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1

Transport of cefodizime, a novel third generation cephalosporin antibiotic, in isolated rat choroid plexus  

SciTech Connect

To characterize the transport system by which cephalosporin antibiotics are accumulated by the choroid plexus, kinetic analysis of cefodizime transport was performed. Accumulation of cefodizime was against an electrochemical potential gradient via a saturable process (Km = 470 microM, Vmax = 174 nmol/ml of tissue per min) that was inhibited by metabolic inhibitors (KCN and 2,4-dinitrophenol), hypothermia, a sulfhydryl reagent (p-hydroxymer-curibenzoic acid) and anion transport inhibitors (probenecid and 4,4'-diisothiocyanostilbene -2,2'-disulfonic acid). Accumulation of cefodizime was inhibited competitively by benzylpenicillin with an inhibition constant of aproximately 100 microM. Cefodizime inhibited competitively the accumulation of benzylpenicillin with an inhibition constant of approximately 500 microM. Kinetic analysis using 16 kinds of beta-lactam antibiotics also supported the view (1) that the transport system of cefodizime is shared by benzylpenicillin and (2) that these beta-lactam antibiotics are transported via a common transport system. These findings indicate that the major transport system of cephalosporin antibiotics in the rat choroid plexus is via a carrier-mediated active anion transport process. The affinity of beta-lactam antibiotics for this transport system in the choroid plexus may be a major factor in determining their pharmacokinetics in the cerebrospinal fluid.

Nohjoh, T.; Suzuki, H.; Sawada, Y.; Sugiyama, Y.; Iga, T.; Hanano, M.

1989-07-01

2

Community-acquired pneumonia: impact of empirical antibiotic therapy without respiratory fluoroquinolones nor third-generation cephalosporins.  

PubMed

Guidelines for inpatients with community-acquired pneumonia (CAP) propose to use respiratory fluoroquinolone (RFQ) and/or third-generation cephalosporins (Ceph-3). However, broad-spectrum antibiotic therapy is associated with the emergence of drug-resistant bacteria. We established a guideline in which RFQ and Ceph-3 were excluded as a first course. Our aim was to evaluate the impact of our therapeutic choices for CAP on the length of hospital stay (LOS) and patient outcome. This was a cohort study of patients with CAP from July 2005 to June 2014. We compared patients benefiting from our guideline established in 2008 to those receiving non-consensual antibiotics. Disease severity was evaluated through the Pneumonia Severity Index (PSI). The empirical treatment for PSI III to V was a combination therapy of amoxicillin-clavulanic acid (AMX-C)?+?roxithromycin (RX) or AMX?+?ofloxacin. Adherence to guidelines was defined by the prescription of one of these antibiotic agents. Requirement for intensive care or death defined unfavorable outcome. Among 1,370 patients, 847 were treated according to our guideline (61.8 %, group 1) and 523 without concordant therapy (38.2 %, group 2). The mean PSI was similar: 82 vs. 83, p?>?0.5. The mean LOS was lower in group 1: 7.6 days vs. 9.1 days, p?

Pradelli, J; Risso, K; de Salvador, F G; Cua, E; Ruimy, R; Roger, P-M

2014-10-01

3

CEPHALOSPORIN RESISTANCE AMONG BOVINE SALMONELLA ENTERICA SEROTYPES  

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...

4

In vitro activity of cefquinome, a new cephalosporin, compared with other cephalosporin antibiotics.  

PubMed

The in vitro activity of cefquinome, a new aminothiazolyl cephalosporin with a C-3 bicyclic pyridinium group, was compared with ceftazidime, cefpirome, and cefepime. Cefquinome inhibited members of the Enterobacteriaceae at less than or equal to 0.5 microgram/ml for Escherichia coli, Klebsiella pneumoniae, K. oxytoca, Citrobacter diversus, Salmonella Shigella, Proteus mirabilis, Morganella, and Providencia. Although most Citrobacter freundii and Enterobacter cloacae were inhibited by less than 2 micrograms/ml, some strains resistant to ceftazidime were resistant, [minimum inhibitory concentration (MIC) greater than 16 micrograms/ml]. Serratia marcescens were inhibited by less than 1 microgram/ml and Pseudomonas aeruginosa by 8 micrograms/ml similar to the activity of cefepime. The majority of Haemophilus influenzae and Neisseria gonorrhoeae were inhibited by less than 0.25 microgram/ml. Most enterococci had cefquinome MICs of 4-8 micrograms/ml. Cefquinome was extremely active against group-A streptococci and Streptococcus pneumoniae with MICs less than 0.12 microgram/ml. 90% of methicillin-susceptible Staphylococcus aureus 90% were inhibited by 2 micrograms/ml. Overall, the in vitro activity of cefquinome was comparable with aminothiazolyl cephalosporins. It inhibited some Enterobacter and Citrobacter freundii resistant to ceftazidime as did cefpirome and cefepime. Cefquinome was not destroyed by the common plasmid beta-lactamases TEM-1, TEM-2, SHV-1, or by the chromosomal beta-lactamases of Klebsiella, Branhamella, and Pseudomonas, but it was hydrolyzed by TEM-3, TEM-5, and TEM-9. Its activity was not adversely decreased in different medium or protein, and minimum bactericidal concentrations (MBCs) for most species except for Enterobacter were within a dilution of MICs. PMID:1611848

Chin, N X; Gu, J W; Fang, W; Neu, H C

1992-01-01

5

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

PubMed

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

1990-04-01

6

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

PubMed

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

2014-07-01

7

Forecasting cephalosporin and monobactam antibiotic half-lives in humans from data collected in laboratory animals.  

PubMed Central

The postdistribution half-lives of 10 cephalosporin and 2 monobactam antibiotics in humans were predicted from data obtained in other mammals. This forecasting was accomplished with the allometric equation t1/2 = aWb, where a is the y intercept and b is the slope obtained from the log-log plot of antibiotic half-life (t1/2) versus body weight (W). Dimensionless similarity criteria were used to produce a biological clock for ceftizoxime elimination. The creation of the biological clock, which measured physiologic time (heartbeats) rather than chronologic time (minutes), demonstrated that ceftizoxime half-life was identical in five mammals. This methodology will contribute to infectious disease research through a greater understanding of pharmacokinetic scaling in mammals. PMID:3927836

Mordenti, J

1985-01-01

8

Determination of cephalosporin antibiotics in water samples by optimised solid phase extraction and high performance liquid chromatography with ultraviolet detector  

Microsoft Academic Search

A reliable and robust analytical method based on solid phase extraction (SPE) and high performance liquid chromatography (HPLC) with ultraviolet (UV) detector was developed for the simultaneous determination of five cephalosporin antibiotics (Ceftazidime, Cefradine, Cefaclor, Cefotaxime and Cefoperazone) in various water samples. Under optimised conditions, it was applicable to preconcentrate up to 500?ml of water samples in the OASIS HLB

Penghua Wang; Tao Yuan; Jiangyong Hu; Youming Tan

2011-01-01

9

Environmental fate of ceftiofur sodium, a cephalosporin antibiotic. Role of animal excreta in its decomposition  

SciTech Connect

The degradation of ceftiofur sodium, a wide-spectrum cephalosporin antibiotic, was studied in the urine and feces of cattle, in three soils, and in buffers of pH 5, 7, and 9. Photodegradation was also studied. Fortification of cattle feces with ({sup 14}C)ceftiofur showed that it was quickly degraded to microbiologically inactive metabolites. Sterilization of the cattle feces inhibited the degradation of ceftiofur, which suggests that microorganisms or heat-labile substances may be responsible for the degradation. The t{sub 1/2} values of aerobic degradation of ceftiofur sodium in California, Florida, and Wisconsin soil were found to be 22.2, 49.0, and 41.4 days, respectively. Hydrolysis of ceftiofur, as measured by either HPLC or microbiological methods, was accelerated by increasing pH. The t{sub 1/2} values at pH 5, 7, and 9 were 100.3, 8.0, and 4.2 days, respectively, at 22{degree}C and dramatically increased at 47{degree}C. The photodegradation of ceftiofur, as determined by HPLC and a microbiological method, showed that after initial degradation for several days the rate of degradation was minimal, probably due to a protective film formed from degradation products. A major role for feces in the degradation of ceftiofur was observed, although other pathways of degradation such as soil, light, and water were also important.

Gilbertson, T.J.; Hornish, R.E.; Jaglan, P.S.; Koshy, K.T.; Nappier, J.L.; Stahl, G.L.; Cazers, A.R.; Nappier, J.M.; Kubicek, M.F.; Hoffman, G.A.; Hamlow, P.J. (Upjohn Co., Kalamazoo, MI (USA))

1990-03-01

10

Optimization of anti-pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: II. cephalosporins and penicillins.  

PubMed

Acute pulmonary exacerbations (APE) are well-described complications of cystic fibrosis (CF) and are associated with progressive morbidity and mortality. Despite aggressive management with two or more intravenous anti-pseudomonal agents, approximately 25% of exacerbations will result in a loss of lung function. The aim of this review is to provide an evidence-based summary of pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies utilizing anti-pseudomonal cephalosporins (i.e., ceftazidime and cefepime) and penicillins (i.e., piperacillin-tazobactam and ticarcillin-clavulanate) in the treatment of APE and to identify areas where further study is warranted. The ceftazidime and cefepime dosing ranges from the literature are 200-400?mg/kg/day divided every 6-8?hr, maximum 8-12?g/day, and 150-200?mg/kg/day divided every 6-8?hr, up to 6-8?g/day, respectively. The literature supported dosing ranges for piperacillin and ticarcillin are 350-600?mg/kg/day divided every 4?hr, maximum 18-24?g/day of piperacillin component, and 400-750?mg/kg/day divided every 6?hr, up to 24-30?g/day of ticarcillin component, respectively. As a large portion of CF patients will not regain their lung function following an APE, we suggest the need to optimize antibiotic dosing and dosing regimens used to treat an APE in efforts to improve outcomes for CF patients infected with Pseudomonas aeruginosa. Future studies are needed to determine the clinical efficacy of higher than FDA-approved doses of ceftazidime, cefepime, and ticarcillin-clavulanate in APE. The usefulness of high dose piperacillin (>600?mg/kg/day) may be limited due to treatment-related adverse effects. Further understanding of these adverse effects in CF patients is needed. PMID:22949297

Zobell, Jeffery T; Waters, C Dustin; Young, David C; Stockmann, Chris; Ampofo, Krow; Sherwin, Catherine M T; Spigarelli, Michael G

2013-02-01

11

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

PubMed

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

2015-03-01

12

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

PubMed

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

2012-09-24

13

The intramammary efficacy of first generation cephalosporins against Staphylococcus aureus mastitis in mice.  

PubMed

Staphylococcus aureus-induced mastitis in cattle causes important financial losses in the dairy industry due to lower yield and bad milk quality. Although S. aureus is susceptible to many antimicrobials in vitro, treatment often fails to cure the infected udder. Hence, comprehensive evaluation of antimicrobials against S. aureus mastitis is desirable to direct treatment strategies. The mouse mastitis model is an elegant tool to evaluate antimicrobials in vivo while circumventing the high costs associated with bovine experiments. An evaluation of the antimicrobial efficacy of the intramammary (imam) applied first generation cephalosporins cefalexin, cefalonium, cefapirin and cefazolin, was performed using the S. aureus mouse mastitis model. In vivo determination of the effective dose 2log(10) (ED(2log10)), ED(4log10), protective dose 50 (PD(50)) and PD(100) in mouse mastitis studies, support that in vitro MIC data of the cephalosporins did not fully concur with the in vivo clinical outcome. Cefazolin was shown to be the most efficacious first generation cephalosporin to treat S. aureus mastitis whereas the MIC data indicate that cefalonium and cefapirin were more active in vitro. Changing the excipient for imam application from mineral oil to miglyol 812 further improved the antimicrobial efficacy of cefazolin, confirming that the excipient can influence the in vivo efficacy. Additionally, statistical analysis of the variation of S. aureus-infected, excipient-treated mice from fourteen studies emphasizes the strength of the mouse mastitis model as a fast, cost-effective and highly reproducible screening tool to assess the efficacy of antimicrobial compounds against intramammary S. aureus infection. PMID:22677480

Demon, Dieter; Ludwig, Carolin; Breyne, Koen; Guédé, David; Dörner, Julia-Charlotte; Froyman, Robrecht; Meyer, Evelyne

2012-11-01

14

Association of Veterinary Third-Generation Cephalosporin Use with the Risk of Emergence of Extended-Spectrum-Cephalosporin Resistance in Escherichia coli from Dairy Cattle in Japan  

PubMed Central

The use of extended-spectrum cephalosporins in food animals has been suggested to increase the risk of spread of Enterobacteriaceae carrying extended-spectrum ?-lactamases to humans. However, evidence that selection of extended-spectrum cephalosporin–resistant bacteria owing to the actual veterinary use of these drugs according to criteria established in cattle has not been demonstrated. In this study, we investigated the natural occurrence of cephalosporin-resistant Escherichia coli in dairy cattle following clinical application of ceftiofur. E. coli isolates were obtained from rectal samples of treated and untreated cattle (n?=?20/group) cultured on deoxycholate-hydrogen sulfide-lactose agar in the presence or absence of ceftiofur. Eleven cefazoline-resistant isolates were obtained from two of the ceftiofur-treated cattle; no cefazoline-resistant isolates were found in untreated cattle. The cefazoline-resistant isolates had mutations in the chromosomal ampC promoter region and remained susceptible to ceftiofur. Eighteen extended-spectrum cephalosporin–resistant isolates from two ceftiofur-treated cows were obtained on ceftiofur-supplemented agar; no extended-spectrum cephalosporin–resistant isolates were obtained from untreated cattle. These extended-spectrum cephalosporin–resistant isolates possessed plasmid-mediated ?-lactamase genes, including blaCTX-M-2 (9 isolates), blaCTX-M-14 (8 isolates), or blaCMY-2 (1 isolate); isolates possessing blaCTX-M-2 and blaCTX-M-14 were clonally related. These genes were located on self-transmissible plasmids. Our results suggest that appropriate veterinary use of ceftiofur did not trigger growth extended-spectrum cephalosporin–resistant E. coli in the bovine rectal flora; however, ceftiofur selection in vitro suggested that additional ceftiofur exposure enhanced selection for specific extended-spectrum cephalosporin–resistant ?-lactamase-expressing E. coli clones PMID:24755996

Sato, Toyotaka; Okubo, Torahiko; Usui, Masaru; Yokota, Shin-ichi; Izumiyama, Satoshi; Tamura, Yutaka

2014-01-01

15

Association of veterinary third-generation cephalosporin use with the risk of emergence of extended-spectrum-cephalosporin resistance in Escherichia coli from dairy cattle in Japan.  

PubMed

The use of extended-spectrum cephalosporins in food animals has been suggested to increase the risk of spread of Enterobacteriaceae carrying extended-spectrum ?-lactamases to humans. However, evidence that selection of extended-spectrum cephalosporin-resistant bacteria owing to the actual veterinary use of these drugs according to criteria established in cattle has not been demonstrated. In this study, we investigated the natural occurrence of cephalosporin-resistant Escherichia coli in dairy cattle following clinical application of ceftiofur. E. coli isolates were obtained from rectal samples of treated and untreated cattle (n?=?20/group) cultured on deoxycholate-hydrogen sulfide-lactose agar in the presence or absence of ceftiofur. Eleven cefazoline-resistant isolates were obtained from two of the ceftiofur-treated cattle; no cefazoline-resistant isolates were found in untreated cattle. The cefazoline-resistant isolates had mutations in the chromosomal ampC promoter region and remained susceptible to ceftiofur. Eighteen extended-spectrum cephalosporin-resistant isolates from two ceftiofur-treated cows were obtained on ceftiofur-supplemented agar; no extended-spectrum cephalosporin-resistant isolates were obtained from untreated cattle. These extended-spectrum cephalosporin-resistant isolates possessed plasmid-mediated ?-lactamase genes, including bla(CTX-M-2) (9 isolates), bla(CTX-M-14) (8 isolates), or bla(CMY-2) (1 isolate); isolates possessing bla(CTX-M-2) and bla(CTX-M-14) were clonally related. These genes were located on self-transmissible plasmids. Our results suggest that appropriate veterinary use of ceftiofur did not trigger growth extended-spectrum cephalosporin-resistant E. coli in the bovine rectal flora; however, ceftiofur selection in vitro suggested that additional ceftiofur exposure enhanced selection for specific extended-spectrum cephalosporin-resistant ?-lactamase-expressing E. coli clones. PMID:24755996

Sato, Toyotaka; Okubo, Torahiko; Usui, Masaru; Yokota, Shin-Ichi; Izumiyama, Satoshi; Tamura, Yutaka

2014-01-01

16

Cephalosporins in veterinary medicine - ceftiofur use in food animals.  

PubMed

Cephalosporins are an important class of antibacterial agents in use today for both humans and animals. Four generations of cephalosporins have evolved, all of which contain the beta-lactam sub-structure first found in penicillin. The range of cephalosporins available for use in food-producing animals, which is the subject of this review, is limited compared to humans. A few first- and second-generation cephalosporins are approved worldwide strictly for treatment of mastitis infections in dairy cattle. A third-generation cephalosporin, ceftiofur, and a fourth-generation cephalosporin, cefquinome, have been developed strictly for veterinary use. Cefquinome has been approved in several countries for the treatment of respiratory disease in cattle and swine, foot rot in cattle and for mastitis in dairy cattle. Ceftiofur has worldwide approvals for respiratory disease in swine, ruminants (cattle, sheep and goats) and horses and has also been approved for foot rot and metritis infections in cattle. Ceftiofur has also been approved in various countries for early mortality infections in day-old chicks and turkey poults. This review summarizes cephalosporin use in general terms, and provides an overview of ceftiofur, in terms of its spectrum of activity, indications, metabolism, and degradation in the environment. The safety of ceftiofur is also reviewed, with respect to food-animal residues, rapid metabolism and degradation, and non-persistence of ceftiofur in the environment. The environmental fragility of cephalosporins have not been explored generally, but may be an important characteristic of this antibiotic class with respect to safety of use in animals. PMID:12052187

Hornish, Rex E; Kotarski, Susan F

2002-07-01

17

The Presence of Urinary Nitrites Is a Significant Predictor of Pediatric Urinary Tract Infection Susceptibility to First and Third-Generation Cephalosporins  

Microsoft Academic Search

Background: Previous studies in adults have refuted the use of nitrites as a predictor of bacterial resistance to both trimethoprim-sulfamethoxazole and cephalosporins. Some centers now consider first-line outpatient therapy with an oral third-generation cephalosporin appropriate for young children. Objective: The objective of this study was to determine if nitrite-negative pediatric urinary tract infections (UTIs) were more likely than nitrite-positive UTIs

Dany Weisz; Jamie A. Seabrook; Rodrick K. Lim

2010-01-01

18

Study on gamma and electron beam sterilization of third generation cephalosporins cefdinir and cefixime in solid state  

NASA Astrophysics Data System (ADS)

The effect of gamma radiation from 60Co source and 2 MeV e-beam was studied on two thermolabile cephalosporin antibiotics viz cefdinir and cefixime in solid state. The parameters studied to assess radiolytic degradation were loss of chemical and microbiological potency, change in optical rotation, electronic and vibrational absorption characteristics, thermal behavior and color modification. ESR spectroscopic study, HPLC related impurity profile, thermogram and Raman spectrum are applied in deducing the nature of radiolytic impurities and their formation hypotheses. Cefixime is radiation sensitive, whereas cefdinir has acceptable radiation resistance at 25 kGy dose. The nature of radiolytic related impurities and their concentrations indicates that the lactam ring is not highly susceptible to direct radiation attack, which otherwise is considered very sensitive to stress (thermal, chemical and photochemical).

Singh, Babita K.; Parwate, Dilip V.; Das Sarma, Indrani B.; Shukla, Sudhir K.

2010-10-01

19

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...

20

Analysis of Salmonella enterica with reduced susceptibility to the third-generation cephalosporin ceftriaxone isolated from U.S. cattle during 2000-2004.  

PubMed

Over the past decade enteric bacteria in Europe, Africa, and Asia have become increasingly resistant to cephalosporin antimicrobial agents. This is largely due to the spread of genes encoding extended-spectrum beta-lactamase (ESBL) enzymes that can inactivate many cephalosporins. Recently, these resistance mechanisms have been identified in Salmonella isolated from humans in the United States. Due to the potential for transmission of resistant bacteria to humans via food animals, Salmonella animal isolates were monitored for ESBL production. During 2000-2004, Salmonella cattle slaughter isolates (n = 3,984) were tested, and 97 (2.4%) of these were found to have decreased susceptibility (minimum inhibitory concentration [MIC] >32 microg/ml) to the third-generation cephalosporin ceftriaxone. The majority of these were serotypes Newport (58) and Agona (14), some of which were genetically indistinguishable by pulsed field gel electrophoresis (PFGE) analysis. None of the isolates had an ESBL phenotype; all were susceptible to the fourth-generation cephalosporins cefepime and cefquinome. PCR and sequence analysis for resistance genes detected the bla(CMY-2) gene in 93 isolates and the bla(TEM-1) gene in 12 isolates; however, neither gene encodes an ESBL. These data indicate that bovine Salmonella isolates from the United States with decreased susceptibility or resistance to ceftriaxone do not exhibit an ESBL phenotype and most contain the bla(CMY-2) gene. PMID:19025468

Frye, Jonathan G; Fedorka-Cray, Paula J; Jackson, Charlene R; Rose, Markus

2008-12-01

21

Pharmacodynamics of TD-1792, a Novel Glycopeptide-Cephalosporin Heterodimer Antibiotic Used against Gram-Positive Bacteria, in a Neutropenic Murine Thigh Model  

PubMed Central

TD-1792 is a novel glycopeptide-cephalosporin heterodimer investigational antibiotic that displays potent bactericidal effects against clinically relevant Gram-positive organisms in vitro. The present studies evaluated the in vivo pharmacokinetics (PK) and pharmacodynamics (PD) of TD-1792 in the neutropenic murine thigh infection animal model. TD-1792, dosed subcutaneously (SC), produced dose-dependent reduction in the thigh bacterial burden of several organisms, including methicillin-susceptible and -resistant strains of Staphylococcus aureus and Staphylococcus epidermidis (MSSA, MRSA, MSSE, MRSE, respectively), penicillin-susceptible strains of Streptococcus pneumoniae (PSSP), Streptococcus pyogenes, and vancomycin-intermediate-susceptible Staphylococcus aureus (VISA). In single-dose efficacy studies, the 1-log10 CFU kill effective dose (ED1-log kill) estimates for TD-1792 ranged from 0.049 to 2.55 mg/kg of body weight administered SC, and the bacterial burden was reduced by up to 3 log10 CFU/g from pretreatment values. Against S. aureus ATCC 33591 (MRSA), the total 24-h log10 stasis dose (EDstasis) and ED1-logkill doses for TD-1792 were 0.53 and 1.11 mg/kg/24 h, respectively, compared to 23.4 and 54.6 mg/kg/24 h for vancomycin, indicating that TD-1762 is 44- to 49-fold more potent than vancomycin. PK-PD analysis of data from single-dose and dose-fractionation studies for MRSA (ATCC 33591) demonstrated that the total-drug 24-h area under the concentration-time curve-to-MIC ratio (AUC/MIC ratio) was the best predictor of efficacy (r2 = 0.826) compared to total-drug maximum plasma concentration of drug-to-MIC ratio (Cmax/MIC ratio; r2 = 0.715) and percent time that the total-drug plasma drug concentration remains above the MIC (%Time>MIC; r2 = 0.749). The magnitudes of the total-drug AUC/MIC ratios associated with net bacterial stasis, a 1-log10 CFU reduction from baseline and near maximal effect, were 21.1, 37.2, and 51.8, respectively. PK-PD targets based on such data represent useful inputs for analyses to support dose selection decisions for clinical studies of patients. PMID:22155835

Okusanya, Olanrewaju O.; Skinner, Robert; Shaw, Jeng-Pyng; Obedencio, Glenmar; Ambrose, Paul G.; Blais, Johanne; Bhavnani, Sujata M.

2012-01-01

22

Antibiotic Sensitivity Profiles Determined with an Escherichia coli Gene Knockout Collection: Generating an Antibiotic Bar Code ? †  

PubMed Central

We have defined a sensitivity profile for 22 antibiotics by extending previous work testing the entire KEIO collection of close to 4,000 single-gene knockouts in Escherichia coli for increased susceptibility to 1 of 14 different antibiotics (ciprofloxacin, rifampin [rifampicin], vancomycin, ampicillin, sulfamethoxazole, gentamicin, metronidazole, streptomycin, fusidic acid, tetracycline, chloramphenicol, nitrofurantoin, erythromycin, and triclosan). We screened one or more subinhibitory concentrations of each antibiotic, generating more than 80,000 data points and allowing a reduction of the entire collection to a set of 283 strains that display significantly increased sensitivity to at least one of the antibiotics. We used this reduced set of strains to determine a profile for eight additional antibiotics (spectinomycin, cephradine, aztreonem, colistin, neomycin, enoxacin, tobramycin, and cefoxitin). The profiles for the 22 antibiotics represent a growing catalog of sensitivity fingerprints that can be separated into two components, multidrug-resistant mutants and those mutants that confer relatively specific sensitivity to the antibiotic or type of antibiotic tested. The latter group can be represented by a set of 20 to 60 strains that can be used for the rapid typing of antibiotics by generating a virtual bar code readout of the specific sensitivities. Taken together, these data reveal the complexity of intrinsic resistance and provide additional targets for the design of codrugs (or combinations of drugs) that potentiate existing antibiotics. PMID:20065048

Liu, Anne; Tran, Lillian; Becket, Elinne; Lee, Kim; Chinn, Laney; Park, Eunice; Tran, Katherine; Miller, Jeffrey H.

2010-01-01

23

Antibiotic consumption and antibiotic stewardship in Swedish hospitals  

PubMed Central

Background The aim of this paper was to describe and analyze the effect of antibiotic policy changes on antibiotic consumption in Swedish hospitals and to review antibiotic stewardship in Swedish hospitals. Results The main findings were: 1) Antibiotic consumption has significantly increased in Swedish hospitals over the last decade. The consumption of cephalosporins has decreased, whereas that of most other drugs including piperacillin-tazobactam, carbapenems, and penicillinase-sensitive and -resistant penicillins has increased and replaced cephalosporins. 2) Invasive infections caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae have increased, but the proportion of pathogens resistant to third-generation cephalosporins causing invasive infections is still very low in a European and international perspective. Furthermore, the following gaps in knowledge were identified: 1) lack of national, regional, and local data on the incidence of antibiotic resistance among bacteria causing hospital-acquired infections e.g. bloodstream infections and hospital-acquired pneumonia—data on which standard treatment guidelines should be based; 2) lack of data on the incidence of Clostridium difficile infections and the effect of change of antibiotic policies on the incidence of C. difficile infections and infections caused by antibiotic-resistant pathogens; and 3) lack of prospective surveillance programs regarding appropriate antibiotic treatment, including selection of optimal antimicrobial drug regimens, dosage, duration of therapy, and adverse ecological effects such as increases in C. difficile infections and emergence of antibiotic-resistant pathogens. Conclusions Evidence-based actions to improve antibiotic use and to slow down the problem of antibiotic resistance need to be strengthened. The effect of such actions should be analyzed, and standard treatment guidelines should be continuously updated at national, regional, and local levels. PMID:24724823

Skoog, Gunilla; Ternhag, Anders; Giske, Christian G.

2014-01-01

24

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.

2011-01-01

25

Antibiotics  

MedlinePLUS

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 ...

26

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...

27

Production of Cephalosporin C by Paecilomyces persicinus P-10  

PubMed Central

After the growth of Paecilomyces persicinus P-10 in a glucose-peptone medium, filtrates were collected and analyzed for antibiotic antivity. Activities against Salmonella gallinarum ATCC 3030 and Alcaligenes faecalis ATCC 8750 (penicillin N-resistant strain) were obtained. Part of the former activity was readily inactivated by penicillinase. The fraction active against A. faecalis was isolated by passage through Amberlite XAD-2 and Amberlite IRA-68. The powder eventually obtained was subjected to paper chromatography followed by bioautography, and the activity obtained corresponded to that of a sample of cephalosporin C. Thin-layer chromatography was also employed to verify the presence of cephalosporin C in the P-10 powder. The active solids were further purified by means of paper chromatography in a solvent system consisting of n-butanol-acetic acid-water (60:15:25, vol/vol). The material obtained from this procedure yielded an infrared absorption spectrum identical to that of cephalosporin C. Similarly, the ultraviolet absorption of the purified preparation coincided with that of cephalosporin C. Exposure of the purified solids to cephalosporinase resulted in rapid inactivation of the antibiotic. In addition to penicillin N and cephalosporin C, filtrates of P. persicinus P-10 also contained deacetylcephalosporin C, deacetoxycephalosporin C, and cephalosporin P. PMID:4157343

Pisano, M. A.; Vellozzi, E. M.

1974-01-01

28

Recent Developments in Electroanalytical Chemistry of Cephalosporins and Cefamycins  

Microsoft Academic Search

Cephalosporins (I, R = H) and cefamycins (I, R = OCH3) are antibiotics with a broad spectrum of antimicrobial and antibacterial properties. These compounds contain a ?-lactam ring which is fused with a six-membered dihydrothiazine ring bearing substituents R and R in the side-chains at C-3 and C-7 (I)(Table I).

Petr Zuman; Vera Kapetanovi?; Mara Aleksi?

2000-01-01

29

Dissemination of cephalosporin resistance genes between Escherichia coli strains from farm animals and humans by specific plasmid lineages.  

PubMed

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 Been, Mark; Lanza, Val F; 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

2014-12-01

30

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

2014-01-01

31

Eradication of bacterial persisters with antibiotic-generated hydroxyl radicals.  

PubMed

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 capable of yielding a phenotypically antibiotic-tolerant subpopulation of cells, often called persisters, within populations of Mycobacterium smegmatis and M. tuberculosis. We find that persisters are distinct from the larger antibiotic-susceptible population, as a small drop in dissolved oxygen (DO) saturation (20%) allows for their survival in the face of bactericidal antibiotics. In contrast, if high levels of DO are maintained, all cells succumb, sterilizing the culture. With increasing evidence that bactericidal antibiotics induce cell death through the production of reactive oxygen species (ROS), we hypothesized that the drop in DO decreases the concentration of ROS, thereby facilitating persister survival, and maintenance of high DO yields sufficient ROS to kill persisters. Consistent with this hypothesis, the hydroxyl-radical scavenger thiourea, when added to M. smegmatis cultures maintained at high DO levels, rescues the persister population. Conversely, the antibiotic clofazimine, which increases ROS via an NADH-dependent redox cycling pathway, successfully eradicates the persister population. Recent work suggests that environmentally induced antibiotic tolerance of bulk populations may result from enhanced antioxidant capabilities. We now show that the small persister subpopulation within a larger antibiotic-susceptible population also shows differential susceptibility to antibiotic-induced hydroxyl radicals. Furthermore, we show that stimulating ROS production can eradicate persisters, thus providing a potential strategy to managing persistent infections. PMID:22778419

Grant, Sarah Schmidt; Kaufmann, Benjamin B; Chand, Nikhilesh S; Haseley, Nathan; Hung, Deborah T

2012-07-24

32

Do antibiotic residues in soils play a role in amplification and transmission of antibiotic resistant bacteria in cattle populations?  

PubMed Central

When we consider factors that contribute to the emergence, amplification, and persistence of antibiotic resistant bacteria, the conventional assumption is that antibiotic use is the primary driver in these processes and that selection occurs primarily in the patient or animal. Evidence suggests that this may not always be the case. Experimental trials show that parenteral administration of a third-generation cephalosporin (ceftiofur) in cattle has limited or short-term effects on the prevalence of ceftiofur-resistant bacteria in the gastrointestinal tract. While this response may be sufficient to explain a pattern of widespread resistance to cephalosporins, approximately two-thirds of ceftiofur metabolites are excreted in the urine raising the possibility that environmental selection plays an important additive role in the amplification and maintenance of antibiotic resistant E. coli on farms. Consequently, we present a rationale for an environmental selection hypothesis whereby excreted antibiotic residues such as ceftiofur are a significant contributor to the proliferation of antibiotic resistant bacteria in food animal systems. We also present a mathematical model of our hypothesized system as a guide for designing experiments to test this hypothesis. If supported for antibiotics such as ceftiofur, then there may be new approaches to combat the proliferation of antibiotic resistance beyond the prudent use mantra. PMID:23874327

Call, Douglas R.; Matthews, Louise; Subbiah, Murugan; Liu, Jinxin

2013-01-01

33

Outcome of Cephalosporin Treatment for Serious Infections Due to Apparently Susceptible Organisms Producing Extended-Spectrum b-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

DAVID L. PATERSON; WEN-CHIEN KO; ANNE VON GOTTBERG; JOSE MARIA CASELLAS; LUTFIYE MULAZIMOGLU; KEITH P. KLUGMAN; ROBERT A. BONOMO; LOUIS B. RICE; JOSEPH G. MCCORMACK; VICTOR L. YU

34

Azithromycin Resistance Is Coevolving with Reduced Susceptibility to Cephalosporins in Neisseria gonorrhoeae in Ontario, Canada  

PubMed Central

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 (AZMr) 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 AZMr isolates in Ontario, Canada. Nineteen AZMr 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 AZMr 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 AZMr 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 AZMr 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

2014-01-01

35

Oxidative Stress Enhances Cephalosporin Resistance of Enterococcus faecalis through Activation of a Two-Component Signaling System.  

PubMed

Enterococcus faecalis is a low-GC Gram-positive bacterium, a normal resident of the gastrointestinal (GI) tract, and an important hospital-acquired pathogen. An important risk factor for hospital-acquired enterococcal infections is prior therapy with broad-spectrum cephalosporins, antibiotics that impair cell wall biosynthesis by inhibiting peptidoglycan cross-linking. Enterococci are intrinsically resistant to cephalosporins; however, environmental factors that modulate cephalosporin resistance have not been described. While searching for the genetic determinants of cephalosporin resistance in E. faecalis, we unexpectedly discovered that oxidative stress, whether from external sources or derived from endogenous metabolism, drives enhanced intrinsic resistance to cephalosporins. A particular source of oxidative stress, H2O2, activates signaling through the CroR-CroS two-component signaling system, a known determinant of cephalosporin resistance in E. faecalis. We find that CroR-CroS is required for adaptation to H2O2 stress and that H2O2 potentiates the activities of cephalosporins against E. faecalis when the CroR-CroS signaling system is nonfunctional. Rather than directly detecting H2O2, our data suggest that the CroR-CroS system responds to cell envelope damage caused by H2O2 exposure in order to promote cell envelope repair and enhanced cephalosporin resistance. PMID:25331701

Djori?, Dušanka; Kristich, Christopher J

2015-01-01

36

Kinetic spectrofluorimetric determination of certain cephalosporins in human plasma.  

PubMed

An accurate, reliable, specific and sensitive kinetic spectrofluorimetric method was developed for the determination of seven cephalosporin antibiotics namely cefotaxime sodium, cephapirin sodium, cephradine dihydrate, cephalexin monohydrate, cefazoline sodium, ceftriaxone sodium and cefuroxime sodium. The method is based on their degradation under an alkaline condition producing fluorescent products. The factors affecting the degradation and the determination were studied and optimized. The reaction is followed spectrofluorimetrically by measuring the rate of change of fluorescence intensity at specified emission wavelength. The initial rate and fixed time methods were used for the construction of calibration graphs to determine the concentration of the studied drugs. The calibration graphs are linear in the concentration ranges 0.2-1.2 microg mL(-1) and 0.2-2.2 microg mL(-1) using the initial rate and fixed time methods, respectively. The results were statistically validated and checked through recovery studies. The method has been successfully applied for the determination of the studied cephalosporins in commercial dosage forms. The high sensitivity of the proposed method allows the determination of investigated cephalosporins in human plasma. The statistical comparisons of the results with the reference methods show an excellent agreement and indicate no significant difference in accuracy and precision. PMID:19084655

Omar, Mahmoud A; Abdelmageed, Osama H; Attia, Tamer Z

2009-02-15

37

In silico analysis of different generation ? lactams antibiotics with penicillin binding protein-2 of Neisseria meningitidis for curing meningococcal disease.  

PubMed

Neisseria meningitidis is a gram negative, diplococcic pathogen responsible for the meningococcal disease and fulminant septicemia. Penicillin-binding proteins-2 (PBPs) is crucial for the cell wall biosynthesis during cell proliferation of N. meningitidis and these are the target for ?-lactam antibiotics. For many years penicillin has been recognized as the antibiotic for meningococcal disease but the meningococcus has seemed to be antibiotic resistance. In the present work we have verified the molecular interaction of Penicillin binding protein-2 N. meningitidis to different generation of ?-lactam antibiotics and concluded that the third generation of ?-lactam antibiotics shows efficient binding with Penicillin binding protein-2 of N. meningitidis. On the basis of binding efficiency and inhibition constant, ceftazidime emerged as the most efficient antibiotic amongst the other advanced ?-lactam antibiotics against Penicillin-binding protein-2 of N. meningitidis. PMID:25118647

Tripathi, Vijay; Tripathi, Pooja; Srivastava, Navita; Gupta, Dwijendra

2014-12-01

38

Understanding the patterns of antibiotic susceptibility of bacteria causing urinary tract infection in West Bengal, India.  

