2012. Ninety-six (41.5%) packages were labeled "antibiotic free" and 40 (17.3%) were labeled "organic," with the remaining 95 (41.1%) making neither label claim. Salmonella were recovered from 56 (24.2%) packages, and the recovery rate was not different between product types. Five percent of packages contained Salmonella carrying the extended-spectrum cephalosporin resistance gene bla(CMY-2), representing 21.4% of Salmonella isolates. Campylobacter spp. were recovered from 10.8% of packages, with observed recovery rates similar for the three product types. Using selective media, we recovered Escherichia coli harboring bla(CMY-2) from over half (53.7%) of packages, with similar recovery rates for all product types. In addition, we recovered E. coli carrying bla(CTX-M) from 6.9% of packages, and E. coli with QRDR mutations from 8.2% of packages. Fluoroquinolone-resistant E. coli recovered using selective media were more common (p<0.05) in conventional (18.9%) compared to organic (0) and antibiotic-free (2.1%) packages. Our results indicate that, regardless of product type, fresh retail chicken breast is commonly contaminated with enteric pathogens associated with foodborne illness and commensal bacteria harboring genes conferring resistance to critically important antimicrobial drugs. PMID:25405393

Mollenkopf, Dixie F; Cenera, Johana K; Bryant, Erin M; King, Christy A; Kashoma, Isaac; Kumar, Anand; Funk, Julie A; Rajashekara, Gireesh; Wittum, Thomas E



Nucleoside antibiotics: biosynthesis, regulation, and biotechnology.  


The alarming rise in antibiotic-resistant pathogens has coincided with a decline in the supply of new antibiotics. It is therefore of great importance to find and create new antibiotics. Nucleoside antibiotics are a large family of natural products with diverse biological functions. Their biosynthesis is a complex process through multistep enzymatic reactions and is subject to hierarchical regulation. Genetic and biochemical studies of the biosynthetic machinery have provided the basis for pathway engineering and combinatorial biosynthesis to create new or hybrid nucleoside antibiotics. Dissection of regulatory mechanisms is leading to strategies to increase the titer of bioactive nucleoside antibiotics. PMID:25468791

Niu, Guoqing; Tan, Huarong



Proces models for production of ?-lactam antibiotics  

Microsoft Academic Search

Great progress has been made in the modelling of biotechnical processes using filamentous microorganisms. This paper deals\\u000a with cultivations of Penicillium chrysogenum for the production of Penicillin and of Acremonium chrysogenum for the production of Cephalosporin C. The properties of the processes and the existing models are reviewed. Models are presented\\u000a for both processes that consider aspects which are important

K.-H. Bellgardt


Transport of sulfonamide antibiotics in small fields during monsoon season  

NASA Astrophysics Data System (ADS)

Transport and fate of 3 sulfonamide antibiotics (sulfamethoxazole, sulfadimethoxine and sulfamethazine) were studied in small agricultural land during monsoon period. The experiment has been conducted in 2 typical sandy loam potato fields of South Korea after application of the veterinary antibiotics and bromide. Precipitation was measured by AWS (Automatic Weather Station) near the fields during the whole monsoon season. Runoff generation was estimated by multislot divisors in combination with pressure sensor. Concentration of the target antibiotics and the conservative tracer in runoff, soil-water and soil was determined using HPLC-MS-MS and Br selected electrode. Transport simulation has been performed with Hydrus-2D program which can consider soil characteristics, climate condition, adsorption/desorption and degradation. Results from the measurements and modeling focus on the role of heavy rainfall, of related the ratio of runoff and infiltration in terms of the selected antibiotics distribution and fate. Bromide on topsoil was moved into soil as increasing rainfall loading. On the contrary, the sulfonamides were relatively retarded in upper soil layer owing to adsorption onto soil particles. Different patterns of runoff were observed, and slope and rain intensity was representative factor in this study. Distribution of target pharmaceuticals was strongly dependent on constitution of furrow and ridge in the agricultural fields. Modeling results positively matched with background studies that describe physico-chemical properties of the sulfonamides, interaction between soil and the antibiotic group, solute transport through vadose zone and runoff induction by storm events.

Park, J. Y.; Huwe, B.; Kolb, A.; Tenhunen, J.



In Vitro and In Vivo Properties of Ro 63-9141, a Novel Broad-Spectrum Cephalosporin with Activity against Methicillin-Resistant Staphylococci  

Microsoft Academic Search

Ro 63-9141 is a new member of the pyrrolidinone-3-ylidenemethyl cephem series of cephalosporins. Its anti- bacterial spectrum was evaluated against significant gram-positive and gram-negative pathogens in compar- ison with those of reference drugs, including cefotaxime, cefepime, meropenem, and ciprofloxacin. Ro 63-9141 showed high antibacterial in vitro activity against gram-positive bacteria except ampicillin-resistant entero- cocci, particularly vancomycin-resistant strains of Enterococcus faecium.




Rare Case of Failure by an Automated System To Detect Extended-Spectrum bLactamase in a Cephalosporin-Resistant Klebsiella pneumoniae Isolate  

Microsoft Academic Search

Several tests used for the detection of extended-spectrum- b-lactamase (ESBL)-producing enterobacterial isolates have been evaluated in past studies. Detection of ESBLs by the Vitek GNS-506 panel (Bio-Merieux, Marcy l'Etoile, France) is based on the comparison of the reduction in growth by cefo- taxime-clavulanate and ceftazidime-clavulanate with the re- duction caused by the cephalosporins alone. The test has been proven reliable

Leonidas S. Tzouvelekis



Antibiotic prophylaxis in gynecological surgery.  


A randomized prospective study was undertaken at the Obstetrics and Gynecology Clinic of the Catholic University of Rome in order to evaluate the effectiveness of two wide spectrum antibiotics: mezlocillin and cefotetan. Both drugs were administered 2 g i.v. 15 to 20 minutes preoperatively to allow optimal serum and tissue levels of antibiotic at the moment of bacterial innoculation. 184 patients undergoing elective gynecological surgery for nonmalignant disease were considered eligible for the study (124 pts abdominal hysterectomy, 58 pts vaginal hysterectomy). We found no statistically significant differences between the results obtained with the two drugs. PMID:2090769

Oliva, G C; Fratoni, A; Papadia, L; Pieroni, A; Paparella, P L; Mancuso, S



MICROBIOLOGY: Noninherited Resistance to Antibiotics  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required. Why is it that the rate of mortality of bacteria exposed to bactericidal antibiotics declines with time but sensitive cells survive for hours or even days of exposure? The mechanisms responsible for this persistence have perplexed microbiologists for decades. In his Perspective, Levin discusses a pair of recent studies (Balaban et al., Miller et al.) that shed light on the mechanisms responsible for this phenomenon and the way in which these bacterial persisters emerge. Levin also considers the potential clinical implications of this non-inherited form of resistance to antibiotics.

Bruce R. Levin (Emory University; Department of Biology)



Effects of intramammary antibiotic therapy during the dry period on the performance of Lacaune dairy sheep under intensive management.  


Often the only way to ensure profitability of Lacaune dairy sheep is intensive management, which requires appropriate dry-period treatment to ensure animal productivity and health. The present study aimed to investigate the effects of intramammary antibiotic dry therapy on the performance and health of Lacaune sheep under intensive management. We recorded data for 5981 complete lactation periods that followed a dry period. A total of 2402 lactation periods were preceded by a dry period involving intramammary administration of 300 mg of cephapirin benzathine (antibiotic group) and 3579 lactation periods were preceded by dry periods with no treatment (control group). The following on-farm yield data were collected for individual lactation periods: length of the subsequent lactation period; total milk yield per lactation period; daily milk yield and length of the subsequent dry period. Data on confounding factors that might affect productivity were also recorded, including the individual ewe, number of lactation periods and length of the previous dry period. Milk quality was assessed using data on somatic cell count (SCC) and content of protein and fat taken from the Spanish National Official Milk Yield Recording System. Antibiotic dry therapy significantly improved total yield per lactation period, which was 429±151·1 l in the antibiotic group and 412±165·5 l in the control group, as well as the daily milk yield, which was 1986±497·0 and 1851±543·2 ml/d, respectively (both P<0·0001). The initial dry period was significantly longer in the antibiotic group than in the control group, and dry period length correlated inversely with yield variables such us total yield per lactation period (r=-0·055; P<0·0001) and yield per day in milk (r=-0·039; P<0·0001). As a result, milk yield records systematically underestimated the positive effects of antibiotic dry therapy. Antibiotic dry therapy also significantly improved milk quality. Milk from the antibiotic group showed 50% lower SCC (573±1326 vs. 1022±2126 cells/ml; P<0·0001) and slightly higher content in fat (7·33±0·91 vs. 7·15±0·87%) and protein (5·63±0·44 vs. 5·44±0·4%). The results of this study suggest that cephalosporin dry therapy of Lacaune dairy sheep increases milk production and improves milk quality during subsequent lactation periods. PMID:25467529

Hernandez, Fernando; Elvira, Laura; Fernández, Beatriz; Egea, Marta; Gonzalez-Bulnes, Antonio; Gonzalez-Martin, Juan V; Astiz, Susana



Dissemination of health information through social networks: Twitter and antibiotics  

PubMed Central

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

Scanfeld, Vanessa; Larson, Elaine L.



Antibiotic and Antimicrobial Resistance: Threat Report 2013  


... Address What's this? Submit What's this? Submit Button Antibiotic Resistance Threats in the United States, 2013 Recommend on Facebook Tweet Share Compartir This report, Antibiotic resistance threats in the United States, 2013 gives a ...


Alliance for the Prudent Use of Antibiotics  


... this National Action Plan for Combating Antibiotic-Resistant Bacteria The latest issue of our Highlights has been ... have a national strategy to combat antibiotic-resistant bacteria, to better protect our children and grandchildren from ...


What Can Be Done about Antibiotic Resistance?  


... in the community, and reducing antibiotic use in animal farming and agriculture. Experts agree that a global system for tracking antibiotic resistance is needed. It would serve as an indicator ...


Antibiotic resistance: location, location, location  

Microsoft Academic Search

Antibiotic resistance surveys are published widely, citing percentage resistance rates, sometimes for vast transcontinental regions. Such data seem straightforward, but when one drills deeper, great complexity emerges. Rates for methicillin resistance among Staphylococcus aureus from bacteraemias vary from <1% to 50% among European countries, and vary greatly among both hospitals and hospital units. Methicillin-resistant S. aureus (MRSA) resistance rates are

D. M. Livermore; A. Pearson



Antibiotic resistance in probiotic bacteria  

PubMed Central

Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. The main probiotic bacteria are strains belonging to the genera Lactobacillus and Bifidobacterium, although other representatives, such as Bacillus or Escherichia coli strains, have also been used. Lactobacillus and Bifidobacterium are two common inhabitants of the human intestinal microbiota. Also, some species are used in food fermentation processes as starters, or as adjunct cultures in the food industry. With some exceptions, antibiotic resistance in these beneficial microbes does not constitute a safety concern in itself, when mutations or intrinsic resistance mechanisms are responsible for the resistance phenotype. In fact, some probiotic strains with intrinsic antibiotic resistance could be useful for restoring the gut microbiota after antibiotic treatment. However, specific antibiotic resistance determinants carried on mobile genetic elements, such as tetracycline resistance genes, are often detected in the typical probiotic genera, and constitute a reservoir of resistance for potential food or gut pathogens, thus representing a serious safety issue. PMID:23882264

Gueimonde, Miguel; Sánchez, Borja; G. de los Reyes-Gavilán, Clara; Margolles, Abelardo



New Antibiotic Approved by FDA  

NSDL National Science Digital Library

Last week, the FDA approved Zyvox (known generically as linezolid), the first in a new class of synthetic antibacterial drugs -- called oxazolidinones -- designed to treat a number of drug-resistant infections. Zyvox has proven effective in treatment of infections associated with vancomycin-resistant Enterococcus faecium (VREF) as well as hospital-acquired pneumonia and complicated skin and skin structure infections, including cases caused by methicillin-resistant Staphylococcus aureus (MRSA). This is the first drug to be approved in over 40 years for fighting hospital-acquired infections that are resistant to antibiotics. "It comes at a time when we were literally running out of antibiotics," said Dr. Robert C. Moellering Jr., physician-in-chief of Boston's Beth Israel-Deaconness Hospital, in a recent AP news article. In an attempt to preserve the long-term effectiveness of Zyvox and discourage microbes from developing renewed resistance, some doctors are calling for cautious use of the drug for only the worst antibiotic-resistant infections. This week's In The News takes a look at this new development and its consequences for antibiotic resistant bacteria.

Ramanujan, Krishna.


Short communication: Rapid antibiotic screening tests detect antibiotic residues in powdered milk products  

Microsoft Academic Search

Rapid antibiotic screening tests are widely used in the dairy industry to monitor milk for the presence of antibiotic residues above regulated levels. Given the persistent concern over contamination of milk products with antibiotic residues, we investigated the utility of IDEXX Snap test devices (IDEXX Laboratories Inc., Westbrook, ME) as tools for detecting antibiotic residues in powdered milk products. Five

J. Kneebone; P. C. W. Tsang; D. H. Townson



Assessing the combined effects from two kinds of cephalosporins on green alga (Chlorella pyrenoidosa) based on response surface methodology.  