PubMed

Urinary tract infection (UTI) is one of the most common infectious diseases at the community level. In order to assess the adequacy of empirical therapy, the susceptibility of antibiotics and resistance pattern of bacteria responsible for UTI in West Bengal, India, were evaluated throughout the period of 2008-2013. The infection reports belonging to all age groups and both sexes were considered. Escherichia coli was the most abundant uropathogen with a prevalence rate of 67.1%, followed by Klebsiella spp. (22%) and Pseudomonas spp. (6%). Penicillin was least effective against UTI-causing E. coli and maximum susceptibility was recorded for the drugs belonging to fourth generation cephalosporins. Other abundant uropathogens, Klebsiella spp., were maximally resistant to broad-spectrum penicillin, followed by aminoglycosides and third generation cephalosporin. The antibiotic resistance pattern of two principal UTI pathogens, E. coli and Klebsiella spp. in West Bengal, appears in general to be similar to that found in other parts of the Globe. Higher than 50% resistance were observed for broad-spectrum penicillin. Fourth generation cephalosporin and macrolides seems to be the choice of drug in treating UTIs in Eastern India. Furthermore, improved maintenance of infection incident logs is needed in Eastern Indian hospitals in order to facilitate regular surveillance of the occurrence of antibiotic resistance patterns, since such levels continue to change. PMID:25278932

Saha, Sunayana; Nayak, Sridhara; Bhattacharyya, Indrani; Saha, Suman; Mandal, Amit K; Chakraborty, Subhanil; Bhattacharyya, Rabindranath; Chakraborty, Ranadhir; Franco, Octavio L; Mandal, Santi M; Basak, Amit

2014-01-01

39

Understanding the patterns of antibiotic susceptibility of bacteria causing urinary tract infection in West Bengal, India  

PubMed Central

Urinary tract infection (UTI) is one of the most common infectious diseases at the community level. In order to assess the adequacy of empirical therapy, the susceptibility of antibiotics and resistance pattern of bacteria responsible for UTI in West Bengal, India, were evaluated throughout the period of 2008–2013. The infection reports belonging to all age groups and both sexes were considered. Escherichia coli was the most abundant uropathogen with a prevalence rate of 67.1%, followed by Klebsiella spp. (22%) and Pseudomonas spp. (6%). Penicillin was least effective against UTI-causing E. coli and maximum susceptibility was recorded for the drugs belonging to fourth generation cephalosporins. Other abundant uropathogens, Klebsiella spp., were maximally resistant to broad-spectrum penicillin, followed by aminoglycosides and third generation cephalosporin. The antibiotic resistance pattern of two principal UTI pathogens, E. coli and Klebsiella spp. in West Bengal, appears in general to be similar to that found in other parts of the Globe. Higher than 50% resistance were observed for broad-spectrum penicillin. Fourth generation cephalosporin and macrolides seems to be the choice of drug in treating UTIs in Eastern India. Furthermore, improved maintenance of infection incident logs is needed in Eastern Indian hospitals in order to facilitate regular surveillance of the occurrence of antibiotic resistance patterns, since such levels continue to change. PMID:25278932

Saha, Sunayana; Nayak, Sridhara; Bhattacharyya, Indrani; Saha, Suman; Mandal, Amit K.; Chakraborty, Subhanil; Bhattacharyya, Rabindranath; Chakraborty, Ranadhir; Franco, Octavio L.; Mandal, Santi M.; Basak, Amit

2014-01-01

40

Cephalosporin and Aminoglycoside Concentrations in Peritoneal Capsular Fluid in Rabbits  

PubMed Central

To study the penetration of antibiotics into peritoneal tissue fluid, a subcutaneous tissue capsule model was modified by implanting multiple, perforated spherical capsules in the peritoneal cavity of rabbits. Capsules became vascularized, encased in connective tissue, and filled with fluid having a mean protein concentration of 3.6 g/100 ml. Capsular fluid was obtained by percutaneous needle aspiration and assayed for antibiotic by the disk plate bioassay technique. Cephalosporins were administered intramuscularly at a dose of 30 mg/kg. Mean peak concentrations of cephaloridine and cefazolin were significantly higher than cephalothin and cephapirin in capsular fluids, but the percent penetration (ratio of capsular mean peak to serum mean peak) ranged from 8.7 to 16.9% and was not significantly different among the cephalosporins. At 24 h the capsular concentration of cefazolin was significantly greater than for the other cephalosporins (P < 0.001). Lower rabbit serum protein binding observed at high in vivo concentrations may have enabled cefazolin to penetrate capsular fluid, but in vitro protein binding studies did not confirm a decrease in serum protein binding at high concentrations within the clinical range. Kanamycin and amikacin showed comparable capsular fluid peak concentrations as did gentamicin and tobramycin. The percent penetration ranged from 15.2 to 34.5% for the aminoglycosides. The only statistical difference was that amikacin penetration was significantly higher than that for tobramycin. Mean capsular concentrations of amikacin, cefazolin, and cephaloridine compared most favorably with the minimum inhibitory concentration of gram-negative bacilli at the dosages used in this study. Images PMID:1008548

Gerding, Dale N.; Hall, Wendell H.; Schierl, Elizabeth A.; Manion, Robert E.

1976-01-01

41

MurAA Is Required for Intrinsic Cephalosporin Resistance of Enterococcus faecalis  

PubMed Central

Enterococcus faecalis is a low-GC Gram-positive bacterium that is intrinsically resistant to cephalosporins, antibiotics that target cell wall biosynthesis. To probe the mechanistic basis for intrinsic resistance, a library of transposon mutants was screened to identify E. faecalis strains that are highly susceptible to ceftriaxone, revealing a transposon mutant with a disruption in murAA. murAA is predicted to encode a UDP-N-acetylglucosamine 1-carboxyvinyl transferase that catalyzes the first committed step in peptidoglycan synthesis: phosphoenolpyruvate (PEP)-dependent conversion of UDP-N-acetylglucosamine to UDP-N-acetylglucosamine-enolpyruvate. In-frame deletion of murAA, but not its homolog in the E. faecalis genome (murAB), led to increased susceptibility of E. faecalis to cephalosporins. Furthermore, expression of murAA enhanced cephalosporin resistance in an E. faecalis mutant lacking IreK (formerly PrkC), a key kinase required for cephalosporin resistance. Further genetic analysis revealed that MurAA catalytic activity is necessary but not sufficient for this role. Collectively, our data indicate that MurAA and MurAB have distinct roles in E. faecalis physiology and suggest that MurAA possesses a unique property or activity that enables it to enhance intrinsic resistance of E. faecalis to cephalosporins. PMID:22290954

Vesi?, Dušanka

2012-01-01

42

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

43

Antibiotic consumption and its influence on the resistance in Enterobacteriaceae  

PubMed Central

Background Increasing bacterial resistance to antibiotics is one of the most serious problems in current medicine. An important factor contributing to the growing prevalence of multiresistant bacteria is application of antibiotics. This study aimed at analyzing the development of resistance of Enterobacteriaceae to selected beta-lactam, fluoroquinolone and aminoglycoside antibiotics in the University Hospital Olomouc and assessing the effect of selection pressure of these antibiotics. Methods For the period between 1 January 2000 and 31 December 2011, resistance of Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae and Proteus mirabilis to third- and fourth-generation cephalosporins, meropenem, piperacillin/tazobactam, fluoroquinolones and aminoglycosides was retrospectively studied. For the assessment of selection pressure of antibiotics, a parameter of defined daily dose in absolute annual consumption (DDDatb) based on the ATC/DDD classification and in relative annual consumption (RDDDatb) as the number of defined daily doses per 100 bed-days was used. The relationship between frequency of strains resistant to a particular antibiotic and antibiotic consumption was assessed by linear regression analysis using Spearman’s correlation. The level of statistical significance was set at p?antibiotic in the following cases: piperacillin/tazobactam in Klebsiella pneumoniae, gentamicin in Klebsiella pneumoniae and Escherichia coli and amikacin in Escherichia coli and Enterobacter cloacae. Also, there was significant correlation between resistance to ceftazidime and consumption of piperacillin/tazobactam in Klebsiella pneumoniae and Escherichia coli. No relationship was found between consumption of third- and fourth-generation cephalosporins and resistance to ceftazidime or between fluoroquinolone consumption and resistance to ciprofloxacin. Conclusion The study showed the effects of both direct and indirect selection pressure on increasing resistance to gentamicin, amikacin, piperacillin/tazobactam and ceftazidime. Given the fact that no correlation was found between resistance to fluoroquinolones and consumption of either primary or secondary antibiotics, we assume that the increasing resistance to fluoroquinolones is probably due to circulation of resistance genes in the bacterial population and that this resistance was not affected by reduced use of these antibiotics. PMID:25027417

2014-01-01

44

Heteroresistance to cephalosporins and penicillins in Acinetobacter baumannii.  

PubMed

Heteroresistance to antimicrobial agents may affect susceptibility test results and therapeutic success. In this study, we investigated heteroresistance to cephalosporins and penicillins in Acinetobacter baumannii, a major pathogen causing nosocomial infections. Two A. baumannii isolates exhibited heteroresistance to ampicillin-sulbactam, ticarcillin-clavulanic acid, cefepime, and cefpirome, showing a distinct colony morphology of circular rings within the inhibition halos. Pulsed-field gel electrophoresis (PFGE) and outer membrane protein (OMP) analysis demonstrated that subpopulations around the disks/Etest strips and the original strains all belonged to the same PFGE type and OMP profile. Population analysis profile (PAP) showed the presence of heteroresistant subpopulations with high cefepime resistance levels in two isolates (008 and 328). Interestingly, A. baumannii 008 contained two peaks: one was grown in the presence of up to 1 ?g of cefepime/ml, the other apparently occurred when the concentration of cefepime was raised to 256 ?g/ml. After serial passages without exposure to cefepime, the PAP curve maintained the same trend observed for the original strain of A. baumannii 008. However, the PAP curve showed a shift to relatively lower cefepime resistance (from 256 to 64 ?g/ml) in A. baumannii 328 after 10 passages in antibiotic-free Mueller-Hinton agar plates. Convergence to a monotypic resistance phenotype did not occur. Growth rate analysis revealed that slower growth in resistant subpopulations may provide a strategy against antibiotic challenge. To our knowledge, this is the first report of heteroresistance to cephalosporins and penicillins in A. baumannii. PMID:22189112

Hung, Kuei-Hsiang; Wang, Ming-Cheng; Huang, Ay-Huey; Yan, Jing-Jou; Wu, Jiunn-Jong

2012-03-01

45

Antibiotic susceptibilities of bacteria isolated within the oral flora of Florida blacktip sharks: guidance for empiric antibiotic therapy.  

PubMed

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

2014-01-01

46

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.

2014-01-01

47

Ready for a world without antibiotics? The Pensičres 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 Pensičres 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

2012-01-01

48

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

PubMed

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 Pensičres 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

Carlet, Jean; Jarlier, Vincent; Harbarth, Stephan; Voss, Andreas; Goossens, Herman; Pittet, Didier

2012-01-01

49

[PCR rationale for use of oral cephalosporins by oral surgery procedures].  

PubMed

The article presents the experience of PCR detection of DNA of pathogenic germs inducing odontogenic inflammation. Pus samples of 48 patients aged 18 to 68 years undergoing oral surgery because of apical periodontal lesions and pericoronitis. The results showed microorganisms associations revealed by PCR are sensitive to III generation cephalosporins. Effective oral regimen included 400 mg Ceftibuten once daily. The PCR results thus served as a rationale for use of oral cephalosporins by oral surgery procedures proved by clinical and immunological data in postoperative period. PMID:25588340

Tsarev, V N; Chuvilkin, V I; Akhmedov, G D; Chuvilkina, E I; Gadzhiev, F N; Nikitin, I V

2014-01-01

50

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

1994-01-01

51

IN-VITRO SUSCEPTIBILITY OF ESCHERICHIA COLI ISOLATED FROM FECES OF US DAIRY CATTLE TO CEPHALOSPORINS  

Technology Transfer Automated Retrieval System (TEKTRAN)

Background: The objective of this study was to obtain baseline antimicrobial susceptibility data on E. coli isolated from feces of US dairy cows to the 4th generation cephalosporins (4-GC) cefquinome and cefepime. Cefquinome is licensed for therapeutic use in cattle and swine in Europe, and cefepime...

52

[Antibiotic-associated diarrhea].  

PubMed

The incidence of antibiotic-associated diarrhea (AAD) differs with the antibiotic and varies from 15 - 25 %. Most cases of AAD are directly or indirectly caused by alterations of gut microflora by the antibiotics resulting in clinically mild AAD cases due to functional disturbances of intestinal carbohydrate or bile acid metabolism. Alternatively, changes in the gut flora allow pathogens to proliferate. Clostridium difficile is responsible for 10 - 15 % of all cases of AAD and almost of all cases of antibiotic-associated pseudomembraneous colitis. There is also a growing body of evidence which supports the responsibility of Klebsiella oxytoca for the development of antibiotic-associated hemorrhagic colitis. Diagnosing Clostridium difficile-associated diarrhea should be based both on fecal-cytotoxin detection and culture. With respect to specific therapy, metronidazol has become the first choice whereas treatment with oral vancomycin should be reserved for patients who have contraindications or intolerance to or who have failed to respond to metronidazole. Probiotics such as Sacharomyces boulardii can reduce the risk of development. Restrictive antibiotic policies (e. g. restricting clindamycin and cephalosporins) and the implementation of a comprehensive hospital infection control have also been shown to be effective in reducing the incidence of AAD. PMID:16456762

Schröder, O; Gerhard, R; Stein, J

2006-02-01

53

Application of a capillary-assembled microfluidic system for separation of cephalosporins.  

PubMed

This paper demonstrates a simple and easy setting up of a fused-silica capillary-assembled microfluidic system (?CE). This system incorporates a split-flow pressure injection of the sample into a microfluidic system made from PDMS and a short (?20 cm) length of fused-silica capillary as a separation unit. The on-capillary detection was carried out by fiber optic spectrometry. A mixture of six cephalosporin antibiotics was separated in the ?CE system and the obtained results were compared to those achievable by conventional CE. The six components could be separated within 8.5 min with the number of theoretical plates around 10?000. PMID:24789628

Koczka, Peter I; Gaspar, Attila

2014-09-01

54

Pediatric Infection and Intestinal Carriage Due to Extended-Spectrum-Cephalosporin-Resistant Enterobacteriaceae  

PubMed Central

The objective of this study is to describe the epidemiology of intestinal carriage with extended-spectrum-cephalosporin-resistant Enterobacteriaceae in children with index infections with these organisms. Patients with resistant Escherichia coli or Klebsiella bacteria isolated from the urine or a normally sterile site between January 2006 and December 2010 were included in this study. Available infection and stool isolates underwent phenotypic and molecular characterization. Clinical data relevant to the infections were collected and analyzed. Overall, 105 patients were identified with 106 extended-spectrum-cephalosporin-resistant E. coli (n = 92) or Klebsiella (n = 14) strains isolated from urine or a sterile site. Among the 27 patients who also had stool screening for resistant Enterobacteriaceae, 17 (63%) had intestinal carriage lasting a median of 199 days (range, 62 to 1,576). There were no significant differences in demographic, clinical, and microbiological variables between those with and those without intestinal carriage. Eighteen (17%) patients had 37 subsequent resistant Enterobacteriaceae infections identified: 31 urine and 6 blood. In a multivariable analysis, antibiotic intake in the 91 days prior to subsequent urine culture was significantly associated with subsequent urinary tract infection with a resistant organism (hazard ratio, 14.3; 95% confidence interval [CI], 1.6 to 130.6). Intestinal carriage and reinfection were most commonly due to bacterial strains of the same sequence type and with the same resistance determinants as the index extended-spectrum-cephalosporin-resistant Enterobacteriaceae, but carriage and reinfection with different resistant Enterobacteriaceae strains also occurred. PMID:24798269

Qin, Xuan; Oron, Assaf P.; Adler, Amanda L.; Wolter, Daniel J.; Berry, Jessica E.; Hoffman, Lucas; Weissman, Scott J.

2014-01-01

55

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

2004-01-01

56

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

57

Evaluation of eight different cephalosporins for detection of cephalosporin resistance in Salmonella enterica and Escherichia coli.  

PubMed

This study evaluates the efficacy of eight different cephalosporins for detection of cephalosporin resistance mediated by extended spectrum beta-lactamases (ESBL) and plasmidic AmpC beta-lactamases in Salmonella and Escherichia coli. A total of 138 E. coli and 86 Salmonella isolates with known beta-lactamase genes were tested for susceptibility toward cefoperazone, cefotaxime, cefpodoxime, cefquinome, ceftazidime, ceftiofur, ceftriaxone, and cefuroxime using minimum inhibitory concentration determinations and disc diffusion. The collection consisted of 84 ampicillin-susceptible, 57 ampicillin-resistant but cephalosporin-susceptible, 56 ESBL isolates and 19 isolates with plasmidic AmpC, as well as 10 ampC hyper-producing E. coli. The minimum inhibitory concentration distributions and zone inhibitions varied with the tested compound. Ampicillin-resistant isolates showed reduced susceptibility to the cephalosporins compared to ampicillin-susceptible isolates. Cefoperazone, cefquinome, and cefuroxime were not useful in detecting isolates with ESBL or plasmidic AmpC. The best substances for detection were cefotaxime, cefpodoxime, and ceftriaxone, whereas ceftazidime and ceftiofur were not as efficient. Ceftriaxone may be the recommended substance for monitoring because of some ability in separating ampC hyper-producing E. coli from ESBL and plasmidic AmpC isolates. PMID:20624078

Aarestrup, Frank M; Hasman, Henrik; Veldman, Kees; Mevius, Dik

2010-12-01

58

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 Stĺlsby

2012-01-01

59

The environmental release and fate of antibiotics.  

PubMed

Antibiotics have been used as medical remedies for over 50 years and have recently emerged as new pollutants in the environment. This review encompasses the fate of several antibiotics in the environment, including sulfonamides, nitrofurans, terfenadines, cephalosporins and cyclosporins. It investigates the cycle of transfer from humans and animals including their metabolic transformation. The results show that antibiotic metabolites are of considerable persistence and are localized to ground-water and drinking water supplies. Furthermore, the results also show that several phases of the cycle of antibiotics in the environment are not well understood, such as how low concentrations of antibiotic metabolites in the diet affect humans and animals. This review also shows that improved wastewater decontamination processes are remediating factors for these emerging pollutants. The results obtained here may help legislators and authorities in understanding the fate and transformation of antibiotics in the environment. PMID:24456854

Manzetti, Sergio; Ghisi, Rossella

2014-02-15

60

Pharmacological aspects of the antibiotics used for urological diagnostic procedures.  

PubMed

Surgical antimicrobial prophylaxis is the use of an antibiotic before, during, or shortly after a urological procedure to prevent postoperative infections such as urinary tract or wound infection. The optimal antimicrobial drug must be microbiologically active against the most frequent potential pathogens and have good pharmacological properties. Correct timing of antimicrobial prophylaxis is the first critical issue in determining treatment efficacy. The antibiotic must be administered before the start of the surgical procedure in order to ensure a high tissue level at the time of microbial contamination. If using an oral antibiotic, this must be administered 1-3 hours before the operation and a parenteral antibiotic should be administered at the induction of anaesthesia. The antibiotics potentially useful for antimicrobial prophylaxis are the beta-lactams, cotrimoxazole, fluoroquinolones, and fosfomycin trometamol. The criteria for choosing the optimal antibiotic include an appropriate antimicrobial spectrum, favourable pharmacokinetic parameters (especially good tissue penetration), and elevated safety or tolerability. The use of cotrimoxazole must be restricted due to increasing chemoresistance. Unfortunately fluoroquinolone-based regimens, once the mainstay of prophylaxis guidelines, are increasingly ineffective due to a constant increase in multidrug-resistant (MDR) Gram-negative bacteria. The same concerns apply with regard to the second and third generation cephalosporins that have problems of resistance and, if administered orally, do not sufficiently penetrate prostatic tissue. An appropriate beta-lactam could be an aminopenicillin combined with a beta-lactamase inhibitor. Fosfomycin trometamol can also be a good potential choice due to its elevated activity against MDR Gram-negative bacteria and its favourable pharmacokinetic parameters, including an elevated penetration into prostatic tissue. PMID:25245708

Mazzei, Teresita; Diacciati, Sara

2014-10-01

61

Cross-sectional study on fecal carriage of Enterobacteriaceae with resistance to extended-spectrum cephalosporins in primary care patients.  

PubMed

The aim of this study was to gain knowledge of the local epidemiology of extended-spectrum cephalosporin-resistant bacteria in primary care patients in a Swiss community. Fecal swabs were obtained from 291 primary care patients. Phenotyping and genotyping methods were used for further characterization of the isolates. Risk factors associated with carriage of ß-lactam-resistant strains were determined. Extended-spectrum cephalosporin-resistant Enterobacteriaceae were detected in 15 (5.2%) of the primary care patients. Thirteen isolates were CTX-M producers, one produced SHV-12, and three carried CMY-2. The pathogenic pandemic clone Escherichia coli ST131 was detected in 26.6% of the patients. Two patients (13.3%) carried two distinct strains simultaneously. There was a statistically significant risk of carriage of resistant strains for persons with a history of antibiotic therapy 4 months before sampling (p=0.05), markedly for therapy with ß-lactam (p=0.01). Age, gender, or history of hospitalization 4 months before sampling was not a risk factor for the acquisition of resistant bacteria in the analyzed patients. The relatively low prevalence of extended-spectrum cephalosporin-resistant strains in the community reflects the nationwide restrictive policy of antibiotic prescription as well as local implementation thereof. Nevertheless, our study shows that a potent antimicrobial resistance reservoir is present in primary care patients. PMID:23611297

Nüesch-Inderbinen, Magdalena T; Abgottspon, Helga; Zurfluh, Katrin; Nüesch, Hans J; Stephan, Roger; Hächler, Herbert

2013-10-01

62

Changing patterns and widening of antibiotic resistance in Shigella spp. over a decade (2000-2011), Andaman Islands, India.  

PubMed

SUMMARY This study is a part of the surveillance study on childhood diarrhoea in the Andaman and Nicobar Islands; here we report the drug resistance pattern of recent isolates of Shigella spp. (2006-2011) obtained as part of that study and compare it with that of Shigella isolates obtained earlier during 2000-2005. During 2006-2011, stool samples from paediatric diarrhoea patients were collected and processed for isolation and identification of Shigella spp. Susceptibility to 22 antimicrobial drugs was tested and minimum inhibitory concentrations were determined for third-generation cephalosporins, quinolones, amoxicillin-clavulanic acid combinations and gentamicin. A wide spectrum of antibiotic resistance was observed in the Shigella strains obtained during 2006-2011. The proportions of resistant strains showed an increase from 2000-2005 to 2006-2011 in 20/22 antibiotics tested. The number of drug resistance patterns increased from 13 in 2000-2005 to 43 in 2006-2011. Resistance to newer generation fluoroquinolones, third-generation cephalosporins and augmentin, which was not observed during 2000-2005, appeared during 2006-2011. The frequency of resistance in Shigella isolates has increased substantially between 2000-2006 and 2006-2011, with a wide spectrum of resistance. At present, the option for antimicrobial therapy in shigellosis in Andaman is limited to a small number of drugs. PMID:24763083

Bhattacharya, D; Bhattacharya, H; Sayi, D S; Bharadwaj, A P; Singhania, M; Sugunan, A P; Roy, S

2015-02-01

63

Bacteriology and antibiotic resistance pattern in community acquired urinary tract infection.  

PubMed

Extensive use of antibiotics have resulted in development of resistance among most commonly used drugs in community acquired urinary tract infection (UTI). This study was conducted to identify the resistance pattern in community acquired UTI .We collected urine for routine examination and culture from suprapubic urine in all the cases to avoid any contamination. E. Coli was the most common organism identified. Among oral antibiotics, there was high degree of resistance to penicillin group and cephalosporin groups. Among parentral antibiotics, all the cephalosporins were variably resistant except cephaperazone-salbactum. PMID:23942441

Sharan, Rajiv; Kumar, Dhananjay; Mukherjee, B

2013-07-01

64

Value of integron detection for predicting antibiotic resistance in patients with Gram-negative septicaemia.  

PubMed

Multidrug-resistant Enterobacteriaceae are a major public health threat and complicate the choice of drugs for empirical antibiotic therapy, especially in sepsis patients who require rapid, appropriate treatment. The objective of this study was to examine the value of integrons as a global predictive marker of acquired antibiotic resistance in septicaemia-causing Enterobacteriaceae by direct detection in positive blood cultures. The integron genetic marker can be detected in a single test, whereas multiple PCRs are needed to detect the hundreds of known antibiotic resistance genes. A total of 166 positive blood cultures were included in the study, and integrons were detected with a quantitative PCR method both in positive blood cultures and isolated Enterobacteriaceae. The results of integron detection directly on positive blood cultures were consistent in 98.8% of cases with integron detection in isolated Enterobacteriaceae. Negative predictive values (NPVs) were >90% for resistance to third-generation cephalosporins, aminoglycosides, ciprofloxacin and trimethoprim/sulfamethoxazole. In the current context of antibiotic stewardship, these good NPVs indicate that this method might be useful for preserving broad-spectrum antibiotics. The results of this proof-of-concept study must be confirmed in order to demonstrate the clinical relevance of integron detection, not only in positive blood cultures but also, to gain time, in raw biological samples. PMID:25130099

Barraud, Olivier; François, Bruno; Chainier, Delphine; Vignaud, Julie; Ploy, Marie-Cécile

2014-10-01

65

Presumptive identification of sulphonamide and antibiotic residues in milk by microbial inhibitor tests  

Microsoft Academic Search

A microbial procedure is described for the presumptive identification of some antibiotic and sulphonamide residues in milk. Penicillins, cephalosporins, sulphonamides and streptomycin residues are tested using three different agar media and two microorganisms. The identification is reached by enclosing in the media four different substances to reverse the normal action of the antibiotics and sulphonamides under investigation.

P. Aureli; A. M. Ferrini; V. Mannoni

1996-01-01

66

Augmentation of antibiotic nephrotoxicity by endotoxemia in the rabbit.  

PubMed

The acute renal failure complicating bacterial septicemia has multiple potential causes, prominent among which are endotoxemic and antibiotic nephrotoxic injury. Because the toxic interactions of endotoxin and antibiotics cannot be manipulated for study in human disease, we have developed a model of this interaction in the rabbit. Toxicity was assessed by quantification of tubular necrosis and serum creatinine concentrations 48 hr after single-dose i.v. endotoxin and/or antibiotic administration. A minimally nephrotoxic quantity of endotoxin (Escherichia coli lipopolysaccharide 0111:B4, 0.5 mg/kg b.w.) significantly increased the nephrotoxicity of the cephalosporins cephaloglycin (60 mg/kg) and cephaloridine (90 mg/kg) and the aminoglycoside neomycin (60 mg/kg), each of which was mildly-to-minimally damaging by itself. In studies of the acute functional effects of endotoxemia, the lipopolysaccharide had different effects on the renal handling of the two cephalosporins. Endotoxin increased the uptake of cephaloglycin, but decreased uptake of cephaloridine, in renal cortex in the first 0.5 hr after antibiotic administration. However, a prolonged elevation of serum levels of cephaloridine allowed later uptake of toxic amounts of this cephalosporin. Although these findings suggest a role of altered transport in the endotoxin-cephalosporin toxic synergy, the synergy was not reduced when cephaloglycin was given 1.5 hr before the endotoxin, a time which allows substantial elimination of antibiotic before the endotoxemic insult. Studies in another laboratory have demonstrated an endotoxin-induced increase of cortical concentrations of aminoglycosides, which could be a mechanism of the augmented toxicity seen in the present study. It is concluded that endotoxemia causes significant augmentation of the nephrotoxicity of cephalosporin and aminoglycoside antibiotics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:4020678

Tune, B M; Hsu, C Y

1985-08-01

67

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.; Muńoz-Villagrán, Claudia M.; de la Torre, Erick; Tantaleán, Juan C.; Vásquez, Claudio C.; Pérez-Donoso, José M.

2012-01-01

68

Cephalosporin C acylase in the autolysis of filamentous fungi.  

PubMed

Cephalosporin C acylase activity was studied using fluorescamine determination of free--NH2 groups produced in the deacylation of cephalosporin C by the enzyme. Fourteen fungi from different genera were studied and low extracellular cephalosporin C acylase activity was found in the genera Aspergillus, Fusarium and Penicillium. Forty one fungi of these genera were checked but not all presented acylase activity. The enzyme was generally found to be an extracellular enzyme and during the process of autolysis its activity increased with incubation time and with increasing pH of the medium. In no case was beta-lactamase activity detected. Penicillium rugulosum and Penicillium griseofulvum were identified as good cephalosporin C acylase producers. Deacetyl esterase activity was also detected in these fungi. PMID:1972399

Reyes, F; Martinez, M J; Alfonso, C; Copa-Patino, J L; Soliveri, J

1990-02-01

69

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.

2009-01-01

70

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

2011-01-01

71

Industrial production of beta-lactam antibiotics.  

PubMed

The industrial production of beta-lactam antibiotics by fermentation over the past 50 years is one of the outstanding examples of biotechnology. Today, the beta-lactam antibiotics, particularly penicillins and cephalosporins, represent the world's major biotechnology products with worldwide dosage form sales of approximately 15 billion US dollars or approximately 65% of the total world market for antibiotics. Over the past five decades, major improvements in the productivity of the producer organisms, Penicillium chrysogenum and Acremonium chrysogenum (syn. Cephalosporium acremonium) and improved fermentation technology have culminated in enhanced productivity and substantial cost reduction. Major fermentation producers are now estimated to record harvest titers of 40-50 g/l for penicillin and 20-25 g/l for cephalosporin C. Recovery yields for penicillin G or penicillin V are now >90%. Chemical and enzymatic hydrolysis process technology for 6-aminopenicillanic acid or 7-aminocephalosporanic acid is also highly efficient (approximately 80-90%) with new enzyme technology leading to major cost reductions over the past decade. Europe remains the dominant manufacturing area for both penicillins and cephalosporins. However, due to ever increasing labor, energy and raw material costs, more bulk manufacturing is moving to the Far East, with China, Korea and India becoming major production countries with dosage form filling becoming more dominant in Puerto Rico and in Ireland. PMID:12679848

Elander, R P

2003-06-01

72

Resistance of uropathogenic bacteria to first-line antibiotics in mexico city: A multicenter susceptibility analysis  

PubMed Central

Abstract Background Growing antibiotic resistance demands the constant reassessment of antimicrobial efficacy, particularly in countries with wide antibiotic abuse, where higher resistance prevalence is often found. Knowledge of resistance trends is particularly important when prescribing antibiotics empirically, as is usually the case for urinary tract infections (UTIs). Currently, in Mexico City, ampicillin, cotrimoxazole (trimethoprim/sulfamethoxazole), and ciprofloxacin are used as “first-line” antibiotic treatment for UTI. Objective The aim of this study was to analyze the resistance of bacterial isolates to antibiotics, with a focus on first-line antibiotics, in Mexican pediatric patients and sexually active or pregnant female outpatients. Methods In this multicenter susceptibility analysis, bacterial isolates from urine samples collected from pediatric patients and sexually-active or pregnant female outpatients presenting with acute, uncomplicated UTIs in Mexico City from January 2006 through June 2006, were included in the study. Samples were tested for susceptibility to 10 antibiotics by the disk-diffusion method. Results Four-hundred and seventeen bacterial isolates were derived from sexually active or pregnant female outpatients (324 Escherichia coli) and pediatric patients (93 Klebsiella pneumoniae). We found a high prevalence of resistance towards the drugs used as “first-line” when treating UTIs: ampicillin, cotrimoxazole, and ciprofloxacin (79%, 60%, and 24% resistance, respectively). Ninety-eight percent of K pneumoniae isolates were resistant to ampicillin, whereas 66% of the E coli isolates were resistant to cotrimoxazole. Resistance towards third-generation cephalosporins was also high (6%–8% of E coli and 10%–28% of K pneumoniae). This was possibly caused by chromosomal ?-lactamases, as 30% of all isolates were also resistant to amoxicillin/clavulanate. In contrast, 98% of the E coli isolates and 84% of the K pneumoniae strains (96% of all isolates) were found to be susceptible to nitrofurantoin, which has been in clinical use for much longer than most other drugs in this study. Conclusion In these urine samples from laboratories in Mexico City, resistance of K pneumoniae and E coli isolates to first-line treatment (ampicillin, cotrimoxazole, or ciprofloxacin) of UTI was high, whereas most E coli and K pneumoniae isolates were susceptible to nitrofurantoin and the fourth-generation cephalosporin cefepime. (Curr Ther Res Clin Exp. 2007;68:120–126) Copyright © 2007 Excerpta Medica, Inc. PMID:24678125

Arredondo-García, José Luis; Soriano-Becerril, Diana; Solórzano-Santos, Fortino; Arbo-Sosa, Antonio; Coria-Jiménez, Rafael; Arzate-Barbosa, Patricia

2007-01-01

73

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.

1988-05-01

74

Improvement of cephalosporin C production by recombinant DNA integration in Acremonium chrysogenum.  

PubMed

Cephalosporins are widely used as anti-infectious beta-lactam antibiotics in clinic. For the purpose of increasing the yield of cephalosporin C (CPC) fermentation, especially in an industrial strain, A. chrysogenum genes cefEF and cefG, which encode the ultimate and penultimate steps in CPC biosynthesis, cefT, which encodes a CPC efflux pump, and vgb, which encodes a bacterial hemoglobin gene were transformed in various combinations into an industrial strain of A. chrysogenum. Both PCR and Southern blotting indicated that the introduced genes were integrated into the chromosome of A. chrysogenum. Carbon monoxide difference spectrum absorbance assay was performed and the result showed that Vitreoscilla hemoglobin was successfully expressed in A. chrysogenum and had biological activity. HPLC analysis of fermentation broth of recombinant A. chrysogenum showed that most transformants had a higher CPC production level than the parental strain. Multiple transformants containing an additional copy of cefG showed a significant increase in CPC production. However, cefT showed little effect on CPC production in this high producer. The highest improvement of CPC titer was observed in the mutant with an extra copy of cefG + cefEF + vgb whose CPC production was increased by 116.3%. This was the first report that three or more genes were introduced simultaneously into A. chrysogenum. Our results also demonstrated that the combination of these genes had a synergy effect in a CPC high producer. PMID:19787461

Liu, Yan; Gong, Guihua; Xie, Liping; Yuan, Ning; Zhu, Chunbao; Zhu, Baoquan; Hu, Youjia

2010-02-01

75

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

PubMed

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, Km values were all in the micromolar range (1.5-8.1 ?M), whereas kcat 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

2014-12-01

76

Antibiotic sensitivity pattern of bacterial pathogens in the intensive care unit of Fatmawati Hospital, Indonesia  

PubMed Central

Objective To evaluate the sensitivity pattern of bacterial pathogens in the intensive care unit (ICU) of a tertiary care of Fatmawati Hospital Jakarta Indonesia. Methods A cross sectional retrospective study of bacterial pathogen was carried out on a total of 722 patients that were admitted to the ICU of Fatmawati Hospital Jakarta Indonesia during January 2009 to March 2010. All bacteria were identified by standard microbiologic methods, and their antibiotic susceptibility testing was performed using disk diffusion method. Results Specimens were collected from 385 patients who were given antimicrobial treatment, of which 249 (64.68%) were cultured positive and 136 (35.32%) were negative. The most predominant isolate was Pseudomonas aeruginosa (P. aeruginosa) (26.5%) followed by Klebsiella pneumoniae (K. pneumoniae) (15.3%) and Staphylococcus epidermidis (14.9%). P. aeruginosa isolates showed high rate of resistance to cephalexin (95.3%), cefotaxime (64.1%), and ceftriaxone (60.9%). Amikacin was the most effective (84.4%) antibiotic against P. aeruginosa followed by imipenem (81.2%), and meropenem (75.0%). K. pneumoniae showed resistance to cephalexin (86.5%), ceftriaxone (75.7%), ceftazidime (73.0%), cefpirome (73.0%) and cefotaxime (67.9%), respectively. Conclusions Most bacteria isolated from ICU of Fatmawati Hospital Jakarta Indonesia were resistant to the third generation of cephalosporins, and quinolone antibiotics. Regular surveillance of antibiotic susceptibility patterns is very important for setting orders to guide the clinician in choosing empirical or directed therapy of infected patients. PMID:23569722

Radji, Maksum; Fauziah, Siti; Aribinuko, Nurgani

2011-01-01

77

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

PubMed

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

2012-04-01

78

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

2014-01-01

79

Antibiotic associated diarrhoea: infectious causes.  

PubMed

Nearly 25% of antibiotic associated diarrhoeas (AAD) is caused by Clostridium difficile, making it the commonest identified and treatable pathogen. Other pathogens implicated infrequently include Clostridium perfringens, Staphylococcus aureus, Klebsiella oxytoca, Candida spp. and Salmonella spp. Most mild cases of AAD are due to non-infectious causes which include reduced break down of primary bile acids and decrease metabolism of carbohydrates, allergic or toxic effects of antibiotic on intestinal mucosa and pharmacological effect on gut motility. The antibiotics most frequently associated with C. difficile associated diarrhoea are clindamycin, cephalosporin, ampicillin and amoxicillin. Clinical presentation may vary from mild diarrhoea to severe colitis and pseudomembranous colitis associated with high morbidity and mortality. The most sensitive and specific diagnostic test for C. difficile infection is tissue culture assay for cytotoxicity of toxin B. Commercial ELISA kits are available. Though less sensitive, they are easy to perform and are rapid. Withdrawal of precipitating antibiotic is all that is needed for control of mild to moderate cases. For severe cases of AAD, oral metronidazole is the first line of treatment, and oral vancomycin is the second choice. Probiotics have been used for recurrent cases. PMID:17642966

Ayyagari, A; Agarwal, J; Garg, A

2003-01-01

80

Comparative in vitro activities of aztreonam, ciprofloxacin, norfloxacin, ofloxacin, HR 810 (a new cephalosporin), RU28965 (a new macrolide), and other agents against enteropathogens.  

PubMed Central

The in vitro activity of drugs currently used in the treatment of diarrhea against 595 enteropathogens from worldwide sources was compared with that of six newly developed antibiotics, ciprofloxacin; norfloxacin; ofloxacin; aztreonam; HR810, an expanded-spectrum cephalosporin; and RU28965, a new macrolide. In contrast with ampicillin and chloramphenicol, trimethoprim-sulfamethoxazole showed an excellent activity against all of the enteropathogens tested, except Campylobacter species. Ciprofloxacin had the highest activity, with an overall 90% MIC of less than or equal to 0.097 micrograms/ml, except for Campylobacter species (0.39 micrograms/ml). Unlike other cephalosporins, HR810 showed a satisfactory activity against Campylobacter species (90% MIC of 3.12 micrograms/ml). RU28965 was three times less active than erythromycin against Campylobacter species. PMID:3158276

Goossens, H; De Mol, P; Coignau, H; Levy, J; Grados, O; Ghysels, G; Innocent, H; Butzler, J P

1985-01-01

81

Bio-inspired synthesis yields a tricyclic indoline that selectively resensitizes methicillin-resistant Staphylococcus aureus (MRSA) to ?-lactam antibiotics.  

PubMed

The continuous emergence of resistant bacteria has become a major worldwide health threat. The current development of new antibacterials has lagged far behind. To discover reagents to fight against resistant bacteria, we initiated a chemical approach by synthesizing and screening a small molecule library, reminiscent of the polycyclic indole alkaloids. Indole alkaloids are a class of structurally diverse natural products, many of which were isolated from plants that have been used as traditional medicine for millennia. Specifically, we adapted an evolutionarily conserved biosynthetic strategy and developed a concise and unified diversity synthesis pathway. Using this pathway, we synthesized 120 polycyclic indolines that contain 26 distinct skeletons and a wide variety of functional groups. A tricyclic indoline, Of1, was discovered to selectively potentiate the activity of ?-lactam antibiotics in multidrug-resistant methicillin-resistant Staphylococcus aureus (MRSA), but not in methicillin-sensitive S. aureus. In addition, we found that Of1 itself does not have antiproliferative activity but can resensitize several MRSA strains to the ?-lactam antibiotics that are widely used in the clinic, such as an extended-spectrum ?-lactam antibiotic amoxicillin/clavulanic acid and a first-generation cephalosporin cefazolin. These data suggest that Of1 is a unique selective resistance-modifying agent for ?-lactam antibiotics, and it may be further developed to fight against resistant bacteria in the clinic. PMID:24019472

Podoll, Jessica D; Liu, Yongxiang; Chang, Le; Walls, Shane; Wang, Wei; Wang, Xiang

2013-09-24

82

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.

Kulacoglu, Hakan

2015-01-01

83

Evaluation of the role of prophylactic antibiotics in elective laparoscopic cholecystectomy: a prospective randomized trial.  

PubMed

At present the use of prophylactic antibiotics in elective laparoscopic cholecystectomy is controversial. This prospective study was carried out to define the role of prophylactic antibiotics in elective laparoscopic cholecystectomy to prevent postoperative infection. Ninety three patients were randomly placed in two groups. Group A comprised of 40 while group B consisted of 53 patients. Patients in Group A received 1.5 grams of second generation cephalosporin (cefuroxime sodium) diluted in 100ml of normal saline, at the time of induction of anesthesia. Group B patients received an equal volume of normal saline only. A sample of gall bladder bile was collected by direct gall bladder puncture intra-operatively for aerobic and anaerobic culture. Age, sex, weight of the patient, American Society of Anesthesiologists classification grade, presence of diabetes mellitus, episodes of colic 30 days preceding surgery, intra-operative gall bladder rupture, stone and / or bile spillage, results of bile culture, gall bladder histology, length of hospital stay, and number of septic complications were recorded and analyzed. In group A, one patient (2.5%) had post operative wound infection and in group B, two patients (3.8%) had post operative infection which was statistically similar (p>0.1). There was no difference between the two groups in terms of demographic, intra operative and post operative denominators. Therefore the study concluded that prophylactic antibiotics did not have a significant role to play in prevention of postoperative wound infection in elective laparoscopic cholecystectomy. PMID:16910066

Kuthe, Sachin Anant; Kaman, Lileswar; Verma, Ganga Ram; Singh, Rajinder

2006-01-01

84

[Antibiotic therapy in cystic fibrosis. II Antibiotic strategy].  

PubMed

Antibiotherapy is one of the main treatments of cystic fibrosis, contributing to a better nutritional and respiratory status and a prolonged survival. The choice of antibiotics depends on quantitative and qualitative analysis of sputum, bacteria resistance phenotypes and severity of infection. Haemophilus influenzae infection can be treated orally with the association of amoxicillin-clavulanic acid or a cephalosporin. Staphylococcus aureus generally remains sensitive to usual antibiotics; in case of a methicillin-resistant strain, an oral bitherapy or a parenteral cure can be proposed. Treatment of Pseudomonas aeruginosa is different in case of first colonization or chronic infection: in first colonization, parenteral antibiotherapy (beta-lactams-aminoglycosids) followed by inhaled antibiotherapy may eradicate the bacteria; in chronic infections, exacerbations require parenteral bi-antibiotherapy (beta-lactams or quinolons and aminoglycosids) for 15 to 21 days, inhaled antibiotics between the cures being useful to decrease the number of exacerbation. A careful monitoring of antibiotherapy is necessary because of possible induction of bacterial resistance, nephrotoxicity and ototoxicity of aminosids and allergy to beta-lactams. PMID:10911533

Sermet-Gaudelus, I; Ferroni, A; Gaillard, J L; Silly, C; Chretiennot, C; Lenoir, G; Berche, P

2000-06-01

85

Macrolide antibiotics in paediatric infectious diseases.  

PubMed

Erythromycin and other macrolides have enjoyed a renaissance in the 1970s, 1980s and 1990s secondary to the discovery of "new' pathogens such as Chlamydia, Legionella, Campylobacter and Mycoplasma spp. Erythromycin is an important therapeutic agent in the paediatric age group for several reasons: (a) it exhibits proven efficacy for a wide range of infections (upper and lower respiratory tract infections, skin/skin structure infections, prophylaxis of endocarditis/acute rheumatic fever/ophthalmia neonatorum and pre-colonic surgery, campylobacteriosis, chlamydial and ureaplasmal infections, diphtheria, whooping cough, streptococcal pharyngitis) and gastrointestinal (GI) dysmotility states; (b) intravenous formulations are widely available; and (c) it is available in a number of formulations as a generic product, which is likely to result in significant cost savings. Nevertheless, erythromycin and similar earlier macrolides are characterised by a number of drawbacks including a narrow spectrum of antimicrobial activity, unfavourable pharmacokinetic properties and poor GI tolerability. Newer macrolides such as clarithromycin and azithromycin are useful in serving the needs of paediatric patients who are erythromycin-intolerant or who have infections caused by organisms that are intrinsically erythromycin-resistant, or for which a high percentage of strains are resistant (e.g. Haemophilus influenzae, Helicobacter pylori, Mycobacterium avium complex). In addition, these newer macrolides may be considered as alternatives to oral amoxicillin-clavulanic acid, second or third generation cephalosporins, or erythromycin plus sulphonamide in this patient population. Selection between specific macrolides and between macrolides and other antibiotics in the paediatric population is likely to depend, at least for the immediate future, on separate comparisons of product availability, cost, effectiveness and tolerability profiles. PMID:8706592

Guay, D R

1996-04-01

86

Epidemic and virulence characteristic of Shigella spp. with extended-spectrum cephalosporin resistance in Xiaoshan District, Hangzhou, China  

PubMed Central

Background Shigellae have become increasingly resistant to the extended-spectrum cephalosporin (ESC) worldwide and pose a great challenge to anti-infection treatment options. The purpose of this study was to determine the resistance, cephalosporin resistance mechanisms, virulence characteristic and genotype of ESC-resistant Shigella. Methods From 2008 to 2012, Shigella isolates collected from diarrhea patients were detected for antibiotics sensitivity by disk diffusion, cephalosporin resistance determinants and virulence genes using polymerase chain reaction (PCR) and genotyping through enterobacterial repetitive intergenic consensus sequence PCR (ERIC-PCR). Results A total of 356 Shigella isolates were gathered, and 198 (55.6%, 58?S. flexneri and 140?S. sonnei) were resistant to ESC. All ESC-resistant isolates were susceptible to imipenem, and only 0.5% isolate was resistant to piperacillin/tazobactam. ESC-resistant S. flexneri showed high degrees of resistance to ampicillin (100%), ampicillin/sulbactam (96.6%), piperacillin (100%), trimethoprim/sulfamethoxazole (74.1%), ciprofloxacin (74.1%), levofloxacin (53.4%), ceftazidime (58.6%) and cefepime (58.6%). ESC-resistant S. sonnei exhibited high resistance rates to ampicillin (100%), piperacillin (100%) and trimethoprim/sulfamethoxazole (96.4%). Cephalosporin resistance genes were confirmed in 184 ESC-resistant isolates. blaCTX-M types (91.8%, mainly blaCTX-M-14, blaCTX-M-15 and blaCTX-M-57) were most prevalent, followed by blaOXA-30 (26.3%). Over 99.0% ESC-resistant isolates harbored virulence genes ial, ipaH, virA and sen. However, set1 were more prevalent in ESC-resistant S. flexneri isolates than in S. sonnei isolates. ERIC-PCR results showed that 2 and 3 main genotypes were detected in ESC-resistant S. flexneri and S. sonnei, respectively. Conclusion Our findings indicated that a high prevalence of ESC-resistant Shigella mediated mainly by blaCTX-M with stronger resistance and virulence, and the existence of specific clones responsible for these Shigella infection in the region studied. PMID:24886028

2014-01-01

87

Assessing the Contributions of the LiaS Histidine Kinase to the Innate Resistance of Listeria monocytogenes to Nisin, Cephalosporins, and Disinfectants  

PubMed Central

The Listeria monocytogenes LiaSR two-component system (2CS) encoded by lmo1021 and lmo1022 plays an important role in resistance to the food preservative nisin. A nonpolar deletion in the histidine kinase-encoding component (?liaS) resulted in a 4-fold increase in nisin resistance. In contrast, the ?liaS strain exhibited increased sensitivity to a number of cephalosporin antibiotics (and was also altered with respect to its response to a variety of other antimicrobials, including the active agents of a number of disinfectants). This pattern of increased nisin resistance and reduced cephalosporin resistance in L. monocytogenes has previously been associated with mutation of a second histidine kinase, LisK, which is a predicted regulator of liaS and a penicillin binding protein encoded by lmo2229. We noted that lmo2229 transcription is increased in the ?liaS mutant and in a ?liaS ?lisK double mutant and that disruption of lmo2229 in the ?liaS ?lisK mutant resulted in a dramatic sensitization to nisin but had a relatively minor impact on cephalosporin resistance. We anticipate that further efforts to unravel the complex mechanisms by which LiaSR impacts on the antimicrobial resistance of L. monocytogenes could facilitate the development of strategies to increase the susceptibility of the pathogen to these agents. PMID:22327581

Collins, Barry; Guinane, Caitriona M.; Ross, R. Paul

2012-01-01

88

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.

2009-01-01

89

Antibiotics Quiz  

MedlinePLUS

... 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 ...

90

Neisseria gonorrhoeae Strain with Reduced Susceptibilities to Extended-Spectrum Cephalosporins  

PubMed Central

The spread of Neisseria gonorrhoeae strains with reduced susceptibility to extended-spectrum cephalosporins is an increasing public health threat. Using Etest and multiantigen sequence typing, we detected sequence type 1407, which is associated with reduced susceptibilities to extended-spectrum cephalosporins, in 4 major populated regions in California, USA, in 2012. PMID:24964277

Gose, Severin; Castro, Lina; Chung, Kathleen; Bernstein, Kyle; Samuel, Micheal; Bauer, Heidi; Pandori, Mark

2014-01-01

91

Relentless increase of resistance to fluoroquinolones and expanded-spectrum cephalosporins in Escherichia coli: 20 years of surveillance in resource-limited settings from Latin America.  

PubMed

Previous studies on commensal Escherichia coli from healthy children in the Bolivian Chaco have shown remarkable resistance rates to the old antibiotics since the early 1990s, and the emergence of resistance to newer drugs (fluoroquinolones and expanded-spectrum cephalosporins) in the 2000s. Here we report the results of a new survey conducted in 2011 in the same setting. Rectal swabs were obtained from 482 healthy children (aged 6-72 months) from three urban areas of the Bolivian Chaco. Screening for antibiotic-resistant E. coli was performed by a direct plating method, as in the previous studies. The blaCTX-M genes were investigated by PCR/sequencing, and CTX-M-producing isolates were subjected to genotyping and detection of several plasmid-mediated quinolone resistance mechanisms. Results showed high rates of resistance to nalidixic acid (76%), ciprofloxacin (44%) and expanded-spectrum cephalosporins (12.4%), demonstrating a relentless increase of resistance to those drugs over the past two decades. CTX-M-type extended-spectrum beta-lactamases were found to be widespread (12%, 97% of extended-spectrum beta-lactamase producers). Compared with the previous studies, CTX-M-producing E. coli underwent a dramatic dissemination (120-fold increase since early 2000s) and a radical change of dominant CTX-M groups (CTX-M-1 and CTX-M-9 groups versus CTX-M-2 group). Most CTX-M producers were not susceptible to quinolones (91%), and 55% carried plasmid-mediated quinolone resistance genes (different combinations of aac(6')-Ib-cr, qnrB and qepA). This study shows the rapid and remarkable increasing trend for resistance to fluoroquinolones and expanded-spectrum cephalosporins in one of the poorest regions of Latin America, and underscores the need for urgent control strategies aimed at preserving the efficacy of those drugs in similar settings. PMID:22414066

Bartoloni, A; Pallecchi, L; Riccobono, E; Mantella, A; Magnelli, D; Di Maggio, T; Villagran, A L; Lara, Y; Saavedra, C; Strohmeyer, M; Bartalesi, F; Trigoso, C; Rossolini, G M

2013-04-01

92

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

2014-01-01

93

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.

2014-01-01

94

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

2014-01-01

95

The Beta Lactam Antibiotics as an Empirical Therapy in a Developing Country: An Update on Their Current Status and Recommendations to Counter the Resistance against Them  

PubMed Central

In a developing country like India, where the patients have to bear the cost of their healthcare, the microbiological culture and the sensitivity testing of each and every infection is not feasible. Moreover, there are lacunae in the data storage, management and the sharing of knowledge with respect to the microorganisms which are prevalent in the local geographical area and with respect to the antibiotics which are effective against them. Thus, an empirical therapy for treating infections is imperative in such a setting. The beta lactam antibiotics have been widely used for the empirical treatment of infections since the the discovery of penicillin. Many generations of beta lactams have been launched with, the claims of a higher sensitivity and less resistance, but their sensitivity has drastically decreased over time. Thus, the preference for beta lactams, especially the cephalosporins, as an empirical therapy, among the prescribers was justified initially, but the current sensitivity patterns do not support their empirical use in hospital and community acquired infections. There is a need for increasing the awareness and the attitudinal change among the prescribers, screening of the antibiotic prescriptions, the strict implementation of antibiotic policies in hospital settings, restricting the hospital supplies and avoiding the prescriptions of beta lactams, a regular census of the local sensitivity patterns to formulate and update the antibiotic policies, upgradation of the laboratory facilities for a better and faster detection of the isolates, proper collection, analyses and sharing of the data and the encouragement of the research and development of newer antibiotics with novel mechanisms of action. PMID:23905143

Thakuria, Bhaskar; Lahon, Kingshuk

2013-01-01

96

Genomic Epidemiology of Klebsiella pneumoniae in Italy and Novel Insights into the Origin and Global Evolution of Its Resistance to Carbapenem Antibiotics.  

PubMed

Klebsiella pneumoniae is at the forefront of antimicrobial resistance for Gram-negative pathogenic bacteria, as strains resistant to third-generation cephalosporins and carbapenems are widely reported. The worldwide diffusion of these strains is of great concern due to the high morbidity and mortality often associated with K. pneumoniae infections in nosocomial environments. We sequenced the genomes of 89 K. pneumoniae strains isolated in six Italian hospitals. Strains were selected based on antibiotypes, regardless of multilocus sequence type, to obtain a picture of the epidemiology of K. pneumoniae in Italy. Thirty-one strains were carbapenem-resistant K. pneumoniae carbapenemase producers, 29 were resistant to third-generation cephalosporins, and 29 were susceptible to the aforementioned antibiotics. The genomes were compared to all of the sequences available in the databases, obtaining a data set of 319 genomes spanning the known diversity of K. pneumoniae worldwide. Bioinformatic analyses of this global data set allowed us to construct a whole-species phylogeny, to detect patterns of antibiotic resistance distribution, and to date the differentiation between specific clades of interest. Finally, we detected an ?1.3-Mb recombination that characterizes all of the isolates of clonal complex 258, the most widespread carbapenem-resistant group of K. pneumoniae. The evolution of this complex was modeled, dating the newly detected and the previously reported recombination events. The present study contributes to the understanding of K. pneumoniae evolution, providing novel insights into its global genomic characteristics and drawing a dated epidemiological scenario for this pathogen in Italy. PMID:25367909

Gaiarsa, Stefano; Comandatore, Francesco; Gaibani, Paolo; Corbella, Marta; Dalla Valle, Claudia; Epis, Sara; Scaltriti, Erika; Carretto, Edoardo; Farina, Claudio; Labonia, Maria; Landini, Maria Paola; Pongolini, Stefano; Sambri, Vittorio; Bandi, Claudio; Marone, Piero; Sassera, Davide

2015-01-01

97

Asexual Cephalosporin C Producer Acremonium chrysogenum Carries a Functional Mating Type Locus?  

PubMed Central

Acremonium chrysogenum, the fungal producer of the pharmaceutically relevant ?-lactam antibiotic cephalosporin C, is classified as asexual because no direct observation of mating or meiosis has yet been reported. To assess the potential of A. chrysogenum for sexual reproduction, we screened an expressed sequence tag library from A. chrysogenum for the expression of mating type (MAT) genes, which are the key regulators of sexual reproduction. We identified two putative mating type genes that are homologues of the ?-box domain gene, MAT1-1-1 and MAT1-1-2, encoding an HPG domain protein defined by the presence of the three invariant amino acids histidine, proline, and glycine. In addition, cDNAs encoding a putative pheromone receptor and pheromone-processing enzymes, as well as components of a pheromone response pathway, were found. Moreover, the entire A. chrysogenum MAT1-1 (AcMAT1-1) gene and regions flanking the MAT region were obtained from a genomic cosmid library, and sequence analysis revealed that in addition to AcMAT1-1-1 and AcMAT1-1-2, the AcMAT1-1 locus comprises a third mating type gene, AcMAT1-1-3, encoding a high-mobility-group domain protein. The ?-box domain sequence of AcMAT1-1-1 was used to determine the phylogenetic relationships of A. chrysogenum to other ascomycetes. To determine the functionality of the AcMAT1-1 locus, the entire MAT locus was transferred into a MAT deletion strain of the heterothallic ascomycete Podospora anserina (the Pa?MAT strain). After fertilization with a P. anserina MAT1-2 (MAT+) strain, the corresponding transformants developed fruiting bodies with mature ascospores. Thus, the results of our functional analysis of the AcMAT1-1 locus provide strong evidence to hypothesize a sexual cycle in A. chrysogenum. PMID:18689517

Pöggeler, Stefanie; Hoff, Birgit; Kück, Ulrich

2008-01-01

98

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

2013-01-01

99

The exocellular DD-carboxypeptidase-endopeptidase of Streptomyces albus G. Interaction with beta-lactam antibiotics.  

PubMed

Kinetically, the three-step model proposed for the interaction between beta-lactam antibiotics and the exocellular DD-carboxypeptidases-transpeptidases of Streptomyces R61 and Actinomadura R39 [Frčre, Ghuysen & Iwatsubo (1975) Eur. J. Biochem. 57, 343--357; Fuad, Frčre, Ghuysen, Duez & Iwatsubo (1976) Biochem. J. 155, 623--629] applies to the interaction between the much less penicillin-sensitive exocellular DD-carboxypeptidase-endopeptidase of Streptomyces albus G and at least phenoxymethylpenicillin, cephalothin and cephalosporin C. The penicillin resistance of the albus G enzyme is mainly due to the low efficiency with which the first reversible complex formed with the antibiotic (complex EI) undergoes transformation into a second more stable complex EI*. Analysis of the ternary interaction between enzyme, NalphaNepsilon-diacetyl-L-lysyl-D-alanyl-D-alanine (Ac2-L-Lys-D-Ala-D-Ala) and cephalosporin C indicates a non-competitive mechanism. PMID:105727

Frčre, J M; Geurts, F; Ghuysen, J M

1978-12-01

100

Evidence for Induction of Integron-Based Antibiotic Resistance by the SOS Response in a Clinical Setting  

PubMed Central

Bacterial resistance to ?-lactams may rely on acquired ?-lactamases encoded by class 1 integron-borne genes. Rearrangement of integron cassette arrays is mediated by the integrase IntI1. It has been previously established that integrase expression can be activated by the SOS response in vitro, leading to speculation that this is an important clinical mechanism of acquiring resistance. Here we report the first in vivo evidence of the impact of SOS response activated by the antibiotic treatment given to a patient and its output in terms of resistance development. We identified a new mechanism of modulation of antibiotic resistance in integrons, based on the insertion of a genetic element, the gcuF1 cassette, upstream of the integron-borne cassette blaOXA-28 encoding an extended spectrum ?-lactamase. This insertion creates the fused protein GCUF1-OXA-28 and modulates the transcription, the translation, and the secretion of the ?-lactamase in a Pseudomonas aeruginosa isolate (S-Pae) susceptible to the third generation cephalosporin ceftazidime. We found that the metronidazole, not an anti-pseudomonal antibiotic given to the first patient infected with S-Pae, triggered the SOS response that subsequently activated the integrase IntI1 expression. This resulted in the rearrangement of the integron gene cassette array, through excision of the gcuF1 cassette, and the full expression the ?-lactamase in an isolate (R-Pae) highly resistant to ceftazidime, which further spread to other patients within our hospital. Our results demonstrate that in human hosts, the antibiotic-induced SOS response in pathogens could play a pivotal role in adaptation process of the bacteria. PMID:22719259

Hocquet, Didier; Llanes, Catherine; Thouverez, Michelle; Kulasekara, Hemantha D.; Bertrand, Xavier; Plésiat, Patrick; Mazel, Didier; Miller, Samuel I.

2012-01-01

101

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

2007-01-01

102

Polyamines reduce oxidative stress in Escherichia coli cells exposed to bactericidal antibiotics.  

PubMed

Bactericidal antibiotics (fluoroquinolones, aminoglycosides and cephalosporins) at their sublethal concentrations were able to produce hydroxyl radicals, hydrogen peroxide and superoxide anions (ROS) in Escherichia coli cells, which resulted in damage to proteins and DNA. The cells responded to oxidative stress by a 2-3-fold increase in cell polyamines (putrescine, spermidine) produced as a consequence of upregulation of ornithine decarboxylase (ODC). Relief of oxidative stress by cessation of culture aeration or addition of antioxidants substantially diminished or even completely abolished polyamine accumulation observed in response to antibiotics. Alternatively, inhibition of polyamine synthesis resulted in enhancement of oxidative stress in antibiotic-processed cells. When added to antibiotic-inhibited culture, polyamines reduced intracellular ROS production and thereby prevented damage to proteins and DNA. These effects eventually resulted in a substantial increase in cell viability, growth recovery and antibiotic resistance that were more strongly expressed in polyamine-deficient mutants. PMID:22138596

Tkachenko, Alexander G; Akhova, Anna V; Shumkov, Mikhail S; Nesterova, Larisa Yu

2012-02-01

103

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

2005-01-01

104

Phage-Antibiotic Synergy (PAS): ?-Lactam and Quinolone Antibiotics Stimulate Virulent Phage Growth  

PubMed Central

Although the multiplication of bacteriophages (phages) has a substantial impact on the biosphere, comparatively little is known about how the external environment affects phage production. Here we report that sub-lethal concentrations of certain antibiotics can substantially stimulate the host bacterial cell's production of some virulent phage. For example, a low dosage of cefotaxime, a cephalosporin, increased an uropathogenic Escherichia coli strain's production of the phage ?MFP by more than 7-fold. We name this phenomenon Phage-Antibiotic Synergy (PAS). A related effect was observed in diverse host-phage systems, including the T4-like phages, with ?-lactam and quinolone antibiotics, as well as mitomycin C. A common characteristic of these antibiotics is that they inhibit bacterial cell division and trigger the SOS system. We therefore examined the PAS effect within the context of the bacterial SOS and filamentation responses. We found that the PAS effect appears SOS-independent and is primarily a consequence of cellular filamentation; it is mimicked by cells that constitutively filament. The fact that completely unrelated phages manifest this phenomenon suggests that it confers an important and general advantage to the phages. PMID:17726529

Trojet, Sabrina N.; Prčre, Marie-Françoise; Krisch, H.M.

2007-01-01

105

Comparative Study of the Susceptibilities of Major Epidemic Clones of Methicillin-Resistant Staphylococcus aureus to Oxacillin and to the New Broad-Spectrum Cephalosporin Ceftobiprole?  

PubMed Central

Multidrug-resistant strains of Staphylococcus aureus continue to increase in frequency worldwide, both in hospitals and in the community, raising serious problems for the chemotherapy of staphylococcal disease. Ceftobiprole (BPR; BAL9141), the active constituent of the prodrug ceftobiprole medocaril (BAL5788), is a new cephalosporin which was already shown to have powerful activity against a number of bacterial pathogens, including S. aureus. In an effort to test possible limits to the antibacterial spectrum and efficacy of BPR, we examined the susceptibilities of the relatively few pandemic methicillin-resistant S. aureus (MRSA) clones that are responsible for the great majority of cases of staphylococcal disease worldwide. We also included in the tests the highly oxacillin-resistant subpopulations that are present with low frequencies in the cultures of these clones. Such subpopulations may represent a natural reservoir from which MRSA strains with decreased susceptibility to BPR may emerge in the future. We also tested the efficacy of BPR against MRSA strains with reduced susceptibility to vancomycin and against MRSA strains carrying the enterococcal vancomycin resistance gene complex. BPR was shown to be uniformly effective against all these resistant MRSA strains, and the mechanism of superb antimicrobial activity correlated with the strikingly increased affinity of the cephalosporin against penicillin-binding protein 2A, the protein product of the antibiotic resistance determinant mecA. PMID:18505853

Chung, Marilyn; Antignac, Aude; Kim, Choonkeun; Tomasz, Alexander

2008-01-01

106

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

PubMed

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

2014-02-01

107

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.

2014-01-01

108

Combating Antibiotic Resistance  

MedlinePLUS

... diseases. back to top Antibiotics Fight Bacteria, Not Viruses Antibiotics are meant to be used against bacterial ... antibiotics kill bacteria, they are not effective against viruses. Therefore, they will not be effective against viral ...

109

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

PubMed

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

2013-11-01

110

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

2014-01-01

111

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

2014-01-01

112

New antibiotics for antibiotic-resistant bacteria  

PubMed Central

The need for new antibiotics to effectively treat antibiotic-resistant infections remains unfulfilled. Despite the well-publicised concern over this issue, only two novel antibiotic classes have been introduced in the past 20 years alongside several new agents of existing classes. Accordingly, the current antibiotic armoury remains inadequate to meet the challenges posed by resistance today. More worryingly, there are very few new agents being developed that can be expected to replace existing antibiotics that succumb to the rising tide of resistance. PMID:20948644

Stubbings, William

2009-01-01

113

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.

1987-05-01

114

Sample preservation for the analysis of antibiotics in water.  

PubMed

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, Damiŕ

2014-11-21

115

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

1999-01-01

116

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

PubMed

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

2014-09-01

117

Cefquinome (HR 111V). In vitro evaluation of a broad-spectrum cephalosporin indicated for infections in animals.  

PubMed

Cefquinome (formerly HR 111V), an aminothiazolyl cephalosporin, was compared with cefepime, cefpirome, cefotaxime, and ceftazidime against 681 clinical cultures and a challenge set of bacteria with well-characterized resistance mechanisms. Cefquinome minimum inhibitory concentrations (MIC90) for the enterobacteriaceae ranged from < or = 0.12-2 micrograms/ml with the highest MIC (4 micrograms/ml) obtained among Citrobacter freundii, Enterobacter cloacae, and Providencia stuartii strains. A total of 90% of the Pseudomonas aeruginosa were inhibited by cefquinome at < or = 8 micrograms/ml. Cefquinome activity of particular note for Gram-positive isolates included Corynebacterium jeikeium (MIC90, 8 micrograms/ml) and enterococci (MIC50, 4-8 micrograms/ml). Oxacillin-resistant Staphylococcus aureus was 32-fold less susceptible (MIC90, 16 micrograms/ml) to cefquinome than oxacillin-susceptible (MIC90, 0.5 micrograms/ml) strains. Cefquinome was very potent against fastidious isolates such as Moraxella catarrhalis (MIC90, 0.25-2 micrograms/ml); Haemophilus influenzae (MIC90, 0.06-1 micrograms/ml), Neisseria gonorrhoeae (MIC90, 0.06-0.5 micrograms/ml), and Streptococcus species (MIC90, < or = 0.03-006 micrograms/ml). When tested against organisms possessing Bush group 2 enzymes (including extended spectrum beta-lactamases), cefquinome remained active (MIC, < or = 8 micrograms/ml) against the majority of strains. This compound should be very active against pathogens generally found in animal infections and possesses a potency and spectrum comparable to the "fourth-generation" cephalosporins (cefepime and cefpirome) being investigated for human infectious diseases. PMID:7867299

Murphy, S P; Erwin, M E; Jones, R N

1994-09-01

118

Metabolism of oral cephalothin and related cephalosporins in the rat  

PubMed Central

The fate of orally administered [14C]cephalothin has been studied in the rat. This antibiotic undergoes degradation in the gut followed by the subsequent absorption of a portion of the degradation products. About 50% of the administered radioactivity appears in the urine as a mixture of thienylacetylglycine, thienylacetamidoethanol and an unidentified polar metabolite. Evidence is presented indicating that thienylacetamidoethanol arises by the enzymic reduction of a metabolic intermediate, thienylacetamidoacetaldehyde. The metabolic fate of cephalothin is very similar to that of cephaloram reported earlier. The fate of [14C]cephaloridine and 7-phenoxy[1-14C]acetamidocephalosporin was also investigated. In addition to the expected metabolites, about 5% of the cephaloridine dose is absorbed unchanged. With 7-phenoxy[1-14C]acetamidocephalosporin, 15% of the dose is recovered in urine as deacetyl-7-phenoxy[1-14C]acetamidocephalosporin. PMID:16742517

Sullivan, H. R.; McMahon, R. E.

1967-01-01

119

Factors affecting cure when treating bovine clinical mastitis with cephalosporin-based intramammary preparations  

PubMed Central

Data were collated for an independent scientific analysis from 2 international, multicenter studies that had compared the efficacy of 3 different cephalosporin-containing intramammary preparations in the treatment of clinical mastitis in dairy cattle [cefalexin (first generation) in combination with kanamycin; cefquinome (fourth generation); and cefoperazone (third generation)]. Quarters were assessed using standard bacteriological techniques before treatment and at 16 and 25 d posttreatment. Additional data were also available on individual cows and study farms, including parity, breed, and cow somatic cell count histories, herd bulk milk somatic cell counts, and farm management regimens. Sufficient data for analysis were available from a total of 491 cases on 192 farms in 3 countries (United Kingdom, France, and Germany) with up to 16 cases being recruited from any one farm. Clinical cases were of diverse etiology, representing both contagious and environmental pathogens. Univariable analysis demonstrated that quarters in the cefalexin + kanamycin and cefquinome treatment groups were not significantly different from each other, but were both significantly more likely to be pathogen free posttreatment than quarters in the cefoperazone group. Multivariable analysis was undertaken using conventional random effects models. Two models were built, with the first incorporating only information available to the practitioner at the time of treatment and the second including all information collected during the study. These models indicated that country, pretreatment rectal temperature (above-normal temperature associated with an increased chance of being pathogen free posttreatment), individual cow somatic cell count (increased somatic cell count associated with a decreased chance of being pathogen free posttreatment), and pathogen (Staphylococcus aureus isolation associated with a decreased chance of being pathogen free posttreatment) were useful predictors of pathogen free status; parity, yield, bulk milk somatic cell counts, and other farm management factors were not. The importance of country in the analysis demonstrates the need to generate local data when assessing treatment regimens. In addition, these results suggest that the factors important in predicting the outcome of treatment of clinical mastitis cases may be dissimilar to those reported to affect the likelihood of cure when treating subclinical intramammary infections. PMID:19389951

Bradley, A. J.; Green, M. J.

2009-01-01

120

Factors affecting cure when treating bovine clinical mastitis with cephalosporin-based intramammary preparations.  

PubMed

Data were collated for an independent scientific analysis from 2 international, multicenter studies that had compared the efficacy of 3 different cephalosporin-containing intramammary preparations in the treatment of clinical mastitis in dairy cattle [cefalexin (first generation) in combination with kanamycin; cefquinome (fourth generation); and cefoperazone (third generation)]. Quarters were assessed using standard bacteriological techniques before treatment and at 16 and 25 d posttreatment. Additional data were also available on individual cows and study farms, including parity, breed, and cow somatic cell count histories, herd bulk milk somatic cell counts, and farm management regimens. Sufficient data for analysis were available from a total of 491 cases on 192 farms in 3 countries (United Kingdom, France, and Germany) with up to 16 cases being recruited from any one farm. Clinical cases were of diverse etiology, representing both contagious and environmental pathogens. Univariable analysis demonstrated that quarters in the cefalexin + kanamycin and cefquinome treatment groups were not significantly different from each other, but were both significantly more likely to be pathogen free posttreatment than quarters in the cefoperazone group. Multivariable analysis was undertaken using conventional random effects models. Two models were built, with the first incorporating only information available to the practitioner at the time of treatment and the second including all information collected during the study. These models indicated that country, pretreatment rectal temperature (above-normal temperature associated with an increased chance of being pathogen free posttreatment), individual cow somatic cell count (increased somatic cell count associated with a decreased chance of being pathogen free posttreatment), and pathogen (Staphylococcus aureus isolation associated with a decreased chance of being pathogen free posttreatment) were useful predictors of pathogen free status; parity, yield, bulk milk somatic cell counts, and other farm management factors were not. The importance of country in the analysis demonstrates the need to generate local data when assessing treatment regimens. In addition, these results suggest that the factors important in predicting the outcome of treatment of clinical mastitis cases may be dissimilar to those reported to affect the likelihood of cure when treating subclinical intramammary infections. PMID:19389951

Bradley, A J; Green, M J

2009-05-01

121

Ion-paired extraction of cephalosporins in acetone prior to their analysis by capillary liquid chromatography in environmental water and meat samples.  