The present work evaluated the combined effects of cefradine and ceftazidime on the green alga Chlorella pyrenoidosa using response surface methodologies (RSM). After a 48?h-exposure, the population growth rate (PGR), the chlorophyll-a content and the SOD content of the alga increased with increased concentrations of two antibiotics. However, the three responses did not continue to demonstrate significant increases once antibiotic concentrations exceed a moderate level. Three two order polynomial regression equations were obtained to describe well the relationship between the responses of the alga and the two antibiotics' concentration (R(2)?=?0.9997, 0.9292 and 0.9039, respectively). Three 3?D-surface graphs and their contour plots showed directly the changing trends of the alga under the combined effects of two antibiotics. This study for the first time employed the RSM in ecotoxicology, which indicated that the RSM should be placed under a feasible and a potential application prospect in toxicity assessment. PMID:25684417

Guo, Ruixin; Xie, Weishu; Chen, Jianqiu



Antibiotic sensitivity pattern of uropathogens from pregnant women with urinary tract infection in Abakaliki, Nigeria  

PubMed Central

Background Urinary tract infection (UTI) is a common bacterial infection during pregnancy and a significant cause of perinatal and maternal morbidity and mortality. The causative bacteria have remained virtually the same although with variations in individual prevalence. There has been an increasing resistance by these bacteria to the commonly available antibiotics. Objectives To determine the prevalence of UTI, the common causative bacteria, and their antibiotic sensitivity pattern among pregnant women with UTI. Methodology This is a descriptive study that was carried out at the Obstetrics Department of two tertiary institutions in Abakaliki, Ebonyi State, Nigeria (Federal Medical Center and Ebonyi State University Teaching Hospital) over a period of 12 months. Midstream urine specimens from selected pregnant women with clinical features of UTI were collected for microscopy, culture, and sensitivity. The results were analyzed with the 2008 Epi Info™ software. Results A total of 542 pregnant women presented with symptoms of UTI and were recruited for the study over the study period. Of the 542 pregnant women, 252 (46.5%) had significant bacteriuria with positive urine culture and varying antibiotic sensitivity pattern. The prevalence of symptomatic UTI was 3%. Escherichia coli was the most common bacteria isolated with a percentage of 50.8%. Other isolated micro organisms included Stapylococcus aereus (52 cultures, 20.6%), Proteus mirabilis (24 cultures, 9.5%), S. saprophyticus (18 cultures, 7.1%), Streptococcus spp. (14 cultures, 5.6%), Citrobacter spp. (5 cultures, 2.0%), Klebsiella spp. (4 cultures, 1.6%), Enterobacter spp. (4 cultures, 1.6%), and Pseudomonas spp. (3 cultures, 1.2%). Levofloxacin had the highest overall antibiotic sensitivity of 92.5%. Others with overall antibiotic sensitivity pattern greater than 50% included cefpodoxime (87.3%), ofloxacin (77.4%), ciprofloxacin (66.7%), ceftriaxone (66.7%), and gentamicin (50.8%). Conclusion E. coli was the most common etiological agent of UTI in pregnancy with Enterococcus (Staphylococcus) gaining prominence. Cephalosporin and quinolones were shown to be very effective against the organisms causing UTI in these pregnant women. PMID:24324344

Onoh, RC; Umeora, OUJ; Egwuatu, VE; Ezeonu, PO; Onoh, TJP



Overcoming the current deadlock in antibiotic research.  


Antibiotic-resistant bacteria are on the rise, making it harder to treat bacterial infections. The situation is aggravated by the shrinking of the antibiotic development pipeline. To finance urgently needed incentives for antibiotic research, creative financing solutions are needed. Public-private partnerships (PPPs) are a successful model for moving forward. PMID:24698433

Schäberle, Till F; Hack, Ingrid M



New antibiotics from bacterial natural products  

Microsoft Academic Search

For the past five decades, the need for new antibiotics has been met largely by semisynthetic tailoring of natural product scaffolds discovered in the middle of the 20th century. More recently, however, advances in technology have sparked a resurgence in the discovery of natural product antibiotics from bacterial sources. In particular, efforts have refocused on finding new antibiotics from old

Jon Clardy; Michael A Fischbach; Christopher T Walsh



New business models for antibiotic innovation  

PubMed Central

The increase in antibiotic resistance and the dearth of novel antibiotics have become a growing concern among policy-makers. A combination of financial, scientific, and regulatory challenges poses barriers to antibiotic innovation. However, each of these three challenges provides an opportunity to develop pathways for new business models to bring novel antibiotics to market. Pull-incentives that pay for the outputs of research and development (R&D) and push-incentives that pay for the inputs of R&D can be used to increase innovation for antibiotics. Financial incentives might be structured to promote delinkage of a company’s return on investment from revenues of antibiotics. This delinkage strategy might not only increase innovation, but also reinforce rational use of antibiotics. Regulatory approval, however, should not and need not compromise safety and efficacy standards to bring antibiotics with novel mechanisms of action to market. Instead regulatory agencies could encourage development of companion diagnostics, test antibiotic combinations in parallel, and pool and make transparent clinical trial data to lower R&D costs. A tax on non-human use of antibiotics might also create a disincentive for non-therapeutic use of these drugs. Finally, the new business model for antibiotic innovation should apply the 3Rs strategy for encouraging collaborative approaches to R&D in innovating novel antibiotics: sharing resources, risks, and rewards. PMID:24646116

Shah, Tejen A.



The determinants of the antibiotic resistance process  

Microsoft Academic Search

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 com- prehensively review the

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



The epidemiology of antibiotic resistance in Campylobacter  

Microsoft Academic Search

Antibiotic resistance, particularly with the fluoroquinolones and macrolide antibiotics, has now emerged globally with thermophilic campylobacters, including Campylobacter jejuni and C. coli, giving rise to concerns about how these organisms have acquired such resistance characteristics, as well as consequences for human and animal treatment. This review examines (i) the clinical epidemiology of antibiotic resistance in human and animal thermophilic campylobacters,

John E. Moore; Mary D. Barton; Iain S. Blair; Deborah Corcoran; James S. G. Dooley; Séamus Fanning; Isabelle Kempf; Albert J. Lastovica; Colm J. Lowery; Motoo Matsuda; David A. McDowell; Ann McMahon; B. Cherie Millar; Juluri R. Rao; Paul J. Rooney; Bruce S. Seal; William J. Snelling; Ola Tolba



Are Sewage Treatment Plants Promoting Antibiotic Resistance?  

Microsoft Academic Search

There is widespread speculation that sewage treatment plants (STPs) and aquatic environments in general may be breeding grounds for antibiotic resistant bacteria. We examine the question of whether low concentrations of antibiotics in STPs can provide or contribute to a selective pressure facilitating the acquisition or proliferation of antibiotic resistance among bacteria in the receiving environment. Examination of available literature

Karen L. Jury; Stuart J. Khan; Tony Vancov; Richard M. Stuetz; Nicholas J. Ashbolt



Home intravenous antibiotic treatment in cystic fibrosis  

Microsoft Academic Search

The prognosis for patients with cystic fibrosis who are colonised with Pseudomonas aeruginosa has improved as a result of the regular use of intravenous antibiotics; however, this necessitates long periods of hospitalisation. Home intravenous antibiotic treatment has potential advantages over hospital treatment. We describe our experience during the first 20 months of using a system of home intravenous antibiotic treatment

J Gilbert; T Robinson; J M Littlewood



A High-Throughput Screen for Antibiotic Drug Discovery  

PubMed Central

We describe an ultra-high-throughput screening platform enabling discovery and/or engineering of natural product antibiotics. The methodology involves creation of hydrogel-in-oil emulsions in which recombinant microorganisms are co-emulsified with bacterial pathogens; antibiotic activity is assayed by use of a fluorescent viability dye. We have successfully utilized both bulk emulsification and microfluidic technology for the generation of hydrogel microdroplets that are size-compatible with conventional flow cytometry. Hydrogel droplets are ~25 pL in volume, and can be synthesized and sorted at rates exceeding 3,000 drops/s. Using this technique, we have achieved screening throughputs exceeding 5 million clones/day. Proof-of-concept experiments demonstrate efficient selection of antibiotic-secreting yeast from a vast excess of negative controls. In addition, we have successfully used this technique to screen a metagenomic library for secreted antibiotics that kill the human pathogen Staphylococcus aureus. Our results establish the practical utility of the screening platform, and we anticipate that the accessible nature of our methods will enable others seeking to identify and engineer the next generation of antibacterial biomolecules. PMID:23955804

Scanlon, Thomas C.; Dostal, Sarah M.; Griswold, Karl E.



A high-throughput screen for antibiotic drug discovery.  


We describe an ultra-high-throughput screening platform enabling discovery and/or engineering of natural product antibiotics. The methodology involves creation of hydrogel-in-oil emulsions in which recombinant microorganisms are co-emulsified with bacterial pathogens; antibiotic activity is assayed by use of a fluorescent viability dye. We have successfully utilized both bulk emulsification and microfluidic technology for the generation of hydrogel microdroplets that are size-compatible with conventional flow cytometry. Hydrogel droplets are ?25?pL in volume, and can be synthesized and sorted at rates exceeding 3,000?drops/s. Using this technique, we have achieved screening throughputs exceeding 5?million clones/day. Proof-of-concept experiments demonstrate efficient selection of antibiotic-secreting yeast from a vast excess of negative controls. In addition, we have successfully used this technique to screen a metagenomic library for secreted antibiotics that kill the human pathogen Staphylococcus aureus. Our results establish the practical utility of the screening platform, and we anticipate that the accessible nature of our methods will enable others seeking to identify and engineer the next generation of antibacterial biomolecules. PMID:23955804

Scanlon, Thomas C; Dostal, Sarah M; Griswold, Karl E



Acquired antibiotic resistance among wild animals: the case of Iberian Lynx (Lynx pardinus).  


The selective pressure generated by the clinical misuse of antibiotics has been the major driving force leading to the emergence of antibiotic resistance among bacteria. Antibiotics or even resistant bacteria are released into the environment and contaminate the surrounding areas. Human and animal populations in contact with these sources are able to become reservoirs of these resistant organisms. Then, due to the convergence between habitats, the contact of wild animals with other animals, humans, or human sources is now more common and this leads to an increase in the exchange of resistance determinants between their microbiota. Indeed, it seems that wildlife populations living in closer proximity to humans have higher levels of antibiotic resistance. Now, the Iberian Lynx (Lynx pardinus) is a part of this issue, being suggested as natural reservoir of acquired resistant bacteria. The emerging public health concern regarding microbial resistance to antibiotics is becoming true: the bacteria are evolving and are now affecting unintentional hosts. PMID:25220796

Sousa, Margarida; Gonçalves, Alexandre; Silva, Nuno; Serra, Rodrigo; Alcaide, Eva; Zorrilla, Irene; Torres, Carmen; Caniça, Manuela; Igrejas, Gilberto; Poeta, Patrícia



Antibiotic susceptibility and molecular epidemiology of Acinetobacter calcoaceticus–baumannii complex strains isolated from a referral hospital in northern Vietnam  

PubMed Central

Acinetobacter calcoaceticus–baumannii complex is a common cause of hospital-acquired infections (HAIs) globally, remarkable for its high rate of antibiotic resistance, including to carbapenems. There are few data on the resistance of A. baumannii in Vietnam, which are essential for developing evidence-based treatment guidelines for HAIs. Antibiotic susceptibility testing was conducted by VITEK®2, and pulsed-field gel electrophoresis (PFGE) was performed on 66 clinical A. baumannii complex isolates recovered during 2009 at the National Hospital of Tropical Diseases (NHTD), a referral hospital in Hanoi, Vietnam. Basic demographic and clinical data were collected and analysed using descriptive statistics. Most isolates came from lower respiratory tract specimens (59; 89.4%) from intensive care unit (ICU) patients [64/65 (98.5%) with available data] who had been admitted to NHTD for ?2 days [42/46 (91.3%) with available data]. More than 90% of the isolates were resistant to the tested ?-lactamase/?-lactamase inhibitors, cephalosporins, carbapenems, fluoroquinolones and trimethoprim/sulfamethoxazole. Moreover, 25.4% (16/63) were resistant to all tested ?-lactams, quinolones and aminoglycosides. All isolates remained sensitive to colistin and 58.7% were susceptible to tigecycline. Of the 66 isolates, 49 could be classified into eight PFGE types (A–H). Every PFGE type, except D, had cluster(s) of three or more isolates with a temporal relationship. In conclusion, these data suggest a significant rise in A. baumannii antibiotic resistance in Vietnam. Clustering within PFGE types supports cross-transmission of A. baumannii within the ICU at NHTD. Increased research and resources in optimising treatment, infection control and antibiotic stewardship are needed. PMID:25540720

Van, Trang Dinh; Dinh, Quynh-Dao; Vu, Phu Dinh; Nguyen, Trung Vu; Pham, Ca Van; Dao, Trinh Tuyet; Phung, Cam Dac; Hoang, Ha Thu Thi; Tang, Nga Thi; Do, Nga Thuy; Nguyen, Kinh Van; Wertheim, Heiman



Antibiotics induce redox-related physiological alterations as part of their lethality  

PubMed Central

Deeper understanding of antibiotic-induced physiological responses is critical to identifying means for enhancing our current antibiotic arsenal. Bactericidal antibiotics with diverse targets have been hypothesized to kill bacteria, in part by inducing production of damaging reactive species. This notion has been supported by many groups but has been challenged recently. Here we robustly test the hypothesis using biochemical, enzymatic, and biophysical assays along with genetic and phenotypic experiments. We first used a novel intracellular H2O2 sensor, together with a chemically diverse panel of fluorescent dyes sensitive to an array of reactive species to demonstrate that antibiotics broadly induce redox stress. Subsequent gene-expression analyses reveal that complex antibiotic-induced oxidative stress responses are distinct from canonical responses generated by supraphysiological levels of H2O2. We next developed a method to quantify cellular respiration dynamically and found that bactericidal antibiotics elevate oxygen consumption, indicating significant alterations to bacterial redox physiology. We further show that overexpression of catalase or DNA mismatch repair enzyme, MutS, and antioxidant pretreatment limit antibiotic lethality, indicating that reactive oxygen species causatively contribute to antibiotic killing. Critically, the killing efficacy of antibiotics was diminished under strict anaerobic conditions but could be enhanced by exposure to molecular oxygen or by the addition of alternative electron acceptors, indicating that environmental factors play a role in killing cells physiologically primed for death. This work provides direct evidence that, downstream of their target-specific interactions, bactericidal antibiotics induce complex redox alterations that contribute to cellular damage and death, thus supporting an evolving, expanded model of antibiotic lethality. PMID:24803433

Dwyer, Daniel J.; Belenky, Peter A.; Yang, Jason H.; MacDonald, I. Cody; Martell, Jeffrey D.; Takahashi, Noriko; Chan, Clement T. Y.; Lobritz, Michael A.; Braff, Dana; Schwarz, Eric G.; Ye, Jonathan D.; Pati, Mekhala; Vercruysse, Maarten; Ralifo, Paul S.; Allison, Kyle R.; Khalil, Ahmad S.; Ting, Alice Y.; Walker, Graham C.; Collins, James J.



Antibiotics induce redox-related physiological alterations as part of their lethality.  