PubMed

Ion-pair extraction of cephalosporins from aqueous solution into acetone by the addition of ammonium sulfate to a 1:2 (v/v) acetone-water solvent was carried out followed by their determination using reversed-phase capillary liquid chromatography. The analytes included are cephoperazone, cefquinome, cephalexin, cephapirin, cephaloniun, cephamandole, cephazolin and cephadroxile. In order to form the ion-pair, hexadecyltrimethylammonium bromide (CTAB) was selected as cationic ion-pairing agent at a concentration of 0.9 mM using 10mM phosphate buffer at pH 8 as the optimum condition for the aqueous solution. The applied methodology, named salting-out assisted liquid/liquid extraction (SALLE) involves the use of 1.25 g of ammonium sulfate as salting-out agent. The separation of cephalosporins using a Luna C18 (150 mm × 0.3mm, 5 µm, 100 Ĺ) column was achieved under the following conditions: a gradient program combining solvent A (0.1% formic acid in water, pH 4) and solvent B (acetonitrile-methanol (50:50, v/v)), at a flow rate of 20 µl min(-1), column temperature 35°C and injection volume 7 µl with UV detection at 250 nm. The limits of quantification for the studied compounds were between 4.3 and 22.7 ?g/L for water samples and 4.1 and 73.3 ?g/kg in the case of beef samples, lower than the maximum residue limits permitted by the EU for this kind of food. The developed methodology has demonstrated its suitability for the analysis of these widely applied antibiotics in environmental water and meat samples, including beef and pork muscle, with high sensitivity, precision and satisfactory recoveries. PMID:24054686

Quesada-Molina, Carolina; García-Campańa, Ana M; del Olmo-Iruela, Monsalud

2013-10-15

122

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

PubMed

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

2014-01-01

123

Potent cephalosporinase inhibitors: 7 beta-[2-(1, 3-dithiolan-2-ylidene) acetamido] cephalosporins and related compounds.  

PubMed Central

Cephalosporins possessing a 1, 3-dithiolane, 1, 3-dithiane, or 1, 3-dithietane ring on their 7 beta-substituents showed potent inhibitory activity against cephaloridine hydrolysis by cephalosporinases purified from proteus morganii, Proteus rettgeri, and Proteus inconstans, which were not inhibited by clavulanic acid, a well-known beta-lactamase inhibitor. The mode of inhibition was competitive. The dithiolane cephalosporins themselves were stable against hydrolysis by the beta-lactamases tested. A combination of a dithiolane cephalosporin and cephaloridine synergistically inhibited in vitro growth of strains of P. morganii, P. rettgeri, P. inconstans, Enterobacter aerogenes, Enterobacter cloacae, and Serratia marcescens. PMID:6979310

Ohya, S; Miyadera, T; Yamazaki, M

1982-01-01

124

Reversibility of antibiotic resistance  

PubMed Central

Although theoretically attractive, the reversibility of resistance has proven difficult in practice, even though antibiotic resistance mechanisms induce a fitness cost to the bacterium. Associated resistance to other antibiotics and compensatory mutations seem to ameliorate the effect of antibiotic interventions in the community. In this paper the current understanding of the concepts of reversibility of antibiotic resistance and the interventions performed in hospitals and in the community are reviewed. PMID:24836051

2014-01-01

125

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)

2006-05-20

126

Antibiotic-induced neurotoxicity.  

PubMed

Antibiotic neurotoxicity is rare but can cause significant morbidity when it occurs. The risk of antibiotic neurotoxicity appears to be highest in patients who are older, have impaired renal function, or have preexisting neurologic conditions. This review describes the clinical features of the most common antibiotic toxicities affecting the nervous system: seizures, encephalopathy, optic neuropathy, peripheral neuropathy, and exacerbation of myasthenia gravis. PMID:25348743

Bhattacharyya, Shamik; Darby, Ryan; Berkowitz, Aaron L

2014-12-01

127

Systemic Antibiotics for Acne  

Microsoft Academic Search

Antibiotic therapy for acne is very common. Antibiotics are frequently used in acne, either systemically or topically. Systemic antibiotics are indicated as treatment of moderate and quite severe acne or if acne is considered as very serious by the patient for psychological or social reasons. Results are very often excellent, but failure is possible; in this case using another treatment,

J. Meynadier; M. Alirezai

1998-01-01

128

Designed to penetrate: Time-resolved interaction of single antibiotic molecules with bacterial pores  

NASA Astrophysics Data System (ADS)

Membrane permeability barriers are among the factors contributing to the intrinsic resistance of bacteria to antibiotics. We have been able to resolve single ampicillin molecules moving through a channel of the general bacterial porin, OmpF (outer membrane protein F), believed to be the principal pathway for the -lactam antibiotics. With ion channel reconstitution and high-resolution conductance recording, we find that ampicillin and several other efficient penicillins and cephalosporins strongly interact with the residues of the constriction zone of the OmpF channel. Therefore, we hypothesize that, in analogy to substrate-specific channels that evolved to bind certain metabolite molecules, antibiotics have "evolved" to be channel-specific. Molecular modeling suggests that the charge distribution of the ampicillin molecule complements the charge distribution at the narrowest part of the bacterial porin. Interaction of these charges creates a region of attraction inside the channel that facilitates drug translocation through the constriction zone and results in higher permeability rates.

Nestorovich, Ekaterina M.; Danelon, Christophe; Winterhalter, Mathias; Bezrukov, Sergey M.

2002-07-01

129

Antibiotic susceptibility of streptococcus pyogenes isolated from respiratory tract infections in dakar, senegal.  

PubMed

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

2013-01-01

130

Efficacy evaluation of some antibiotics against syrian brucella spp isolates, in vitro.  

PubMed

Brucellosis is an endemic zoonosis in Syria, affecting large numbers of animals and there are an increasing number of cases in humans. The aim of this study is to investigate the in vitro efficacy of various traditional and new antibiotics against 89 Brucella isolates (isolated from domestic animals) collected from different Syrian regions. Minimum inhibitory concentrations (MICs) of seventeen antibiotics were determined. Ciprofloxacin and ofloxacin were the most effective antibiotics, whereas sparfloxacin, levofloxacin, doxycycline and tetracycline had a moderate activity. In contrast, moxifloxacin and rifampicin had a low activity, while streptomycin, spiramycin and cephalosporines were ineffective. As a result, we come to the conclusion that a combination between one effective quinolone and doxycycline has a good efficacy against Brucella. Further in vivo studies are necessary to support this suggestion. PMID:24031952

Safi, Mazen; Al-Mariri, Ayman

2012-10-01

131

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

2013-01-01

132

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.  

PubMed

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 2006ż2008 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

2014-11-26

133

Genetic Architecture of Intrinsic Antibiotic Susceptibility  

PubMed Central

Background Antibiotic exposure rapidly selects for more resistant bacterial strains, and both a drug's chemical structure and a bacterium's cellular network affect the types of mutations acquired. Methodology/Principal Findings To better characterize the genetic determinants of antibiotic susceptibility, we exposed a transposon-mutagenized library of Escherichia coli to each of 17 antibiotics that encompass a wide range of drug classes and mechanisms of action. Propagating the library for multiple generations with drug concentrations that moderately inhibited the growth of the isogenic parental strain caused the abundance of strains with even minor fitness advantages or disadvantages to change measurably and reproducibly. Using a microarray-based genetic footprinting strategy, we then determined the quantitative contribution of each gene to E. coli's intrinsic antibiotic susceptibility. We found both loci whose removal increased general antibiotic tolerance as well as pathways whose down-regulation increased tolerance to specific drugs and drug classes. The beneficial mutations identified span multiple pathways, and we identified pairs of mutations that individually provide only minor decreases in antibiotic susceptibility but that combine to provide higher tolerance. Conclusions/Significance Our results illustrate that a wide-range of mutations can modulate the activity of many cellular resistance processes and demonstrate that E. coli has a large mutational target size for increasing antibiotic tolerance. Furthermore, the work suggests that clinical levels of antibiotic resistance might develop through the sequential accumulation of chromosomal mutations of small individual effect. PMID:19462005

Tavazoie, Saeed

2009-01-01

134

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

2011-01-01

135

Minimal nephrotoxicity with cephalosporin-aminoglycoside combinations in patients with neoplastic disease.  

PubMed Central

Patients with cancer and suspected sepsis were treated in a prospective, randomized trial with one of four cephalosporin-aminoglycoside combinations: cephalothin and tobramycin; cephalothin and gentamicin; cefamandole and tobramycin; or cefamandole and gentamicin. Carbenicillin was added if the absolute granulocyte count was less than 1,000/mm3. Of 199 patients receiving 20 to more doses of an aminoglycoside and having serial determination of serum creatinines, nephrotoxicity developed in seven (3.5%) given any of the four combinations. There were no significant differences between patients receiving either cephalosporin or either aminoglycoside. Nephrotoxicity developed less frequently among children (2 or 125; 1.6%) than adults (5 of 74; 6.8%). PMID:7081979

Brown, A E; Quesada, O; Armstrong, D

1982-01-01

136

Resistance to extended-spectrum cephalosporins, caused by PER1  -lactamase, in M Salmonella typhimurium from Istanbul, Turkey  

Microsoft Academic Search

Summary. Two Salmonellu typhimurium isolates were studied, one as a representative from a series of neonatal meningitis cases treated at an Istanbul teaching hospital, the other from a gastro-enteritis case seen at a different Istanbul hospital. Both isolates were resistant to extended-spectrum cephalosporins, as well as penicillins, aminoglycosides and chlor- amphenicol. Cephalosporin resistance depended on production of PER- 1 p-lactamase,

H. Vahaboglu; L. M. C. Hall; L. Mulazimoglu; S. Dodanli; I. Yildirim; D. M. Livermore

1995-01-01

137

Metabolic engineering of ?-oxidation in Penicillium chrysogenum for improved semi-synthetic cephalosporin biosynthesis.  

PubMed

Industrial production of semi-synthetic cephalosporins by Penicillium chrysogenum requires supplementation of the growth media with the side-chain precursor adipic acid. In glucose-limited chemostat cultures of P. chrysogenum, up to 88% of the consumed adipic acid was not recovered in cephalosporin-related products, but used as an additional carbon and energy source for growth. This low efficiency of side-chain precursor incorporation provides an economic incentive for studying and engineering the metabolism of adipic acid in P. chrysogenum. Chemostat-based transcriptome analysis in the presence and absence of adipic acid confirmed that adipic acid metabolism in this fungus occurs via ?-oxidation. A set of 52 adipate-responsive genes included six putative genes for acyl-CoA oxidases and dehydrogenases, enzymes responsible for the first step of ?-oxidation. Subcellular localization of the differentially expressed acyl-CoA oxidases and dehydrogenases revealed that the oxidases were exclusively targeted to peroxisomes, while the dehydrogenases were found either in peroxisomes or in mitochondria. Deletion of the genes encoding the peroxisomal acyl-CoA oxidase Pc20g01800 and the mitochondrial acyl-CoA dehydrogenase Pc20g07920 resulted in a 1.6- and 3.7-fold increase in the production of the semi-synthetic cephalosporin intermediate adipoyl-6-APA, respectively. The deletion strains also showed reduced adipate consumption compared to the reference strain, indicating that engineering of the first step of ?-oxidation successfully redirected a larger fraction of adipic acid towards cephalosporin biosynthesis. PMID:22525490

Veiga, Tânia; Gombert, Andreas K; Landes, Nils; Verhoeven, Maarten D; Kiel, Jan A K W; Krikken, Arjen M; Nijland, Jeroen G; Touw, Hesselien; Luttik, Marijke A H; van der Toorn, John C; Driessen, Arnold J M; Bovenberg, Roel A L; van den Berg, Marco A; van der Klei, Ida J; Pronk, Jack T; Daran, Jean-Marc

2012-07-01

138

In Vitro and In Vivo Activities of a New Cephalosporin, FR264205, against Pseudomonas aeruginosa  

Microsoft Academic Search

FR264205 is a novel parenteral 3-aminopyrazolium cephalosporin. This study evaluated the in vitro and in vivo activities of FR264205 against Pseudomonas aeruginosa. The MIC of FR264205 at which 90% of 193 clinical isolates of P. aeruginosa were inhibited was 1 g\\/ml, 8- to 16-fold lower than those of ceftazidime (CAZ), imipenem (IPM), and ciprofloxacin (CIP). FR264205 also exhibited this level

Shinobu Takeda; Toru Nakai; Yoshimi Wakai; Fumiaki Ikeda; Kazuo Hatano

2007-01-01

139

Antibiotic resistance and phylogenetic characterization of Acinetobacter baumannii strains isolated from commercial raw meat in Switzerland.  

PubMed

The spread of antibiotic-resistant bacteria through food has become a major public health concern because some important human pathogens may be transferred via the food chain. Acinetobacter baumannii is one of the most life-threatening gram-negative pathogens; multidrug-resistant (MDR) clones of A. baumannii are spreading worldwide, causing outbreaks in hospitals. However, the role of raw meat as a reservoir of A. baumannii remains unexplored. In this study, we describe for the first time the antibiotic susceptibility and fingerprint (repetitive extragenic palindromic PCR [rep-PCR] profile and sequence types [STs]) of A. baumannii strains found in raw meat retailed in Switzerland. Our results indicate that A. baumannii was present in 62 (25.0%) of 248 (CI 95%: 19.7 to 30.9%) meat samples analyzed between November 2012 and May 2013, with those derived from poultry being the most contaminated (48.0% [CI 95%: 37.8 to 58.3%]). Thirty-nine strains were further tested for antibiotic susceptibility and clonality. Strains were frequently not susceptible (intermediate and/or resistant) to third- and fourth-generation cephalosporins for human use (i.e., ceftriaxone [65%], cefotaxime [32%], ceftazidime [5%], and cefepime [2.5%]). Resistance to piperacillin-tazobactam, ciprofloxacin, colistin, and tetracycline was sporadically observed (2.5, 2.5, 5, and 5%, respectively), whereas resistance to carbapenems was not found. The strains were genetically very diverse from each other and belonged to 29 different STs, forming 12 singletons and 6 clonal complexes (CCs), of which 3 were new (CC277, CC360, and CC347). RepPCR analysis further distinguished some strains of the same ST. Moreover, some A. baumannii strains from meat belonged to the clonal complexes CC32 and CC79, similar to the MDR isolates responsible for human infections. In conclusion, our findings suggest that raw meat represents a reservoir of MDR A. baumannii and may serve as a vector for the spread of these pathogens into both community and hospital settings. PMID:25364933

Lupo, Agnese; Vogt, Debora; Seiffert, Salome N; Endimiani, Andrea; Perreten, Vincent

2014-11-01

140

Bacterial Profile, Antibiotic Sensitivity and Resistance of Lower Respiratory Tract Infections in Upper Egypt  

PubMed Central

Background Lower respiratory tract infections (LRTI) account for a considerable proportion of morbidity and antibiotic use. We aimed to identify the causative bacteria, antibiotic sensitivity and resistance of hospitalized adult patients due to LRTI in Upper Egypt. Methods A multicentre prospective study was performed at 3 University Hospitals for 3 years. Samples included sputum or bronchoalveolar lavage (BAL) for staining and culture, and serum for serology. Samples were cultured on 3 bacteriological media (Nutrient, Chocolate, MacConkey's agars). Colonies were identified via MicroScan WalkAway-96. Pneumoslide IgM kit was used for detection of atypical pathogens via indirect immunofluorescent assay. Results The predominant isolates in 360 patients with CAP were S. pneumoniae (36%), C. pneumoniae (18%), and M. pneumoniae (12%). A higher sensitivity was recorded for moxifloxacin, levofloxacin, macrolides, and cefepime. A higher of resistance was recorded for doxycycline, cephalosporins, and ?-lactam-?-lactamase inhibitors. The predominant isolates in 318 patients with HAP were, methicillin-resistant Staphylococcus aureus; MRSA (23%), K. pneumoniae (14%), and polymicrobial in 12%. A higher sensitivity was recorded for vancomycin, ciprofloxacin, and moxifloxacin. Very high resistance was recorded for ?-lactam-?-lactamase inhibitors and cephalosporins. The predominant organisms in 376 patients with acute exacerbation of chronic obstructive pulmonary diseases (AECOPD) were H. influnzae (30%), S. pneumoniae (25%), and M. catarrhalis (18%). A higher sensitivity was recorded for moxifloxacin, macrolides and cefepime. A higher rate of resistance was recorded for aminoglycosides and cephalosporins. Conclusions The most predominant bacteria for CAP in Upper Egypt are S. pneumoniae and atypical organisms, while that for HAP are MRSA and Gram negative bacteria. For acute exacerbation of COPD, H. influnzae was the commonest organism. Respiratory quinolones, macrolides, and cefepime are the most efficient antibiotics in treatment of LRTI in our locality. PMID:24106606

Agmy, Gamal; Mohamed, Sherif; Gad, Yaser; Farghally, Esam; Mohammedin, Hamdy; Rashed, Hebba

2013-01-01

141

SCE-129, Antipseudomonal Cephalosporin: In Vitro and In Vivo Antibacterial Activities  

PubMed Central

SCE-129 [3-(4-carbamoyl-1-pyridiniomethyl)-7?-(d-?-sulfophenylacetamido)-ceph-3-em-4-carboxylate monosodium salt], a new semisynthetic cephalosporin, shows potent in vitro antibacterial activities against Pseudomonas aeruginosa and some gram-positive bacteria, whereas it shows lower activity against many gram-negative rods. Against clinical isolates of P. aeruginosa this cephalosporin exhibited higher activity than did carbenicillin, and against the strains of Staphylococcus aureus, SCE-129 had similar activity to carbenicillin. Variations in pH, addition of horse serum, and type of growth medium had no significant effects on the activity of the cephalosporin; however, the inoculum size had some effect on the activity. SCE-129 is an effective bactericidal agent against P. aeruginosa and S. aureus. The protective effects of SCE-129 in mice infected with P. aeruginosa and S. aureus were more potent than those of carbenicillin. The protective effects of SCE-129 on Pseudomonas infection in mice varied according to the dosage schedule and the challenge dose. In a multiple dose schedule, a smaller amount of SCE-129 was necessary than that in a single dose schedule. The effects of SCE-129 after subcutaneous or intraperitoneal administration were more potent than were those by intravenous administration. No protective effect was observed by oral administration. PMID:417670

Tsuchiya, Kanji; Kondo, Masahiro; Nagatomo, Hiroshi

1978-01-01

142

[Sensitivity to various antibiotics of coagulase-negative staphylococci isolated from samples of milk from Dutch dairy cattle].  

PubMed

During recent years the prevalence of coagulase-negative staphylococci in milk samples from Dutch dairy cows has increased. In 1999 16.2% of the bacteria isolated from milk collected from cows with subclinical mastitis were coagulase-negative staphylococci. In 2004 this proportion was 42.2%. The proportion of coagulase-negative staphylococci of the bacteria isolated from milk samples from cows with clinical mastitis was 7.3% in 1999 and 14.1% in 2004. In this study, the susceptibility of 108 coagulase-negative staphylococci to oxacillin, cefquinome, streptomycin, neomycin, penicillin, and the combination of nafcillin, penicillin, and streptomycin was tested. The isolates were cultured from milk collected from cows with mastitis and typed using the Api-Staph system. Eight species were identified. Staphylococcus chromogenes was the predominant species (41.7%), followed by Staphylococcus xylosus (15.7%) and Staphylococcus simulans (10.2%). With the agar dilution method all strains proved to be sensitive to cefquinome and 90% to oxacillin. Three isolates (2.8%) were mecA-positive. Despite the agar dilution results, these three isolates should be considered resistant to all beta-lactam antibiotics (penicillins, penicillins combined with a beta-lactamase inhibitor and all generations of cephalosporins). In the agar diffusion test, all isolates proved to be sensitive to the combination of nafcillin-penicillin-streptomycin, 99% were sensitive to neomycin and 1% intermediate sensitive, and 95% were sensitive to streptomycin, 4% resistant, and 1% intermediate sensitive. The coagulase-negative staphylococci were highly resistant to penicillin (37.4%), although the level of resistance varied between species, from 0% for Staphylococcus simulans to 100% for Staphylococcus saprophyticus. Because coagulase-negative staphylococci are resistant to several antibiotics, sensitivity testing is important for targeted treatment of mastitis. PMID:17436810

Sampimon, O C; Vernooij, J C A; Mevius, D J; Sol, J

2007-03-15

143

Antibiotics in the environment  

PubMed Central

Molecules with antibiotic properties, produced by various microbes, have been around long before mankind recognized their usefulness in preventing and treating bacterial infections. Bacteria have therefore been exposed to selection pressures from antibiotics for very long times, however, generally only on a micro-scale within the immediate vicinity of the antibiotic-producing organisms. In the twentieth century we began mass-producing antibiotics, mainly synthetic derivatives of naturally produced antibiotic molecules, but also a few entirely synthetic compounds. As a consequence, entire bacterial communities became exposed to unprecedented antibiotic selection pressures, which in turn led to the rapid resistance development we are facing today among many pathogens. We are, rightly, concerned about the direct selection pressures of antibiotics on the microbial communities that reside in or on our bodies. However, other environments, outside of our bodies, may also be exposed to antibiotics through different routes, most often unintentionally. There are concerns that increased selection pressures from antibiotics in the environment can contribute to the recruitment of resistance factors from the environmental resistome to human pathogens. This paper attempts to 1) provide a brief overview of environmental exposure routes of antibiotics, 2) provide some thoughts about our current knowledge of the associated risks for humans as well as ecosystems, and 3) indicate management options to reduce risks. PMID:24646081

2014-01-01

144

[Sensitivity spectrum of Francisella tularensis to antibiotics and synthetic antibacterial drugs].  

PubMed

Sensitivity of 6 F. tularensis strains to 57 antibiotics and synthetic antibacterial drugs was studied. It was shown that the strains were highly sensitive to aminoglycosides, tetracyclines, anzamycins, quinolones, chloramphenicol, nitrofurantoin, nitroxoline, novobiocin and fusidin and resistant to penicillins, cephalosporins, polypeptides, vancomycin and sulfanylamides. The interrace differences in F. tularensis could be detected only by sensitivity to erythromycin, oleandomycin and spiramycin. There was observed no cross resistance to streptomycin and other aminoglycosides in F. tularensis. Assay of F. tularensis sensitivity to antibacterial drugs of various groups with the rapid photometric procedure and the agar diffusion method revealed that the results were highly comparable. PMID:2610533

Vasi'lev, N T; Oborin, V A; Vasi'lev, P G; Glushkova, O V; Kravets, I D; Levchuk, B A

1989-09-01

145

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.

2013-01-01

146

Platforms for antibiotic discovery.  

PubMed

The spread of resistant bacteria, leading to untreatable infections, is a major public health threat but the pace of antibiotic discovery to combat these pathogens has slowed down. Most antibiotics were originally isolated by screening soil-derived actinomycetes during the golden era of antibiotic discovery in the 1940s to 1960s. However, diminishing returns from this discovery platform led to its collapse, and efforts to create a new platform based on target-focused screening of large libraries of synthetic compounds failed, in part owing to the lack of penetration of such compounds through the bacterial envelope. This article considers strategies to re-establish viable platforms for antibiotic discovery. These include investigating untapped natural product sources such as uncultured bacteria, establishing rules of compound penetration to enable the development of synthetic antibiotics, developing species-specific antibiotics and identifying prodrugs that have the potential to eradicate dormant persisters, which are often responsible for hard-to-treat infections. PMID:23629505

Lewis, Kim

2013-05-01

147

Management of meningitis due to antibiotic-resistant Acinetobacter species  

PubMed Central

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

2009-01-01

148

Antibiotic prescriptions in children  

Microsoft Academic Search

Results: In the year surveyed, 511270 antibiotic prescriptions in 219 257 children were identified. In all, 52.9% of children received at least one antibiotic; this percentage decreased with age, ranging from 70.4% in children 1-2 years old to 35.8% in children >11 years old. Fifty-two per cent of inhabitants under the age of 15 years were treated with systemic antibiotics

D. Resi; M. Milandri; M. L. Moro; Viale Aldo Moro

2003-01-01

149

Antibiotic susceptibility survey of Neisseria gonorrhoeae in Thailand.  

PubMed

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

1992-08-01

150

Simultaneous determination of different antibiotic residues in bovine and in porcine kidneys by solid-phase fluorescence immunoassay.  

PubMed

Parallux, a solid-phase fluorescence immunoassay (SPFIA) developed for antibiotic residue detection in milk, was used for analysis of bovine and porcine kidney tissue. Four tetracyclines, 2 broad-spectrum cephalosporins, 3 beta-lactam antibiotics, and cephapirin were detected in one run after minimal sample preparation. This commercially available test system is designed as cartridges, each with a combination of 1-4 tests. One cartridge can be used to detect 4 analytes in the same sample, or 1 or 2 analytes in different samples. The cartridge with the combination tetracyclines-ceftiofur-penicillin-cephapirin was selected because tetracyclines, beta-lactam antibiotics as well as cephalosporins, are registered for oral or parenteral use in bovines and pigs in Europe. The test is qualitative and is recommended only for screening. Tetracycline, oxytetracycline, chlortetracycline, and doxycycline were easily detected at 300 ppb with the tetracyclines channel; ceftiofur at 1000 ppb and cefquinome at 200 ppb with the ceftiofur channel; penicillin G, ampicillin, and amoxicillin at 50 ppb with the penicillin channel; and cephapirin at 100 ppb with the cephapirin channel. These levels are equal to or lower than the corresponding maximal residue limits in kidney tissue. Cephalexin was not detected. The SPFIA test can be used as an alternative to classical inhibition tests and for post-screening inhibitor- positive kidneys, because it detects 3 specific groups of antibiotics, which enables selection of specific confirmatory methods for identification and quantification. PMID:12723911

Okerman, Lieve; De Wasch, Katia; Van Hoof, Jan; Smedts, Walter

2003-01-01

151

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.

1995-01-01

152

Prescription antibiotics for outpatients in Bangladesh: a cross-sectional health survey conducted in three cities  

PubMed Central

Background Antibiotics prescribing by physicians have gained due importance across the globe, mainly because of an increase in antibiotic usage, prevalence of infections and drug resistances. The present study is aimed to evaluate the physicians prescribing pattern of antibiotics, their usages by outpatients and disease conditions for which the antibiotics are prescribed in three cities of Bangladesh. Methods This cross sectional health survey was carried out with a self designed standard questionnaire by manual data collection over a three months period (20.03.2013 to 20.06.2013) at three adjacent cities Jessore Sadar, Monirampur and Keshabpur upazila respectively. The data were collected from the patient’s prescription and by directly interviewing the patients who were prescribed at least one antibiotic during the study period. WHO Anatomical Therapeutic Chemical (ATC) classifications for antibiotics was used and descriptive statistics were applied to the collected data and analyzed using Microsoft Excel software. Modified Wald method was applied to calculate 95% CI. Results A total of 900 prescriptions were analyzed during the study period. It was found that the prescriber prescribed antibiotics to the patients who were suffering mainly from cold and fever, infections, diarrhea and gonorrhea. The highest prescribed antibiotic groups were cephalosporins (31.78%), macrolides (27.33%), quinolones (16.33%), penicillins (7.11%), and metronidazoles (6.78%) respectively. Two or more antibiotics were prescribed in 25.44% of prescriptions. A total of 66.89% prescriptions had complete information on dosage form, 57% had complete direction for antibiotics use and 64.22% patients completed full course of antibiotics. Although 83% prescriptions have no clinical test for using antibiotics, even though the percentages of patients’ disease recovery were 61.78% and incompliance were 38.22%. Conclusion From this research, it is observed that physicians prescribed antibiotics rationally in some cases but needs to ensure in all cases of prescription. Because irrational use leads to the spread of bacterial resistance to antibiotics and related health problems, our findings have important implications for public education and the enforcement of regulations regarding the prescription of antibiotics in Bangladesh. PMID:24755269

2014-01-01

153

Inhaled antibiotics to treat lung infection.  

PubMed

The development of inhaled antibiotics to treat lung infection is an active field, with four approved products in the USA and more in the late stages of clinical development. The efficacies of TOBI® tobramycin (Novartis) and Cayston® aztreonam lysate (Gilead), the approved inhaled antibiotics for cystic fibrosis (CF) patients colonized with Pseudomonas aeruginosa, have been well documented. Recent approvals for a second-generation tobramycin solution, Bethkis®, and a tobramycin powder formulation in a dry-powder inhaler (DPI), TOBI Podhaler®, indicate that the inhaled antibiotic marketplace in CF is becoming very competitive. Other indications are also receiving interest. While there have been a number of recent reviews from a clinical, technical or regulatory perspective in the field of inhaled antibiotics, as well as others focused on a specific product or data from a recent clinical trial, there have not been any that describe the patent coverage of these products. This review addresses that missing piece. PMID:24237172

Cipolla, David; Chan, Hak-Kim

2013-09-01

154

The future of antibiotics.  

PubMed

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

Spellberg, Brad

2014-01-01

155

?-lactams and florfenicol antibiotics remain bioactive in soils while ciprofloxacin, neomycin, and tetracycline are neutralized.  

PubMed

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

2011-10-01

156

Neisseria gonorrhoeae and extended-spectrum cephalosporins in California: surveillance and molecular detection of mosaic penA  

PubMed Central

Background The spread of Neisseria gonorrhoeae strains with mosaic penA alleles and reduced susceptibility to extended-spectrum cephalosporins is a major public health problem. While much work has been performed internationally, little is known about the genetics or molecular epidemiology of N. gonorrhoeae isolates with reduced susceptibility to extended-spectrum cephalosporins in the United States. The majority of N. gonorrhoeae infections are diagnosed without a live culture. Molecular tools capable of detecting markers of extended-spectrum cephalosporin resistance are needed. Methods Urethral N. gonorrhoeae isolates were collected from 684 men at public health clinics in California in 2011. Minimum inhibitory concentrations (MICs) to ceftriaxone, cefixime, cefpodoxime and azithromycin were determined by Etest and categorized according to the U.S. Centers for Disease Control 2010 alert value breakpoints. 684 isolates were screened for mosaic penA alleles using real-time PCR (RTPCR) and 59 reactive isolates were subjected to DNA sequencing of their penA alleles and Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST). To increase the specificity of the screening RTPCR in detecting isolates with alert value extended-spectrum cephalosporin MICs, the primers were modified to selectively amplify the mosaic XXXIV penA allele. Results Three mosaic penA alleles were detected including two previously described alleles (XXXIV, XXXVIII) and one novel allele (LA-A). Of the 29 isolates with an alert value extended-spectrum cephalosporin MIC, all possessed the mosaic XXXIV penA allele and 18 were sequence type 1407, an internationally successful strain associated with multi-drug resistance. The modified RTPCR detected the mosaic XXXIV penA allele in urethral isolates and urine specimens and displayed no amplification of the other penA alleles detected in this study. Conclusion N. gonorrhoeae isolates with mosaic penA alleles and reduced susceptibility to extended-spectrum cephalosporins are currently circulating in California. Isolates with the same NG-MAST ST, penA allele and extended-spectrum cephalosporin MICs have caused treatment failures elsewhere. The RTPCR assay presented here may be useful for the detection of N. gonorrheoae isolates and clinical specimens with reduced extended-spectrum cephalosporin MICs in settings where antimicrobial susceptibility testing is unavailable. In an era of increasing antimicrobial resistance and decreasing culture capacity, molecular assays capable of detecting extended-spectrum cephalosporin of resistance are essential to public health. PMID:24305088

2013-01-01

157

Efficacy of BAL5788, a Prodrug of Cephalosporin BAL9141, in a Mouse Model of Acute Pneumococcal Pneumonia  

PubMed Central

BAL5788 is a water-soluble prodrug of BAL9141, a new broad-spectrum cephalosporin with high levels of in vitro activity against methicillin- and vancomycin-resistant staphylococci and penicillin-resistant streptococci. In plasma BAL5788 is rapidly converted to BAL9141. We studied the activity of BAL5788 in a mouse model of acute pneumococcal pneumonia. Leukopenic female Swiss albino mice were challenged intratracheally with 107 CFU of clinical Streptococcus pneumoniae strains P-52181 (Pens Cros Ctxs), P-15986 (Penr Cros Ctxs), P-40422 (Penr Cror Ctxr), and P-40984 (Penr Cror Ctxr). Infected mice received subcutaneous (s.c.) injections of BAL5788 or ceftriaxone starting 3 h after pneumococcal challenge. Uninfected nonleukopenic mice received single s.c. doses of BAL5788 to determine the BAL9141 concentration-time profiles in serum and lungs. Untreated control mice died within 5 days postinfection. Ten-day cumulative survival rates for infected mice receiving BAL5788 (total daily doses of BAL9141 equivalents, 2.1 to 75 mg/kg of body weight) ranged from 57 to 100%, whereas with ceftriaxone (total daily doses, 10 to 400 mg/kg), the survival rates varied between 13 and 100%. In mice infected with P-15986, the survival rates achieved with BAL5788 (BAL9141 equivalent, 8.4 mg/kg) and those achieved with ceftriaxone (50 mg/kg) were significantly different (93 versus 13%; P < 0.0001) in favor of BAL5788; the outcomes of the trials with all other strains were not significantly different between the two antibiotics, but markedly lower doses of BAL5788 than ceftriaxone were required to obtain similar survival rates. Pharmacokinetic data showed that BAL9141 was effective against the four pneumococcal strains tested at very low values of the time above the MIC (T > MIC), which ranged from 9 to 18% of the dosing interval, whereas the values of T > MICs for ceftriaxone ranged from 30 to 50% of the dosing interval. PMID:15047508

Azoulay-Dupuis, E.; Bédos, J. P.; Mohler, J.; Schmitt-Hoffmann, A.; Schleimer, M.; Shapiro, S.

2004-01-01

158

Antibiotics, skin and soft tissue infection and meticillin-resistant Staphylococcus aureus: cause and effect.  

PubMed

Staphylococcus aureus is not a new cause of skin and soft tissue infection, but the significance of the Panton-Valentine leukocidin toxin and the spread of several clones carrying different staphylococcal cassette chromosome (SCC) mecA gene cassette types have given it a new lease of life. This is a clinical area with several epidemic strains causing major problems around the world, most notably in the USA. While most attention focuses on treatment, prevention should be the goal. Traditional infection control measures, such as good hand hygiene and barrier precautions, are usually emphasised. Most importantly, we should not forget the underlying cause of meticillin-resistant Staphylococcus aureus (MRSA), namely antibiotic use. In both community and hospital, exposure to beta-lactams, in particular cephalosporins, and also sometimes quinolones and macrolides, is likely to promote the transmission, colonisation and increased virulence of MRSA. Future antibiotic policies should consider this, particularly in an era of widespread MRSA screening. PMID:19560675

Gould, Ian M

2009-07-01

159

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)

2010-03-08

160

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

2009-01-01

161

Effects of six antibiotics and their binary mixtures on growth of Pseudokirchneriella subcapitata.  

PubMed

The effect of ampicillin (AMP), amoxicillin (AMX), cephalotin (CEP), ciprofloxacin (CPF), gentamycin (GEN), and vancomycin (VAN) have been examined individually and as binary mixtures, on a non-target aquatic organism, the green alga Pseudokichneriella subcapitata. The ?-lactam antibiotics AMP and AMX were not toxic to the alga at concentrations up to 2000mgl(-1) (less than 10% of algal growth inhibition), whereas the fluoroquinolone CPF, and the aminoglycoside GEN were the most toxic antibiotics, with an EC50=11.3±0.7mgl(-1) and 19.2±0.5mgl(-1), respectively. The cephalosporin CEP and the glycopeptide VAN were less toxic than the last two mentioned, showing an EC50>600mgl(-1) and 724±20mgl(-1), respectively. The toxicological interactions of binary mixtures were predicted by the two classical models of additivity: concentration addition (CA) and independent action (IA), and compared to the experimentally determined toxicities over a range of concentrations between 1 and 50mgl(-1). In all cases a clear synergistic effect was observed, showing that single compound toxicity data are not adequate for the prediction of aquatic toxicities of antibiotic mixtures. Risk assessment was performed by calculating the ratio between predicted environmental concentrations (PEC) and the predicted no effect concentration (PNEC). All the antibiotics tested, excepting GEN, have a potential ecological risk, taking into account the PEC of hospital effluents from Buenos Aires, Argentina. These risks increase when antibiotics are present in binary mixtures. PMID:25483375

Magdaleno, A; Saenz, M E; Juárez, A B; Moretton, J

2015-03-01

162

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.

2014-01-01

163

Prediction of Hydrolysis Pathways and Kinetics for Antibiotics under Environmental pH Conditions: A Quantum Chemical Study on Cephradine.  

PubMed

Understanding hydrolysis pathways and kinetics of many antibiotics that have multiple hydrolyzable functional groups is important for their fate assessment. However, experimental determination of hydrolysis encounters difficulties due to time and cost restraint. We employed the density functional theory and transition state theory to predict the hydrolysis pathways and kinetics of cephradine, a model of cephalosporin with two hydrolyzable groups, two ionization states, two isomers and two nucleophilic attack directions. Results showed that the hydrolysis of cephradine at pH = 8.0 proceeds via opening of the ?-lactam ring followed by intramolecular amidation. The predicted rate constants at different pH conditions are of the same order of magnitude as the experimental values, and the predicted products are confirmed by experiment. This study identified a catalytic role of the carboxyl group in the hydrolysis, and implies that the carboxyl group also plays a catalytic role in the hydrolysis of other cephalosporin and penicillin antibiotics. This is a first attempt to quantum chemically predict hydrolysis of an antibiotic with complex pathways, and indicates that to predict hydrolysis products under the environmental pH conditions, the variation of the rate constants for different pathways with pH should be evaluated. PMID:25590945

Zhang, Haiqin; Xie, Hongbin; Chen, Jingwen; Zhang, Shushen

2015-02-01

164

Antibiotics produced by Streptomyces.  

PubMed

Streptomyces is a genus of Gram-positive bacteria that grows in various environments, and its shape resembles filamentous fungi. The morphological differentiation of Streptomyces involves the formation of a layer of hyphae that can differentiate into a chain of spores. The most interesting property of Streptomyces is the ability to produce bioactive secondary metabolites, such as antifungals, antivirals, antitumorals, anti-hypertensives, immunosuppressants, and especially antibiotics. The production of most antibiotics is species specific, and these secondary metabolites are important for Streptomyces species in order to compete with other microorganisms that come in contact, even within the same genre. Despite the success of the discovery of antibiotics, and advances in the techniques of their production, infectious diseases still remain the second leading cause of death worldwide, and bacterial infections cause approximately 17 million deaths annually, affecting mainly children and the elderly. Self-medication and overuse of antibiotics is another important factor that contributes to resistance, reducing the lifetime of the antibiotic, thus causing the constant need for research and development of new antibiotics. PMID:22975171

Procópio, Rudi Emerson de Lima; Silva, Ingrid Reis da; Martins, Mayra Kassawara; Azevedo, Joăo Lúcio de; Araújo, Janete Magali de

2012-01-01

165

[The history of antibiotics].  

PubMed

The development of chemical compounds for the treatment of infectious diseases may be divided into three phases: a) the discovery in the 1600s in South America of alkaloid extracts from the bark of the cinchona tree and from the dried root of the ipecacuanha bush, which proved effective against, respectively, malaria (quinine) and amoebic dysentery (emetine); b) the development of synthetic drugs, which mostly took place in Germany, starting with Paul Ehrlich's (1854-1915) discovery of salvarsan (1909), and crowned with Gerhard Domagk's (1895-1964) discovery of the sulfonamides (1930s); and c) the discovery of antibiotics. The prime example of the latter is the development of penicillin in the late 1920s following a discovery by a solitary research scientist who never worked in a team and never as part of a research programme. It took another ten years or so before drug-quality penicillin was produced, with research now dependent on being conducted in large collaborative teams, frequently between universities and wealthy industrial companies. The search for new antibiotics began in earnest in the latter half of the 1940s and was mostly based on soil microorganisms. Many new antibiotics were discovered in this period, which may be termed «the golden age of antibiotics». Over the past three decades, the development of new antibiotics has largely stalled, while antibiotic resistance has increased. This situation may require new strategies for the treatment of infectious diseases. PMID:24326504

Yazdankhah, Siamak; Lassen, Jřrgen; Midtvedt, Tore; Solberg, Claus Ola

2013-12-10

166

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

2013-01-01

167

A colorimetric assay for the determination of acetyl xylan esterase or cephalosporin C acetyl esterase activities using 7-amino cephalosporanic acid, cephalosporin C, or acetylated xylan as substrate.  

PubMed

A bromothymol blue-based colorimetric assay has been devised to screen for acetyl xylan esterase or cephalosporin C (CPC) deacetylase activities using 7-amino cephalosporanic acid (7-ACA), CPC, or acetylated xylan as substrate. These enzymes are not screened with their natural substrates because of the tedious procedures available previously. Acetyl xylan esterase from Bacillus pumilus CECT 5072 was cloned, expressed in Escherichia coli Rosetta (DE3), and characterized using this assay. Similar K(M) values for 7-ACA and CPC were obtained when compared with those described using HPLC methods. The assay is easy to perform and can be carried out in robotic high-throughput colorimetric devices normally used in directed evolution experiments. The assay allowed us to detect improvements in activity at a minimum of twofold with a very low coefficient of variance in 96-well plates. This method is significantly faster and more convenient to use than are known HPLC and pH-stat procedures. PMID:17651681

Martínez-Martínez, Irene; Montoro-García, Silvia; Lozada-Ramírez, José Daniel; Sánchez-Ferrer, Alvaro; García-Carmona, Francisco

2007-10-15

168

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

1994-01-01

169

The future of new oral antibiotics including the quinolones.  

PubMed

It is estimated that more than 110 million dollars' worth of oral antibiotics will have been sold in Canada in 1987. In the next few years several new oral antimicrobial agents will reach the market, including beta-lactamase inhibitors, cephalosporins, monobactams, erythromycins and quinolones. Most of these new agents have a broader spectrum of antibacterial activity than the presently available oral antibiotics. A few have a longer half-life and can be administered once a day. The new oral drugs, especially the quinolones and possibly beta-lactams, will now be used to treat infections that in the past could be treated only parenterally. Exacerbations of pulmonary infections due to Pseudomonas aeruginosa in cystic fibrosis can now be successfully treated at home with the new quinolones. Osteomyelitis, arthritis, pneumonia and pyelonephritis will most likely be treated at home in the future. In severe infections patients will be admitted to hospital for short courses of parenteral therapy, followed by oral treatment. If used appropriately the new oral agents may lead to new approaches to the treatment of infectious diseases. PMID:3275479

Bergeron, M G

1988-01-01

170

Aspergillomarasmine A overcomes metallo-?-lactamase antibiotic resistance.  

PubMed

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

2014-06-26

171

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

PubMed

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; Solŕ-Ginés, Marc; Moreno, Miguel A; Fraile, Lorenzo; Migura-Garcia, Lourdes

2015-03-01

172

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

2013-01-01

173

Oral versus intravenous antibiotics for community acquired lower respiratory tract infection in a general hospital: open, randomised controlled trial.  

PubMed Central

OBJECTIVE--To see whether there is a difference in outcome between patients treated with oral and intravenous antibiotics for lower respiratory tract infection. DESIGN--Open controlled trial in patients admitted consecutively and randomised to treatment with either oral co-amoxiclav, intravenous followed by oral co-amoxiclav, or intravenous followed by oral cephalosporins. SETTING--Large general hospital in Dublin. PATIENTS--541 patients admitted for lower respiratory tract infection during one year. Patients represented 87% of admissions with the diagnosis and excluded those who were immunocompromised and patients with severe life threatening infection. MAIN OUTCOME MEASURES--Cure, partial cure, extended antibiotic treatment, change of antibiotic, death, and cost and duration of hospital stay. RESULTS--There were no significant differences between the groups in clinical outcome or mortality (6%). However, patients randomised to oral co-amoxiclav had a significantly shorter hospital stay than the two groups given intravenous antibiotic (median 6 v 7 and 9 days respectively). In addition, oral antibiotics were cheaper, easier to administer, and if used routinely in the 800 or so patients admitted annually would lead to savings of around 176,000 pounds a year. CONCLUSIONS--Oral antibiotics in community acquired lower respiratory tract infection are at least as efficacious as intraveous therapy. Their use reduces labour and equipment costs and may lead to earlier discharge from hospital. PMID:7787537

Chan, R.; Hemeryck, L.; O'Regan, M.; Clancy, L.; Feely, J.

1995-01-01

174

Determination of cephalosporins in raw bovine milk by high-performance liquid chromatography.  

PubMed

A high-performance liquid chromatographic (HPLC) method based on solid-phase extraction was developed for the determination of cefazolin, cefoperazone, cefquinome and ceftiofur in raw bovine milk. The milk fat was removed by centrifugation and the cephalosporins were extracted in acetonitrile. The extract was cleaned up by solid-phase extraction on an octadecyl sorbent. The compounds were separated by ion-paired gradient HPLC on a phenyl column with ultraviolet detection at 270 nm. The limits of detection estimated by a conservative model were 11 microg/kg for cefazolin and cefoperazone and 7 microg/kg for cequinome and ceftiofur. The mean recoveries were 86-88% for cefazolin, 91-93% for cefoperazone, 69-72% for cefquinome and 84-88% for ceftiofur in the concentration range 20-200 microg/kg. PMID:10895940

Sřrensen, L K; Snor, L K

2000-06-16

175

[Effectiveness and disposition of the newly developed cephalosporin cefquinome in puerperal septicemia and toxemia in gilts].  

PubMed

Epizootiological, clinical, bacteriological and haematological studies were carried out to assess the effectiveness of the recently developed cephalosporin preparation Cefquinome in the treatment of the puerperal septicaemia and toxaemia syndrome. Cefquinome was administered at three different doses (1, 2 and 4 mg/kg BW) to 188 sows with feverish puerperal illness. Amoxicillin (7 mg/kg BW) was used as a control drug. In 41% of cases endometritis was a monoinfection whereas in 70% of mammary infections mixed infections were diagnosed. Results showed that for therapy of puerperal septicaemia and toxaemia Cefquinome at doses of 2 mg/kg BW and 4 mg/kg BW is clearly more effective than the control drug Amoxicillin and Cefquinome at its lowest dose of 1 mg/kg BW. PMID:10326238

Heinritzi, K; Hagn, J

1999-04-01

176

Impact of antibiotic exposure on occurrence of nosocomial carbapenem-resistant Acinetobacter baumannii infection: A case control study.  

PubMed

Carbapenem-resistant Acinetobacter baumannii (CRAB) infection is one of the most important healthcare associated diseases worldwide. Although antibiotic use is recognized as a risk factor for CRAB infection, the impact of antibiotic class and length of use on CRAB infection is still unclear. A case-control study was conducted in adult intensive care units and general wards of Songklanagarind Hospital, a tertiary-care hospital in southern Thailand, to investigate the effect of different antibiotic exposure and the duration of use on the risk of developing CRAB infection. Cases were defined as patients with carbapenem-susceptible A. baumannii (CSAB) or CRAB infection. Controls were randomly selected from patients and matched 1:1 with cases using ward and date of admission. Multinomial logistic regression was used to compute relative risk ratios (RRR) and 95% confidence intervals (CI) for CRAB infection. Of 197 cases with A. baumannii infection, there were 139 with CRAB infection and 58 with CSAB infection. Compared to the control group, use of fluoroquinolones, broad-spectrum cephalosporins and carbapenems for more than three days increased the risk of CRAB infection with RRR (95% CI) of 81.2 (38.1-862.7), 31.3 (9.9-98.7) and 112.1 (7.1-1770.6), respectively. The RRR (95% CI) for one to three day treatment of fluoroquinolones, broad-spectrum cephalosporins and carbapenems were 5.4 (0.8-38.7), 6.2 (0.1-353.2) and 63.3 (15.6-256.9), respectively. Long-term use of certain antibiotics and even short term use of carbapenems increased the risk of CRAB infection. In this setting, use of these antibiotics, especially carbapenems, should be limited to reduce CRAB infection. PMID:25454216

Chusri, Sarunyou; Silpapojakul, Kachornsakdi; McNeil, Edward; Singkhamanan, Kamonnut; Chongsuvivatwong, Virasakdi

2015-02-01

177

Biodegradable antibiotic delivery systems.  

PubMed

Bacterial infection in orthopaedic surgery can be devastating, and is associated with significant morbidity and poor functional outcomes, which may be improved if high concentrations of antibiotics can be delivered locally over a prolonged period of time. The two most widely used methods of doing this involve antibiotic-loaded polymethylmethacrylate or collagen fleece. The former is not biodegradable and is a surface upon which secondary bacterial infection may occur. Consequently, it has to be removed once treatment has finished. The latter has been used successfully as an adjunct to systemic antibiotics, but cannot effect a sustained release that would allow it to be used on its own, thereby avoiding systemic toxicity. This review explores the newer biodegradable carrier systems which are currently in the experimental phase of development and which may prove to be more effective in the treatment of osteomyelitis. PMID:21282751

El-Husseiny, M; Patel, S; MacFarlane, R J; Haddad, F S

2011-02-01

178

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.

1982-09-01

179

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.

2014-01-01

180

Antibiotics in Animal Products  

NASA Astrophysics Data System (ADS)

The administration of antibiotics to animals to prevent or treat diseases led us to be concerned about the impact of these antibiotics on human health. In fact, animal products could be a potential vehicle to transfer drugs to humans. Using appropri ated mathematical and statistical models, one can predict the kinetic profile of drugs and their metabolites and, consequently, develop preventive procedures regarding drug transmission (i.e., determination of appropriate withdrawal periods). Nevertheless, in the present chapter the mathematical and statistical concepts for data interpretation are strictly given to allow understanding of some basic pharma-cokinetic principles and to illustrate the determination of withdrawal periods

Falcăo, Amílcar C.

181

Evolution of antibiotic resistance by human and bacterial niche construction.  

PubMed

Antibiotic treatment by humans generates strong viability selection for antibiotic-resistant bacterial strains. The frequency of host antibiotic use often determines the strength of this selection, and changing patterns of antibiotic use can generate many types of behaviors in the population dynamics of resistant and sensitive bacterial populations. In this paper, we present a simple model of hosts dimorphic for their tendency to use/avoid antibiotics and bacterial pathogens dimorphic in their resistance/sensitivity to antibiotic treatment. When a constant fraction of hosts uses antibiotics, the two bacterial strain populations can coexist unless host use-frequency is above a critical value; this critical value is derived as the ratio of the fitness cost of resistance to the fitness cost of undergoing treatment. When strain frequencies can affect host behavior, the dynamics may be analyzed in the light of niche construction. We consider three models underlying changing host behavior: conformism, the avoidance of long infections, and adherence to the advice of public health officials. In the latter two, we find that the pathogen can have quite a strong effect on host behavior. In particular, if antibiotic use is discouraged when resistance levels are high, we observe a classic niche-construction phenomenon of maintaining strain polymorphism even in parameter regions where it would not be expected. PMID:15856691

Boni, Maciej F; Feldman, Marcus W

2005-03-01

182

Pharmacokinetics of cephem antibiotics in exudate of pelvic retroperitoneal space after radical hysterectomy and pelvic lymphadenectomy.  

PubMed Central

Many cephalosporin antibiotics have recently been invented and attempts have been made to use them clinically. The choice of which of these drugs should be used has been difficult in gynecology. The efficacies of these drugs depend on their antibacterial spectra, potencies, and concentrations in tissues. This study was designed to investigate the pharmacokinetics of various cephem antibiotics in the exudate of the retroperitoneal space that is formed after radical hysterectomy and pelvic lymphadenectomy. These cephem antibiotics were cefoxitin, cefotiam, cefotetan, cefpiramide, cefminox, cefotaxime, ceftizoxime, cefoperazone, cefmenoxime, cefbuperazone, ceftazidime, cefpimizole, flomoxef, and cefuzonam. The maximum concentrations after administration of a 1-g dose in the exudate of the pelvic retroperitoneal space were 37.9 micrograms/ml with cefminox, 30.3 micrograms/ml with cefpimizole, 21.6 micrograms/ml with flomoxef, 21.5 micrograms/ml with ceftazidime, and 17.6 micrograms/ml with cefbuperazone, which were relatively high. When selecting antibiotics for prophylactic use against infections in the retroperitoneal space after radical hysterectomy and pelvic lymphadenectomy, on the basis of drug transfer, flomoxef, cefminox, cefbuperazone, ceftazidime, and cefpimizole were considered to be the drugs of first choice at a dose of 1 g. PMID:2393276

Ito, K; Hayasaki, M; Tamaya, T

1990-01-01

183

Efficient biocatalyst for large-scale synthesis of cephalosporins, obtained by combining immobilization and site-directed mutagenesis of penicillin acylase.  

PubMed

We describe the rational design of a new efficient biocatalyst and the development of a sustainable green process for the synthesis of cephalosporins bearing a NH? group on the acyl side chain. The new biocatalyst was developed starting from the WT penicillin acylase (PA) from Escherichia coli by combining enzyme mutagenesis, in position ?146 and ?24 (?F24A/?F146Y), and immobilization on an appropriate modified industrial support, glyoxyl Eupergit C250L. The obtained derivative was used in the kinetically controlled synthesis of cephalexin, cefprozil and cefaclor and compared to the WT-PA and an already described mutant, PA-?F24A, with improved properties. The new biocatalyst posses a very high ratio between the rates of the synthesis and two undesired hydrolyses (acylating ester and the amidic product). In particular, a very low amidase activity was observed with PA-?F24A/?F146Y and, consequently, the hydrolysis of the produced antibiotic was avoided during the process. Taking advantage of this property, higher conversions in the synthesis of cephalexin (99% versus 76%), cefaclor (99% versus 65%) and cefprozil (99% versus 60%) were obtained compared to the WT enzyme. Furthermore, the new mutant also show a higher synthetic activity compared to PA-?F24A immobilized on the same support, allowing the maximum yields to be achieved in very short reaction times. The production of cephalexin with the immobilized ?F24A/?F146Y acylase has been developed on a pre-industrial scale (30 l). After 20 cycles, the average yield was 93%. The biocatalyst showed good stability properties and no significant decrease in performance. PMID:22228258

Cecchini, Davide A; Pavesi, Roberto; Sanna, Sara; Daly, Simona; Xaiz, Roberto; Pregnolato, Massimo; Terreni, Marco

2012-09-01

184

Health Care Competition, Antibiotic Use, and Antibiotic Resistance in Taiwan  

Microsoft Academic Search

While antibiotics are critical to modern health care, their overuse has fostered an- tibiotic resistance. Since patients in many settings prefer to visit doctors who freely prescribe antibiotics, doctors may have an incentive to attract patients through greater prescription. This paper examines the eect of health care competition on antibiotic prescription in a large, nationally-representative sample of outpatient visits from

Daniel Bennett; Tsai-Ling Lauderdale; Che-Lun Hung

185

Antibiotics: When Do They Help  

MedlinePLUS

... Help select new symptom Antibiotics: When Do They Help Definition When To Call Care Advice Photos Select ... bacterial. Consider their perspective. Bacterial Infections: Antibiotics can help and will be prescribed Bacterial infections are much ...

186

Best antibiotics for buccal delivery  

E-print Network

The purpose of the research was to identify the clinical and commercial benefits of switching from intravenous (IV) to buccal delivery of antibiotics. then, the research continued to select 3-5 antibiotics that best met ...

Goldberg, Manijeh Nazari

2011-01-01

187

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

2012-02-01

188

Resistance to antibiotics: are we in the post-antibiotic era?  

PubMed

Serious infections caused by bacteria that have become resistant to commonly used antibiotics have become a major global healthcare problem in the 21st century. They not only are more severe and require longer and more complex treatments, but they are also significantly more expensive to diagnose and to treat. Antibiotic resistance, initially a problem of the hospital setting associated with an increased number of hospital-acquired infections usually in critically ill and immunosuppressed patients, has now extended into the community causing severe infections difficult to diagnose and treat. The molecular mechanisms by which bacteria have become resistant to antibiotics are diverse and complex. Bacteria have developed resistance to all different classes of antibiotics discovered to date. The most frequent type of resistance is acquired and transmitted horizontally via the conjugation of a plasmid. In recent times new mechanisms of resistance have resulted in the simultaneous development of resistance to several antibiotic classes creating very dangerous multidrug-resistant (MDR) bacterial strains, some also known as "superbugs". The indiscriminate and inappropriate use of antibiotics in outpatient clinics, hospitalized patients and in the food industry is the single largest factor leading to antibiotic resistance. In recent years, the number of new antibiotics licensed for human use in different parts of the world has been lower than in the recent past. In addition, there has been less innovation in the field of antimicrobial discovery research and development. The pharmaceutical industry, large academic institutions or the government are not investing the necessary resources to produce the next generation of newer safe and effective antimicrobial drugs. In many cases, large pharmaceutical companies have terminated their anti-infective research programs altogether due to economic reasons. The potential negative consequences of all these events are relevant because they put society at risk for the spread of potentially serious MDR bacterial infections. PMID:16216651

Alanis, Alfonso J

2005-01-01

189

Leading articles Antibiotic resistance  

Microsoft Academic Search

Antibiotic resistance is of current concern. This concern has extended beyond those professionally involved in the diagnosis and management of infection: the subject is increasingly reported in the media; new surveillance systems have been established by the WHO, 1 the CDC 2 and the PHLS (M. Wale, personal communication); and in the UK a sub-committee of the House of Lords

R. G. Finch

1998-01-01

190

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

191

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)

1995-06-30

192

ATTACK OF THE SUPERBUGS: ANTIBIOTIC RESISTANCE  

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.

Yim, Grace; Quarterly, The S.

193

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

2014-01-01

194

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

2014-01-01

195

Selection of antibiotic resistance at very low antibiotic concentrations.  

PubMed

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

Sandegren, Linus

2014-05-01

196

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

2011-01-01

197

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

J. D. D. PITOUT; K. S. THOMSON; N. D. HANSON; A. F. EHRHARDT; E. S. MOLAND; C. C. SANDERS

1998-01-01

198

Description and evaluation of the influence of veterinary presence on the use of antibiotics and sulfonamides in dairy herds.  

PubMed

A longitudinal study was conducted over 2 years to identify types of antibiotics and sulfonamides used in Michigan dairy herds for disease prevention and treatment, to determine patterns of use of antibiotics and sulfonamides by herd size and animal age group, and to determine the influence of veterinary presence during diagnosis on the types of antimicrobials used for disease treatments. In order of frequency, the most commonly used preventive antibiotic and sulfonamides were penicillins, tetracyclines, aminoglycosides, and cephalosporins, making up over 86% of all antimicrobials used for disease prevention. The most commonly used therapeutic antibiotics and sulfonamides were penicillins, tetracyclines, aminoglycosides, and sulfonamides, making up over 81% of all antimicrobial drugs used for disease treatment. Cows received the greatest number of drugs, followed by calves (cattle from birth to weaning). Young stock (cattle from weaning to first calving) received the lowest number of drugs. All herds had similar patterns of drug use for the 3 age groups, regardless of herd size. With the exception of polymyxin and chloramphenicol, producers used antibiotics on their own more than with a veterinarian present or on the advice of a veterinarian. Overall, veterinary presence was significantly associated with increased use of tetracyclines, sulfonamides, and nitrofurans, and decreased use of penicillins and aminoglycosides. Implications for drug residue prevention strategies are discussed, with emphasis on the role of the practicing veterinarian. PMID:1644649

Kaneene, J B; Miller, R

1992-07-01

199

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, Desirče; Valverde, Aránzazu; Ruiz-Garbajosa, Patricia

2014-01-01

200

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

1990-01-01

201

Spectroscopic analytical study for the charge-transfer complexation of certain cephalosporins with chloranilic acid.  

PubMed

Studies were carried out to develop a simple, rapid and accurate spectrophotometric method for the analysis of fifteen cephalosporins. The method depends on the charge-transfer complexation reaction between any of these drugs as an n-electron donor and p-chloranilic acid (p-CA) as a pi-acceptor to form a violet chromogen measured at 520 nm. Different variables affecting the reaction were studied and optimized. Under the optimum conditions, linear relationships with good correlation coefficients (0.9986-0.9996) were found between the absorbances and the concentrations of the studied drugs in the range of 4-1,200 microg ml(-1). The limits of assay detection ranged from 2.54 to 42.83 microg ml(-1). The accuracy and precision of the method were satisfactory. The method was successfully applied to an analysis of the studied drugs in their pharmaceutical formulations; the recovery percentages ranged from 96.76 +/- 0.87% to 100.50 +/- 1.30%. The interaction sites were confirmed by UV/VIS, IR, 1H-NMR techniques. Molecular modeling for the interaction was used for deriving an equation for calculating the epsilon value for a particular drug. This equation gave a perfect prediction for the degree of interaction of the investigated drugs with the p-CA reagent. PMID:12608760

Saleh, Gamal A; Askal, Hassan F; Darwish, Ibrahim A; El-Shorbagi, Abdel-Nasser A

2003-02-01

202

In Vitro Activities of Cephalosporins and Quinolones against Escherichia coli Strains Isolated from Diarrheic Dairy Calves  

PubMed Central

The in vitro activities of several cephalosporins and quinolones against 195 strains of Escherichia coli isolated from dairy calves affected by neonatal diarrhea were determined. One hundred thirty-seven of these strains produced one or more potential virulence factors (F5, F41, F17, cytotoxic necrotizing factor, verotoxin, and the eae gene), but the remaining 58 strains did not produce any of these factors. From 11 to 18% of the E. coli strains were resistant to cephalothin, nalidixic acid, enoxacin, and enrofloxacin. However, cefuroxime, cefotaxime, and cefquinome were highly effective against the E. coli isolates tested. Some significant differences (P < 0.05) in resistance to quinolones between the strains producing potential virulence factors and nonfimbriated, nontoxigenic, eae-negative strains were found. Thus, eae-positive, necrotoxigenic, and verotoxigenic (except for nalidixic acid) E. coli strains were significantly more sensitive to nalidixic acid, enoxacin, and enrofloxacin than nonfimbriated, nontoxigenic, eae-negative strains. Moreover, eae-positive strains were significantly more sensitive to enoxacin and enrofloxacin than F5-positive strains. Thus, the results of this study suggest that the bovine E. coli strains that produce some potential virulence factors are more sensitive to quinolones than those that do not express these factors. PMID:10049259

Orden, José Antonio; Ruiz-Santa-Quiteria, José Antonio; García, Silvia; Cid, Dolores; de la Fuente, Ricardo

1999-01-01

203

In vitro activities of cephalosporins and quinolones against Escherichia coli strains isolated from diarrheic dairy calves.  

PubMed

The in vitro activities of several cephalosporins and quinolones against 195 strains of Escherichia coli isolated from diary calves affected by neonatal diarrhea were determined. One hundred thirty-seven of these strains produced one or more potential virulence factors (F5, F41, F17, cytotoxic necrotizing factor, verotoxin, and the eae gene), but the remaining 58 strains did not produce any of these factors. From 11 to 18% of the E. coli strains were resistant to cephalothin, nalidixic acid, enoxacin, and enrofloxacin. However, cefuroxime, cefotaxime, and cefquinome were highly effective against the E. coli isolates tested. Some significant differences (P < 0.05) in resistance to quinolones between the strains producing potential virulence factors and nonfimbriated, nontoxigenic, eae-negative strains were found. Thus, eae-positive, necrotoxigenic, and verotoxigenic (except for nalidixic acid) E. coli strains were significantly more sensitive to nalidixic acid, enoxacin, and enrofloxacin than nonfimbriated, nontoxigenic, eae-negative strains. Moreover, eae-positive strains were significantly more sensitive to enoxacin and enrofloxacin than F5-positive strains. Thus, the result of this study suggest that the bovine E. coli strains that produce some potential virulence factors are more sensitive to quinolones than those that do not express these factors. PMID:10049259

Orden, J A; Ruiz-Santa-Quiteria, J A; García, S; Cid, D; De La Fuente, R

1999-03-01

204

Advanced treatment of cephalosporin pharmaceutical wastewater by nano-coated electrode and perforated electrode.  

PubMed

The objective of this study was to investigate the degradation of nonbiodegradable organic pollutants in biologically cephalosporin pharmaceutical wastewater using different electrodes such as non-nano-scale electrode (traditional coated), nano-scale (nano-coated) electrode, and perforated electrode after biotreatment. The traditional coated electrode plate, nano-coated electrode plate, and two different perforated titanium dioxide (TiO2) electrode plates with an average pore size of 10 ?m and 20 ?m were chosen as the anode. The results demonstrated that traditional coated electrode, nano-scale electrode, and perforated electrode could effectively remove nonbiodegradable organic pollutants from pharmaceutical wastewater. The perforated electrode with an average pore size of 10 ?m exhibited the best degradation effect with a 90 % decrease in the chemical oxygen demand (COD) (COD content reduced from 320 mg L(-1) to 32 mg L(-1)). During catalytic degradation, the electrical conductivity of pharmaceutical wastewater increased and the pH increased and finally reached equilibrium. It was also found that the perforated TiO2 electrode produced relatively large amounts of dissolved oxygen during the catalytic oxidation process, reaching above 4 mg L(-1), whereas the nano-coated electrode produced little dissolved oxygen. The biotoxicities of all wastewater samples increased firstly then decreased slightly during the electrical catalytic oxidation, but the final biotoxicities were all higher than initial ones. PMID:24967559

Yang, Bo; Zuo, Jiane; Gan, Lili; Yu, Xin; Liu, Fenglin; Tang, Xinyao; Wang, Yajiao

2014-09-19

205

Comparative pharmacokinetics and clinical experience with a new cephalosporin-derivative: cefazolin.  

PubMed

In a cross-over study in 12 normal individuals, the pharmacokinetic parameters of cefalotin, cefradine and cefazolin were determined after intravenous injection of 1,000 mg of each substance. The microbiological activities in urine and serum were determined using the agar diffusion test; the pharmacokinetic data were calculated by a computer system on the basis of a Fortran programme. Cefazolin has significantly higher serum concentrations than the other two cephalosporins, distinctly longer serum half-lives, higher protein binding, and smaller apparent volumina of distribution. In 36 inpatients with mainly chronical and acute infections of the urinary tract, we tested the antibacterial effectivity, the compatibility, and the application modalities of cefazolin. In 29 patients we had a satisfactory clinical result, in 25 cases we achieved the elimination of bacteria by the end of the therapy. The compatibility of cefazolin was good; apart from a minor, reversible, liver-specific increase in enzymes in 6 patients, no side effects could be detected. PMID:1097207

Lode, H; Gebert, S; Hendrischk, A

1975-01-01

206

Disposition of the cephalosporin cefepime in normal and renally impaired subjects.  

PubMed

The metabolism and disposition of an iv-administered, 1000 mg (100 microCi) single dose of the 14C-labeled cephalosporin cefepime was studied in healthy and renally impaired male volunteers. The 14C-label was located in the methyl group of the N-methyl pyrrolidine (NMP) moiety at the 3'-position of cefepime. Concentrations of cefepime and its metabolites were determined in plasma and urine as a function of time after drug administration. Cefepime comprised 95 and 76% of the total plasma radioactivity in subjects with normal and impaired renal functions, respectively. The elimination half-life of cefepime was 2 hr in normal volunteers and increased to 4 and 12 hr in subjects with moderate and severe renal impairment, respectively. Steady-state volume of distribution was about 18 liters and was independent of the degree of renal impairment. Cefepime was primarily excreted unchanged in the urine of normal subjects, as 87.9% of the total recovered radioactivity. The major cefepime metabolites, NMP N-oxide, the 7-epimer of cefepime and NMP, constituted 6.8, 2.5, and less than 1% of the total radioactivity excreted in urine, respectively. As the severity of renal impairment increased, the proportion of radioactivity recovered in urine as cefepime decreased and that of NMP-N-oxide increased. Our results indicate that cefepime undergoes minimal metabolism and is excreted primarily as unchanged drug in urine in humans with normal kidney functions. PMID:1673424

Barbhaiya, R H; Knupp, C A; Forgue, S T; Matzke, G R; Halstenson, C E; Opsahl, J A; Pittman, K A

1991-01-01

207

Asexual Cephalosporin C Producer Acremonium chrysogenum Carries a Functional Mating Type Locus  

Microsoft Academic Search

Acremonium chrysogenum, the fungal producer of the pharmaceutically relevant -lactam antibiotic cepha- losporin C, is classified as asexual because no direct observation of mating or meiosis has yet been reported. To assess the potential of A. chrysogenum for sexual reproduction, we screened an expressed sequence tag library from A. chrysogenum for the expression of mating type (MAT) genes, which are

Stefanie Poggeler; Birgit Hoff; Ulrich Kuck

2008-01-01

208

Core-shell supramolecular gelatin nanoparticles for adaptive and "on-demand" antibiotic delivery.  

PubMed

The treatment of bacterial infection is one of the most challenging tasks in the biomedical field. Antibiotics were developed over 70 years and are regarded as the most efficient type of drug to treat bacterial infection. However, there is a concern that the overuse of antibiotics can lead to a growing number of multidrug-resistant bacteria. The development of antibiotic delivery systems to improve the biodistribution and bioavailability of antibiotics is a practical strategy for reducing the generation of antibiotic resistance and increasing the lifespan of newly developed antibiotics. Here we present an antibiotic delivery system (Van?SGNPs@RBC) based on core-shell supramolecular gelatin nanoparticles (SGNPs) for adaptive and "on-demand" antibiotic delivery. The core composed of cross-linked SGNPs allows for bacterial infection-microenvironment responsive release of antibiotics. The shell coated with uniform red blood cell membranes executes the function of disguise for reducing the clearance by the immune system during the antibiotic delivery, as well as absorbs the bacterial exotoxin to relieve symptoms caused by bacterial infection. This approach demonstrates an innovative and biomimetic antibiotic delivery system for the treatment of bacterial infection with a minimum dose of antibiotics. PMID:24716550

Li, Li-Li; Xu, Jun-Hua; Qi, Guo-Bin; Zhao, Xingzhong; Yu, Faquan; Wang, Hao

2014-05-27

209

Antibiotic resistance in pediatric urology  

PubMed Central

Antibiotics are a mainstay in the treatment of bacterial infections, though their use is a primary risk factor for the development of antibiotic resistance. Antibiotic resistance is a growing problem in pediatric urology as demonstrated by increased uropathogen resistance. Lack of urine testing, nonselective use of prophylaxis, and poor empiric prescribing practices exacerbate this problem. This article reviews antibiotic utilization in pediatric urology with emphasis on modifiable practice patterns to potentially help mitigate the growing rates of antibiotic resistance. This includes urine testing to only treat when indicated and tailor broad-spectrum therapy as able; selective application of antibiotic prophylaxis to patients with high-grade vesicoureteral reflux and hydronephrosis with counseling regarding the importance of compliance; and using local antiobiograms, particularly pediatric-specific antiobiograms, with inpatient versus outpatient data. PMID:24688601

Copp, Hillary L.

2014-01-01

210

[Topical antibiotics in skin infections].  

PubMed

To understand the development of bacterial resistance and multi-resistance following treatment with topical and systemic antibiotics is important for dermatologists. Furthermore the sensitization potential and toxicity of antibiotics applied to large skin areas must be considered. The advantage of many topical antibiotics is evident; extremely high concentrations can be achieved in the infected skin usually without any systemic side effects. When an antibiotic is used both systemically and topically, indications should be weighed carefully for topical use, in order to reduce the likelihood of sensitization to an potential systemic agent. Continuous monitoring of the resistance profile of important bacteria is also desirable, in order to preserve the utility of important "reserve antibiotics". In this review the most important topical antibiotics used in Germany are evaluated with regards to efficacy and safety profile. PMID:15765214

Thaçi, D; Schöfer, H

2005-04-01

211

Antibiotic overuse versus chronic suppression  

Microsoft Academic Search

Because of the increasing use of antibiotics in the inpatient and outpatient setting, the emergence of resistance to antimicrobial\\u000a agents has progressed significantly. Traditionally, antibiotic resistance has been a problem only in the management of complicated\\u000a nosocomial urinary tract infections (UTIs). However, we now are seeing an emergence of antibiotic resistance in uncomplicated\\u000a community-acquired UTIs. Although uncomplicated UTIs constitute most

Kevin Bigelow; Alexis E. Te

2005-01-01

212

Liquid antibiotics in bone cement  

PubMed Central

Objectives The objective of this study was to compare the elution characteristics, antimicrobial activity and mechanical properties of antibiotic-loaded bone cement (ALBC) loaded with powdered antibiotic, powdered antibiotic with inert filler (xylitol), or liquid antibiotic, particularly focusing on vancomycin and amphotericin B. Methods Cement specimens loaded with 2 g of vancomycin or amphotericin B powder (powder group), 2 g of antibiotic powder and 2 g of xylitol (xylitol group) or 12 ml of antibiotic solution containing 2 g of antibiotic (liquid group) were tested. Results Vancomycin elution was enhanced by 234% in the liquid group and by 12% in the xylitol group compared with the powder group. Amphotericin B elution was enhanced by 265% in the liquid group and by 65% in the xylitol group compared with the powder group. Based on the disk-diffusion assay, the eluate samples of vancomycin-loaded ALBC of the liquid group exhibited a significantly larger inhibitory zone than samples of the powder or the xylitol group. Regarding the ALBCs loaded with amphotericin B, only the eluate samples of the liquid group exhibited a clear inhibitory zone, which was not observed in either the xylitol or the powder groups. The ultimate compressive strength was significantly reduced in specimens containing liquid antibiotics. Conclusions Adding vancomycin or amphotericin B antibiotic powder in distilled water before mixing with bone cement can significantly improve the efficiency of antibiotic release than can loading ALBC with the same dose of antibiotic powder. This simple and effective method for preparation of ALBCs can significantly improve the efficiency of antibiotic release in ALBCs. Cite this article: Bone Joint Res 2014;3:246–51. PMID:25104836

Chang, Y. H.; Tai, C. L.; Hsu, H. Y.; Hsieh, P. H.; Lee, M. S.; Ueng, S. W. N.

2014-01-01

213

Natural antibiotic susceptibility of Klebsiella pneumoniae, K. oxytoca, K. planticola, K. ornithinolytica and K. terrigena strains.  