Deeper understanding of antibiotic-induced physiological responses is critical to identifying means for enhancing our current antibiotic arsenal. Bactericidal antibiotics with diverse targets have been hypothesized to kill bacteria, in part by inducing production of damaging reactive species. This notion has been supported by many groups but has been challenged recently. Here we robustly test the hypothesis using biochemical, enzymatic, and biophysical assays along with genetic and phenotypic experiments. We first used a novel intracellular H2O2 sensor, together with a chemically diverse panel of fluorescent dyes sensitive to an array of reactive species to demonstrate that antibiotics broadly induce redox stress. Subsequent gene-expression analyses reveal that complex antibiotic-induced oxidative stress responses are distinct from canonical responses generated by supraphysiological levels of H2O2. We next developed a method to quantify cellular respiration dynamically and found that bactericidal antibiotics elevate oxygen consumption, indicating significant alterations to bacterial redox physiology. We further show that overexpression of catalase or DNA mismatch repair enzyme, MutS, and antioxidant pretreatment limit antibiotic lethality, indicating that reactive oxygen species causatively contribute to antibiotic killing. Critically, the killing efficacy of antibiotics was diminished under strict anaerobic conditions but could be enhanced by exposure to molecular oxygen or by the addition of alternative electron acceptors, indicating that environmental factors play a role in killing cells physiologically primed for death. This work provides direct evidence that, downstream of their target-specific interactions, bactericidal antibiotics induce complex redox alterations that contribute to cellular damage and death, thus supporting an evolving, expanded model of antibiotic lethality. PMID:24803433

Dwyer, Daniel J; Belenky, Peter A; Yang, Jason H; MacDonald, I Cody; Martell, Jeffrey D; Takahashi, Noriko; Chan, Clement T Y; Lobritz, Michael A; Braff, Dana; Schwarz, Eric G; Ye, Jonathan D; Pati, Mekhala; Vercruysse, Maarten; Ralifo, Paul S; Allison, Kyle R; Khalil, Ahmad S; Ting, Alice Y; Walker, Graham C; Collins, James J



Resistance to Antibiotics Mediated by Target Alterations  

NASA Astrophysics Data System (ADS)

The development of resistance to antibiotics by reductions in the affinities of their enzymatic targets occurs most rapidly for antibiotics that inactivate a single target and that are not analogs of substrate. In these cases of resistance (for example, resistance to rifampicin), numerous single amino acid substitutions may provide large decreases in the affinity of the target for the antibiotic, leading to clinically significant levels of resistance. Resistance due to target alterations should occur much more slowly for those antibiotics (penicillin, for example) that inactivate multiple targets irreversibly by acting as close analogs of substrate. Resistance to penicillin because of target changes has emerged, by unexpected mechanisms, only in a limited number of species. However, inactivating enzymes commonly provide resistance to antibiotics that, like penicillin, are derived from natural products, although such enzymes have not been found for synthetic antibiotics. Thus, the ideal antibiotic would be produced by rational design, rather than by the modification of a natural product.

Spratt, Brian G.



Use of antibiotics in plant agriculture.  


Antibiotics are essential for control of bacterial diseases of plants, especially fire blight of pear and apple and bacterial spot of peach. Streptomycin is used in several countries; the use of oxytetracycline, oxolinic acid and gentamicin is limited to only a few countries. Springtime antibiotic sprays suppress pathogen growth on flowers and leaf surfaces before infection; after infection, antibiotics are ineffective. Antibiotics are applied when disease risk is high, and consequently the majority of orchards are not treated annually. In 2009 in the United States, 16,465 kg (active ingredient) was applied to orchards, which is 0.12% of the total antibiotics used in animal agriculture. Antibiotics are active on plants for less than a week, and significant residues have not been found on harvested fruit. Antibiotics have been indispensable for crop protection in the United States for more than 50 years without reports of adverse effects on human health or persistent impacts on the environment. PMID:22849276

Stockwell, V O; Duffy, B



Super Bug Antibiotics and Evolution  

NSDL National Science Digital Library

Sam, a pre-med college student, routinely gets dialysis and develops a urinary tract infection. The infection is from a bacterium that the news media is calling a "superbug" from India. Sam does some internet searches to find out more information about his condition. He examines popular news stories, primary literature, and considers what the United States should do about the increased prevalence of antibiotic resistance. To explore this issue, students form groups in which they are a politician, a parent, or a doctor, with each student bringing different information to the discussion. The case also discusses evolutionary principles and how they connect to antibiotic resistance. The case was developed for an introductory biology course taken by science majors who are not majoring in biology. It could be used in any introductory biology course or even as an introduction for a specific course on evolution.

Kristy Jean Wilson



Microbes : too smart for antibiotics?  

NSDL National Science Digital Library

This lesson packet builds on a peer-reviewed article about antibiotic resistance in microorganisms. The packet contains discussion questions about the article, instructions for an activity about hand washing that uses fake, fluorescent 'germs,' and two handouts of ideas for student activities. The first handout is appropriate for general biology students, and the second is designed for advanced, AP, or first-year undergraduate students. In many of the activities, students create a product, such as a public service announcement about antibiotic resistance (at the general level) or a funny presentation of the ways that bacteria can swap DNA (at the advanced level). The packet also provides correlations to national science standards and a suggested timetable for the activities. Copyright 2005 Eisenhower National Clearinghouse

Peggy Deichstetter



Antibiotic Treatment (Topical\\/Systemic)  

Microsoft Academic Search

\\u000a The role of bacteria in the pathogenesis of chronic rhinosinusitis (CRS) with and without nasal polyps is still controversial.\\u000a Contrary to acute rhinosinusitis, CRS often exhibits polymicrobial infections with Gram-positive, Gram-negative, and anaerobic\\u000a bacteria present. Bacterial biofilms, intracellular residency, and exotoxins potentially contribute to the inflammatory processes\\u000a of CRS. Macrolide antibiotics have anti-inflammatory, immunomodulatory, antimucus, and antibacterial actions. There is

Roland Giger; Basile N. Landis; Nicholas W. Stow; Jean-Silvain Lacroix


Introduction to the macrolide antibiotics  

Microsoft Academic Search

\\u000a Macrolide antibiotics are an old and well-established class of antimicrobial agents that have long played a significant role\\u000a in the chemotherapy of infectious diseases[1-3]. Among the most important characteristics of the macrolide class are a moderately broad spectrum of antimicrobial activity,\\u000a an orally effective route of administration, and a relatively high margin of safety (high therapeutic index). Although macrolides\\u000a have

Herbert A. Kirst


Antibiotics and the gut microbiota.  


Antibiotics have been a cornerstone of innovation in the fields of public health, agriculture, and medicine. However, recent studies have shed new light on the collateral damage they impart on the indigenous host-associated communities. These drugs have been found to alter the taxonomic, genomic, and functional capacity of the human gut microbiota, with effects that are rapid and sometimes persistent. Broad-spectrum antibiotics reduce bacterial diversity while expanding and collapsing membership of specific indigenous taxa. Furthermore, antibiotic treatment selects for resistant bacteria, increases opportunities for horizontal gene transfer, and enables intrusion of pathogenic organisms through depletion of occupied natural niches, with profound implications for the emergence of resistance. Because these pervasive alterations can be viewed as an uncoupling of mutualistic host-microbe relationships, it is valuable to reconsider antimicrobial therapies in the context of an ecological framework. Understanding the biology of competitive exclusion, interspecies protection, and gene flow of adaptive functions in the gut environment may inform the design of new strategies that treat infections while preserving the ecology of our beneficial constituents. PMID:25271726

Modi, Sheetal R; Collins, James J; Relman, David A



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

Technology Transfer Automated Retrieval System (TEKTRAN)

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...


The use of molecular biology to reprogram Streptomyces to make polyketide antibiotics more efficiently, and create novel secondary metabolites  

Microsoft Academic Search

Recent advances in the molecular genetics of Streptomyces have increased our understanding of polyketide antibiotic biosynthesis, to the point where recombinant DNA approaches to generate novel structures are possible. Our understanding of how antibiotic pathways are regulated and integrated into central metabolism also provides the opportunity for strain manipulation to enhance productivity.

Hrvoje Petkovi?; Daslav Hrauneli; Peter Raspor; Iain Hunter



Optimizing antibiotic selection in treating COPD exacerbations  

PubMed Central

Our understanding of the etiology, pathogenesis and consequences of acute exacerbations of chronic obstructive pulmonary disease (COPD) has increased substantially in the last decade. Several new lines of evidence demonstrate that bacterial isolation from sputum during acute exacerbation in many instances reflects a cause-effect relationship. Placebo-controlled antibiotic trials in exacerbations of COPD demonstrate significant clinical benefits of antibiotic treatment in moderate and severe episodes. However, in the multitude of antibiotic comparison trials, the choice of antibiotics does not appear to affect the clinical outcome, which can be explained by several methodological limitations of these trials. Recently, comparison trials with nontraditional end-points have shown differences among antibiotics in the treatment of exacerbations of COPD. Observational studies that have examined clinical outcome of exacerbations have repeatedly demonstrated certain clinical characteristics to be associated with treatment failure or early relapse. Optimal antibiotic selection for exacerbations has therefore incorporated quantifying the risk for a poor outcome of the exacerbation and choosing antibiotics differently for low risk and high risk patients, reserving the broader spectrum drugs for the high risk patients. Though improved outcomes in exacerbations with antibiotic choice based on such risk stratification has not yet been demonstrated in prospective controlled trials, this approach takes into account concerns of disease heterogeneity, antibiotic resistance and judicious antibiotic use in exacerbations. PMID:18488427

Siddiqi, Attiya; Sethi, Sanjay



[Efficiency of antibiotics in children with acute respiratory infection complicated by pneumonia dependent on the acetylation type in the Far North regions].  


Clinical characteristics of some diseases are defined by the phenotype of metabolic reactions, for example N-acetylation. Genetic polymorphism due to the activity of N-acetyltransferase (N-AT) is common in the majority of human populations. Consequently, persons with "slow" or "fast" acetylation phenotype should be identified. N-AT catalyzes acetylation of a number of medical products. Efficiency of pharmacotherapy is mostly associated with the specific features of medical products biotransformation. The processes of biotransformation with participation of acetyltransferase, monooxygenase or other ferment systems are under the gene control. The aim of the study was to characterize the features of the clinical course of acute respiratory infection complicated by pneumonia as dependent on the acetylation phenotype to predict the character of the disease and optimize the used antibiotic therapy among the native population (Yakut) and the arrived (Russian) in the Far North Regions (Sakha, Yakutia). 112 children with acute respiratory infections complicated by pneumonia and 49 practically healthy ones were examined. For the children with low N-AT activity (less than 30%) it was recommended to be treated with gentamicin which directly takes part in the acetylation and provides the antibiotic therapy efficiency in 80% of the cases. The use of cephalosporin antibiotics (beta-lactams), the metabolism of which is not directly connected with acetylation reactions provided the efficiency in 20% of the cases. PMID:25051713

Erbasskaia, A V; Ivanova, V V; Govorova, L V; Belova, V V; Bulovskaia, L N



Simultaneous determination of most prescribed antibiotics in multiple urban wastewater by SPE-LC-MS/MS.  


A rapid analytical method was developed for the application of a long-term monitoring (>one year) of the most prescribed and often in hospitals used antibiotics in diverse wastewaters of an urban sewage treatment plant (STP). Additionally to the selected multi-class antibiotics amoxicillin, penicillin V and piperacillin (penicillins), cefotaxime and cefuroxime (cephalosporins), azithromycin, clarithromycin and roxithromycin (macrolids), ciprofloxacin and levofloxacin-ofloxacin (fluoroquinolones), clindamycin (lincosamide), doxycycline (tetracycline), sulfamethoxazole (sulfonamide) and trimethoprim (dihydrofolate reductase inhibitor), the bioactive metabolite clindamycin-sulfoxide, the reserve antibiotic vancomycin (glycopeptide) and as tracer of the STP the anticonvulsant carbamazepine and the antifungal fluconazole were involved. The analytical method combines a low-sample-volume solid phase extraction (SPE), followed by a chromatographic separation using a reversed phase (RP) and hydrophilic interaction liquid chromatography (HILIC) technique, respectively, coupled to a triple quadrupole mass spectrometer. Detection was performed with multiple reaction monitoring (MRM) measured with positive electrospray ionization (ESI+). The extraction efficiency of different SPE cartridges and optimized pH-values of the preparation procedure were tested. Finally, the extraction of antibiotics was realized with the Oasis HLB cartridge and a pH adjustment at 3.5. An external calibration curve in diluted blank urine was used for quality control of the sample set of daily composite samples of the STP for the duration of one year monitoring. The squared coefficient of determination (r(2)) in the concentration range (20-20,000ng/L or 100-100,000ng/L) of the calibration curves for the method was higher than 0.99 for all determined substances. The limit of quantification (LoQ) ranged between 0.8ng/L (azithromycin) and 245.1ng/L (vancomycin). Furthermore, a standard addition was used for quantification in wastewater samples. The process efficiencies ranged from 20% (doxycycline) to 134% (cefuroxime) in influent samples and from 31% (doxycycline) to 171% (cefuroxime) in effluent samples of the STP. All selected substances have been found in wastewater samples. Cefuroxime, doxycycline, levofloxacin, piperacillin, sulfamethoxazole and carbamazepine showed highest concentrations up to 6.2?g/L. PMID:25171505

Rossmann, Julia; Schubert, Sara; Gurke, Robert; Oertel, Reinhard; Kirch, Wilhelm



Resistance to Antibiotics of Clinical Relevance in the Fecal Microbiota of Mexican Wildlife  

E-print Network

. Birds, especially, seem to be dispersing resistant bacteria generated by the use of antibiotics in food production animals [46]. Both Los Tuxtlas and Uxpanapa are areas of intense bird migratory activity [47], which could be a contributing factor... pressures and/or resistant bacteria seem to be more common at ground level; and indicators of ATBR prevalence and mobility seem to increase the closer animals are to human settlements. However, other indicators, such as resistance to synthetic antibiotics...

Cristóbal-Azkarate, Jurgi; Dunn, Jacob C.; Day, Jennifer M. W.; Amábile-Cuevas, Carlos F.



Probiotics or antibiotics: future challenges in medicine.  


Genetic and environmental factors can affect the intestinal microbiome and microbial metabolome. Among these environmental factors, the consumption of antibiotics can significantly change the intestinal microbiome of individuals and consequently affect the corresponding metagenome. The term 'probiotics' is related to preventive medicine rather than therapeutic procedures and is, thus, considered the opposite of antibiotics. This review discusses the challenges between these opposing treatments in terms of the following points: (i) antibiotic resistance, the relationship between antibiotic consumption and microbiome diversity reduction, antibiotic effect on the metagenome, and disease associated with antibiotics; and (ii) probiotics as living drugs, probiotic effect on epigenetic alterations, and gut microbiome relevance to hygiene indulgence. The intestinal microbiome is more specific for individuals and may be affected by environmental alterations and the occurrence of diseases. PMID:25525206

Nami, Yousef; Haghshenas, Babak; Abdullah, Norhafizah; Barzegari, Abolfazl; Radiah, Dayang; Rosli, Rozita; Khosroushahi, Ahmad Yari



Heteroresistance at the Single-Cell Level: Adapting to Antibiotic Stress through a Population-Based Strategy and Growth-Controlled Interphenotypic Coordination  

PubMed Central

ABSTRACT Heteroresistance refers to phenotypic heterogeneity of microbial clonal populations under antibiotic stress, and it has been thought to be an allocation of a subset of “resistant” cells for surviving in higher concentrations of antibiotic. The assumption fits the so-called bet-hedging strategy, where a bacterial population “hedges” its “bet” on different phenotypes to be selected by unpredicted environment stresses. To test this hypothesis, we constructed a heteroresistance model by introducing a blaCTX-M-14 gene (coding for a cephalosporin hydrolase) into a sensitive Escherichia coli strain. We confirmed heteroresistance in this clone and that a subset of the cells expressed more hydrolase and formed more colonies in the presence of ceftriaxone (exhibited stronger “resistance”). However, subsequent single-cell-level investigation by using a microfluidic device showed that a subset of cells with a distinguishable phenotype of slowed growth and intensified hydrolase expression emerged, and they were not positively selected but increased their proportion in the population with ascending antibiotic concentrations. Therefore, heteroresistance—the gradually decreased colony-forming capability in the presence of antibiotic—was a result of a decreased growth rate rather than of selection for resistant cells. Using a mock strain without the resistance gene, we further demonstrated the existence of two nested growth-centric feedback loops that control the expression of the hydrolase and maximize population growth in various antibiotic concentrations. In conclusion, phenotypic heterogeneity is a population-based strategy beneficial for bacterial survival and propagation through task allocation and interphenotypic collaboration, and the growth rate provides a critical control for the expression of stress-related genes and an essential mechanism in responding to environmental stresses. PMID:24520060

Wang, Xiaorong; Kang, Yu; Luo, Chunxiong; Zhao, Tong; Liu, Lin; Jiang, Xiangdan; Fu, Rongrong; An, Shuchang; Chen, Jichao; Jiang, Ning; Ren, Lufeng; Wang, Qi; Baillie, J. Kenneth; Gao, Zhancheng; Yu, Jun



Increase in resistance to extended-spectrum cephalosporins in Salmonella isolated from retail chicken products in Japan.  