PubMed

The natural susceptibility of 221 Klebsiella strains to 71 antibiotics was examined. The strains were isolated from clinical specimens and the environment, and belonged to K. pneumoniae subsp. pneumoniae (n = 40), K. pneumoniae subsp. ozaenae (37), K. pneumoniae subsp. rhinoscleromatis (10), K. oxytoca (44), K. planticola (40), K. ornithinolytica (25) and K. terrigena (25). MIC values were determined by a microdilution procedure in IsoSensitest broth according to the German standard (DIN). All Klebsiella spp. were naturally resistant or intermediate to amoxicillin, ticarcillin and to antibiotics to which other Enterobacteriaceae are also intrinsically resistant. Klebsiella spp. were naturally sensitive or intermediate to several penicillins, all tested cephalosporins, aminoglycosides, quinolones, tetracyclines, trimethoprim, cotrimoxazole, chloramphenicol and nitrofurantoin. K. pneumoniae subsp. ozaenae and subsp. rhinoscleromatis strains were generally more susceptible to antibiotics than strains of other Klebsiella taxa. K pneumoniae subsp. rhinoscleromatis was the most susceptible taxon, being highly susceptible to cefuroxime, anti-folates and naturally intermediate to erythromycin and clarithromycin. K. pneumoniae subsp. ozaenae was most susceptible to glycopeptides. K. oxytoca and K. terrigena strains were least susceptible to cefazoline, cefoperazone and fosfomycin, respectively. The results of the present study describe a database of the natural antimicrobial susceptibility of Klebsiella spp., which can be used for the validation of antibiotic susceptibility results of these bacteria. MIC patterns to beta-lactams indicate the expression of chromosomally encoded class A gamma-lactamases in all the species, including the subspecies of K. pneumoniae. Similar natural susceptibility patterns of K. planticola and K. ornithinolytica to all tested antibiotics support the status of K. ornithinolytica as a biovar of K. planticola. PMID:11339246

Stock, I; Wiedemann, B

2001-05-01

214

Colonization and Persistence of Antibiotic-Resistant Enterobacteriaceae Strains in Infants Nursed in Two Neonatal Intensive Care Units in East London, United Kingdom?  

PubMed Central

Stool samples were collected from infants nursed in two neonatal intensive care units (NICUs) in East London, United Kingdom. The aim of the study was to determine the incidence of and risk factors for the carriage of multiresistant Enterobacteriaceae strains (MRE; resistant to three or more classes of antibiotic) and the extent of the persistence of resistant strains following discharge. Sixty-two (50%) of 124 infants had acquired MRE by 2 weeks of postnatal age, and 69 (56%) infants had acquired MRE by discharge. The proportions of infants at 2 weeks carrying strains that were resistant to antibiotics were the following: tetracycline, 79%; amoxicillin, 78%; cephalosporins, 31%; trimethoprim, 20%; piperacillin-tazobactam, 11%; chloramphenicol, 9%; and aminoglycoside, 4%. A gestational age of less than 26 weeks was a risk factor for colonization with MRE at discharge, but not at 2 weeks. Analysis within a NICU showed that exposure of an infant to a specific antibiotic in the NICU was not a risk factor for the carriage of a strain resistant to that antibiotic. Estimates of persistence from discharge to 6 months were the following: for tetracycline, 57% (95% confidence intervals [CI], 0.35 to 0.87); chloramphenicol, 49% (95% CI, 0.20 to 0.83); trimethoprim, 45% (95% CI, 0.22 to 0.74); piperacillin-tazobactam, 42% (95% CI, 0.20 to 0.71); and augmentin, 34% (95% CI, 0.11 to 0.66). Strains resistant to cephalosporins or aminoglycosides showed lower levels of persistence. Nine of 34 infants (26.5%) with Escherichia coli and 4 (7.1%) of 56 infants with Klebsiella spp. at discharge carried strains indistinguishable by randomly amplified polymorphic DNA and antibiotic susceptibility patterns at 6 months. MRE were found at high frequency in the infants during their stay in the NICU and persisted in a proportion of infants. PMID:18039801

Millar, Michael; Philpott, Alex; Wilks, Mark; Whiley, Angela; Warwick, Simon; Hennessy, Enid; Coen, Pietro; Kempley, Stephen; Stacey, Fiona; Costeloe, Kate

2008-01-01

215

Antibiotic-associated diarrhoea.  

PubMed

Diarrhoea is a common complication of antimicrobial therapy. The term antibiotic-associated diarrhoea (AAD) is often considered synonymous with Clostridium difficile. In fact, AAD can develop through a variety of mechanisms and manifest through a broad range of clinical signs and symptoms. For improved prevention and recognition of AAD, it is important to understand the pathophysiology and risk factors for AAD. Although Clostridium difficile continues to be the most common identifiable pathogen of AAD, many patients with AAD can be managed through a variety of conservative measures. This review focuses on some of the important distinctions between nonspecific AAD and antibiotic-associated colitis. In addition, the most recent data on important risk factors for the development of AAD are summarised. Given its pathogenicity, there will be an emphasis on the early diagnosis, treatment and prevention of Clostridium difficile-associated diarrhoea. AAD is a common clinical problem that can progress to severe, life-threatening disease if not recognised quickly. Better awareness of risk factors can lead to the most efficacious treatment of this disorder: primary prevention. PMID:16610966

Coté, Gregory A; Buchman, Alan L

2006-05-01

216

Low or High Doses of Cefquinome Targeting Low or High Bacterial Inocula Cure Klebsiella pneumoniae Lung Infections but Differentially Impact the Levels of Antibiotic Resistance in Fecal Flora  

PubMed Central

The combination of efficacious treatment against bacterial infections and mitigation of antibiotic resistance amplification in gut microbiota is a major challenge for antimicrobial therapy in food-producing animals. In rats, we evaluated the impact of cefquinome, a fourth-generation cephalosporin, on both Klebsiella pneumoniae lung infection and intestinal flora harboring CTX-M-producing Enterobacteriaceae. Germfree rats received a fecal flora specimen from specific-pathogen-free pigs, to which a CTX-M-producing Escherichia coli strain had been added. K. pneumoniae cells were inoculated in the lungs of these gnotobiotic rats by using either a low (105 CFU) or a high (109 CFU) inoculum. Without treatment, all animals infected with the low or high K. pneumoniae inoculum developed pneumonia and died before 120 h postchallenge. In the treated groups, the low-inoculum rats received a 4-day treatment of 5 mg/kg of body weight cefquinome beginning at 24 h postchallenge (prepatent phase of the disease), and the high-inoculum rats received a 4-day treatment of 50 mg/kg cefquinome beginning when the animals expressed clinical signs of infection (patent phase of the disease). The dose of 50 mg/kg targeting the high K. pneumoniae inoculum cured all the treated rats and resulted in a massive amplification of CTX-M-producing Enterobacteriaceae. A dose of 5 mg/kg targeting the low K. pneumoniae inoculum cured all the rats and averted an outbreak of clinical disease, all without any amplification of CTX-M-producing Enterobacteriaceae. These findings might have implications for the development of new antimicrobial treatment strategies that ensure a cure for bacterial infections while avoiding the amplification of resistance genes of human concern in the gut microbiota of food-producing animals. PMID:24395228

Vasseur, Maleck V.; Laurentie, Michel; Rolland, Jean-Guy; Perrin-Guyomard, Agnčs; Henri, Jérôme; Ferran, Aude A.; Toutain, Pierre-Louis

2014-01-01

217

Low or high doses of cefquinome targeting low or high bacterial inocula cure Klebsiella pneumoniae lung infections but differentially impact the levels of antibiotic resistance in fecal flora.  

PubMed

The combination of efficacious treatment against bacterial infections and mitigation of antibiotic resistance amplification in gut microbiota is a major challenge for antimicrobial therapy in food-producing animals. In rats, we evaluated the impact of cefquinome, a fourth-generation cephalosporin, on both Klebsiella pneumoniae lung infection and intestinal flora harboring CTX-M-producing Enterobacteriaceae. Germfree rats received a fecal flora specimen from specific-pathogen-free pigs, to which a CTX-M-producing Escherichia coli strain had been added. K. pneumoniae cells were inoculated in the lungs of these gnotobiotic rats by using either a low (10(5) CFU) or a high (10(9) CFU) inoculum. Without treatment, all animals infected with the low or high K. pneumoniae inoculum developed pneumonia and died before 120 h postchallenge. In the treated groups, the low-inoculum rats received a 4-day treatment of 5 mg/kg of body weight cefquinome beginning at 24 h postchallenge (prepatent phase of the disease), and the high-inoculum rats received a 4-day treatment of 50 mg/kg cefquinome beginning when the animals expressed clinical signs of infection (patent phase of the disease). The dose of 50 mg/kg targeting the high K. pneumoniae inoculum cured all the treated rats and resulted in a massive amplification of CTX-M-producing Enterobacteriaceae. A dose of 5 mg/kg targeting the low K. pneumoniae inoculum cured all the rats and averted an outbreak of clinical disease, all without any amplification of CTX-M-producing Enterobacteriaceae. These findings might have implications for the development of new antimicrobial treatment strategies that ensure a cure for bacterial infections while avoiding the amplification of resistance genes of human concern in the gut microbiota of food-producing animals. PMID:24395228

Vasseur, Maleck V; Laurentie, Michel; Rolland, Jean-Guy; Perrin-Guyomard, Agnčs; Henri, Jérôme; Ferran, Aude A; Toutain, Pierre-Louis; Bousquet-Mélou, Alain

2014-01-01

218

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

PubMed

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

2013-01-01

219

Metabolic regulation of antibiotic resistance.  

PubMed

It is generally assumed that antibiotics and resistance determinants are the task forces of a biological warfare in which each resistance determinant counteracts the activity of a specific antibiotic. According to this view, antibiotic resistance might be considered as a specific response to an injury, not necessarily linked to bacterial metabolism, except for the burden that the acquisition of resistance might impose on the bacteria (fitness costs). Nevertheless, it is known that changes in bacterial metabolism, such as those associated with dormancy or biofilm formation, modulate bacterial susceptibility to antibiotics (phenotypic resistance), indicating that there exists a linkage between bacterial metabolism and antibiotic resistance. The analyses of the intrinsic resistomes of bacterial pathogens also demonstrate that the building up of intrinsic resistance requires the concerted action of many elements, several of which play a relevant role in the bacterial metabolism. In this article, we will review the current knowledge on the linkage between bacterial metabolism and antibiotic resistance and will discuss the role of global metabolic regulators such as Crc in bacterial susceptibility to antibiotics. Given that growing into the human host requires a metabolic adaptation, we will discuss whether this adaptation might trigger resistance even in the absence of selective pressure by antibiotics. PMID:21645016

Martínez, José L; Rojo, Fernando

2011-09-01

220

Bacterial resistance to aminoglycoside antibiotics.  

PubMed

The aminoglycoside antibiotics are broad-spectrum antibacterial compounds that are used extensively for the treatment of many bacterial infections. In view of the current concerns over the global rise in antibiotic-resistant microorganisms, there has been renewed interest in the mechanisms of resistance to the aminoglycosides, including the superfamily of aminoglycoside-modifying enzymes. PMID:9211644

Davies, J; Wright, G D

1997-06-01

221

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.

2008-01-01

222

Antibiotics: Opportunities for Genetic Manipulation  

Microsoft Academic Search

New antibiotics can still be discovered by the development of novel screening procedures. Notable successes over the last few years include the monobactams, beta-lactamase inhibitors (clavulanic acid) and new glycopeptides in the antibacterial field; antiparasitic agents such as avermectins; and herbicidal antibiotics like bialaphos. In the future we can expect the engineering of genes from 'difficult' pathogens, including mycobacteria and

D. A. Hopwood

1989-01-01

223

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

2014-01-01

224

Putrescine Reduces Antibiotic-Induced Oxidative Stress as a Mechanism of Modulation of Antibiotic Resistance in Burkholderia cenocepacia  

PubMed Central

Communication of antibiotic resistance among bacteria via small molecules is implicated in transient reduction of bacterial susceptibility to antibiotics, which could lead to therapeutic failures aggravating the problem of antibiotic resistance. Released putrescine from the extremely antibiotic-resistant bacterium Burkholderia cenocepacia protects less-resistant cells from different species against the antimicrobial peptide polymyxin B (PmB). Exposure of B. cenocepacia to sublethal concentrations of PmB and other bactericidal antibiotics induces reactive oxygen species (ROS) production and expression of the oxidative stress response regulator OxyR. We evaluated whether putrescine alleviates antibiotic-induced oxidative stress. The accumulation of intracellular ROS, such as superoxide ion and hydrogen peroxide, was assessed fluorometrically with dichlorofluorescein diacetate, while the expression of OxyR and putrescine synthesis enzymes was determined in luciferase assays using chromosomal promoter-lux reporter system fusions. We evaluated wild-type and isogenic deletion mutant strains with defects in putrescine biosynthesis after exposure to sublethal concentrations of PmB and other bactericidal antibiotics. Exogenous putrescine protected against oxidative stress induced by PmB and other antibiotics, whereas reduced putrescine synthesis resulted in increased ROS generation and a parallel increased sensitivity to PmB. Of the 3 B. cenocepacia putrescine-synthesizing enzymes, PmB induced only BCAL2641, an ornithine decarboxylase. This study reveals BCAL2641 as a critical component of the putrescine-mediated communication of antibiotic resistance and as a plausible target for designing inhibitors that would block the communication of such resistance among different bacteria, ultimately reducing the window of therapeutic failure in treating bacterial infections. PMID:24820075

El-Halfawy, Omar M.

2014-01-01

225

Axenomycins, New Cestocidal Antibiotics  

PubMed Central

Axenomycins are a new group of macrolide antibiotics isolated from the fermentation broth of Streptomyces lisandri n.sp. They exhibit anthelmintic activity against tapeworms (Cestoda). Three different fractions, A, B, and D, have been obtained, the most active fraction being axenomycin D. The activities of the axenomycin complex and axenomycin D against Hymenolepis nana in mice, Taenia pisiformis, Dipylidium caninum, and Diphyllobothrium sp. in dogs, and Moniezia expansa, M. benedeni, and Avitellina centripunctata in lambs were studied in experimentally and naturally infected animals. Axenomycins were effective and well tolerated by the oral route. Worm reduction rates after a single oral dose were 90 to 100% with 5 to 10 mg of axenomycin D/kg and 50 to 100% with 20 mg of axenomycin complex/kg. PMID:4790622

Bruna, C. Della; Ricciardi, M. L.; Sanfilippo, A.

1973-01-01

226

Resistance to selected beta-lactam antibiotics.  

PubMed

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

2014-07-16

227

Bacterial evolution of antibiotic hypersensitivity  

PubMed Central

The evolution of resistance to a single antibiotic is frequently accompanied by increased resistance to multiple other antimicrobial agents. In sharp contrast, very little is known about the frequency and mechanisms underlying collateral sensitivity. In this case, genetic adaptation under antibiotic stress yields enhanced sensitivity to other antibiotics. Using large-scale laboratory evolutionary experiments with Escherichia coli, we demonstrate that collateral sensitivity occurs frequently during the evolution of antibiotic resistance. Specifically, populations adapted to aminoglycosides have an especially low fitness in the presence of several other antibiotics. Whole-genome sequencing of laboratory-evolved strains revealed multiple mechanisms underlying aminoglycoside resistance, including a reduction in the proton-motive force (PMF) across the inner membrane. We propose that as a side effect, these mutations diminish the activity of PMF-dependent major efflux pumps (including the AcrAB transporter), leading to hypersensitivity to several other antibiotics. More generally, our work offers an insight into the mechanisms that drive the evolution of negative trade-offs under antibiotic selection. PMID:24169403

Lázár, Viktória; Pal Singh, Gajinder; Spohn, Réka; Nagy, István; Horváth, Balázs; Hrtyan, Mónika; Busa-Fekete, Róbert; Bogos, Balázs; Méhi, Orsolya; Csörg?, Bálint; Pósfai, György; Fekete, Gergely; Szappanos, Balázs; Kégl, Balázs; Papp, Balázs; Pál, Csaba

2013-01-01

228

Oriented immobilization and characterization of a poly-lysine-tagged cephalosporin C acylase on glyoxyl agarose support.  

PubMed

Cephalosporin C acylase (CCA), an important industrial enzyme for the production of 7-aminocephalosporanic acid, has very limited and scattered surface lysine residues. A mutant of cephalosporin C acylase (mCCA) has been designed to fuse a poly-lysine tag to the C-terminal of the ?-subunit, which is far away from the active site. The free mCCA showed a near equal specific activity with the wild-type CCA, while a much higher activity recovery was obtained for the mCCA than its wild-type counterpart after immobilization on glyoxyl agarose support (73.3 versus 53.3 %). The mCCA's oriented immobilization enables it to obtain a higher substrate affinity and even a higher thermal stability than the wild-type enzyme. The improvement of stability might be attributed to the multipoint covalent attachment by the oriented enzyme immobilization via the adhered poly-lysine tag, which prevents the dissociation of the ?-subunit of CCA from the support. PMID:25448633

Luo, Hui; Zhao, Huan; Chang, Yanhong; Wang, Qixin; Yu, Huimin; Shen, Zhongyao

2015-02-01

229

Microbial uropathogens and their antibiotic resistance profile from hospitalized patients in Central Alabama.  

PubMed

Urinary tract infections remain a common problem in inpatient care. They are highly challenging to provide effective initial therapy without sensitivity data. The purpose of this study was to survey the uropathogens and their sensitivity profile at a hospital in Central Alabama and to guide experiential antibiotic selection. This was the first reported study on bacterial uropathogens and their antibiotic resistance profile at this Central Alabama hospital. The survey period was between July 2009 and June 2010, a total of 473 urine cultures were reviewed and susceptibility testing was determined using the Clinical and Laboratory Standards Institute (CLSI) microdilution method. The results indicated that Escherichia coli (45.5%) was the most common organism, followed by Klebsiella pneumoniae (18.2%), Pseudomonas aeruginosa (10.1%), Proteus mirabilis (7.8%), Enterobacter cloacae (4.2%), methicillin-resistant Staphylococcus aureus (3.0%), Klebsiella oxytoca and Citrobacter freundii (1.5%), Morganella morganii (1.3%), and the other species (7.0%). For the 215 E. coli isolates, imipenem and cephalosporins (except for cefazolin) had the highest sensitivity (99-100%, P < 0.05). In contrast, ampicillin had the highest resistance (57%, P < 0.05) as compared to other antibiotics (about 30%) including ampicillin/ sulbactam, ciprofloxacin, levofloxacin, tetracycline, and trimethoprim/sulfamethoxazole. The major finding of this study was that ciprofloxacin, levofloxacin and trimethoprim/sulfamethoxazole had comparable sensitivity patterns for Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter cloacae, the most common uropathogens at this Central Alabama hospital. Additionally, this study found that E. coli had a resistant rate of 31% to ciprofloxacin and levofloxacin compared to the resistance rate of 28.4% and 15.8% in earlier reports (Lee et al. 2010; Rattanaumpawan et al. 2010), likely indicating the continuing evolution of resistance due to antibiotic exposure. It is imperative to monitor the resistance of P. aeruginosa considering their high resistance to imipenem found in this study. PMID:23330509

Qian, Li; Camara, Tracy; Taylor, J Kyle; Jones, Kathy W

2012-01-01

230

Diverse Antibiotic Resistance Genes in Dairy Cow Manure  

PubMed Central

ABSTRACT Application of manure from antibiotic-treated animals to crops facilitates the dissemination of antibiotic resistance determinants into the environment. However, our knowledge of the identity, diversity, and patterns of distribution of these antibiotic resistance determinants remains limited. We used a new combination of methods to examine the resistome of dairy cow manure, a common soil amendment. Metagenomic libraries constructed with DNA extracted from manure were screened for resistance to beta-lactams, phenicols, aminoglycosides, and tetracyclines. Functional screening of fosmid and small-insert libraries identified 80 different antibiotic resistance genes whose deduced protein sequences were on average 50 to 60% identical to sequences deposited in GenBank. The resistance genes were frequently found in clusters and originated from a taxonomically diverse set of species, suggesting that some microorganisms in manure harbor multiple resistance genes. Furthermore, amid the great genetic diversity in manure, we discovered a novel clade of chloramphenicol acetyltransferases. Our study combined functional metagenomics with third-generation PacBio sequencing to significantly extend the roster of functional antibiotic resistance genes found in animal gut bacteria, providing a particularly broad resource for understanding the origins and dispersal of antibiotic resistance genes in agriculture and clinical settings. PMID:24757214

Wichmann, Fabienne; Udikovic-Kolic, Nikolina; Andrew, Sheila; Handelsman, Jo

2014-01-01

231

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

PubMed

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

2014-11-15

232

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

2009-01-01

233

Antibiotics in the clinical pipeline in 2011  

Microsoft Academic Search

The emergence of multi-drug-resistant bacteria and the lack of new antibiotics in the antibiotic drug development pipeline, especially those with new modes of action, is a major health concern. This review lists the 20 new antibiotics launched since 2000 and records the 40 compounds currently in active clinical development. Compounds in the pipeline from new antibiotic classes are reviewed in

Mark S Butler; Matthew A Cooper

2011-01-01

234

Antibiotic prophylaxis for arthroscopic surgery.  

PubMed

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

2006-04-01

235

Antibiotics in third molar surgery.  

PubMed

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

2014-01-01

236

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

2014-01-01

237

Simultaneous multiresponse optimization of an HPLC method to separate seven cephalosporins in plasma and amniotic fluid: application to validation and quantification of cefepime, cefixime and cefoperazone.  

PubMed

An HPLC method for the separation of seven cephalosporins [Cefepime (CEP), ceftazidime (CTA), ceftizaxime (CTI), ceftriaxone (CTR), cefotaxime (COT), cefixime (CIX) and cefoperazone (COP)] in human plasma and amniotic fluid has been developed. Optimization of the chromatographic method was performed in three steps: a series of initial experiments followed by two sets of experiments based on different experimental designs. The initial experiments were performed to decide the basic analytical requirements of the method. Then screening experiment fractional factorial design was used in order to decrease the number of parameters by eliminating parameters which having insignificant effect on responses. The parameters having significant effect were further optimized through a full factorial design. Having studied two responses (retention times and resolutions), a desirability function that assess the responses together, was used to find experimental conditions where the system generated desirable results. The desirable results were obtained with XTerra C18 (250 mm x 4.6mm, 5 microm i.d.) column, 40 mM phosphate buffer, pH 3.2, 18% MeOH, 0.85 mL min(-1) flow rate and 32 degrees C column temperature. Gradient elution with MeOH was applied. A simple and efficient solid-phase extraction was applied for the preparation of plasma and amniotic fluid samples. The validation parameters of the method were evaluated in accordance with ICH guideline. The method validated was applied to the analysis of CEP and COP in maternal venous, fetal venous and fetal arterial plasma, and to the analysis of CIX in maternal venous plasma and amniotic fluid. PMID:19782200

Nemutlu, Emirhan; Kir, Sedef; Katlan, Doruk; Beksaç, M Sinan

2009-11-15

238

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

PubMed

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

2014-04-01

239

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

PubMed

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

1992-02-01

240

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

PubMed

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

2014-05-01

241

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" (www.kineticcity.com) 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 (;)

2005-01-01

242

Heat inactivation of beta-lactam antibiotics in milk.  

PubMed

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

2008-06-01

243

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...

244

World alliance against antibiotic resistance: The WAAAR declaration against antibiotic resistance.  

PubMed

We must change how antibiotics are used and adopt proactive strategies, similar to those used to save endangered species. Preservation of the efficacy of antibiotics and to stabilization of antibiotic-susceptible bacterial ecosystems should be global goals. PMID:25534919

Carlet, Jean

2015-01-01

245

Ferrate(VI) oxidation of ?-lactam antibiotics: reaction kinetics, antibacterial activity changes, and transformation products.  

PubMed

Oxidation of ?-lactam antibiotics by aqueous ferrate(VI) was investigated to determine reaction kinetics, reaction sites, antibacterial activity changes, and transformation products. Apparent second-order rate constants (kapp) were determined in the pH range 6.0-9.5 for the reaction of ferrate(VI) with penicillins (amoxicillin, ampicillin, cloxacillin, and penicillin G), a cephalosporin (cephalexin), and several model compounds. Ferrate(VI) shows an appreciable reactivity toward the selected ?-lactams (kapp for pH 7 = 110-770 M(-1) s(-1)). The pH-dependent kapp could be well explained by considering species-specific reactions between ferrate(VI) and the ?-lactams (with reactions occurring at thioether, amine, and/or phenol groups). On the basis of the kinetic results, the thioether is the main reaction site for cloxacillin and penicillin G. In addition to the thioether, the amine is a reaction site for ampicillin and cephalexin, and amine and phenol are reaction sites for amoxicillin. HPLC/MS analysis showed that the thioether of ?-lactams was transformed to stereoisomeric (R)- and (S)-sulfoxides and then to a sulfone. Quantitative microbiological assay of ferrate(VI)-treated ?-lactam solutions indicated that transformation products resulting from the oxidation of cephalexin exhibited diminished, but non-negligible residual activity (i.e., ?24% as potent as the parent compound). For the other ?-lactams, the transformation products showed much lower (<5%) antibacterial potencies compared to the parent compounds. Overall, ferrate(VI) oxidation appears to be effective as a means of lowering the antibacterial activities of ?-lactams, although alternative approaches may be necessary to achieve complete elimination of cephalosporin activities. PMID:25073066

Karlesa, Anggita; De Vera, Glen Andrew D; Dodd, Michael C; Park, Jihye; Espino, Maria Pythias B; Lee, Yunho

2014-09-01

246

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

PubMed

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

2014-11-14

247

Whole-Genome Phylogenomic Heterogeneity of Neisseria gonorrhoeae Isolates with Decreased Cephalosporin Susceptibility Collected in Canada between 1989 and 2013.  

PubMed

A large-scale, whole-genome comparison of Canadian Neisseria gonorrhoeae isolates with high-level cephalosporin MICs was used to demonstrate a genomic epidemiology approach to investigate strain relatedness and dynamics. Although current typing methods have been very successful in tracing short-chain transmission of gonorrheal disease, investigating the temporal evolutionary relationships and geographical dissemination of highly clonal lineages requires enhanced resolution only available through whole-genome sequencing (WGS). Phylogenomic cluster analysis grouped 169 Canadian strains into 12 distinct clades. While some N. gonorrhoeae multiantigen sequence types (NG-MAST) agreed with specific phylogenomic clades or subclades, other sequence types (ST) and closely related groups of ST were widely distributed among clades. Decreased susceptibility to extended-spectrum cephalosporins (ESC-DS) emerged among a group of diverse strains in Canada during the 1990s with a variety of nonmosaic penA alleles, followed in 2000/2001 with the penA mosaic X allele and then in 2007 with ST1407 strains with the penA mosaic XXXIV allele. Five genetically distinct ESC-DS lineages were associated with penA mosaic X, XXXV, and XXXIV alleles and nonmosaic XII and XIII alleles. ESC-DS with coresistance to azithromycin was observed in 5 strains with 23S rRNA C2599T or A2143G mutations. As the costs associated with WGS decline and analysis tools are streamlined, WGS can provide a more thorough understanding of strain dynamics, facilitate epidemiological studies to better resolve social networks, and improve surveillance to optimize treatment for gonorrheal infections. PMID:25378573

Demczuk, Walter; Lynch, Tarah; Martin, Irene; Van Domselaar, Gary; Graham, Morag; Bharat, Amrita; Allen, Vanessa; Hoang, Linda; Lefebvre, Brigitte; Tyrrell, Greg; Horsman, Greg; Haldane, David; Garceau, Richard; Wylie, John; Wong, Tom; Mulvey, Michael R

2015-01-01

248

Prophylactic antibiotics in aesthetic surgery.  

PubMed

Improvements in infection prevention practices over the past several decades have enhanced outcomes following aesthetic surgery. However, surgical site infections (SSI) continue to result in increased morbidity, mortality, and cost of care. The true incidence rate of SSI in aesthetic surgery is unknown due to the lack of a national surveillance system, but studies of SSI across surgical specialties have suggested that many of these infections are preventable. Patient-related factors-including obesity, glycemic control, and tobacco use-may contribute to the development of SSI following aesthetic surgery. In terms of SSI prevention, proper handwashing and surgical skin preparation are integral. Furthermore, the administration of prophylactic antibiotics has been shown to reduce SSI following many types of surgical procedures. Unfortunately, there are few large, randomized studies examining the role of prophylactic antibiotics in aesthetic surgery. The authors review the medical literature, discuss the risks of antibiotic overutilization, and detail nonpharmacological methods for reducing the risk of SSI. PMID:21131462

Lane, Michael A; Young, V Leroy; Camins, Bernard C

2010-01-01

249

Combination antibiotic therapy in pediatrics.  

PubMed

Combinations of beta-lactam and aminoglycoside antibiotics are frequently used in the treatment of pediatric infections. At our institution, amikacin has been the sole aminoglycoside utilized for the past five years. Such regimens are used empirically in specific patient populations to treat the pathogens most likely to be responsible for a symptom complex, e.g., sepsis in the immunocompromised host, pneumonitis in patients with cystic fibrosis, neonatal infections such as sepsis or meningitis, and infections in patients with intestinal perforations. Beta-lactam and aminoglycoside combinations are employed as definitive therapy when synergistic interactions can be predicted, such as in systemic Pseudomonas infections, viridans streptococcal endocarditis, or enterococcal infections. In all of these circumstances, we have utilized amikacin extensively as the sole aminoglycoside, with highly satisfactory results. In vitro antibiotic synergy studies, including those employing aminoglycosides such as amikacin, may be used to predict in vivo antibiotic interactions. However, definitions of in vitro synergy vary with the laboratory method used to evaluate synergy. Furthermore, recent data from our laboratory suggest that the absence of demonstrated in vitro synergy between amikacin and imipenem may not correlate with improved survival of neutropenic rats with gram-negative sepsis that are treated with both agents. Thus, in vitro studies of synergy may underestimate the frequency of improved outcomes with combination antibiotics, especially with amikacin and imipenem. There are potential risks associated with the use of multiple, broad-spectrum antibiotics, including fungal or bacterial superinfection and increased drug toxicity. Although the former is common in pediatric patients, aminoglycoside (amikacin) toxicity has rarely been a problem. Combination antibiotic regimens that include an aminoglycoside such as amikacin continue to have an important role in pediatrics and should be used empirically or definitively for the specific indications discussed. PMID:3728528

Chadwick, E G; Yogev, R; Shulman, S T

1986-06-30

250

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.

2012-04-01

251

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)

2004-09-10

252

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  

PubMed Central

In the United States, the blaCMY-2 gene contained within incompatibility type A/C (IncA/C) plasmids is frequently identified in extended-spectrum-cephalosporin-resistant (ESCr) Escherichia coli strains from both human and cattle sources. Concerns have been raised that therapeutic use of ceftiofur in cattle may increase the prevalence of ESCr E. coli. We report that herd ESCr E. coli fecal and hide prevalences throughout the residency of cattle at a feedlot, including during the period of greatest ceftiofur use at the feedlot, were either not significantly different (P ? 0.05) or significantly less (P < 0.05) than the respective prevalences at arrival. Longitudinal sampling of cattle treated with ceftiofur demonstrated that once the transient increase of ESCr E. coli shedding that follows ceftiofur injection abated, ceftiofur-injected cattle were no more likely than untreated members of the same herd to shed ESCr E. coli. Pulsed-field gel electrophoresis (PFGE) genotyping, antibiotic resistance phenotyping, screening for presence of the blaCMY-2 gene, and plasmid replicon typing were performed on 312 ESCr E. coli isolates obtained during six sampling periods spanning the 10-month residence of cattle at the feedlot. The identification of only 26 unique PFGE genotypes, 12 of which were isolated during multiple sampling periods, suggests that clonal expansion of feedlot-adapted blaCMY-2 E. coli strains contributed more to the persistence of blaCMY-2 than horizontal transfer of IncA/C plasmids between E. coli strains at this feedlot. We conclude that therapeutic use of ceftiofur at this cattle feedlot did not significantly increase the herd prevalence of ESCr E. coli. PMID:23354706

Griffin, Dee; Kuehn, Larry A.; Brichta-Harhay, Dayna M.

2013-01-01

253

Organic or Antibiotic-Free Labeling Does Not Impact the Recovery of Enteric Pathogens and Antimicrobial-Resistant Escherichia coli from Fresh Retail Chicken.  

PubMed

Abstract 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 blaCMY-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 blaCMY-2 from over half (53.7%) of packages, with similar recovery rates for all product types. In addition, we recovered E. coli carrying blaCTX-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

2014-12-01

254

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

PubMed

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

2015-02-01

255

What Can Be Done about Antibiotic Resistance?  

MedlinePLUS

... is allowed to purchase an antibiotic, although these laws are not always enforced. Antibiotics have also been sold over the Internet, a commerce mechanism with little governmental oversight that reaches across ...

256

Unraveling the physiological complexities of antibiotic lethality.  

PubMed

We face an impending crisis in our ability to treat infectious disease brought about by the emergence of antibiotic-resistant pathogens and a decline in the development of new antibiotics. Urgent action is needed. This review focuses on a less well-understood aspect of antibiotic action: the complex metabolic events that occur subsequent to the interaction of antibiotics with their molecular targets and play roles in antibiotic lethality. Independent lines of evidence from studies of the action of bactericidal antibiotics on diverse bacteria collectively suggest that the initial interactions of drugs with their targets cannot fully account for the antibiotic lethality and that these interactions elicit the production of reactive oxidants including reactive oxygen species that contribute to bacterial cell death. Recent challenges to this concept are considered in the context of the broader literature of this emerging area of research. Possible ways that this new knowledge might be exploited to improve antibiotic therapy are also considered. PMID:25251995

Dwyer, Daniel J; Collins, James J; Walker, Graham C

2015-01-01

257

Influence of the treatment of Listeria monocytogenes and Salmonella enterica serovar Typhimurium with citral on the efficacy of various antibiotics.  

PubMed

The main goal of this work was to study the bacterial adaptive responses to antibiotics induced by sublethal concentration of citral on first-and second-generation cells of Listeria monocytogenes serovar 4b (CECT 4032) and Salmonella enterica serovar Typhimurium (CECT 443). The first-generation cells were not pretreated with citral, while the second-generation cells were obtained from cells previously exposed to citral during 5?h. The trials were conducted at 37°C. The presence of citral in the culture medium and the antibiotic strips resulted in a reduced minimum inhibitory concentration (MIC) for the first-generation cells of Listeria monocytogenes serovar 4b and Salmonella Typhimurium. This result was observed for almost all the antibiotics, compared with the same microorganisms of the control group (without citral), which could represent an additive effect. For Listeria serovar 4b, the second-generation cells of the test group maintained the same susceptibility to antibiotics compared with cells in the control group and in the test group of the first generation. The second-generation cells of the control group indicated that the Salmonella Typhimurium maintained the same sensitivity to the antibiotics tested compared with the first generation of this group, except in the case of erythromycin, which exhibited an increased MIC value. With respect to the second-generation cells of Salmonella Typhimurium, the presence of citral determined a decrease in the antibiotic susceptibility for almost all of the antibiotics, except colistin, compared with the first-generation of the test group, which can be seen by increase of MIC values. In conclusion, the presence of citral in the culture medium of Listeria 4b and Salmonella Typhimurium increased the antibiotic susceptibility of the first generations, while we observed an increase in antibiotic resistance in the second generation of Salmonella Typhimurium. PMID:24494856

Zanini, Surama F; Silva-Angulo, Angela B; Rosenthal, Amauri; Aliaga, Dolores Rodrigo; Martínez, Antonio

2014-04-01

258

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

2013-01-01

259

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.

260

Antibiotic Resistance Due to Reduced Uptake  

Microsoft Academic Search

The introduction of antibiotic therapy for the treatment of bacterial infections has led to a greatly increased human lifespan\\u000a compared to that in the pre-antibiotic era. However, a disturbing trend has also been noted in that, within a very short period\\u000a of time following the introduction of a new antibiotic, resistance to that antibiotic begins to emerge, a factor that

Joseph B. McPhee; Sandeep Tamber; Michelle D. Brazas; Shawn Lewenza; Robert E. W. Hancock

261

Delivery of antibiotics with polymeric particles.  

PubMed

Despite the wide use of antibiotics, bacterial infection is still one of the leading causes of hospitalization and mortality. The clinical failure of antibiotic therapy is linked with low bioavailability, poor penetration to bacterial infection sites, and the side effects of antibiotics, as well as the antibiotic resistance properties of bacteria. Antibiotics encapsulated in nanoparticles or microparticles made up of a biodegradable polymer have shown great potential in replacing the administration of antibiotics in their "free" form. Polymeric particles provide protection to antibiotics against environmental deactivation and alter antibiotic pharmacokinetics and biodistribution. Polymeric particles can overcome tissue and cellular barriers and deliver antibiotics into very dense tissues and inaccessible target cells. Polymeric particles can be modified to target or respond to particular tissues, cells, and even bacteria, and thereby facilitate the selective concentration or release of the antibiotic at infection sites, respectively. Thus, the delivery of antibiotics with polymeric particles augments the level of the bioactive drug at the site of infection while reducing the dosage and the dosing frequency. The end results are improved therapeutic effects as well as decreased "pill burden" and drug side effects in patients. The main objective of this review is to analyze recent advances and current perspectives in the use of polymeric antibiotic delivery systems in the treatment of bacterial infection. PMID:24548540

Xiong, Meng-Hua; Bao, Yan; Yang, Xian-Zhu; Zhu, Yan-Hua; Wang, Jun

2014-11-30

262

Do topical antibiotics help corneal epithelial trauma?  

PubMed Central

Topical antibiotics are routinely used in emergency rooms to treat corneal trauma, although no published evidence supports this treatment. In a noncomparative clinical trial, 351 patients with corneal epithelial injuries were treated without antibiotics. The infection rate was 0.7%, suggesting that such injuries can be safely and effectively managed without antibiotics. A comparative clinical trial is neither warranted nor feasible. PMID:8268742

King, J. W.; Brison, R. J.

1993-01-01

263

ANTIBIOTIC TRANSPORT VIA RUNOFF AND SOIL LOSS  

Technology Transfer Automated Retrieval System (TEKTRAN)

Research has verified the occurrence of veterinary antibiotics in manure, agricultural fields, and surface waters, yet no research has evaluated transport of antibiotics from agricultural fields. We quantified the transportability of antibiotics from agricultural fields where manure or effluent is a...

264

Antibiotic prophylaxis in total hip arthroplasty  

Microsoft Academic Search

We have assessed the effect of different regimes of antibiotic prophylaxis on the survival of total hip implants, comparing antibiotics administered both systemically and in the bone cement, systemically only, in the bone cement only and with no antibiotics given. We studied 10 905 primary cemented total hip replacements, performed for osteoarthritis of the hip and reported to the Norwegian

B. Espehaug; L. B. Engesaeter; S. E. Vollset; L. I. Havelin; N. Langeland

1997-01-01

265

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.

2014-01-01

266

New business models for antibiotic innovation.  

PubMed

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

So, Anthony D; Shah, Tejen A

2014-05-01

267

Genetic Architecture of Intrinsic Antibiotic Susceptibility  

Microsoft Academic Search

Background: Antibiotic exposure rapidly selects for more resistant bacterial strains, and both a drug's chemical structure and a bacterium's cellular network affect the types of mutations acquired. Methodology\\/Principal Findings: To better characterize the genetic determinants of antibiotic susceptibility, we exposed a transposon-mutagenized library of Escherichia coli to each of 17 antibiotics that encompass a wide range of drug classes and

Hany S. Girgis; Alison K. Hottes; Saeed Tavazoie

2009-01-01

268

Overcoming the current deadlock in antibiotic research.  

PubMed

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

2014-04-01

269

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.

2014-01-01

270

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

PubMed

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

2014-01-01

271

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

2013-01-01

272

Evidence-based adjustment of antibiotic in pediatric complicated appendicitis in the era of antibiotic resistance  

Microsoft Academic Search

Introduction  Antibiotic resistance is a global issue especially in developed areas. With the emergence of antibiotic resistant-bacteria,\\u000a the traditional choice of broad spectrum antibiotics may not be effective in complicated appendicitis. We herein report the\\u000a bacteriology and antibiotic susceptibility of intra-operative peritoneal culture in children with acute appendicitis in Hong\\u000a Kong. This may guide us to adjust the choice of antibiotics

Kin Wai Edwin Chan; Kim Hung Lee; Jennifer Wai Cheung Mou; Sing Tak Cheung; Jennifer Dart Yin Sihoe; Yuk Him Tam

2010-01-01

273

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

PubMed

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

2014-05-20

274

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.

2014-01-01

275

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.

2014-01-01

276

Community-onset Escherichia coli infection resistant to expanded-spectrum cephalosporins in low-prevalence countries.  

PubMed

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

Rogers, Benjamin A; 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

2014-01-01

277

Improvement of nebulised antibiotic delivery in cystic fibrosis  

PubMed Central

AIM—To investigate deposition patterns and to assess the delivery rate of two nebuliser systems in children with cystic fibrosis (CF).?METHODS—Thirty three children with CF on regular treatment with nebulised antibiotics had radioisotope scans performed using technetium-99m labelled aerosol antibiotic generated by a Ventstream nebuliser (median mass diameter (MMD), 3.3 µm; delivery rate, 0.075 ml/min) under conditions similar to their routine home practice. The inhomogeneity of the images was scored on a 1-10 rating scale (a low score indicating even distribution of the antibiotic), and stomach deposition was measured as a percentage of overall deposition. Twenty patients had a repeat scan using an Optimist nebuliser (MMD, 1.8 µm; delivery rate, 0.02 ml/min).?RESULTS—The mean inhomogeneity scores were 5.4 in the Ventstream group and 3.5 in the Optimist group. Mean stomach deposition was 17.3% in the 33 patients using the Ventstream nebuliser. There was an inverse relation between height and stomach deposition (r = 0.69). In the 20 patients who had both nebulisers, the mean percentages of stomach deposition for the Ventstream and Optimist nebulisers were 11.8% and 1.6%, respectively. The Ventstream nebuliser delivered antibiotic at an average 2.8 times faster rate than the Optimist nebuliser.?IMPLICATIONS—A smaller particle size results in a more homogenous distribution of the antibiotic in the lungs with decreased stomach deposition. This should not be seen as a recommendation to use the Optimist nebuliser because more antibiotic was delivered to most parts of the lung with the Ventstream because of its increased delivery rate.?? PMID:10086942

Wilson, D.; Burniston, M.; Moya, E.; Parkin, A.; Smye, S.; Robinson, P.; Littlewood, J.

1999-01-01

278

Antibiotic effectiveness: balancing conservation against innovation.  

PubMed

Antibiotic effectiveness is a natural societal resource that is diminished by antibiotic use. As with other such assets, keeping it available requires both conservation and innovation. Conservation encompasses making the best use of current antibiotic effectiveness by reducing demand through vaccination, infection control, diagnostics, public education, incentives for clinicians to prescribe fewer antibiotics, and restrictions on access to newer, last-resort antibiotics. Innovation includes improving the efficacy of current drugs and replenishing effectiveness by developing new drugs. In this paper, I assess the relative benefits and costs of these two approaches to maintaining our ability to treat infections. PMID:25214620

Laxminarayan, Ramanan

2014-09-12

279

Enzymatic glycosylation of the topical antibiotic mupirocin.  

PubMed

Mupirocin is a commercially available antibiotic that acts on bacterial isoleucyl-tRNA synthetase, thereby inhibiting protein synthesis and preventing bacterial infection. An in vitro glycosylation approach was applied to synthesize glycoside derivatives of mupirocin using different NDP-sugars and glycosyltransferase from Bacillus licheniformis. Ultra pressure liquid chromatography-photo diode array analyses of the reaction mixtures revealed the generation of product peak(s). The results were further supported by high-resolution quadruple time of flight electrospray ionization mass spectrometry analyses. The product purified from the reaction mixture with UDP-D-glucose was subjected to NMR analysis, and the structure was determined to be mupirocin 6-O-?-D-glucoside. Other glycoside analogs of mupirocin were determined based on high-resolution mass analyses. Antibacterial activity assays against Staphylococcus aureus demonstrated complete loss of antibacterial activity after glucosylation of mupirocin at the 6-hydroxyl position. PMID:25069899

Parajuli, Prakash; Pandey, Ramesh Prasad; Pokhrel, Anaya Raj; Ghimire, Gopal Prasad; Sohng, Jae Kyung

2014-11-01

280

Emergence, spread and characteristics of Neisseria gonorrhoeae isolates with in vitro decreased susceptibility and resistance to extended-spectrum cephalosporins in Sweden  

Microsoft Academic Search

BackgroundNeisseria gonorrhoeae has developed resistance to most antimicrobials used for treatment. Worryingly, treatment failures with oral extended-spectrum cephalosporins (ESCs) have been reported, especially in the WHO Western Pacific Region, and susceptibility to all ESCs (oral and injectable), the last remaining treatment options in many settings, is decreasing globally.ObjectivesTo examine the emergence, spread and characteristics of Neisseria gonorrhoeae isolates with decreased

Daniel Golparian; Bengt Hellmark; Hans Fredlund; Magnus Unemo

2010-01-01

281

Occurrence and distribution of antibiotic-resistant bacteria and transfer of resistance genes in Lake Taihu.  

PubMed

The overuse of antibiotics has accelerated antibiotic resistance in the natural environment, especially fresh water, generating a potential risk for public health around the world. In this study, antibiotic resistance in Lake Taihu was investigated and this was the first thorough data obtained through culture-dependent methods. High percentages of resistance to streptomycin and ampicillin among bacterial isolates were detected, followed by tetracycline and chloramphenicol. Especially high levels of ampicillin resistance in the western and northern regions were illustrated. Bacterial identification of the isolates selected for further study indicated the prevalence of some opportunistic pathogens and 62.0% of the 78 isolates exhibited multiple antibiotic resistance. The presence of ESBLs genes was in the following sequence: bla(TEM) > bla(SHV) > bla(CTMX) and 38.5% of the isolates had a class I integrase gene. Of all tested strains, 80.8% were able to transfer antibiotic resistance through conjugation. We also concluded that some new families of human-associated ESBLs and AmpC genes can be found in natural environmental isolates. The prevalence of antibiotic resistance and the dissemination of transferable antibiotic resistance in bacterial isolates (especially in opportunistic pathogens) was alarming and clearly indicated the urgency of realizing the health risks of antibiotic resistance to human and animal populations who are dependent on Lake Taihu for water consumption. PMID:24240317

Yin, Qian; Yue, Dongmei; Peng, Yuke; Liu, Ying; Xiao, Lin

2013-01-01

282

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.

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

2014-01-01

283

A global view of antibiotic resistance.  

PubMed

Antibiotic resistance is one of the few examples of evolution that can be addressed experimentally. The present review analyses this resistance, focusing on the networks that regulate its acquisition and its effect on bacterial physiology. It is widely accepted that antibiotics and antibiotic resistance genes play fundamental ecological roles - as weapons and shields, respectively - in shaping the structures of microbial communities. Although this Darwinian view of the role of antibiotics is still valid, recent work indicates that antibiotics and resistance mechanisms may play other ecological roles and strongly influence bacterial physiology. The expression of antibiotic resistance determinants must therefore be tightly regulated and their activity forms part of global metabolic networks. In addition, certain bacterial modes of life can trigger transient phenotypic antibiotic resistance under some circumstances. Understanding resistance thus requires the analysis of the regulatory networks controlling bacterial evolvability, the physiological webs affected and the metabolic rewiring it incurs. PMID:19054120

Martinez, Jose Luis; Fajardo, Alicia; Garmendia, Leonor; Hernandez, Alvaro; Linares, Juan Francisco; Martínez-Solano, Laura; Sánchez, María Blanca

2009-01-01

284

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.

2014-01-01

285

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.

1994-04-01

286

Antibacterial activities in vitro and in vivo and pharmacokinetics of cefquinome (HR 111V), a new broad-spectrum cephalosporin.  

PubMed

Cefquinome is a new injectable aminothiazolyl cephalosporin derivative. It is stable against chromosomally and plasmid-encoded beta-lactamases and has a broad antibacterial spectrum. Staphylococcus aureus, streptococci, Pseudomonas aeruginosa, and members of the family Enterobacteriaceae (Escherichia coli, Salmonella spp., Klebsiella spp., Enterobacter spp., Citrobacter spp., and Serratia marcescens) are inhibited at low concentrations. Cefquinome is also active against many strains of methicillin-resistant staphylococci and enterococci. Its in vitro activity against gram-negative anaerobes is very limited. The high in vitro activity of cefquinome is reflected by its high in vivo efficacy against experimental septicemia due to different gram-positive and gram-negative bacteria. We studied the pharmacokinetic properties of cefquinome in mice, dogs, pigs, and calves. After single parenteral administrations, cefquinome displayed high peak levels, declining with half-lives of about 0.5, 0.9, 1.2, and 1.3 h, respectively. The areas under the concentration-time curve determined for dogs and mice showed linear correlations to the given doses. In dogs the urinary recovery was more than 70% within 24 h of dosing. PMID:2014969

Limbert, M; Isert, D; Klesel, N; Markus, A; Seeger, K; Seibert, G; Schrinner, E

1991-01-01

287

Antibacterial activities in vitro and in vivo and pharmacokinetics of cefquinome (HR 111V), a new broad-spectrum cephalosporin.  

PubMed Central

Cefquinome is a new injectable aminothiazolyl cephalosporin derivative. It is stable against chromosomally and plasmid-encoded beta-lactamases and has a broad antibacterial spectrum. Staphylococcus aureus, streptococci, Pseudomonas aeruginosa, and members of the family Enterobacteriaceae (Escherichia coli, Salmonella spp., Klebsiella spp., Enterobacter spp., Citrobacter spp., and Serratia marcescens) are inhibited at low concentrations. Cefquinome is also active against many strains of methicillin-resistant staphylococci and enterococci. Its in vitro activity against gram-negative anaerobes is very limited. The high in vitro activity of cefquinome is reflected by its high in vivo efficacy against experimental septicemia due to different gram-positive and gram-negative bacteria. We studied the pharmacokinetic properties of cefquinome in mice, dogs, pigs, and calves. After single parenteral administrations, cefquinome displayed high peak levels, declining with half-lives of about 0.5, 0.9, 1.2, and 1.3 h, respectively. The areas under the concentration-time curve determined for dogs and mice showed linear correlations to the given doses. In dogs the urinary recovery was more than 70% within 24 h of dosing. Images PMID:2014969

Limbert, M; Isert, D; Klesel, N; Markus, A; Seeger, K; Seibert, G; Schrinner, E

1991-01-01

288

Antibiotic-associated vulvovaginal candidiasis  

Microsoft Academic Search

Vulvovaginal candidiasis (VVC) is one of the most common causes of vaginitis, and its incidence has increased markedly during\\u000a the past three decades. The widespread overuse of antibiotics has been suggested as one of the major factors contributing\\u000a to the increasing incidence of VVC. However, evidence supporting this association has been limited because few studies with\\u000a rigorous scientific methodology have

Jinping Xu; Jack D. Sobel

2003-01-01

289

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...

290

Antibiotic Modification of Native Grafts: Improving upon nature's scaffolds  

NASA Astrophysics Data System (ADS)

The use of allograft bone in orthopaedics, spine surgery and dentistry is invaluable for helping restore bone defects and promote osteointegration. However, one, and perhaps the most important, problem associated with the use of allograft is infection. It is a devastating complication for patients and physicians alike, and necessitates repeated surgeries, extended treatment and often times results in increased morbidity and poor outcomes. Previous attempts to incorporate antibiotics into allograft by soaking the graft in antibiotic solution have enjoyed limited success in providing adequate protection against bacterial colonization. To overcome problems associated with controlled release systems, I have described a novel chemical modification that allows for the attachment of vancomycin, or other antibiotics, to free amines of allograft bone thus rendering the graft bactericidal over a long time period. This modification, as evaluated by immunohistochemistry, allowed for the uniform and stable attachment of antibiotics to allograft without adversely affecting its potential for incorporation with bone. Modified allograft, placed in the presence of S. aureus, did not allow colonization by bacteria as evaluated by fluorescent imaging, scanning microscopy, and direct bacterial counts. More importantly, inhibition of bacterial colonization resulted in prevention of biofilm formation. Furthermore, I show that the spectrum of activity of the parent antibiotic was maintained, as the construct was not active against E. coli challenges. Comparison of this technology with simple antibiotic incorporation demonstrated that the covalently-coupled antibiotic did not elute from the bone, but rather remained attached and active on the surface for times out to one year, times that are far longer than currently can be achieved with the elution technologies. Despite its potent activity against bacteria, modified bone remained biocompatible allowing attachment of osteoblastic-like cells with no increased toxicity. Furthermore, the antibiotic-modified allograft incorporated well into tibial defects in the rat. Finally, this construct was efficacious in decreasing the severity of infection and host reaction when impacted in an in vivo model of allograft-associated infection. Thus, our proposed modification in surface design serves as a starting point for the development of a new generation of bone grafts that are biologically active at sites of physiological importance.

Ketonis, Constantinos

291

Enhancement of secondary metabolite production using the antibiotic gradient-plate technique.  

PubMed

We have used the antibiotic gradient-plate technique to generate antifungal producing Actinomadura strains that synthesize enhanced quantities of component 3A of a macrocyclic lactam antifungal compound Sch 38516. Seventy-nine colonies were selected from a mixture of rifampicin and spectinomycin gradient plates. The two fermentation extracts described produced an enhanced 3A component (identified with silica gel TLC, HPLC, and bioautography) when compared to the parent culture isolate extracts (no antibiotic selection). PMID:1531080

Gentile, F A; Mayles, B A; Procopio, P L

1992-01-01

292

Protection by antibiotics against myeloperoxidase-dependent cytotoxicity to lung epithelial cells in vitro.  

PubMed Central

Myeloperoxidase, in the presence of noncytotoxic concentrations of H2O2, was used to induce cytotoxicity to the lung epithelial cell line, AKD. When the cationic aminoglycosides, tobramycin and gentamicin were added to the cells in the presence of myeloperoxidase and H2O2, cytotoxicity was completely inhibited. In addition, tobramycin prevented cytotoxicity induced by cystic fibrosis sputum and H2O2. Protection against myeloperoxidase and H2O2 was also observed with the thioether-containing antibiotics, ticarcillin and ceftazidime, but at higher concentrations than with the aminoglycosides. Analysis of spectral properties, dimethylsulfoxide-mediated reduction, and ethyl acetate/NaCl partitioning, demonstrated that aminoglycosides converted HOCl to hydrophilic noncytotoxic chloramines, but were unable to prevent the oxidation of sulfhydryls and methionine by HOCl. In contrast, ticarcillin and ceftazidime were highly effective inhibitors of HOCl-mediated sulfhydryl and methionine oxidation. These results suggest that aminoglycosides protect lung epithelial cells against myeloperoxidase-dependent oxidant injury by binding to anionic cell surfaces and converting HOCl to hydrophilic noncytotoxic chloramines, whereas penicillins and cephalosporins are potent HOCl scavengers capable of protecting critical extracellular molecules against oxidation. PMID:8380814

Cantin, A; Woods, D E

1993-01-01

293

Increase in susceptibility of Pseudomonas aeruginosa to carbapenem antibiotics in low-amino-acid media.  

PubMed Central

The in vitro susceptibility of Pseudomonas aeruginosa PAO1 to carbapenem antibiotics, such as CS-533, was influenced by various concentrations of basic amino acids, i.e., L-lysine, L-histidine, and L-arginine, in agar media. P. aeruginosa PAO1 showed higher susceptibility to carbapenems in minimal medium than it did in rich media such as Mueller-Hinton II agar. The susceptibility was decreased by the addition of a basic amino acid to the minimal medium, whereas it was influenced less by other amino acids. The susceptibility of PAO1 to cephalosporins, piperacillin, quinolones, and gentamicin was not influenced by the addition of a basic amino acid to the minimal medium. A significant change in susceptibility to carbapenems by the addition of a basic amino acid was not observed with D2 protein-deficient mutants of PAO1. Clinical isolates of P. aeruginosa also showed an increase in susceptibility in minimal medium. L-Lysine in minimal medium did not have any influence on the production of D2 protein, beta-lactamases, or penicillin-binding proteins of PAO1 or on the chemical degradation of CS-533. These results strongly indicate that the increase in susceptibility of P. aeruginosa to carbapenems relates to less competition with basic amino acids for permeation through the D2 protein channel of P. aeruginosa. Images PMID:1903911

Fukuoka, T; Masuda, N; Takenouchi, T; Sekine, N; Iijima, M; Ohya, S

1991-01-01

294

[Penetration of antibiotics into the intervertebral disk].  

PubMed

The role of antibiotics in the treatment and prevention of postoperative spondylodiscitis is still controversial. In a group of 15 patients operated on account of lumbar discopathy, the authors investigated the penetration of antibiotics into the intervertebral disc, in correlation to serum levels, when antibiotics were administered during operation. Despite high serum levels rolitetracycline was not detected in extirpated material of the disc, gentamycin reached 2-6% serum levels. The authors give an account of views on the role of antibiotics in the prophylaxis of postoperative spondylodiscitis and recommend their administration in particular in risk groups. They recommend antibiotics in case of early diagnosis of postoperative spondylodiscitis, in the later stages of the disease the role of antibiotics is controversial. PMID:1872117

Vaverka, M; Petrzelová, J

1991-03-01

295

In vitro antibacterial activities of antibiotics against Pseudomonas aeruginosa in peritoneal dialysis fluid.  

PubMed Central

Intraperitoneal antibiotics are used to treat Pseudomonas aeruginosa peritonitis, a serious complication of continuous ambulatory peritoneal dialysis. However, P. aeruginosa killing is often inefficient despite low MBCs. Broth dilution MIC/MBC and time kill curves of tobramycin, amikacin, netilmicin, azlocillin, piperacillin, ceftazidime, cefsulodin, and ciprofloxacin were determined in peritoneal dialysis fluid (PDF), buffered PDF, fluid recovered from patients on continuous ambulatory peritoneal dialysis (RPF), and cation-supplemented Mueller-Hinton broth. MBCs of all antibiotics were 8 to 16 times greater in PDF and RPF than in Mueller-Hinton broth or buffered PDF. Use of the time kill curve technique and Mueller-Hinton broth showed that aminoglycosides killed greater than or equal to 99.9% of P. aeruginosa at 1 h, ciprofloxacin killed greater than or equal to 99.9% at 2 h, and beta-lactams killed greater than or equal to 99.9% at 6 h. In contrast, killing was not demonstrated in PDF by any drug at 6 h and by aminoglycosides only at 24 h. Bactericidal activity was optimal in RPF for ciprofloxacin at 1 h and for aminoglycosides at 2 h; bactericidal activity was not demonstrated in RPF with any beta-lactam (no kill by penicillins; less than 99% kill by cephalosporins). Slow bacterial growth, increased protein binding, and glucose concentrations and other inhibitors may interfere with beta-lactam activity in RPF. These considerations and reported clinical failures and toxicity of aminoglycoside therapy warrant further study of quinolones and drug combinations in P. aeruginosa peritonitis. PMID:3927837

Shalit, I; Welch, D F; San Joaquin, V H; Marks, M I

1985-01-01

296

Effective Antibiotic Resistance Mitigation during Cheese Fermentation ?  

PubMed Central

Controlling antibiotic-resistant (ART) bacteria in cheese fermentation is important for food safety and public health. A plant-maintained culture was found to be a potential source for ART bacterial contamination in cheese fermentation. Antibiotics had a detectable effect on the ART population from contamination in the finished product. The decrease in the prevalence of antibiotic resistance (AR) in retail cheese samples from 2010 compared to data from 2006 suggested the effectiveness of targeted AR mitigation in related products. PMID:21784910

Li, Xinhui; Li, Yingli; Alvarez, Valente; Harper, Willis James; Wang, Hua H.

2011-01-01

297

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

1985-01-01

298

Biochemical Logic of Antibiotic Inactivation and Modification  

Microsoft Academic Search

Bacterial resistance to antibiotics manifests itself in both general and specifi c protection mechanisms. Consequently, the\\u000a characteristics of resistance can be paralleled to those of the mammalian immune response. Antibiotic resistance can be differentiated\\u000a into: (1) nonspecifi c mechanisms that confer general innate immunity to a class of antibiotics (e.g., broad spectrum effl\\u000a ux mechanisms, target modifi cation), and (2)

Vanessa D'Costa; Gerard D. Wright

299

Antibiotrophs: The complexity of antibiotic-subsisting and antibiotic-resistant microorganisms.  

PubMed

Abstract Widespread overuse of antibiotics has led to the emergence of numerous antibiotic-resistant bacteria; among these are antibiotic-subsisting strains capable of surviving in environments with antibiotics as the sole carbon source. This unparalleled expansion of antibiotic resistance reveals the potent and diversified resistance abilities of certain bacterial strains. Moreover, these strains often possess hypermutator phenotypes and virulence transmissibility competent for genomic and proteomic propagation and pathogenicity. Pragmatic and prospicient approaches will be necessary to develop efficient therapeutic methods against such bacteria and to understand the extent of their genomic adaptability. This review aims to reveal the niches of these antibiotic-catabolizing microbes and assesses the underlying factors linking natural microbial antibiotic production, multidrug resistance, and antibiotic-subsistence. PMID:24495094

Woappi, Yvon; Gabani, Prashant; Singh, Arya; Singh, Om V

2014-02-01

300

Antibiotics  

NASA Astrophysics Data System (ADS)

A 28-year-old man was transferred to our hospital and underwent surgery for resection of an aortic graft infected with Klebsiella pneumoniae. Antimicrobial therapy consisted of amikacin, cefazolin, chloramphenicol, sulfamethoxazole, and trimethoprim. A request for amikacin and sulfamethoxazole assays was received by the laboratory along with information that the patient had received tobramycin until 24 h before the serum was obtained.

Anhalt, John P.

301

Mechanisms of antibiotic neurotoxicity in renal failure.  

PubMed

Neurological complications of antibiotics are relatively common in renal failure. Central nervous system neurotoxicity due to penicillin and beta-lactam antibiotics is best documented with fewer accounts of ototoxicity, peripheral nerve toxicity and neuromuscular blockade. In the context of risk stratification, the goal of this review is to explore the mosaic of factors in renal impairment that may contribute to susceptibility to antibiotic neurotoxicity. Improved knowledge of the pathogenesis of these formidable adverse events among the renal failure subjects should help prevent antibiotic neurotoxicity in the future. PMID:15164960

Chow, Kai Ming; Szeto, Cheuk Chun; Hui, Andrew Che-Fai; Li, Philip Kam-Tao

2004-03-01

302

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

303

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

2013-01-01

304

UTILIZATION OF RESTRICTED ANTIBIOTICS IN A UNIVERSITY HOSPITAL IN THAILAND  

Microsoft Academic Search

Antibiotic resistance, a major negative consequence of antibiotic overuse, is an im- portant problem worldwide. Various means have been used to control antibiotic usage including the use of an antibiotic order form (AOF), restricted antibiotic formularies and provision of educational information. The present study was designed to evaluate the use of antimicrobials in a 1,000-bed university hospital. Antimicrobial agents, likely

Sasima Kusuma Na Ayuthya; Oraphan P Matangkasombut; Sayomporn Sirinavin; Kumthorn Malathum; Boonmee Sathapatayavongs

305

Identification of Multiresistant Salmonella Isolates Capable of Subsisting on Antibiotics?  

PubMed Central

This study assessed the ability of Salmonella (572 isolates) to subsist on 12 different antibiotics. The majority (11/12) of the antibiotics enabled subsistence for at least 1 of 140 isolates. Furthermore, 40 isolates were able to subsist on more than one antibiotic. Antibiotic resistance and antibiotic subsistence do not appear to be equivalent. PMID:20173063

Barnhill, Alison E.; Weeks, Katherine E.; Xiong, Nalee; Day, Tim A.; Carlson, Steve A.

2010-01-01

306

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.

2005-01-01

307

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

Microsoft Academic Search

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

Vishal Diwan; Ashok J Tamhankar; Rakesh K Khandal; Shanta Sen; Manjeet Aggarwal; Yogyata Marothi; Rama V Iyer; Karin Sundblad-Tonderski; Cecilia Stĺlsby-Lundborg

2010-01-01

308

[Characterization of Alcaligenes species using analysis of esterase electrophoretic polymorphism and analysis of antibiotic resistance profiles].  

PubMed

The species of an Alcaligenes bacterial strain may be difficult to determine on the basis of conventional phenotype features. Esterase pattern analysis using acrylamide-agar gel electrophoresis and determination of the antimicrobial resistance profile (agar diffusion method) were performed for A. faecalis (34 strains). A. denitrificans subsp xylosoxydans (16 strains) and A. piechaudi (5 strains). The Cistat program (D2 Software) was used for statistical representation of results. The homogeneous, species-specific esterase patterns ensured correct assignment of each strain to one of the three species. Antimicrobial susceptibility was greatest for A. faecalis which was susceptible to both cephalosporins of all generations and aminoglycosides. A. xylosoxydans was the species with the greatest resistance to antimicrobials. A. piechaudii exhibited intermediate susceptibility. PMID:1495848

Bizet, C; Picard, B; Philippon, A; Goullet, P

1992-05-01

309

An In Vitro Study on the Effects of Nisin on the Antibacterial Activities of 18 Antibiotics against Enterococcus faecalis  

PubMed Central

Enterococcus faecalis rank among the leading causes of nosocomial infections worldwide and possesses both intrinsic and acquired resistance to a variety of antibiotics. Development of new antibiotics is limited, and pathogens continually generate new antibiotic resistance. Many researchers aim to identify strategies to effectively kill this drug-resistant pathogen. Here, we evaluated the effect of the antimicrobial peptide nisin on the antibacterial activities of 18 antibiotics against E. faecalis. The MIC and MBC results showed that the antibacterial activities of 18 antibiotics against E. faecalis OG1RF, ATCC 29212, and strain E were significantly improved in the presence of 200 U/ml nisin. Statistically significant differences were observed between the results with and without 200 U/ml nisin at the same concentrations of penicillin or chloramphenicol (p<0.05). The checkerboard assay showed that the combination of nisin and penicillin or chloramphenicol had a synergetic effect against the three tested E. faecalis strains. The transmission electron microscope images showed that E. faecalis was not obviously destroyed by penicillin or chloramphenicol alone but was severely disrupted by either antibiotic in combination with nisin. Furthermore, assessing biofilms by a confocal laser scanning microscope showed that penicillin, ciprofloxacin, and chloramphenicol all showed stronger antibiofilm actions in combination with nisin than when these antibiotics were administered alone. Therefore, nisin can significantly improve the antibacterial and antibiofilm activities of many antibiotics, and certain antibiotics in combination with nisin have considerable potential for use as inhibitors of this drug-resistant pathogen. PMID:24586598

Ling, Junqi; Ma, Jinglei; Huang, Lijia; Zhang, Luodan

2014-01-01

310

Cost of Antibiotic Resistance and the Geometry of Adaptation  

PubMed Central

The distribution of effects of beneficial mutations is key to our understanding of biological adaptation. Yet, empirical estimates of this distribution are scarce, and its functional form is largely unknown. Theoretical models of adaptation predict that the functional form of this distribution should depend on the distance to the optimum. Here, we estimate the rate and distribution of adaptive mutations that compensate for the effect of a single deleterious mutation, which causes antibiotic resistance. Using a system with multiple molecular markers, we estimate the distribution of fitness effects of mutations at two distances from the adaptive peak in 60 populations of Escherichia coli. We find that beneficial mutations, which can contribute to compensatory evolution, occur at very high rates, of the order of 10?5 per genome per generation and can be detected within a few tens of generations. They cause an average fitness increase of 2.5% and 3.6%, depending on the cost of resistance, which is expected under Fisher's geometrical model of adaptation. Moreover, we provide the first description of the distribution of beneficial mutations, segregating during the process of compensatory evolution, to antibiotic resistances bearing different costs. Hence, these results have important implications to understanding the spread and maintenance of antibiotic resistance in bacteria. PMID:22144641

Sousa, Ana; Magalhăes, Sara; Gordo, Isabel

2012-01-01

311

In vitro evaluation of pyridine-2-azo-p-dimethylaniline cephalosporin, a new diagnostic chromogenic reagent, and comparison with nitrocefin, cephacetrile, and other beta-lactam compounds.  

PubMed Central

Pyridine-2-azo-p-dimethylanaline cephalosporin (PADAC), a chromogenic reagent which is purple and changes to yellow upon cleavage of its beta-lactam ring, was evaluated in comparison with other chromogenic cephalosporins. PADAC exhibited little antimicrobial activity against gram-negative bacteria, but did have good activity (minimum inhibitory concentration, 0.12 to 0.5 microgram/ml) against Staphylococcus aureus, a quality comparable to nitrocefin. Nitrocefin, however, demonstrated an unexpected and uniquely potent activity against Streptococcus faecalis (minimum inhibitory concentration, less than or equal to 0.06 to 0.12 microgram/ml) The relative hydrolysis rate of PADAC when subjected to six different beta-lactamases was substantially greater than that of cephacetrile, but less than that of nitrocefin. The relative hydrolysis rates of PADAC and nitrocefin were comparable with type IIIa beta lactamase and the derived from Bacillus cereus. The inhibition of beta-lactamase hydrolysis of the chromogenic cephalosporin substrates by six enzyme-stable inhibitors was generally greater with PADAC than with nitrocefin. Unlike nitrocefin, PADAC mixed with 50% human serum or various broth culture media showed no evidence of color change or degradation over several hours. The subsequent enzyme hydrolysis rates of such mixtures were the same as in phosphate buffer. Beta-lactamase-containing bacterial suspensions and clinical specimens containing such bacteria produced positive visual and spectrophotometric color changes when mixed with PADAC or nitrocefin. Although color changes occurred more slowly with PADAC than with nitrocefin, PADAC was not adversely influenced (non-enzyme-related color change) by the protein content of specimens. PADAC appears to be a promising alternative for beta-lactamase diagnostic testing in the clinical and research microbiology laboratory. PMID:6978350

Jones, R N; Wilson, H W; Novick, W J

1982-01-01

312

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.

2014-01-01

313

Effect of various aminoglycoside antibiotics on glucose formation in isolated rabbit kidney-cortex tubules.  

PubMed

The effect of six aminoglycoside antibiotics on the rate of gluconeogenesis was studied in isolated rabbit kidney-cortex tubules incubated with various substrates. All antibiotics studied did not affect glucose formation from both malate and 2-oxoglutarate. The rank order of the drug-induced inhibition of glucose formation from lactate, pyruvate and propionate was the following: neomycin = gentamicin greater than tobramycin greater than kanamycin = amikacin greater than streptomycin. This in principle corresponds to their ability to diminish pyruvate carboxylation in isolated kidney-cortex mitochondria, as well as to their known nephrotoxic potential observed in vivo. Aminoglycoside antibiotics decreased the respiration of tubule suspension incubated with various substrates. However, the rank order of the inhibition by antibiotics of oxygen uptake was different from that observed for gluconeogenesis, suggesting that the rate of energy generation does not limit glucose formation under conditions studied. PMID:2771859

Michalik, M; G?azewski, S; Bry?a, J

1989-01-01

314

Balance between Exocytosis and Endocytosis Determines the Efficacy of Sterol-Targeting Antibiotics.  

PubMed

Antifungals targeting membrane ergosterol are longstanding, yet indispensable drugs in clinical use. However, the mechanisms by which the cellular membrane domains recognized by these antibiotics are generated remain largely unknown. Here, we demonstrate that the balance between endocytosis and exocytosis in membrane trafficking is a critical factor in the action of sterol-targeting antibiotics. When fission yeast cells were treated with manumycin A, cellular binding and the action of the antifungals filipin, amphotericin B, and theonellamides, all of which are ergosterol-binders, were abolished. Additionally, manumycin A treatment attenuated Cdc42 activity and inhibited exocytosis, while endocytosis was only moderately suppressed. Similar defects in membrane trafficking could be reproduced by heat shock and genetic perturbation, which also abolished the action of the antibiotics. We propose that exocytosis and endocytosis respectively supply and internalize the specific plasma membrane domains recognized by sterol-targeting antibiotics. PMID:25500221

Nishimura, Shinichi; Tokukura, Masato; Ochi, Junko; Yoshida, Minoru; Kakeya, Hideaki

2014-12-18

315

Mechanisms of antibiotic neurotoxicity in renal failure  

Microsoft Academic Search

Neurological complications of antibiotics are relatively common in renal failure. Central nervous system neurotoxicity due to penicillin and ?-lactam antibiotics is best documented with fewer accounts of ototoxicity, peripheral nerve toxicity and neuromuscular blockade. In the context of risk stratification, the goal of this review is to explore the mosaic of factors in renal impairment that may contribute to susceptibility

Kai Ming Chow; Cheuk Chun Szeto; Andrew Che-Fai Hui; Philip Kam-Tao Li

2004-01-01

316

Policies, Policies, Policies! What Antibiotic Policies Work?  

Microsoft Academic Search

ntibiotics should be used rationally in order to improve patient outcome; to contain the cost of treatment and most importantly to prevent the emergence of antibiotic resistance. Unfortunately, inappropriate use of antibiotics appears to be a universal phenomenon and numerous surveys from around the world have shown high rates of inappropriate prescribing. There is abundant circumstantial evidence linking emergence of

Victor Lim

2005-01-01

317

Repairing the broken market for antibiotic innovation.  

PubMed

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

2015-02-01

318

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

1998-01-01

319

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

1999-01-01

320

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

1995-01-01

321

[Rational antibiotic prescribing. Challenges and successes].  