Extended-spectrum ?-lactamase (ESBL)-producing Salmonella are one of the most important public health problems in developed countries. ESBL-producing Salmonella strains have been isolated from humans in Asian countries neighboring Japan, along with strains harboring the plasmid-mediated extended-spectrum cephalosporin (ESC)-resistance gene, ampC (pAmpC). However, only a few studies have investigated the prevalence of ESC-resistant Salmonella in chicken products in Japan, which are the main vehicle of Salmonella transmission. The aim of this study was to investigate the prevalence of ESBL-producing, pAmpC-harboring, or carbapenem-resistant Salmonella in chicken products in Japan. In total, 355 out of 779 (45.6%) chicken product samples collected from 1996-2010 contained Salmonella, resulting in 378 distinct isolates. Of these isolates, 373 were tested for resistance to ESCs, cephamycins, or carbapenems. Isolates that showed resistance to one or more of these antimicrobials were then examined by PCR and DNA sequence analysis for the presence of the bla(CMY), bla(CTX-M), bla(TEM), and bla(SHV) resistance genes. Thirty-five resistant isolates were detected, including 26 isolates that contained pAmpC (bla(CMY-2)), and nine ESBL-producing isolates harboring bla(CTX-M) (n = 4, consisting of two bla(CTX-M-2) and two bla(CTX-M-15 genes)), bla(TEM) (n = 4, consisting of one bla(TEM-20) and three bla(TEM-52) genes), and bla(SHV) (n = 1, bla(SHV-12)). All pAmpC-harboring and ESBL-producing Salmonella isolates were obtained from samples collected after 2005, and the percentage of resistant isolates increased significantly from 0% in 2004 to 27.9% in 2010 (P for trend = 0.006). This increase was caused in part by an increase in the number of Salmonella enterica subsp. enterica serovar Infantis strains harboring an approximately 280-kb plasmid containing bla(CMY-2) in proximity to ISEcp1. The dissemination of ESC-resistant Salmonella containing plasmid-mediated bla(CMY-2) in chicken products indicates the need for the development of continuous monitoring strategies in the interests of public health. PMID:25642944

Noda, Tamie; Murakami, Koichi; Etoh, Yoshiki; Okamoto, Fuyuki; Yatsuyanagi, Jun; Sera, Nobuyuki; Furuta, Munenori; Onozuka, Daisuke; Oda, Takahiro; Asai, Tetsuo; Fujimoto, Shuji



Increase in Resistance to Extended-Spectrum Cephalosporins in Salmonella Isolated from Retail Chicken Products in Japan  

PubMed Central

Extended-spectrum ?-lactamase (ESBL)-producing Salmonella are one of the most important public health problems in developed countries. ESBL-producing Salmonella strains have been isolated from humans in Asian countries neighboring Japan, along with strains harboring the plasmid-mediated extended-spectrum cephalosporin (ESC)-resistance gene, ampC (pAmpC). However, only a few studies have investigated the prevalence of ESC-resistant Salmonella in chicken products in Japan, which are the main vehicle of Salmonella transmission. The aim of this study was to investigate the prevalence of ESBL-producing, pAmpC-harboring, or carbapenem-resistant Salmonella in chicken products in Japan. In total, 355 out of 779 (45.6%) chicken product samples collected from 1996–2010 contained Salmonella, resulting in 378 distinct isolates. Of these isolates, 373 were tested for resistance to ESCs, cephamycins, or carbapenems. Isolates that showed resistance to one or more of these antimicrobials were then examined by PCR and DNA sequence analysis for the presence of the blaCMY, blaCTX-M, blaTEM, and blaSHV resistance genes. Thirty-five resistant isolates were detected, including 26 isolates that contained pAmpC (blaCMY-2), and nine ESBL-producing isolates harboring blaCTX-M (n = 4, consisting of two blaCTX-M-2 and two blaCTX-M-15 genes), blaTEM (n = 4, consisting of one blaTEM-20 and three blaTEM-52 genes), and blaSHV (n = 1, blaSHV-12). All pAmpC-harboring and ESBL-producing Salmonella isolates were obtained from samples collected after 2005, and the percentage of resistant isolates increased significantly from 0% in 2004 to 27.9% in 2010 (P for trend = 0.006). This increase was caused in part by an increase in the number of Salmonella enterica subsp. enterica serovar Infantis strains harboring an approximately 280-kb plasmid containing blaCMY-2 in proximity to ISEcp1. The dissemination of ESC-resistant Salmonella containing plasmid-mediated blaCMY-2 in chicken products indicates the need for the development of continuous monitoring strategies in the interests of public health. PMID:25642944

Noda, Tamie; Murakami, Koichi; Etoh, Yoshiki; Okamoto, Fuyuki; Yatsuyanagi, Jun; Sera, Nobuyuki; Furuta, Munenori; Onozuka, Daisuke; Oda, Takahiro; Asai, Tetsuo; Fujimoto, Shuji



Synthesis, optimization, and characterization of silver nanoparticles from Acinetobacter calcoaceticus and their enhanced antibacterial activity when combined with antibiotics  

PubMed Central

Background The development of nontoxic methods of synthesizing nanoparticles is a major step in nanotechnology to allow their application in nanomedicine. The present study aims to biosynthesize silver nanoparticles (AgNPs) using a cell-free extract of Acinetobacter spp. and evaluate their antibacterial activity. Methods Eighteen strains of Acinetobacter were screened for AgNP synthesis. AgNPs were characterized using various techniques. Reaction parameters were optimized, and their effect on the morphology of AgNPs was studied. The synergistic potential of AgNPs on 14 antibiotics against seven pathogens was determined by disc-diffusion, broth-microdilution, and minimum bactericidal concentration assays. The efficacy of AgNPs was evaluated as per the minimum inhibitory concentration (MIC) breakpoints of the Clinical and Laboratory Standards Institute (CLSI) guidelines. Results Only A. calcoaceticus LRVP54 produced AgNPs within 24 hours. Monodisperse spherical nanoparticles of 8–12 nm were obtained with 0.7 mM silver nitrate at 70°C. During optimization, a blue-shift in ultraviolet-visible spectra was seen. X-ray diffraction data and lattice fringes (d =0.23 nm) observed under high-resolution transmission electron microscope confirmed the crystallinity of AgNPs. These AgNPs were found to be more effective against Gram-negative compared with Gram-positive microorganisms. Overall, AgNPs showed the highest synergy with vancomycin in the disc-diffusion assay. For Enterobacter aerogenes, a 3.8-fold increase in inhibition zone area was observed after the addition of AgNPs with vancomycin. Reduction in MIC and minimum bactericidal concentration was observed on exposure of AgNPs with antibiotics. Interestingly, multidrug-resistant A. baumannii was highly sensitized in the presence of AgNPs and became susceptible to antibiotics except cephalosporins. Similarly, the vancomycin-resistant strain of Streptococcus mutans was also found to be susceptible to antibiotic treatment when AgNPs were added. These biogenic AgNPs showed significant synergistic activity on the ?-lactam class of antibiotics. Conclusion This is the first report of synthesis of AgNPs using A. calcoaceticus LRVP54 and their significant synergistic activity with antibiotics resulting in increased susceptibility of multidrug-resistant bacteria evaluated as per MIC breakpoints of the CLSI standard. PMID:24235826

Singh, Richa; Wagh, Priyanka; Wadhwani, Sweety; Gaidhani, Sharvari; Kumbhar, Avinash; Bellare, Jayesh; Chopade, Balu Ananda



Production of `hybrid' antibiotics by genetic engineering  

Microsoft Academic Search

The recent development of molecular cloning systems in Streptomyces1-4 has made possible the isolation of biosynthetic genes for some of the many antibiotics produced by members of this important genus of bacteria5-10. Such clones can now be used to test the idea that novel antibiotics could arise through the transfer of biosynthetic genes between streptomycetes producing different antibiotics11. The likelihood

D. A. Hopwood; F. Malpartida; H. M. Kieser; H. Ikeda; J. Duncan; I. Fujii; B. A. M. Rudd; H. G. Floss; S. Omura



Coping with antibiotic resistance: contributions from genomics  

Microsoft Academic Search

Antibiotic resistance is a public health issue of global dimensions with a significant impact on morbidity, mortality and\\u000a healthcare-associated costs. The problem has recently been worsened by the steady increase in multiresistant strains and by\\u000a the restriction of antibiotic discovery and development programs. Recent advances in the field of bacterial genomics will\\u000a further current knowledge on antibiotic resistance and help

Gian Maria Rossolini; Maria Cristina Thaller



New antibiotic dosing in infants.  


To prevent the devastating consequences of infection, most infants admitted to the neonatal intensive care unit are exposed to antibiotics. However, dosing regimens are often extrapolated from data in adults and older children, increasing the risk for drug toxicity and lack of clinical efficacy because they fail to account for developmental changes in infant physiology. However, newer technologies are emerging with minimal-risk study designs, including ultra-low-volume assays, pharmacokinetic modeling and simulation, and opportunistic drug protocols. With minimal-risk study designs, pharmacokinetic data and dosing regimens for infants are now available for ampicillin, clindamycin, meropenem, metronidazole, and piperacillin/tazobactam. PMID:25678003

Pineda, Leslie C; Watt, Kevin M



New anticancer antibiotic acts through diradical rearrangement  

SciTech Connect

This paper reports that chemists have found and characterized an anticancer antibiotic, dynemicin A, that may be the fouth of a series of antibiotics that act by metabolic rearrangement to a diradical. If true, diradical precursors may represent an antibiotic strategy that evolved widely in nature. And, there may be many more anticancer antibiotics awaiting discovery. Also, the unique internal trigger that seems to set off the dynemicin rearrangement gives chemists a new understanding of how these compounds work. If, indeed, the anthraquinone nucleus in dynemicin A binds by intercalation between strands of DNA as is now thought, chemists will learn more about how to deliver drugs to specific sites.

Stinson, S. (C and EN, Washington, DC (US))



Tackling antibiotic resistance: the environmental framework.  


Antibiotic resistance is a threat to human and animal health worldwide, and key measures are required to reduce the risks posed by antibiotic resistance genes that occur in the environment. These measures include the identification of critical points of control, the development of reliable surveillance and risk assessment procedures, and the implementation of technological solutions that can prevent environmental contamination with antibiotic resistant bacteria and genes. In this Opinion article, we discuss the main knowledge gaps, the future research needs and the policy and management options that should be prioritized to tackle antibiotic resistance in the environment. PMID:25817583

Berendonk, Thomas U; Manaia, Célia M; Merlin, Christophe; Fatta-Kassinos, Despo; Cytryn, Eddie; Walsh, Fiona; Bürgmann, Helmut; Sørum, Henning; Norström, Madelaine; Pons, Marie-Noëlle; Kreuzinger, Norbert; Huovinen, Pentti; Stefani, Stefania; Schwartz, Thomas; Kisand, Veljo; Baquero, Fernando; Martinez, José Luis



The epidemiology of antibiotic resistance in Campylobacter.  


Antibiotic resistance, particularly with the fluoroquinolones and macrolide antibiotics, has now emerged globally with thermophilic campylobacters, including Campylobacter jejuni and C. coli, giving rise to concerns about how these organisms have acquired such resistance characteristics, as well as consequences for human and animal treatment. This review examines (i) the clinical epidemiology of antibiotic resistance in human and animal thermophilic campylobacters, (ii) an update on resistance rates globally, (iii) surveillance of antimicrobial resistance in campylobacters originating from animals, particularly poultry, (iv) the role of the environment in the acquisition and transmission of antibiotic-resistant campylobacters, as well as (v) issues of biocide resistance in campylobacters. PMID:16716632

Moore, John E; Barton, Mary D; Blair, Iain S; Corcoran, Deborah; Dooley, James S G; Fanning, Séamus; Kempf, Isabelle; Lastovica, Albert J; Lowery, Colm J; Matsuda, Motoo; McDowell, David A; McMahon, Ann; Millar, B Cherie; Rao, Juluri R; Rooney, Paul J; Seal, Bruce S; Snelling, William J; Tolba, Ola



Update on the Management of Antibiotic Allergy  

PubMed Central

Drug allergy to antibiotics may occur in the form of immediate or non-immediate (delayed) hypersensitivity reactions. Immediate reactions are usually IgE-mediated whereas non-immediate hypersensitivity reactions are usually non-IgE or T-cell mediated. The clinical manifestations of antibiotic allergy may be cutaneous, organ-specific (e.g., blood dyscracias, hepatitis, interstitial nephritis), systemic (e.g., anaphylaxis, drug induced hypersensitivity syndrome) or various combinations of these. Severe cutaneous adverse reactions manifesting as Stevens Johnson syndrome or toxic epidermal necrolysis (TEN) may be potentially life-threatening. The management of antibiotic allergy begins with the identification of the putative antibiotic from a detailed and accurate drug history, complemented by validated in-vivo and in-vitro allergological tests. This will facilitate avoidance of the putative antibiotic through patient education, use of drug alert cards, and electronic medical records with in-built drug allergy/adverse drug reaction prescription and dispensing checks. Knowledge of the evidence for specific antibiotic cross-reactivities is also important in patient education. Apart from withdrawal of the putative antibiotic, immunomodulatory agents like high-dose intravenous immunoglobulins may have a role in TEN. Drug desensitization where the benefits outweigh the risks, and where no alternative antibiotics can be used for various reasons, may be considered in certain situations. Allergological issues pertaining to electronic drug allergy alerts, computerized physician prescriptions and decision support systems, and antibiotic de-escalation in antimicrobial stewardship programmes are also discussed. PMID:20358021



The effects of gastric pH and food on the pharmacokinetics of a new oral cephalosporin, cefpodoxime proxetil.  


The effects of alteration of gastric pH and food on the pharmacokinetics of 200 mg doses of cefpodoxime proxetil tablets were studied in two separate randomized, open label, crossover studies in healthy subjects. In the pH study (n = 17 subjects), there was a lead-in period done under fasting conditions, followed by randomization to a four-way crossover of pentagastrin (6 micrograms/kg, subcutaneously), ranitidine (150 mg orally, 10 and 2 hours before dosing with the antibiotic), sodium bicarbonate (12.6 gm), or aluminum hydroxide (120 cc). Gastric pH was determined by nasogastric aspirates before and 10 minutes after the intervention, just before the antibiotic was given. Peak plasma concentrations (Cmax) and area under plasma concentration-time curve (AUC) were highest in fasting and pentagastrin periods and were 35% to 50% lower for all of the other periods (p less than 0.0001). Gastric pH and Cmax and AUC were inversely related (r = 0.66 and r = 0.62; p less than 0.0001 for both). In the food study (n = 16 subjects), there were two lead-in periods, one done while subjects were fasting and one while they were normal diet, followed by randomization to a four-way crossover of either high or low protein diets, or high or low fat diets. There were six meals in each diet. Dosing with the antibiotic was done at the midpoint of the fourth meal. Cmax and AUC were 22% to 34% higher for all diets than for the fasting period (p less than 0.0001), whereas the time to Cmax was unchanged. These studies demonstrated that absorption of cefpodoxime proxetil is best at low gastric pH or in the presence of food, which suggests that the role of gastrointestinal function on the pharmacokinetic profile is complex. PMID:2557183

Hughes, G S; Heald, D L; Barker, K B; Patel, R K; Spillers, C R; Watts, K C; Batts, D H; Euler, A R



The Use and Abuse of Antibiotics and the Development of Antibiotic Resistance  

Microsoft Academic Search

\\u000a The growing problem of antibiotic resistance has made the formerly routine therapy of many infectious diseases challenging,\\u000a and, in rare cases, impossible. The widespread nature of the problem has led some experts to speculate about a “post-antibiotic\\u000a era.” Furthermore, though antibiotic resistance occurs in nature and is an inevitable consequence of even the most prudent\\u000a antibiotic use, it is clear

B. Keith English; Aditya H. Gaur


Chiral separations using the macrocyclic antibiotics: a review  

Microsoft Academic Search

The macrocyclic antibiotics have recently gained popularity as chiral selectors in CE, HPLC and TLC. The macrocyclic antibiotics used for chiral separations include the ansamycins, the glycopeptides, and the polypeptide antibiotic thiostrepton. Although not strictly considered macrocyclic antibiotics, the aminoglycosides are antibiotics that have been used for chiral separations in CE. More chiral analytes have been resolved using the glycopeptides

Timothy J Ward; Alton B Farris III



Simple Models of Antibiotic Cycling Timothy C. Reluga  

E-print Network

: Antibiotic cycling Key words: heterogeneous environments, resistance management 1 #12;Abstract The use of antibiotic usage to control antibiotic resistance. This paper presents a theory for the optimization of antibiotic resistance. While the emergence of drug resistance is a general problem in medicine, antibiotic

Reluga, Tim


Reducing Parental Demand for Antibiotics by Promoting Communication Skills  

ERIC Educational Resources Information Center

Antibiotic-resistant strains of bacteria are continuing to emerge as high rates of antibiotic use persist. Children are among the highest users of antibiotics, with parents influencing physician decision-making regarding antibiotic prescription. An intervention based on Social Cognitive Theory (SCT) to reduce parents' expectations for antibiotics

Alder, Stephen C.; Trunnell, Eric P.; White, George L., Jr.; Lyon, Joseph L.; Reading, James P.; Samore, Matthew H.; Magill, Michael K.



The role of aquatic ecosystems as reservoirs of antibiotic resistant bacteria and antibiotic resistance genes  

Microsoft Academic Search

The widespread and indiscriminate use of antibiotics has led to the development of antibiotic resistance in pathogenic, as well as commensal, microorganisms. Resistance genes may be horizontally or vertically transferred between bacterial communities in the environment. The recipient bacterial communities may then act as a reservoir of these resistance genes. In this study, we report the incidence of antibiotic resistance

P. T. Biyela; J. Lin; C. C. Bezuidenhout


Antibiotic contamination and occurrence of antibiotic-resistant bacteria in aquatic environments of northern Vietnam  

Microsoft Academic Search

The ubiquitous application and release of antibiotics to the environment can result in bacterial antibiotic resistance, which in turn can be a serious risk to humans and other animals. Southeast Asian countries commonly apply an integrated recycling farm system called VAC (Vegetable, Aquaculture and Caged animal). In the VAC environment, antibiotics are released from animal and human origins, which would

Phan Thi Phuong Hoa; Satoshi Managaki; Norihide Nakada; Hideshige Takada; Akiko Shimizu; Duong Hong Anh; Pham Hung Viet; Satoru Suzuki



Clinical Usefulness of the 2010 Clinical and Laboratory Standards Institute Revised Breakpoints for Cephalosporin Use in the Treatment of Bacteremia Caused by Escherichia coli or Klebsiella spp.  

PubMed Central

We investigated the clinical usefulness of the revised 2010 Clinical and Laboratory Standards Institute (CLSI) breakpoints for Escherichia coli and Klebsiella spp. Of 2,623 patients with bacteremia caused by E. coli or Klebsiella spp., 573 who had been treated appropriately with cephalosporin based on the CLSI 2009 guidelines were enrolled. There were no differences in the rates of treatment failure or mortality between the appropriately and inappropriately treated groups according to the CLSI 2010 guidelines. Additionally, in the matched case-control analysis, the treatment failure rate was higher in bacteremic patients with extended-spectrum ?-lactamase- (ESBL-) producing but cephalosporin-susceptible organisms than in those with ESBL-nonproducing isolates when patients with urinary tract infections were excluded (44% and 0%, resp., P = 0.026). In patients with bacteremia caused by E. coli or Klebsiella spp., the revised CLSI 2010 guidelines did not lead to poorer outcomes. However, ESBL production appeared to be associated with poor clinical outcomes in patients with bacteremia from sources other than the urinary tract.

Ku, Nam Su; Chung, Hae-Sun; Choi, Jun Yong; Yong, Dongeun; Lee, Kyungwon; Kim, June Myung; Chong, Yunsop



Quasiexperimental Study of the Effects of Antibiotic Use, Gastric Acid-Suppressive Agents, and Infection Control Practices on the Incidence of Clostridium difficile-Associated Diarrhea in Hospitalized Patients?  

PubMed Central

The objective of this study was to evaluate the effects of antimicrobial drug use, gastric acid-suppressive agent use, and infection control practices on the incidence of Clostridium difficile-associated diarrhea (CDAD) in a 426-bed general teaching hospital in Northern Ireland. The study was retrospective and ecological in design. A multivariate autoregressive integrated moving average (time-series analysis) model was built to relate CDAD incidence with antibiotic use, gastric acid-suppressive agent use, and infection control practices within the hospital over a 5-year period (February 2002 to March 2007). The findings of this study showed that temporal variation in CDAD incidence followed temporal variations in expanded-spectrum cephalosporin use (average delay = 2 months; variation of CDAD incidence = 0.01/100 bed-days), broad-spectrum cephalosporin use (average delay = 2 months; variation of CDAD incidence = 0.02/100 bed-days), fluoroquinolone use (average delay = 3 months; variation of CDAD incidence = 0.004/100 bed-days), amoxicillin-clavulanic acid use (average delay = 1 month; variation of CDAD incidence = 0.002/100 bed-days), and macrolide use (average delay = 5 months; variation of CDAD incidence = 0.002/100 bed-days). Temporal relationships were also observed between CDAD incidence and use of histamine-2 receptor antagonists (H2RAs; average delay = 1 month; variation of CDAD incidence = 0.001/100 bed-days). The model explained 78% of the variance in the monthly incidence of CDAD. The findings of this study highlight a temporal relationship between certain classes of antibiotics, H2RAs, and CDAD incidence. The results of this research can help hospitals to set priorities for restricting the use of specific antibiotic classes, based on the size-effect of each class and the delay necessary to observe an effect. PMID:19289520

Aldeyab, Mamoon A.; Harbarth, Stephan; Vernaz, Nathalie; Kearney, Mary P.; Scott, Michael G.; Funston, Chris; Savage, Karen; Kelly, Denise; Aldiab, Motasem A.; McElnay, James C.



[Health economics and antibiotic therapy].  


In the field of antibiotic therapy, particularly the methods of economic evaluation hold one's attention within the wide range of health economics' applications. Several tools allow a comparison of the outcomes of alternative strategies and thereby guide choices to the most appropriate solutions. After a brief recall of the methods classically used to evaluate health care strategy, the authors stress the importance and difficulty of fixing and applying a correct and satisfactory procedure for evaluation. An evaluation example of antibiotic therapy allows to illustrate the application of the principles confronting a field in which competition is intense and economic stakes stay large--a fact which naturally yields to seek after objective decision making criteria. The health care policies drawn by public authorities as well as the marketing strategies of the health sector trade are partly based on such evaluations. If these techniques are not intended for the practitioner in the first place, they should not be indifferent to him since they influence health authorities and thereby indirectly affect the therapeutic freedom of the physician. PMID:7481251

Leclercq, P; Bigdéli, M



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.  


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. PMID:22007888

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



Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase  

PubMed Central

Conjugative transfer of plasmid DNA via close cell–cell junctions is the main route by which antibiotic resistance genes spread between bacterial strains. Relaxases are essential for conjugative transfer and act by cleaving DNA strands and forming covalent phosphotyrosine linkages. Based on data indicating that multityrosine relaxase enzymes can accommodate two phosphotyrosine intermediates within their divalent metal-containing active sites, we hypothesized that bisphosphonates would inhibit relaxase activity and conjugative DNA transfer. We identified bisphosphonates that are nanomolar inhibitors of the F plasmid conjugative relaxase in vitro. Furthermore, we used cell-based assays to demonstrate that these compounds are highly effective at preventing DNA transfer and at selectively killing cells harboring conjugative plasmids. Two potent inhibitors, clodronate and etidronate, are already clinically approved to treat bone loss. Thus, the inhibition of conjugative relaxases is a potentially novel antimicrobial approach, one that selectively targets bacteria capable of transferring antibiotic resistance and generating multidrug resistant strains. PMID:17630285

Lujan, Scott A.; Guogas, Laura M.; Ragonese, Heather; Matson, Steven W.; Redinbo, Matthew R.



Genotype-by-environment interactions due to antibiotic resistance and adaptation in Escherichia coli.  


Mutations that are beneficial in one environment can have different fitness effects in other environments. In the context of antibiotic resistance, the resulting genotype-by-environment interactions potentially make selection on resistance unpredictable in heterogeneous environments. Furthermore, resistant bacteria frequently fix additional mutations during evolution in the absence of antibiotics. How do these two types of mutations interact to determine the bacterial phenotype across different environments? To address this, I used Escherichia coli as a model system, measuring the effects of nine different rifampicin resistance mutations on bacterial growth in 31 antibiotic-free environments. I did this both before and after approximately 200 generations of experimental evolution in antibiotic-free conditions (LB medium), and did the same for the antibiotic-sensitive wild type after adaptation to the same environment. The following results were observed: (i) bacteria with and without costly resistance mutations adapted to experimental conditions and reached similar levels of competitive fitness; (ii) rifampicin resistance mutations and adaptation to LB both indirectly altered growth in other environments; and (iii) resistant-evolved genotypes were more phenotypically different from the ancestor and from each other than resistant-nonevolved and sensitive-evolved genotypes. This suggests genotype-by-environment interactions generated by antibiotic resistance mutations, observed previously in short-term experiments, are more pronounced after adaptation to other types of environmental variation, making it difficult to predict long-term selection on resistance mutations from fitness effects in a single environment. PMID:23701170

Hall, A R



Analytical methodologies for identifying a polypeptide antibiotic  

Microsoft Academic Search

This article discusses the development of various analytical methods for identification and quantification of residues of antibiotics in meeting international regulatory requirements, and, as an example, overviews the screening, purification, fractionation and analytical assays of bacitracin, a commonly applied polypeptide antibiotic mixture. Attention is focused on the development of chemical methods, as they provide extraordinary performance, in terms of sensitivity

Della Wai-mei Sin; Yiu-chung Wong



Mining metagenomic datasets for antibiotic resistance genes  

Technology Transfer Automated Retrieval System (TEKTRAN)

Antibiotics are medicines that are used to kill, slow down, or prevent the growth of susceptible bacteria. They became widely used in the mid 20th century for controlling disease in humans, animals, and plants, and for a variety of industrial purposes. Antibiotic resistance is a broad term. There ...


Repairing the broken market for antibiotic innovation.  


Multidrug-resistant bacterial diseases pose serious and growing threats to human health. While innovation is important to all areas of health research, it is uniquely important in antibiotics. Resistance destroys the fruit of prior research, making it necessary to constantly innovate to avoid falling back into a pre-antibiotic era. But investment is declining in antibiotics, driven by competition from older antibiotics, the cost and uncertainty of the development process, and limited reimbursement incentives. Good public health practices curb inappropriate antibiotic use, making return on investment challenging in payment systems based on sales volume. We assess the impact of recent initiatives to improve antibiotic innovation, reflecting experience with all sixty-seven new molecular entity antibiotics approved by the Food and Drug Administration since 1980. Our analysis incorporates data and insights derived from several multistakeholder initiatives under way involving governments and the private sector on both sides of the Atlantic. We propose three specific reforms that could revitalize innovations that protect public health, while promoting long-term sustainability: increased incentives for antibiotic research and development, surveillance, and stewardship; greater targeting of incentives to high-priority public health needs, including reimbursement that is delinked from volume of drug use; and enhanced global collaboration, including a global treaty. PMID:25646108

Outterson, Kevin; Powers, John H; Daniel, Gregory W; McClellan, Mark B



Surveillance of antibiotic resistance in European ICUs  

Microsoft Academic Search

Antibiotic resistance among bacteria causing hospital-acquired infections poses a threat, particularly to patients in intensive care units (ICUs). In order to control the spread of resistant bacteria, local, regional and national resistance surveillance data must be used to develop efficient intervention strategies. In an attempt to identify national differences and the dynamics of antibiotic resistance in European ICUs, data have

H. Hanberger; D. Diekema; A. Fluit; R. Jones; M. Struelens; R. Spencer; M. Wolff




Technology Transfer Automated Retrieval System (TEKTRAN)

Regulatory pressures to limit antibiotic use in livestock and recent international marketing agreements that prohibit treating poultry with antibiotics have limited the disease-fighting tools available to poultry and livestock producers, particularly in Europe. There is a need to evaluate potential...


Antibiotic resistance among autochthonous aquatic environmental bacteria.  


Antibiotics are widely used in both human and veterinary medicine and antibiotic-resistant bacteria cause problems in antibiotic therapy. The current study was conducted in the catchment area of the river Swist (Germany) and focuses on the resistance of environmental Rhodospirillaceae to antibiotics used in human medicine. The samples collected reflect different levels of human impact on the environment. In total, 614 isolates were tested for antibiotic susceptibility. About half of these isolates were susceptible to all substances tested. Oxacillin resistance was observed most frequently (41%). Resistant Rhodospirillaceae were detected in wastewater effluent from a municipal sewage treatment plant, as well as in non-polluted upper reaches. The highest multi-resistance level was detected in small tributaries and it surprisingly decreased with an increasing influence of municipal wastewater. It could be shown that the detected resistances were acquired rather than intrinsic. Besides natural occurrence of multi-resistance among non-sulphur purple bacteria, horizontal gene transfer and acquired cross-resistance against veterinary antibiotics are assumed to be important factors. To the authors' knowledge, this is the first study investigating the potential of Rhodospirillaceae as a reservoir for resistance to antibiotics used in human medicine. The consequence for resistance prevalence in human pathogens and for their antibiotic therapy needs evaluation. PMID:23128628

Schreiber, Christiane; Kistemann, Thomas



Occurrence of antibiotics in the aquatic environment  

Microsoft Academic Search

The recent monitoring of drug residues in the aquatic environment has gained much interest as many pharmaceutical compounds can frequently be found in sewage treatment plant (STP) effluents and river water at concentrations up to several ?g\\/l. This article describes the analysis of various water samples for 18 antibiotic substances, from the classes of macrolid antibiotics, sulfonamides, penicillins and tetracyclines.

Roman Hirsch; Thomas Ternes; Klaus Haberer; Karl-Ludwig Kratz



Antibiotic-Resistant Bacteria: There is Hope.  

ERIC Educational Resources Information Center

Argues that reduction in the use of antibiotics would enable antibiotic-sensitive bacteria to flourish. Presents an activity designed to show students how a small, seemingly unimportant difference in doubling time can, over a period of time, make an enormous difference in population size. (DDR)

Offner, Susan



[Rational antibiotic prescribing. Challenges and successes].  


Rational and prudent antibiotic prescribing strategies are important both for the hospital sector as well as for ambulatory medicine. Prerequisites are the availability of antibiotic use and antibiotic resistance data and of infrastructure and trained personnel needed for implementing and evaluating antibiotic policies. Currently, these requirements are not being met sufficiently in Germany. A major challenge in this country is the lack of adequately trained and experienced personnel. On the other hand there are several projects and initiatives supported in part within the national antibiotic resistance control program which have produced some progress and success. One example is GERMAP, the national antibiotic use and resistance atlas covering both human medicine and the veterinary field. Other examples are the recently improved program for continuous hospital antibiotic use, surveillance and feedback and the Antibiotic Stewardship (ABS) training program with establishment of an ABS expert network. Future perspectives include programs for evaluation of practice guideline adherence and the development and evaluation of quality of care indicators. Intermediate and long-term investment is needed in specialty training and certification of a sufficient number of infectious disease physicians, medical microbiologists and infection control doctors/hospital epidemiologists and hospital pharmacists. PMID:23114441

Kern, W V; de With, K



Non-canonical mechanisms of antibiotic resistance  

Microsoft Academic Search

Although the current in vitro methods used for detection and analysis of the phenotypes of antibiotic resistance in the laboratory are well established, other resistance mechanisms of resistance exist which may escape detection using the standard approach. The present article reviews some of these mechanisms which are grouped under the term ‘non-canonical mechanisms’ of antibiotic resistance. Such mechanisms include gene

J. L. Martínez; J. Blázquez; F. Baquero



Antibiotic-resistance cassettes for Bacillus subtilis  

Microsoft Academic Search

The genes encoding resistance to four different antibiotics (erythromycin, kanamycin, tetracycline and spectinomycin) were cloned in the polylinker of various Escherichia coli plasmid vectors. These cassettes can be inserted into cloned Bacillus subtilis (Bs) genes and used to create tagged chromosomal disruptions after recombination into Bs and selection in the presence of the appropriate antibiotic.

Anne-Marie Guérout-Fleury; Kamran Shazand; Niels Frandsen; Patrick Stragier



The biological cost of antibiotic resistance  

Microsoft Academic Search

The frequency and rates of ascent and dissemination of antibiotic resistance in bacterial populations are anticipated to be directly related to the volume of antibiotic use and inversely related to the cost that resistance imposes on the fitness of bacteria. The data available from recent laboratory studies suggest that most, but not all, resistance-determining mutations and accessory elements engender some

Dan I Andersson; Bruce R Levin



Regulation of antibiotic resistance in Staphylococcus aureus  

Microsoft Academic Search

Staphylococcus aureus has a formidable ability to adapt to varying environmental conditions and an extraordinary capacity to rapidly become resistant to virtually all antibiotics. Resistance develops either through mutations and rearrangements within the staphylococcal genome, or by the acquisition of resistance determinants. Antibiotic resistances often impose a fitness burden on the host. Such biological costs can be reduced by tight

Nadine McCallum; Brigitte Berger-Bächi; Maria M. Senn



Regulation of Antibiotic Production by Bacterial Hormones  

Microsoft Academic Search

Antibiotic production is regulated by numerous signals, including the so-called bacterial hormones found in antibiotic producing organisms such as Streptomyces. These signals, the ?-butyrolactones, are produced in very small quantities, which has hindered their structural elucidation and made it difficult to assess whether they are being produced. In this chapter, we describe a rapid small-scale extraction method from either solid

Nai-Hua Hsiao; Marco Gottelt; Eriko Takano



Evolution of resistance to a last-resort antibiotic in Staphylococcus aureus via bacterial competition.  


Antibiotic resistance is a key medical concern, with antibiotic use likely being an important cause. However, here we describe an alternative route to clinically relevant antibiotic resistance that occurs solely due to competitive interactions among bacterial cells. We consistently observe that isolates of Methicillin-resistant Staphylococcus aureus diversify spontaneously into two distinct, sequentially arising strains. The first evolved strain outgrows the parent strain via secretion of surfactants and a toxic bacteriocin. The second is resistant to the bacteriocin. Importantly, this second strain is also resistant to intermediate levels of vancomycin. This so-called VISA (vancomycin-intermediate S. aureus) phenotype is seen in many hard-to-treat clinical isolates. This strain diversification also occurs during in vivo infection in a mouse model, which is consistent with the fact that both coevolved phenotypes resemble strains commonly found in clinic. Our study shows how competition between coevolving bacterial strains can generate antibiotic resistance and recapitulate key clinical phenotypes. PMID:25171407

Koch, Gudrun; Yepes, Ana; Förstner, Konrad U; Wermser, Charlotte; Stengel, Stephanie T; Modamio, Jennifer; Ohlsen, Knut; Foster, Kevin R; Lopez, Daniel



Challenges and future prospects of antibiotic therapy: from peptides to phages utilization  

PubMed Central

Bacterial infections are raising serious concern across the globe. The effectiveness of conventional antibiotics is decreasing due to global emergence of multi-drug-resistant (MDR) bacterial pathogens. This process seems to be primarily caused by an indiscriminate and inappropriate use of antibiotics in non-infected patients and in the food industry. New classes of antibiotics with different actions against MDR pathogens need to be developed urgently. In this context, this review focuses on several ways and future directions to search for the next generation of safe and effective antibiotics compounds including antimicrobial peptides, phage therapy, phytochemicals, metalloantibiotics, lipopolysaccharide, and efflux pump inhibitors to control the infections caused by MDR pathogens. PMID:24860506

Mandal, Santi M.; Roy, Anupam; Ghosh, Ananta K.; Hazra, Tapas K.; Basak, Amit; Franco, Octavio L.



Evolution of resistance to a last-resort antibiotic in Staphyloccocus aureus via bacterial competition  

PubMed Central

Summary Antibiotic resistance is a key medical concern, with antibiotic use likely being an important cause. However, here we describe an alternative route to clinically-relevant antibiotic resistance that occurs solely due to competitive interactions between bacterial cells. We consistently observe that isolates of Methicillin-resistant Staphylococcus aureus diversify spontaneously into two distinct, sequentially arising strains. The first evolved strain outgrows the parent strain via secretion of surfactants and a toxic bacteriocin. The second is resistant to the bacteriocin. Importantly, this second strain is also resistant to intermediate levels of vancomycin. This so-called VISA (vancomycin-intermediate S. aureus) phenotype is seen in many hard-to-treat clinical isolates. This strain diversification also occurs during in vivo infection in a mouse model, consistent with the fact that both coevolved phenotypes resemble strains commonly found in clinic. Our study shows how competition between coevolving bacterial strains can generate antibiotic resistance and recapitulate key clinical phenotypes. PMID:25171407

Koch, Gudrun; Yepes, Ana; Förstner, Konrad U.; Wermser, Charlotte; Stengel, Stephanie T.; Modamio, Jennifer; Ohlsen, Knut; Foster, Kevin R.; Lopez, Daniel



Metabolic engineering of antibiotic factories: new tools for antibiotic production in actinomycetes.  


Actinomycetes are excellent sources for novel bioactive compounds, which serve as potential drug candidates for antibiotics development. While industrial efforts to find and develop novel antimicrobials have been severely reduced during the past two decades, the increasing threat of multidrug-resistant pathogens and the development of new technologies to find and produce such compounds have again attracted interest in this field. Based on improvements in whole-genome sequencing, novel methods have been developed to identify the secondary metabolite biosynthetic gene clusters by genome mining, to clone them, and to express them in heterologous hosts in much higher throughput than before. These technologies now enable metabolic engineering approaches to optimize production yields and to directly manipulate the pathways to generate modified products. PMID:25497361

Weber, Tilmann; Charusanti, Pep; Musiol-Kroll, Ewa Maria; Jiang, Xinglin; Tong, Yaojun; Kim, Hyun Uk; Lee, Sang Yup



N Engl J Med . Author manuscript Antibiotic resistance from food  

E-print Network

N Engl J Med . Author manuscript Page /1 2 Antibiotic resistance from food Denis E. Corpet * X Author Keywords Antibiotic resistance ; antimicrobial resistance ; Escherichia coli ; gut bacteria ; streptomycin ; lactose-fermenting enteric bacilli ; .flow of resistant genes : Resistance to antibiotics

Paris-Sud XI, Université de


Antibiotics: When They Can and Can't Help  


... and most coughs and sore throats. What is "antibiotic resistance?" “Antibiotic resistance” and “bacterial resistance” are two ways of describing the same thing. Usually, antibiotics kill bacteria or stop them from growing. However, ...


Complexation of peptidoglycan intermediates by the lipoglycodepsipeptide antibiotic ramoplanin  

E-print Network

Complexation of peptidoglycan intermediates by the lipoglycodepsipeptide antibiotic ramoplanin) The peptide antibiotic ramoplanin inhibits bacterial peptidoglycan (PG) biosynthesis by interrupting late ramoplanin is structurally less complex than glycopeptide antibiotics such as vancomycin, peptidomimetic

Cudic, Predrag


Laehnemann et al. Genomics of rapid adaptation to antibiotics  

E-print Network

Laehnemann et al. RESEARCH Genomics of rapid adaptation to antibiotics: Convergent evolution of antibiotic resistance in bacteria. The genomic underpinnings of such rapid changes may provide information antibiotic resistance evolution. Results: Our new analyses demonstrate that amplification of a sequence

Beardmore, Robert


21 CFR 333.110 - First aid antibiotic active ingredients.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 2014-04-01 false First aid antibiotic active ingredients. 333.110...PRODUCTS FOR OVER-THE-COUNTER HUMAN USE First Aid Antibiotic Drug Products § 333.110 First aid antibiotic active ingredients. The...



21 CFR 333.110 - First aid antibiotic active ingredients.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 false First aid antibiotic active ingredients. 333.110...PRODUCTS FOR OVER-THE-COUNTER HUMAN USE First Aid Antibiotic Drug Products § 333.110 First aid antibiotic active ingredients. The...



21 CFR 333.110 - First aid antibiotic active ingredients.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false First aid antibiotic active ingredients. 333.110...PRODUCTS FOR OVER-THE-COUNTER HUMAN USE First Aid Antibiotic Drug Products § 333.110 First aid antibiotic active ingredients. The...



21 CFR 333.110 - First aid antibiotic active ingredients.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false First aid antibiotic active ingredients. 333.110...PRODUCTS FOR OVER-THE-COUNTER HUMAN USE First Aid Antibiotic Drug Products § 333.110 First aid antibiotic active ingredients. The...



21 CFR 333.110 - First aid antibiotic active ingredients.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false First aid antibiotic active ingredients. 333.110...PRODUCTS FOR OVER-THE-COUNTER HUMAN USE First Aid Antibiotic Drug Products § 333.110 First aid antibiotic active ingredients. The...



Innovation of novel antibiotics: an economic perspective.  


Despite the public attention to antibiotic overuse and the specter of antimicrobial-resistant pathogens, current infections necessitate the use of antibiotics. Yet, patients and providers may not fully consider the societal cost associated with inappropriate antimicrobial use and subsequent resistance. Policies intended to limit use to minimize resistance must be balanced with the competing concern of underutilization. It is difficult to determine whether research and development incentives or reducing the costs of bringing new antibiotics through expedited review will be sufficient. Likely, the most effective method would be allowing higher prices for use deemed to be clinically appropriate. The ultimate policy goal is to ensure that antibiotics are used appropriately, with the right patients receiving the right medication at the right time, and that the world has a steady stream of future antibiotics to effectively treat the resistant organisms that will inevitably emerge. PMID:25261536

McKellar, Michael R; Fendrick, A Mark



[Antibiotics in animal husbandry: a thorny problem].  


The widespread use of antibiotics in animal husbandry in the Netherlands poses a problem to human health, due to the development of antibiotic resistance. However, agricultural managers have to adjust to an economic reality in which antibiotic use is profitable. In the long term, there has to be far more attention to prevention of infection and biosecurity in animal husbandry so that fewer antibiotics are required and the risks of passing on resistant organisms to the population are limited. An important stimulus would be for the meat-processing industry, the supermarkets and the consumers to impose demands concerning food-safety and to be prepared to pay for them. Alternatively, making antibiotics more expensive is a negative stimulus which could work well. PMID:21118591

Mevius, Dik; Hellebrekers, Ludo J



Retapamulin: a newer topical antibiotic.  


Impetigo is a common childhood skin infection. There are reports of increasing drug resistance to the currently used topical antibiotics including fusidic acid and mupirocin. Retapamulin is a newer topical agent of pleuromutilin class approved by the Food and Drug Administration for treatment of impetigo in children and has been recently made available in the Indian market. It has been demonstrated to have low potential for the development of antibacterial resistance and a high degree of potency against poly drug resistant Gram-positive bacteria found in skin infections including Staphylococcus aureus strains. The drug is safe owing to low systemic absorption and has only minimal side-effect of local irritation at the site of application. PMID:23793314

Dhingra, D; Parakh, A; Ramachandran, S



Tackling antibiotic resistance in India.  


Infectious diseases are major causes of mortality in India. This is aggravated by the increasing prevalence of antimicrobial resistance (AMR) both in the community and in hospitals. Due to the emergence of resistance to all effective antibiotics in nosocomial pathogens, the situation calls for emergency measures to tackle AMR in India. India has huge challenges in tackling AMR, ranging from lack of surveillance mechanisms for monitoring AMR and use; effective hospital control policies; sanitation and non-human use of antimicrobial. The Ministry of Health and Family Welfare of Govt. of India has taken initiatives to tackle AMR. Extensive guidelines have been drafted and a model worksheet has been developed as a roadmap to tackle AMR. PMID:25353717

Wattal, Chand; Goel, Neeraj



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

PubMed Central

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. Wastewater samples collected in the afternoon contained both a higher number and higher levels of antibiotics compared to samples collected in the morning hours. No amikacin was found in the wastewater, but E.coli isolates from all wastewater samples were resistant to amikacin. Although ciprofloxacin was the most prevalent antibiotic detected in the wastewater, E.coli was not resistant to it. Conclusions Antibiotics are entering the aquatic environment of countries like India through hospital effluent. In-depth studies are needed to establish the correlation, if any, between the quantities of antibiotics prescribed in hospitals and the levels of antibiotic residues found in hospital effluent. Further, the effect of this on the development of bacterial resistance in the environment and its subsequent public health impact need thorough assessment. PMID:20626873



Linking microbial community structure and function to characterize antibiotic resistant bacteria and antibiotic resistant genes from cattle feces  

Technology Transfer Automated Retrieval System (TEKTRAN)

There is widespread interest in monitoring the development of antibiotic resistant bacteria and antibiotic resistance genes in agriculturally impacted environments, however little is known about the relationships between bacterial community structure, and antibiotic resistance gene profiles. Cattl...


The antibiotic effects of vitamin D.  


The recent discovery that vitamin D regulates expression of the cathelicidin antimicrobial peptide gene has generated renewed interest in using vitamin D to fight infectious diseases. This review describes the historical use of vitamin D or its sources to treat infections, the mechanism of action through which vitamin D mediates its "antibiotic" effects, findings from epidemiological studies associating vitamin D deficiency with increased susceptibility to infection and clinical trials with vitamin D supplementation to treat or prevent infections. Further studies examining an association between vitamin D levels and cathelicidin expression are discussed. The role of cathelcidin throughout the course of infection from the initial encounter of the pathogen to the resolution of tissue damage and inflammation indicates that individuals need to maintain adequate levels of vitamin D for an optimal immune response. In addition, for treating infections, carefully designed randomized, clinical trials that are appropriately powered to detect modest effects, target populations that are severely deficient in vitamin D,and optimized dose, dosing frequency and safety are needed. PMID:25008764

Guo, Chunxiao; Gombart, Adrian F



Influence of therapeutic ceftiofur treatments of feedlot cattle on fecal and hide prevalences of commensal Escherichia coli resistant to expanded-spectrum cephalosporins, and molecular characterization of resistant isolates  

Technology Transfer Automated Retrieval System (TEKTRAN)

In the United States the bla**CMY-2** gene contained within incompatibility type A/C (IncA/C) plasmids is frequently identified in extended-spectrum cephalosporin-resistant Escherichia coli (ESCr) from both human and cattle sources. Concerns have been raised that therapeutic use of ceftiofur in catt...


Pharmacokinetics of intravitreal antibiotics in endophthalmitis  

PubMed Central

Intravitreal antibiotics are the mainstay of treatment in the management of infectious endophthalmitis. Basic knowledge of the commonly used intravitreal antibiotics, which includes their pharmacokinetics, half-life, duration of action and clearance, is essential for elimination of intraocular infection without any iatrogenic adverse effect to the ocular tissue. Various drugs have been studied over the past century to achieve this goal. We performed a comprehensive review of the antibiotics which have been used for intravitreal route and the pharmacokinetic factors influencing the drug delivery and safety profile of these antibiotics. Using online resources like PubMed and Google Scholar, articles were reviewed. The articles were confined to the English language only. We present a broad overview of pharmacokinetic concepts fundamental for use of intravitreal antibiotics in endophthalmitis along with a tabulated compendium of the intravitreal antibiotics using available literature. Recent advances for increasing bioavailability of antibiotics to the posterior segment with the development of controlled drug delivery devices are also described. PMID:25667683



Gut microbiota disturbance during antibiotic therapy  

PubMed Central

It is known that the gastrointestinal tract (GIT) microbiota responds to different antibiotics in different ways and that while some antibiotics do not induce disturbances of the community, others drastically influence the richness, diversity, and prevalence of bacterial taxa. However, the metabolic consequences thereof, independent of the degree of the community shifts, are not clearly understood. In a recent article, we used an integrative OMICS approach to provide new insights into the metabolic shifts caused by antibiotic disturbance. The study presented here further suggests that specific bacterial lineage blooms occurring at defined stages of antibiotic intervention are mostly associated with organisms that possess improved survival and colonization mechanisms, such as those of the Enterococcus, Blautia, Faecalibacterium, and Akkermansia genera. The study also provides an overview of the most variable metabolic functions affected as a consequence of a ?-lactam antibiotic intervention. Thus, we observed that anabolic sugar metabolism, the production of acetyl donors and the synthesis and degradation of intestinal/colonic epithelium components were among the most variable functions during the intervention. We are aware that these results have been established with a single patient and will require further confirmation with a larger group of individuals and with other antibiotics. Future directions for exploration of the effects of antibiotic interventions are discussed. PMID:24418972

Ferrer, Manuel; Martins dos Santos, Vitor AP; Ott, Stephan J; Moya, Andrés



ARDB—Antibiotic Resistance Genes Database  

PubMed Central

The treatment of infections is increasingly compromised by the ability of bacteria to develop resistance to antibiotics through mutations or through the acquisition of resistance genes. Antibiotic resistance genes also have the potential to be used for bio-terror purposes through genetically modified organisms. In order to facilitate the identification and characterization of these genes, we have created a manually curated database—the Antibiotic Resistance Genes Database (ARDB)—unifying most of the publicly available information on antibiotic resistance. Each gene and resistance type is annotated with rich information, including resistance profile, mechanism of action, ontology, COG and CDD annotations, as well as external links to sequence and protein databases. Our database also supports sequence similarity searches and implements an initial version of a tool for characterizing common mutations that confer antibiotic resistance. The information we provide can be used as compendium of antibiotic resistance factors as well as to identify the resistance genes of newly sequenced genes, genomes, or metagenomes. Currently, ARDB contains resistance information for 13 293 genes, 377 types, 257 antibiotics, 632 genomes, 933 species and 124 genera. ARDB is available at PMID:18832362

Liu, Bo; Pop, Mihai



Molecular Regulation of Antibiotic Biosynthesis in Streptomyces  

PubMed Central

SUMMARY Streptomycetes are the most abundant source of antibiotics. Typically, each species produces several antibiotics, with the profile being species specific. Streptomyces coelicolor, the model species, produces at least five different antibiotics. We review the regulation of antibiotic biosynthesis in S. coelicolor and other, nonmodel streptomycetes in the light of recent studies. The biosynthesis of each antibiotic is specified by a large gene cluster, usually including regulatory genes (cluster-situated regulators [CSRs]). These are the main point of connection with a plethora of generally conserved regulatory systems that monitor the organism's physiology, developmental state, population density, and environment to determine the onset and level of production of each antibiotic. Some CSRs may also be sensitive to the levels of different kinds of ligands, including products of the pathway itself, products of other antibiotic pathways in the same organism, and specialized regulatory small molecules such as gamma-butyrolactones. These interactions can result in self-reinforcing feed-forward circuitry and complex cross talk between pathways. The physiological signals and regulatory mechanisms may be of practical importance for the activation of the many cryptic secondary metabolic gene cluster pathways revealed by recent sequencing of numerous Streptomyces genomes. PMID:23471619

Liu, Gang; Chandra, Govind; Niu, Guoqing



Antibiotic Resistance in Sepsis Patients: Evaluation and Recommendation of Antibiotic Use  

PubMed Central

Background: The appropriate selection of empirical antibiotics based on the pattern of local antibiotic resistance can reduce the mortality rate and increase the rational use of antibiotics. Aims: We analyze the pattern of antibiotic use and the sensitivity patterns of antibiotics to support the rational use of antibiotics in patients with sepsis. Materials and Methods: A retrospective observational study was conducted in adult sepsis patient at one of Indonesian hospital during January-December 2011. Data were collected from the hospital medical record department. Descriptive analysis was used in the processing and interpretation of data. Results: A total of 76 patients were included as research subjects. Lung infection was the highest source of infection. In the 66.3% of clinical specimens that were culture positive for microbes, Klebsiella pneumoniae, Escherichia coli, Staphylococcus hominis were detected with the highest frequency. The six most frequently used antibiotics, levofloxacin, ceftazidime, ciprofloxacin, cefotaxime, ceftriaxone, and erythromycin, showed an average resistance above 50%. Conclusions: The high use of antibiotic with a high level resistance requires a policy to support its rational use. Local microbial pattern based on site infection and pattern of antibiotics sensitivity test can be used as supporting data to optimize appropriateness of empirical antibiotics therapy in sepsis patients. PMID:23923107

Pradipta, Ivan Surya; Sodik, Dian Chairunnisa; Lestari, Keri; Parwati, Ida; Halimah, Eli; Diantini, Ajeng; Abdulah, Rizky



Development of a direct ELISA based on carboxy-terminal of penicillin-binding protein BlaR for the detection of ?-lactam antibiotics in foods.  


?-Lactam antibiotics, including penicillins and cephalosporins, are commonly used in veterinary medicine. Illegal use and abuse of ?-lactams could cause allergy and selected bacterial resistance. BlaR-CTD, the carboxy-terminal of penicillin-recognizing protein BlaR from Bacillus licheniformis ATCC 14580, was utilized in this study to develop a receptor-based ELISA for detection and determination of ?-lactam antibiotics in milk, beef, and chicken. This assay was based on directly competitive inhibition of binding of horseradish peroxidase-labeled ampicillin to the immobilized BlaR-CTD by ?-lactams. The assay was developed as screening test with the option as semiquantitative assay, when the identity of a single type of residual ?-lactam was known. The IC50 values of 15 ?-lactam antibiotics, including benzylpenicillin, ampicillin, amoxicillin, dicloxacillin, oxacillin, nafcillin, cefapirin, cefoperazone, cefalotin, cefazolin, cefquinome, ceftriaxone, cefotaxime, cefalexin, ceftiofur and its metabolite desfuroylceftiofur were evaluated and ranged from 0.18 to 170.81 ?g L(-1). Simple sample extraction method was carried out with only phosphate-buffered saline, and the recoveries of selected ?-lactam antibiotics in milk, beef, and chicken were in the range of 53.27 to 128.29 %, most ranging from 60 to 120 %. The inter-assay variability was below 30 %. Limits of detection in milk, beef, and chicken muscles with cefquinome matrix calibration were 2.10, 30.68, and 31.13 ?g kg(-1), respectively. This study firstly established a rapid, simple, and accurate method for simultaneous detection of 15 ?-lactams in edible tissues, among which 11 ?-lactams controlled by European Union could be detected below maximum residue limits. PMID:24013636

Peng, Juan; Cheng, Guyue; Huang, Lingli; Wang, Yulian; Hao, Haihong; Peng, Dapeng; Liu, Zhenli; Yuan, Zonghui



Fungal Resistance to Plant Antibiotics as a Mechanism of Pathogenesis  

PubMed Central

Many plants produce low-molecular-weight compounds which inhibit the growth of phytopathogenic fungi in vitro. These compounds may be preformed inhibitors that are present constitutively in healthy plants (also known as phytoanticipins), or they may be synthesized in response to pathogen attack (phytoalexins). Successful pathogens must be able to circumvent or overcome these antifungal defenses, and this review focuses on the significance of fungal resistance to plant antibiotics as a mechanism of pathogenesis. There is increasing evidence that resistance of fungal pathogens to plant antibiotics can be important for pathogenicity, at least for some fungus-plant interactions. This evidence has emerged largely from studies of fungal degradative enzymes and also from experiments in which plants with altered levels of antifungal secondary metabolites were generated. Whereas the emphasis to date has been on degradative mechanisms of resistance of phytopathogenic fungi to antifungal secondary metabolites, in the future we are likely to see a rapid expansion in our knowledge of alternative mechanisms of resistance. These may include membrane efflux systems of the kind associated with multidrug resistance and innate resistance due to insensitivity of the target site. The manipulation of plant biosynthetic pathways to give altered antibiotic profiles will also be valuable in telling us more about the significance of antifungal secondary metabolites for plant defense and clearly has great potential for enhancing disease resistance for commercial purposes. PMID:10477313

Morrissey, John P.; Osbourn, Anne E.



Antibiotic prophylaxis in craniotomy: a review.  


The effectiveness of antibiotic prophylaxis (AP) in craniotomies has been clarified through the accumulation of evidence and increased antibiotic knowledge. This paper focuses on the use of AP in craniotomies during different historical periods and collects highly relevant evidence on this issue. This review surveys different AP guidelines and explains why cefazolin was selected by most guidelines. Recent prominent topics, including strategies to update and implement guidelines and antibiotic efficacy in postoperative meningitis and surveillance and decolonization therapies for methicillin-resistant Staphylococcus aureus, are discussed. PMID:24526365

Liu, Weiming; Ni, Ming; Zhang, Yuewei; Groen, Rob J M



Activity 1: Evolution and Antibiotic Resistance  

NSDL National Science Digital Library

This page contains three student activities for learning about evolution of antibiotic resistance. The first activity involves two videos (freely available on the website), follow-up questions, and classroom discussion. The second activity is a survey about antibiotic use/misuse that students are to conduct in their neighborhoods. The third activity is a group effort to produce an educational presentation about antibiotic resistance. There are teacher notes for all three activities. This activity set is part of a larger educational unit on the relevance of evolution to everyday life. This unit is appropriate for middle- or high-school students.

WGBH Educational Foundation; Clear Blue Sky Productions, Inc.


How Nature Morphs Peptide Scaffolds into Antibiotics  

PubMed Central

The conventional notion that peptides are poor candidates for orally available drugs because of protease-sensitive peptide bonds, intrinsic hydrophilicity, and ionic charges contrasts with the diversity of antibiotic natural products with peptide-based frameworks that are synthesized and utilized by Nature. Several of these antibiotics, including penicillin and vancomycin, are employed to treat bacterial infections in humans and have been best-selling therapeutics for decades. Others might provide new platforms for the design of novel therapeutics to combat emerging antibiotic-resistant bacterial pathogens. PMID:19058272

Nolan, Elizabeth M.; Walsh, Christopher T.



Anaerobic bacteria as producers of antibiotics.  


Anaerobic bacteria are the oldest terrestrial creatures. They occur ubiquitously in soil and in the intestine of higher organisms and play a major role in human health, ecology, and industry. However, until lately no antibiotic or any other secondary metabolite has been known from anaerobes. Mining the genome sequences of Clostridium spp. has revealed a high prevalence of putative biosynthesis genes (PKS and NRPS), and only recently the first antibiotic from the anaerobic world, closthioamide, has been isolated from the cellulose degrading bacterium Clostridium cellulolyticum. The successful genetic induction of antibiotic biosynthesis in an anaerobe encourages further investigations of obligate anaerobes to tap their hidden biosynthetic potential. PMID:22854892

Behnken, Swantje; Hertweck, Christian



MICROBIOLOGY: Signaling Antibiotic Resistance in Staphylococci  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required: For 30 years biologists have studied the molecular machinery of staphylococcal bacteria that renders them resistant to b-lactam antibiotics. In a Perspective, Archer and Bosilevac discuss new findings showing that cleavage of a sensor-transducer protein after it binds to a b-lactam antibiotic results in cleavage of the repressor protein that binds to the blaZ gene. b-Lactamase is then produced and binds to and inactivates the antibiotic.

Gordon L. Archer (Medical College of Virginia/Commonwealth University; Departments of Medicine and Microbiology/Immunology)



In vitro Activity of cef pirome against Beta-Lactamase-lnducible and Stably Derepressed Enterobacteriaceae  

Microsoft Academic Search

Most members of the Enterobacteriaceae and Pseudomonas aeruginosa possess an inducible chromosomal class I ?-lactamase. Bacterial strains which produce high levels of ?-lactamase constitutively can be isolated from infections; these de-repressed mutants are responsible for resistance to third-generation cephalosporins and ureidopenicillins. Minimum inhibitory concentrations of cefpirome, a fourth-generation cephalosporin, and other ?-lactam antibiotics were determined for a series of mutants

Giovanni Bonfiglio; Stefania Stefani; Giuseppe Nicoletti



Risk factors for colonization and infection in a hospital outbreak caused by a strain of Klebsiella pneumoniae with reduced susceptibility to expanded-spectrum cephalosporins.  


Between February 2001 and January 2002, an increase in the number of Klebsiella pneumoniae isolates with reduced susceptibility to expanded-spectrum cephalosporins (RSKp) was detected in the neonatal unit of the Juan Canalejo Hospital, and 21 patients were either colonized or infected by the bacterial isolates. The current "gold standard" method for typing K. pneumoniae isolates is pulsed-field gel electrophoresis. However, this technique is expensive and time-consuming. In a search for faster and accurate alternatives to this method, we investigated PCR-based fingerprinting techniques (enterobacterial repetitive intergenic consensus sequence PCR [ERIC-PCR], repetitive extragenic palindromic sequence-based PCR [REP-PCR], and RAPD [randomly amplified polymorphic DNA]) for their ability to characterize K. pneumoniae isolates. The causal agent of the nosocomial outbreak was characterized by these techniques and was found to be a single epidemic strain (RSKp). A multiple regression logistic model was developed to identify potential independent factors associated with colonization and/or infection by RSKp. Logistic regression analysis was applied to all significant variables (P < 0.05) in the univariate analysis, and it was revealed that intubation (odds ratio [OR], 27.0; 95% confidence interval [95%CI], 5.39 to 135.14) and prematurity (OR, 4.4; 95%CI, 0.89 to 21.89) were such independent factors. Moreover, oxime cephalosporins did not appear to be statistically significant. Overall, the results showed that PCR-based techniques are expeditious and useful methods for typing K. pneumoniae isolates. Of the techniques studied, ERIC-PCR showed the highest discriminatory index (D = 0.828), followed by RAPD (D = 0.826) and REP-PCR (D = 0.773) PMID:15365018

Cartelle, Monica; del Mar Tomas, Maria; Pertega, Sonia; Beceiro, Alejandro; Dominguez, M Angeles; Velasco, David; Molina, Francisca; Villanueva, Rosa; Bou, German



Risk Factors for Colonization and Infection in a Hospital Outbreak Caused by a Strain of Klebsiella pneumoniae with Reduced Susceptibility to Expanded-Spectrum Cephalosporins  

PubMed Central

Between February 2001 and January 2002, an increase in the number of Klebsiella pneumoniae isolates with reduced susceptibility to expanded-spectrum cephalosporins (RSKp) was detected in the neonatal unit of the Juan Canalejo Hospital, and 21 patients were either colonized or infected by the bacterial isolates. The current “gold standard” method for typing K. pneumoniae isolates is pulsed-field gel electrophoresis. However, this technique is expensive and time-consuming. In a search for faster and accurate alternatives to this method, we investigated PCR-based fingerprinting techniques (enterobacterial repetitive intergenic consensus sequence PCR [ERIC-PCR], repetitive extragenic palindromic sequence-based PCR [REP-PCR], and RAPD [randomly amplified polymorphic DNA]) for their ability to characterize K. pneumoniae isolates. The causal agent of the nosocomial outbreak was characterized by these techniques and was found to be a single epidemic strain (RSKp). A multiple regression logistic model was developed to identify potential independent factors associated with colonization and/or infection by RSKp. Logistic regression analysis was applied to all significant variables (P < 0.05) in the univariate analysis, and it was revealed that intubation (odds ratio [OR], 27.0; 95% confidence interval [95%CI], 5.39 to 135.14) and prematurity (OR, 4.4; 95%CI, 0.89 to 21.89) were such independent factors. Moreover, oxime cephalosporins did not appear to be statistically significant. Overall, the results showed that PCR-based techniques are expeditious and useful methods for typing K. pneumoniae isolates. Of the techniques studied, ERIC-PCR showed the highest discriminatory index (D = 0.828), followed by RAPD (D = 0.826) and REP-PCR (D = 0.773) PMID:15365018

Cartelle, Monica; del Mar Tomas, Maria; Pertega, Sonia; Beceiro, Alejandro; Dominguez, M. Angeles; Velasco, David; Molina, Francisca; Villanueva, Rosa; Bou, German



Antibiotics Against Plant Disease: VIII. Screening for Nonpolyenic Antifungal Antibiotics Produced by Streptomycetes.  


In a survey of Streptomyces species, methods were designed and followed that would specifically select strains capable of producing heat-stable, nonpolyenic, antifungal antibiotics. Of 500 strains grown in shaken flasks, 240 of the culture liquors contained active factors as demonstrated by paper-disc assay against Mucor ramannianus. Culture filtrates and mycelial extracts of the active strains were examined by ultraviolet spectrophotometry; 166 were nonpolyenic as determined by absorption spectra. Heat-stability tests of the nonpolyenic antibiotics over a broad pH range revealed that 15 were stable under all test conditions, 70 moderately stable, and 81 unstable. Culture liquors containing stable, nonpolyenic antifungal agents were chromatographed with eight solvent systems in an attempt to identify the antibiotics. The producing cultures were studied by cross-antagonism tests to discover similarities with producers of known antibacterial antibiotics. Two of the antibiotics produced by promising strains were identified as cycloheximide and musarin. Six antibiotics, presumably new, were detected. PMID:16349649

Lindenfelser, L A; Shotwell, O L; Bachler, M J; Shannon, G M; Pridham, T G



Antibiotics, Bacteria, and Antibiotic Resistance Genes: Aerial Transport from Cattle Feed Yards via Particulate Matter  

PubMed Central

Background: Emergence and spread of antibiotic resistance has become a global health threat and is often linked with overuse and misuse of clinical and veterinary chemotherapeutic agents. Modern industrial-scale animal feeding operations rely extensively on veterinary pharmaceuticals, including antibiotics, to augment animal growth. Following excretion, antibiotics are transported through the environment via runoff, leaching, and land application of manure; however, airborne transport from feed yards has not been characterized. Objectives: The goal of this study was to determine the extent to which antibiotics, antibiotic resistance genes (ARG), and ruminant-associated microbes are aerially dispersed via particulate matter (PM) derived from large-scale beef cattle feed yards. Methods: PM was collected downwind and upwind of 10 beef cattle feed yards. After extraction from PM, five veterinary antibiotics were quantified via high-performance liquid chromatography with tandem mass spectrometry, ARG were quantified via targeted quantitative polymerase chain reaction, and microbial community diversity was analyzed via 16S rRNA amplification and sequencing. Results: Airborne PM derived from feed yards facilitated dispersal of several veterinary antibiotics, as well as microbial communities containing ARG. Concentrations of several antibiotics in airborne PM immediately downwind of feed yards ranged from 0.5 to 4.6 ?g/g of PM. Microbial communities of PM collected downwind of feed yards were enriched with ruminant-associated taxa and were distinct when compared to upwind PM assemblages. Furthermore, genes encoding resistance to tetracycline antibiotics were significantly more abundant in PM collected downwind of feed yards as compared to upwind. Conclusions: Wind-dispersed PM from feed yards harbors antibiotics, bacteria, and ARGs. Citation: McEachran AD, Blackwell BR, Hanson JD, Wooten KJ, Mayer GD, Cox SB, Smith PN. 2015. Antibiotics, bacteria, and antibiotic resistance genes: aerial transport from cattle feed yards via particulate matter. Environ Health Perspect 123:337–343;? PMID:25633846

McEachran, Andrew D.; Blackwell, Brett R.; Hanson, J. Delton; Wooten, Kimberly J.; Mayer, Gregory D.; Cox, Stephen B.



Abiotic degradation of antibiotic ionophores.  


Hydrolytic and photolytic degradation were investigated for the ionophore antibiotics lasalocid, monensin, salinomycin, and narasin. The hydrolysis study was carried out by dissolving the ionophores in solutions of pH 4, 7, and 9, followed by incubation at three temperatures of 6, 22, and 28 °C for maximum 34 days. Using LC-MS/MS for chemical analysis, lasalocid was not found to hydrolyse in any of the tested environments. Monensin, salinomycin, and narasin were all stable in neutral or alkaline solution but hydrolysed in the solution with a pH of 4. Half-lives at 25 °C were calculated to be 13, 0.6, and 0.7 days for monensin, salinomycin, and narasin, respectively. Absorbance spectra from each compound indicated that only lasalocid is degraded by photolysis (half-life below 1 h) due to an absorbance maximum around 303 nm, and monensin, salinomycin, and narasin are resistant to direct photolysis because they absorb light of environmentally irrelevant wavelengths. PMID:23917220

Bohn, Pernille; Bak, Søren A; Björklund, Erland; Krogh, Kristine A; Hansen, Martin



Suppression of methanogenesis for hydrogen production in single-chamber microbial electrolysis cells using various antibiotics.  


Methanogens can utilize the hydrogen produced in microbial electrolysis cells (MECs), thereby decreasing the hydrogen generation efficiency. However, various antibiotics have previously been shown to inhibit methanogenesis. In the present study antibiotics, including neomycin sulfate, 2-bromoethane sulfonate, 2-chloroethane sulfonate, 8-aza-hypoxanthine, were examined to determine if hydrogen production could be improved through inhibition of methanogenesis but not hydrogen production in MECs. 1.1mM neomycin sulfate inhibited both methane and hydrogen production while 2-chloroethane sulfonate (20mM), 2-bromoethane sulfonate (20mM), and 8-aza-hypoxanthine (3.6mM) can inhibited methane generation and with concurrent increases in hydrogen production. Our results indicated that adding select antibiotics to the mixed species community in MECs could be a suitable method to enhance hydrogen production efficiency. PMID:25841185

Catal, Tunc; Lesnik, Keaton Larson; Liu, Hong



Mechanisms of antibiotic resistance in enterococci.  


Multidrug-resistant (MDR) enterococci are important nosocomial pathogens and a growing clinical challenge. These organisms have developed resistance to virtually all antimicrobials currently used in clinical practice using a diverse number of genetic strategies. Due to this ability to recruit antibiotic resistance determinants, MDR enterococci display a wide repertoire of antibiotic resistance mechanisms including modification of drug targets, inactivation of therapeutic agents, overexpression of efflux pumps and a sophisticated cell envelope adaptive response that promotes survival in the human host and the nosocomial environment. MDR enterococci are well adapted to survive in the gastrointestinal tract and can become the dominant flora under antibiotic pressure, predisposing the severely ill and immunocompromised patient to invasive infections. A thorough understanding of the mechanisms underlying antibiotic resistance in enterococci is the first step for devising strategies to control the spread of these organisms and potentially establish novel therapeutic approaches. PMID:25199988

Miller, William R; Munita, Jose M; Arias, Cesar A



Aerosolized antibiotics in cystic fibrosis: an update.  


Inhaled antibiotic therapy, targeting Pseudomonas aeruginosa, is a fundamental component of cystic fibrosis (CF) management. Tobramycin inhalation solution (TIS) was approved in the United States (US) in 1998. Subsequent research efforts focused on developing products with a reduced treatment time burden. Aztreonam for inhalation solution (AZLI), administered via a more efficient nebulizer than TIS, was approved in the US in 2010. Dry powder for inhalation (DPI) formulations provide alternatives to nebulized therapy: tobramycin powder for inhalation (also known as TIP™) was approved in the US in 2013, and colistimethate sodium DPI received European approval in 2012. Other aerosolized antibiotics and regimens combining inhaled antibiotics are in development. Inhaled antibiotic rotation (e.g., TIS alternating with AZLI) is an important concept being actively tested in CF. PMID:24838090

Fiel, Stanley B



A Strategy for Fighting Antibiotic Resistance  

NSDL National Science Digital Library

The American Society for Microbiology posted this recent paper online, addressing the critical issue of how to fight antibiotic resistance. Several strategies to slow the development of resistance are presented.

Drlica, Karl.


Metagenomic exploration of antibiotic resistance in soil.  


The ongoing development of metagenomic approaches is providing the means to explore antibiotic resistance in nature and address questions that could not be answered previously with conventional culture-based strategies. The number of available environmental metagenomic sequence datasets is rapidly expanding and henceforth offer the ability to gain a more comprehensive understanding of antibiotic resistance at the global scale. Although there is now evidence that the environment constitutes a vast reservoir of antibiotic resistance gene determinants (ARGDs) and that the majority of ARGDs acquired by human pathogens may have an environmental origin, a better understanding of their diversity, prevalence and ecological significance may help predict the emergence and spreading of newly acquired resistances. Recent applications of metagenomic approaches to the study of ARGDs in natural environments such as soil should help overcome challenges concerning expanding antibiotic resistances. PMID:21601510

Monier, Jean-Michel; Demanèche, Sandrine; Delmont, Tom O; Mathieu, Alban; Vogel, Timothy M; Simonet, Pascal