PubMed

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

2012-11-01

322

DETECTION OF ANTIBIOTIC RESIDUES ON CHEESE WHEY  

Microsoft Academic Search

Ewe milk destined to Manchego cheese production was fortified with different ?-lactam antibiotics (penicillin G, amoxicillin, ampicillin, cephalexin and ceftiofur ® ) at concentrations near their correspondent Maximum Residue Level (MRL) (0.5*MRL; MRL and 1.5*MRL). Two vats of 30 L of Manchego cheese were made for each antibiotic studied, and whey was coll ected. By using the Delvotest SP ®

323

Boosting bacterial metabolism to combat antibiotic resistance.  

PubMed

The metabolic state of a bacterial cell influences its susceptibility to antibiotics. In this issue, Peng et al. (2015) show that resistant bacteria can be sensitized to antibiotic treatment through the addition of exogenous metabolites that stimulate central metabolic pathways and increase drug uptake. PMID:25651168

Bhargava, Prerna; Collins, James J

2015-02-01

324

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 ...

325

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

2001-01-01

326

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...

2013-04-01

327

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...

2010-04-01

328

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...

2012-04-01

329

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...

2011-04-01

330

21 CFR 333.110 - First aid antibiotic active ingredients.  

...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...

2014-04-01

331

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

PubMed

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

2015-01-01

332

Innovation of novel antibiotics: an economic perspective.  

PubMed

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

2014-10-15

333

Antibiotic elution from hydroxyapatite cement cranioplasty materials.  

PubMed

Hydroxyapatite cements (HAC) are a contemporary material used for multiple cranioplasty applications. In an effort to decrease the risk of postoperative infection, mixing antibiotics into the material during intraoperative application is frequently done. It has been assumed, but never substantiated, that significant antibiotic release from the material occurs after implantation. Using standardized morphologies, a mixture of a specific HAC (Mimix bone void filler) and tobramycin antibiotic was prepared, hydrated in phosphate-buffered saline, and tested in vitro for as long as 22 days after preparation. The results show that the majority of the antibiotic (91%) was released within the first 24 hours, with the balance being eluted during the next 8 days. Overall, the release of tobramycin from Mimix bone void filler appears to fit the pattern of antibiotic release demonstrated to occur from other bioabsorbable ceramic-type carriers. PMID:15750419

Pietrzak, William S; Eppley, Barry L

2005-03-01

334

Antibiotic resistant Escherichia coli and Salmonella enterica in the beef production and processing chain  

Technology Transfer Automated Retrieval System (TEKTRAN)

Background: Concerns have been raised that extended-spectrum cephalosporin-resistant Escherichia coli (CefR EC), trimethoprim-sulfamethoxazole-resistant E. coli (TxsR EC), extended-spectrum cephalosporin-resistant Salmonella enterica (CefR SE), and nalidixic acid-resistant S. enterica (NalR SE) in c...

335

Transforming User Needs into Functional Requirements for an Antibiotic Clinical Decision Support System  

PubMed Central

Summary Background Many informatics studies use content analysis to generate functional requirements for system development. Explication of this translational process from qualitative data to functional requirements can strengthen the understanding and scientific rigor when applying content analysis in informatics studies. Objective To describe a user-centered approach transforming emergent themes derived from focus group data into functional requirements for informatics solutions and to illustrate these methods to the development of an antibiotic clinical decision support system (CDS). Methods The approach consisted of five steps: 1) identify unmet therapeutic planning information needs via Focus Group Study-I, 2) develop a coding framework of therapeutic planning themes to refine the domain scope to antibiotic therapeutic planning, 3) identify functional requirements of an antibiotic CDS system via Focus Group Study-II, 4) discover informatics solutions and functional requirements from coded data, and 5) determine the types of information needed to support the antibiotic CDS system and link with the identified informatics solutions and functional requirements. Results The coding framework for Focus Group Study-I revealed unmet therapeutic planning needs. Twelve subthemes emerged and were clustered into four themes; analysis indicated a need for an antibiotic CDS intervention. Focus Group Study-II included five types of information needs. Comments from the Barrier/Challenge to information access and Function/Feature themes produced three informatics solutions and 13 functional requirements of an antibiotic CDS system. Comments from the Patient, Institution, and Domain themes generated required data elements for each informatics solution. Conclusion This study presents one example explicating content analysis of focus group data and the analysis process to functional requirements from narrative data. Illustration of this 5-step method was used to develop an antibiotic CDS system, resolving unmet antibiotic prescribing needs. As a reusable approach, these techniques can be refined and applied to resolve unmet information needs with informatics interventions in additional domains. PMID:24454586

Bright, T.J.

2013-01-01

336

Biosynthesis of Enediyne Antitumor Antibiotics  

PubMed Central

The enediyne polyketides are secondary metabolites isolated from a variety of Actinomycetes. All members share very potent anticancer and antibiotic activity, and prospects for the clinical application of the enediynes has been validated with the recent marketing of two enediyne derivatives as anticancer agents. The biosynthesis of these compounds is of interest because of the numerous structural features that are unique to the enediyne family. The gene cluster for five enediynes has now been cloned and sequenced, providing the foundation to understand natures’ means to biosynthesize such complex, exotic molecules. Presented here is a review of the current progress in delineating the biosynthesis of the enediynes with an emphasis on the model enediyne, C-1027. PMID:18397168

Van Lanen, Steven G.; Shen, Ben

2011-01-01

337

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...

338

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

2015-01-01

339

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

PubMed

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

2015-01-01

340

Salmonella typhimurium intercepts Escherichia coli signaling to enhance antibiotic tolerance  

E-print Network

Salmonella typhimurium intercepts Escherichia coli signaling to enhance antibiotic tolerance Nicole Salmonella typhimurium increases its antibiotic toler- ance in response to indole, even though S. typhimurium

Collins, James J.

341

Metabolic fate of SCE-1365, a new broad-spectrum cephalosporin, after parenteral administration to rats and dogs.  

PubMed Central

Disposition of [14C]SCE-1365 was studied in rats and dogs after intramuscular or intravenous injection. The plasma level of [14C]SCE-1365 peaked at 15 min after intramuscular administration and declined rapidly to give half-lives of 27 and 39 min, respectively, in rats and dogs. After intravenous dosage, half-lives were 22 and 32 min, respectively, in rats and dogs. In both animals, the plasma levels of 14C were made up largely of unchanged antibiotic. Binding to plasma protein was 91 and 31%, respectively, in rats and dogs. Tissue levels of [14C]SCE-1365 administered intramuscularly to rats peaked at 15 min and were highest in the kidney and lowest in the brain, with plasma, liver, lung, heart, intestinal wall, and adrenal gland occupying intermediary positions in the order listed. The concentration of [14C]SCE-1365 in erythrocytes was very low, as was the level of the antibiotic in rat fetuses. The milk of rats given [14C]SCE-1365 intramuscularly contained detectable levels of 14C. [14C]SCE-1365 was completely eliminated from the bodies of rats and dogs within 24 to 48 h. In both animals, a large amount of the dosed 14C was excreted in urine as unaltered antibiotic. The remainder was eliminated in the feces via bile. In rats, [14C]SCE-1365 was eliminated by both glomerular filtration (33%) and tubular secretion (67%). An active transport process appeared to be involved in biliary excretion in rats. PMID:6934706

Tanayama, S; Yoshida, K; Adachi, K; Kondo, T

1980-01-01

342

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

PubMed

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

1989-12-01

343

The antibiotic effects of vitamin d.  

PubMed

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

2014-11-12

344

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

2013-01-01

345

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

2013-01-01

346

In Vivo Antibacterial Activity of S-3578, a New Broad-Spectrum Cephalosporin: Methicillin-Resistant Staphylococcus aureus and Pseudomonas aeruginosa Experimental Infection Models  

PubMed Central

The in vivo antibacterial activity of S-3578, a new parental cephalosporin, was compared with those of cefepime, ceftriaxone, ceftazidime, imipenem-cilastatin, and vancomycin. The efficacy of S-3578 against systemic infections caused by methicillin-resistant Staphylococcus aureus (MRSA) SR3637 (50% effective dose [ED50], 7.21 mg/kg of body weight) was almost the same as that of vancomycin. In contrast, cefepime and imipenem-cilastatin were less active against this pathogen (ED50s, >100 and >100 mg/kg, respectively). S-3578 was the most effective compound against penicillin-resistant Streptococcus pneumoniae SR20946 (ED50, 1.98 mg/kg). S-3578 (10 mg/kg) induced a significant reduction in the numbers of viable MRSA SR17764 and Pseudomonas aeruginosa SR10396 organisms in polymicrobial pulmonary infections. The therapeutic efficacy of S-3578 was more potent than that of the combination of vancomycin and ceftazidime. High levels of S-3578 were detected in plasma in vivo, and its efficacy against experimentally induced infections in mice caused by MRSA and P. aeruginosa reflected its potent in vitro activity. We conclude that S-3578 is a promising new cephalosporin for the treatment of infections caused by gram-positive and -negative bacteria, including MRSA and P. aeruginosa. PMID:12878512

Tsuji, Masakatsu; Takema, Morio; Miwa, Hideaki; Shimada, Jingoro; Kuwahara, Shogo

2003-01-01

347

Development and validation of an ultra high performance liquid chromatography tandem mass spectrometry method for determination of 10 cephalosporins and desacetylcefapirin in milk.  

PubMed

A simple, sensitive and reliable analytical method was developed for the simultaneous determination of 10 cephalosporins and desacetylcefapirin in bovine milk by ultra high performance liquid chromatography-positive electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS). Samples were directly purified through HLB cartridge after dilution with 50mM phosphate buffer solution (pH 8.5). Then the eluate was dried under nitrogen and the residue was redissolved in mobile phase. Samples were analyzed by LC-MS/MS on an Acquity UPLC BEH Shield RP18 column with gradient elution. The samples were quantified using ceftiofur-D3 as internal standard. The proposed method was validated according to the European Commission Decision 2002/657/EC. The CC? values were 111, 0.04, 140, 55, 55, 67, 23, 23, 68, 0.10 and 113?g/kg for cefalexin, cefradine, cefacetrile, cefazolin, cefoperazone, cefapirin, cefalonium, cefquinome, desacetylcefapirin, cefotaxime and ceftiofur, respectively. The mean recoveries, repeatability (expressed as coefficient of variation, CVr), and reproducibility (CVR) varied from 94.6% to 117.1%, from 5.6% to 13.6% (CVr), and from 5.9% to 27.9% (CVR), respectively. The method is demonstrated to be suitable for the determination of 10 cephalosporins and desacetylcefapirin in bovine milk. The total time required for the analysis of one sample, including sample preparation, was about 40min. PMID:23747425

Hou, Xiao-Lin; Wu, Yin-Liang; Lv, Yan; Xu, Xiu-Qin; Zhao, Jian; Yang, Ting

2013-07-15

348

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.

1999-01-01

349

Non-prescription antibiotic use in Hungary  

Microsoft Academic Search

Objective  To estimate the extent, prevalence, and trends in non-prescription antibiotic use in Hungary between 2000 and 2004 at national\\u000a and regional levels. To identify determinants of nonprescription antibiotic use.\\u000a \\u000a \\u000a \\u000a Method  Data on non-prescription sales of systemic antibiotics (Anatomical Therapeutic Chemical (ATC) class J01) were analyzed over\\u000a a five-year period. The 2004 version of the World Health Organisation ATC\\/defined daily dose (DDD)

Maria Matuz; Ria Benko; Peter Doro; Gyongyver Soos

2007-01-01

350

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); Joseph M. Bosilevac (Medical College of Virginia/Commonwealth University;Departments of Medicine and Microbiology/Immunology)

2001-03-09

351

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.

2010-01-01

352

Bacterial infections in Lilongwe, Malawi: aetiology and antibiotic resistance  

PubMed Central

Background Life-threatening infections present major challenges for health systems in Malawi and the developing world because routine microbiologic culture and sensitivity testing are not performed due to lack of capacity. Use of empirical antimicrobial therapy without regular microbiologic surveillance is unable to provide adequate treatment in the face of emerging antimicrobial resistance. This study was conducted to determine antimicrobial susceptibility patterns in order to inform treatment choices and generate hospital-wide baseline data. Methods Culture and susceptibility testing was performed on various specimens from patients presenting with possible infectious diseases at Kamuzu Central Hospital, Lilongwe, Malawi. Results Between July 2006 and December 2007 3104 specimens from 2458 patients were evaluated, with 60.1% from the adult medical service. Common presentations were sepsis, meningitis, pneumonia and abscess. An etiologic agent was detected in 13% of patients. The most common organisms detected from blood cultures were Staphylococcus aureus, Escherichia coli, Salmonella species and Streptococcus pneumoniae, whereas Streptococcus pneumoniae and Cryptococcus neoformans were most frequently detected from cerebrospinal fluid. Haemophilus influenzae was rarely isolated. Resistance to commonly used antibiotics was observed in up to 80% of the isolates while antibiotics that were not commonly in use maintained susceptibility. Conclusions There is widespread resistance to almost all of the antibiotics that are empirically used in Malawi. Antibiotics that have not been widely introduced in Malawi show better laboratory performance. Choices for empirical therapy in Malawi should be revised accordingly. A microbiologic surveillance system should be established and prudent use of antimicrobials promoted to improve patient care. PMID:22436174

2012-01-01

353

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

PubMed

?-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

2013-11-01

354

Use of Antibiotic Susceptibility Patterns and Pulsed-Field Gel Electrophoresis To Compare Historic and Contemporary Isolates of Multi-Drug-Resistant Salmonella enterica subsp. enterica Serovar Newport  

PubMed Central

Recently, multi-drug-resistant (MDR) Salmonella enterica subspecies enterica serovar Newport reemerged as a public and animal health problem. The antibiotic resistance of 198 isolates and the pulsed-field gel electrophoresis patterns (PFGE) of 139 isolates were determined. Serovar Newport isolates collected between 1988 and 2001 were included in the study. One hundred seventy-eight isolates were collected from the San Joaquin valley in California and came from dairy cattle clinical samples, human clinical samples, bulk tank milk samples, fecal samples from preweaned calves, and waterways. Twenty clinical isolates from humans from various regions of the United States were also included in the study. Resistance to 18 antibiotics was determined using a disk diffusion assay. PFGE patterns were determined using a single enzyme (XbaI). The PFGE and antibiogram patterns were described using cluster analysis. Although the antibiotic resistance patterns of historic (1988 to 1995) and contemporary (1999 to 2001) isolates were similar, the contemporary isolates differed from the historic isolates by being resistant to cephalosporins and florfenicol and in their general sensitivity to kanamycin and neomycin. With few exceptions, the contemporary isolates clustered together and were clearly separated from the historic isolates. One PFGE-antibiogram cluster combination was predominant for the recent isolates, which were taken from human samples from all parts of the United States, as well as in the isolates from California, indicating a rapid dissemination of this phenotypic strain. The data are consistent with the hypothesis that the reemergence of MDR serovar Newport is not simply an acquisition of further antibiotic resistance genes by the historic isolates but reflects a different genetic lineage. PMID:14711658

Berge, Anna Catharina B.; Adaska, John M.; Sischo, William M.

2004-01-01

355

Agricultural use of antibiotics and the evolution and transfer of antibiotic-resistant bacteria  

PubMed Central

Microbial Resistance to antibiotics is on the rise, in part because of inappropriate use of antibiotics in human medicine but also because of practices in the agricultural industry. Intensive animal production involves giving livestock animals large quantities of antibiotics to promote growth and prevent infection. These uses promote the selection of antibiotic resistance in bacterial populations. The resistant bacteria from agricultural environments may be transmitted to humans, in whom they cause disease that cannot be treated by conventional antibiotics. The author reviews trends in antibiotic use in animal husbandry and agriculture in general. The development of resistance is described, along with the genetic mechanisms that create resistance and facilitate its spread among bacterial species. Particular aspects of resistance in bacterial species common to both the human population and the agrifood industry are emphasized. Control measures that might reverse the current trends are highlighted. PMID:9835883

Khachatourians, G G

1998-01-01

356

Chronological change of antibiotic use and antibiotic resistance in Escherichia coli causing urinary tract infections  

Microsoft Academic Search

Overuse of antibiotics can cause the emergence of resistant bacterial strains. This study retrospectively investigated recent\\u000a trends in Escherichia coli causing urinary tract infections (UTIs), focusing on antibiotic use and antibiotic susceptibilities. Patients diagnosed with\\u000a UTIs caused by E. coli in Akashi Municipal Hospital between April 2004 and March 2010 were enrolled in the study. A total of 858 UTI

Katsumi Shigemura; Kazushi Tanaka; Masayo Adachi; Masuo Yamashita; Soichi Arakawa; Masato Fujisawa

357

JAMA Patient Page: Inappropriate Use of Antibiotics  

MedlinePLUS

... called otitis media ) • Many skin rashes • Bacteria like Staphylococcus aureus (a bacterium that causes serious infections in immune- ... example, to methicillin (a type of antibiotic)-resistant Staphylococcus aureus (MRSA), which can now affect individuals in hospitals ...

358

Alliance for the Prudent Use of Antibiotics  

MedlinePLUS

... have a national strategy to combat antibiotic-resistant bacteria, to better protect our children and grandchildren from ... Community- Associated MRSA" Vol. 31 No. 2: "Nightmare bacteria and the worldwide threat to carbapenems" Vol. 31 ...

359

New Antibiotic May Combat Resistant Bacteria  

MedlinePLUS

... please enable JavaScript. New Antibiotic May Combat Resistant Bacteria Teixobactin shows promise in early experiments, researchers say (* ... that could prove valuable in fighting disease-causing bacteria that no longer respond to older, more frequently ...

360

Danger of Antibiotic Overuse (For Parents)  

MedlinePLUS

... them has resulted in the development of resistant bacteria , which are bacteria that don't respond to antibiotics that may ... types of germs that can make people sick: bacteria and viruses . Although certain bacteria and viruses cause ...

361

Aerosolized antibiotics in cystic fibrosis: an update.  

PubMed

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

2014-06-01

362

Therapeutic strategies to combat antibiotic resistance.  

PubMed

With multidrug resistant bacteria on the rise, new antibiotic approaches are required. Although a number of new small molecule antibiotics are currently in the development pipeline with many more in preclinical development, the clinical options and practices for infection control must be expanded. Biologics and non-antibiotic adjuvants offer this opportunity for expansion. Nevertheless, to avoid known mechanisms of resistance, intelligent combination approaches for multiple simultaneous and complimentary therapies must be designed. Combination approaches should extend beyond biologically active molecules to include smart controlled delivery strategies. Infection control must integrate antimicrobial stewardship, new antibiotic molecules, biologics, and delivery strategies into effective combination therapies designed to 1) fight the infection, 2) avoid resistance, and 3) protect the natural microbiome. This review explores these developing strategies in the context of circumventing current mechanisms of resistance. PMID:25450262

Brooks, Benjamin D; Brooks, Amanda E

2014-11-30

363

An Evaluation of Statewide Strategies to Reduce Antibiotic Overuse  

Microsoft Academic Search

Background: The rapid increase of antibiotic resistance poses a significant threat to human health. Overuse of antibiotics has been linked to rates of antibiotic resistance. This study assessed the utility of two common interventions—1) practice profiling and feedback and 2) patient education materi- als—implemented to decrease antibiotic prescribing for pediatric upper respiratory infections (URIs). Methods: Based on Medicaid regions in

Arch G. Mainous; William J. Hueston; Margaret M. Love; Martin E. Evans; Reginald Finger

2000-01-01

364

The Pros of Procalcitonin: Reducing Antibiotic Duration in the ICU  

E-print Network

Antonio September 9, 2011 Learning Objectives 1. Describe adverse consequences of antibiotic overuse. Consequences of antibiotic overuse i. Promotion of multi-drug resistant (MDR) pathogens 1. Antibiotic use1 The Pros of Procalcitonin: Reducing Antibiotic Duration in the ICU Elizabeth A. Oates, Pharm

Pillow, Jonathan

365

Zinc-induced antibiotic resistance in activated sludge bioreactors  

Microsoft Academic Search

Increased levels of bacterial resistance to antibiotics noted in recent decades poses a significant obstacle to the effective treatment and prevention of disease. Although overuse of antibiotics in agriculture and medicine is partially responsible, environmental exposure to heavy metals may also contribute to antibiotic resistance, even in the absence of antibiotics themselves. In this study, a series of eight lab-scale

Edward Peltier; Joshua Vincent; Christopher Finn; David W. Graham

2010-01-01

366

Novel approaches to developing new antibiotics for bacterial infections  

Microsoft Academic Search

Antibiotics are an essential part of modern medicine. The emergence of antibiotic-resistant mutants among bacteria is seemingly inevitable, and results, within a few decades, in decreased efficacy and withdrawal of the antibiotic from widespread usage. The traditional answer to this problem has been to introduce new antibiotics that kill the resistant mutants. Unfortunately, after more than 50 years of success,

A R M Coates; Y Hu

2007-01-01

367

Direction of aminoacylated transfer RNAs into antibiotic synthesis and peptidoglycan-mediated antibiotic resistance  

PubMed Central

Prokaryotic aminoacylated-transfer RNAs often need to be efficiently segregated between translation and other cellular biosynthetic pathways. Many clinically relevant bacteria, including Streptococcus pneumoniae, Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa direct some aminoacylated-tRNA species into peptidoglycan biosynthesis and/or membrane phospholipid modification. Subsequent indirect peptidoglycan cross-linkage or change in membrane permeability is often a prerequisite for high-level antibiotic resistance. In Streptomycetes, aminoacylated-tRNA species are used for antibiotic synthesis as well as antibiotic resistance. The direction of coding aminoacylated-tRNA molecules away from translation and into antibiotic resistance and synthesis pathways are discussed in this review. PMID:23907010

Shepherd, Jennifer; Ibba, Michael

2013-01-01

368

Early antibiotic treatment in acute necrotising pancreatitis  

Microsoft Academic Search

SummaryDespite improvements in surgical treatment and intensive care, mortality from severe acute pancreatitis remains high. We have carried out a randomised study of 60 consecutive patients with alcohol-induced necrotising pancreatitis to find out whether early antibiotic treatment can improve outcome.30 patients were assigned cefuroxime (4·5 g\\/day intravenously) from admission. In the second group, no antibiotic treatment was given until clinical

V Sainio; E Kemppainen; P Puolakkainen; R Haapiainen; T Schröder; E Kivilaakso; V Valtonen; M Taavitsainen; L Kivisaarl

1995-01-01

369

Transposable multiple antibiotic resistance in Streptococcus pneumoniae  

Microsoft Academic Search

A mobile genetic element, designated Tn1545, was detected in the chromosome of Streptococcus pneumoniae BM4200, a clinical isolate multiply resistant to antibiotics. The 25.3 kb element conferred resistance to kanamycin and structurally related aminoglycosides by synthesis of a 3'-aminoglycoside phosphotranferase type III (aphA-3), to macrolide-lincosamide-streptogramin B-type antibiotics (ermAM), and to tetracycline (tetM). Tn1545 was self-transferable to a recombination deficient S.

Patrice Courvalin; Cécile Carlier

1986-01-01

370

Changes in antibiotic distribution due to pancreatitis.  

PubMed

This work sought to define how pancreatitis affected antibiotic distribution in a perfused rat pancreas model. The distribution kinetics of four antibiotics were examined in control animals and animals with pancreatitis. Meropenem and piperacillin distributed into the extracellular space, and their distribution kinetics were unaffected by pancreatitis. In contrast, in pancreatic cells from animals with pancreatitis, ciprofloxacin showed a reduced uptake and clindamycin showed a reduced distribution. PMID:21402839

Fanning, Kent J; Robertson, Thomas A; Prins, Johannes B; Roberts, Michael S

2011-06-01

371

Changes in Antibiotic Distribution Due to Pancreatitis?  

PubMed Central

This work sought to define how pancreatitis affected antibiotic distribution in a perfused rat pancreas model. The distribution kinetics of four antibiotics were examined in control animals and animals with pancreatitis. Meropenem and piperacillin distributed into the extracellular space, and their distribution kinetics were unaffected by pancreatitis. In contrast, in pancreatic cells from animals with pancreatitis, ciprofloxacin showed a reduced uptake and clindamycin showed a reduced distribution. PMID:21402839

Fanning, Kent J.; Robertson, Thomas A.; Prins, Johannes B.; Roberts, Michael S.

2011-01-01

372

Acquired Antibiotic Resistance Genes: An Overview  

PubMed Central

In this review an overview is given on antibiotic resistance (AR) mechanisms with special attentions to the AR genes described so far preceded by a short introduction on the discovery and mode of action of the different classes of antibiotics. As this review is only dealing with acquired resistance, attention is also paid to mobile genetic elements such as plasmids, transposons, and integrons, which are associated with AR genes, and involved in the dispersal of antimicrobial determinants between different bacteria. PMID:22046172

van Hoek, Angela H. A. M.; Mevius, Dik; Guerra, Beatriz; Mullany, Peter; Roberts, Adam Paul; Aarts, Henk J. M.

2011-01-01

373

Skin Infections and Antibiotic Stewardship: Analysis of Emergency Department Prescribing Practices, 2007–2010  

PubMed Central

Introduction: National guidelines suggest that most skin abscesses do not require antibiotics, and that cellulitis antibiotics should target streptococci, not community-associated MRSA (CA-MRSA). The objective of this study is to describe antimicrobial treatment of skin infections in U.S. emergency departments (EDs) and analyze potential quality measures. Methods: The National Hospital Ambulatory Medical Care Survey (NHAMCS) is a 4-stage probability sample of all non-federal U.S. ED visits. In 2007 NHAMCS started recording whether incision and drainage was performed at ED visits. We conducted a retrospective analysis, pooling 2007–2010 data, identified skin infections using diagnostic codes, and identified abscesses by performance of incision and drainage. We generated national estimates and 95% confidence intervals using weighted analyses; quantified frequencies and proportions; and evaluated antibiotic prescribing practices. We evaluated 4 parameters that might serve as quality measures of antibiotic stewardship, and present 2 of them as potentially robust enough for implementation. Results: Of all ED visits, 3.2% (95% confidence interval 3.1–3.4%) were for skin infection, and 2.7% (2.6–2.9%) were first visits for skin infection, with no increase over time (p=0.80). However, anti-CA-MRSA antibiotic use increased, from 61% (56–66%) to 74% (71–78%) of antibiotic regimens (p<0.001). Twenty-two percent of visits were for abscess, with a non-significant increase (p=0.06). Potential quality measures: Among discharged abscess patients, 87% were prescribed antibiotics (84–90%, overuse). Among antibiotic regimens for abscess patients, 84% included anti-CA-MRSA agents (81–89%, underuse). Conclusion: From 2007–2010, use of anti-CA-MRSA agents for skin infections increased significantly, despite stable visit frequencies. Antibiotics were over-used for discharged abscess cases, and CA-MRSA-active antibiotics were underused among regimens when antibiotics were used for abscess. [West J Emerg Med. 2014;15(3):282–289.] PMID:24868305

Pallin, Daniel J.; Camargo, Carlos A.; Schuur, Jeremiah D.

2014-01-01

374

Probiotics in antibiotic-associated diarrhoea.  

PubMed

Antibiotic-associated diarrhoea is a common event. In some cases, it could represent a life-threatening event. Clostridium difficile colitis is a further distinct complication of antibiotic administration. Treatment options for antibiotic-associated diarrhoea and Clostridium difficile colitis include supplementation with several types of probiotics, as overviewed in this paper. Three randomised, double-blind, controlled clinical trials show a therapeutic effect of Saccharomyces boulardii in antibiotic-associated diarrhoea. The efficacy of Lactobacillus acidophilus and bulgaricus has also been ascertained in two double-blind controlled studies. Other studies focusing on Lactobacillus as a new preventive agent for antibiotic-associated diarrhoea are not double-blind. Among these, a positive effect of Lactobacillus rhamnosus GG, Bifidobacterium longum and Enterococcus faecium SF68 has been reported. Effectiveness of probiotics in antibiotic-associated diarrhoea has, therefore, a consistent scientific rationale, however few studies have performed an assessment of bacterial recovery in stools, and this approach may be helpful in deciding a more rigorous dose standardisation. PMID:12408447

Cremonini, F; Di Caro, S; Santarelli, L; Gabrielli, M; Candelli, M; Nista, E C; Lupascu, A; Gasbarrini, G; Gasbarrini, A

2002-09-01

375

DNA-Aptamers Binding Aminoglycoside Antibiotics  

PubMed Central

Aptamers are short, single stranded DNA or RNA oligonucleotides that are able to bind specifically and with high affinity to their non-nucleic acid target molecules. This binding reaction enables their application as biorecognition elements in biosensors and assays. As antibiotic residues pose a problem contributing to the emergence of antibiotic-resistant pathogens and thereby reducing the effectiveness of the drug to fight human infections, we selected aptamers targeted against the aminoglycoside antibiotic kanamycin A with the aim of constructing a robust and functional assay that can be used for water analysis. With this work we show that aptamers that were derived from a Capture-SELEX procedure targeting against kanamycin A also display binding to related aminoglycoside antibiotics. The binding patterns differ among all tested aptamers so that there are highly substance specific aptamers and more group specific aptamers binding to a different variety of aminoglycoside antibiotics. Also the region of the aminoglycoside antibiotics responsible for aptamer binding can be estimated. Affinities of the different aptamers for their target substance, kanamycin A, are measured with different approaches and are in the micromolar range. Finally, the proof of principle of an assay for detection of kanamycin A in a real water sample is given. PMID:24566637

Nikolaus, Nadia; Strehlitz, Beate

2014-01-01

376

Potential Ecological and Human Health Impacts of Antibiotics and Antibiotic-Resistant Bacteria from Wastewater Treatment Plants  

Microsoft Academic Search

The occurrence of antibiotics and other pharmaceuticals in the environment has become an increasing public concern as recent environmental monitoring activities reveal the presence of a broad range of persistent pharmaceuticals in soil and water. Studies show that municipal wastewater treatment plants (WWTPs) are important point sources of antibiotics and antibiotic-resistant bacteria in the environment. The fate of antibiotics and

Sungpyo Kim; Diana S. Aga

2007-01-01

377

Solid phase extraction using magnetic core mesoporous shell microspheres with C18-modified interior pore-walls for residue analysis of cephalosporins in milk by LC-MS/MS.  

PubMed

A fast and effective extraction method has been developed for measuring the residue of cephalosporins (cefalexin, cefazolin, cefoperazone) in milk by using magnetic core-mesoporous shell microspheres with C18-functionalized interior pore-walls (C18-Fe3O4@mSiO2) as adsorbent. With no need for any protein precipitation procedure, the cephalosporins were directly adsorbed onto the C18-Fe3O4@mSiO2 microspheres through hydrophobic interaction with C18-groups (Octadecyl functional groups) functionalized in the interior walls of mesopore channels while the abundant proteins in milk sample were excluded out of the channel due to the size exclusion effect. Thereafter, the cephalosporins-absorbed C18-Fe3O4@mSiO2 microspheres were rapidly isolated by placing a magnet, and followed by liquid chromatography-tandem mass spectrometry analysis after eluted by methanol. Various parameters which could affect the extraction performance were optimised. The newly developed extraction method was successfully applied in determination of cephalosporin residues in milk samples, offering a valuable alternative to simplify and speed up the sample preparation step. PMID:24360441

Liu, Xiaodan; Yu, Yingjia; Zhao, Meiyan; Zhang, Haiying; Li, Yan; Duan, Gengli

2014-05-01

378

Antibiotic Resistance Analysis of Fecal Coliforms to Determine Fecal Pollution Sources in a Mixed-Use Watershed  

Microsoft Academic Search

Antibiotic resistance analysis was performed on fecal coliform(FC) bacteria from a mixed-use watershed to determine thesource, human or nonhuman, of fecal coliform contamination. The study consisted of discriminant analysis of antibioticresistance patterns generated by exposure to fourconcentrations of six antibiotics (ampicillin, gentamicinsulfate, kanamycin, spectinomycin dihydrochloride,streptomycin sulfate, and tetracycline hydrochloride). Areference database was constructed from 1125 fecal coliformisolates from the following

Brian S. Burnes

2003-01-01

379

Induction kinetics of the Staphylococcus aureus cell wall stress stimulon in response to different cell wall active antibiotics  

PubMed Central

Background Staphylococcus aureus activates a protective cell wall stress stimulon (CWSS) in response to the inhibition of cell wall synthesis or cell envelope damage caused by several structurally and functionally different antibiotics. CWSS induction is coordinated by the VraSR two-component system, which senses an unknown signal triggered by diverse cell wall active agents. Results We have constructed a highly sensitive luciferase reporter gene system, using the promoter of sas016 (S. aureus N315), which detects very subtle differences in expression as well as measuring > 4 log-fold changes in CWSS activity, to compare the concentration dependence of CWSS induction kinetics of antibiotics with different cell envelope targets. We compared the effects of subinhibitory up to suprainhibitory concentrations of fosfomycin, D-cycloserine, tunicamycin, bacitracin, flavomycin, vancomycin, teicoplanin, oxacillin, lysostaphin and daptomycin. Induction kinetics were both strongly antibiotic- and concentration-dependent. Most antibiotics triggered an immediate response with induction beginning within 10 min, except for tunicamycin, D-cycloserine and fosfomycin which showed lags of up to one generation before induction commenced. Induction characteristics, such as the rate of CWSS induction once initiated and maximal induction reached, were strongly antibiotic dependent. We observed a clear correlation between the inhibitory effects of specific antibiotic concentrations on growth and corresponding increases in CWSS induction kinetics. Inactivation of VraR increased susceptibility to the antibiotics tested from 2- to 16-fold, with the exceptions of oxacillin and D-cycloserine, where no differences were detected in the methicillin susceptible S. aureus strain background analysed. There was no apparent correlation between the induction capacity of the various antibiotics and the relative importance of the CWSS for the corresponding resistance phenotypes. Conclusion CWSS induction profiles were unique for each antibiotic. Differences observed in optimal induction conditions for specific antibiotics should be determined and taken into account when designing and interpreting CWSS induction studies. PMID:21251258

2011-01-01

380

21 CFR 510.106 - Labeling of antibiotic and antibiotic-containing drugs intended for use in milk-producing animals.  

...2014-04-01 2014-04-01 false Labeling of antibiotic and antibiotic-containing drugs intended for use in milk-producing...Rulings and Decisions § 510.106 Labeling of antibiotic and antibiotic-containing drugs intended...

2014-04-01

381

21 CFR 510.106 - Labeling of antibiotic and antibiotic-containing drugs intended for use in milk-producing animals.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 false Labeling of antibiotic and antibiotic-containing drugs intended for use in milk-producing...Rulings and Decisions § 510.106 Labeling of antibiotic and antibiotic-containing drugs intended...

2012-04-01

382

21 CFR 510.106 - Labeling of antibiotic and antibiotic-containing drugs intended for use in milk-producing animals.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false Labeling of antibiotic and antibiotic-containing drugs intended for use in milk-producing...Rulings and Decisions § 510.106 Labeling of antibiotic and antibiotic-containing drugs intended...

2013-04-01

383

21 CFR 510.106 - Labeling of antibiotic and antibiotic-containing drugs intended for use in milk-producing animals.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Labeling of antibiotic and antibiotic-containing drugs intended for use in milk-producing...Rulings and Decisions § 510.106 Labeling of antibiotic and antibiotic-containing drugs intended...

2011-04-01

384

21 CFR 510.106 - Labeling of antibiotic and antibiotic-containing drugs intended for use in milk-producing animals.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Labeling of antibiotic and antibiotic-containing drugs intended for use in milk-producing...Rulings and Decisions § 510.106 Labeling of antibiotic and antibiotic-containing drugs intended...

2010-04-01

385

Antibiotic Prescribing Practices for Catheter Urine Culture Results  

PubMed Central

Background: The literature suggests that positive results of catheter urine cultures frequently lead to unnecessary antimicrobial prescribing, which therefore represents an important target for stewardship. Objective: To assess the appropriateness of antibiotic prescribing in response to the results of urine cultures from patients with indwelling urinary catheters. Methods: This retrospective study was conducted at a tertiary care centre and involved adults with indwelling urinary catheters from whom urine specimens were obtained for culture. Patients with positive or negative culture results were identified from microbiology laboratory reports. The medical records of consecutive patients were screened to select a sample of 80 inpatients (40 per group). Abstracted patient histories were independently evaluated by an expert panel of 3 infectious diseases consultants blinded to the decisions of prescribers and of fellow panelists. The primary end point was concordance of each patient’s treatment decision (with respect to the indication) between the expert panel (based on majority agreement, i.e., at least 2 of the 3 expert panelists) and the prescriber. The secondary end points were unnecessary days of therapy and selected outcomes over a predefined period after urine was obtained for culture. Results: A total of 591 charts were screened to generate the targeted number of patients. Baseline demographic characteristics were comparable for the 2 groups, except antibiotic exposure before urine collection was significantly more frequent for the group with negative culture results. The treatment decision was concordant in 40% (16/40) of the patients with a positive culture result and 85% (34/40) of those with a negative culture result (p < 0.001). The most common reason for discordance was administration of antibiotics when not indicated (23 of 24 patients with a positive result and 5 of 6 patients with a negative result), which accounted for 165 and 32 unnecessary days of therapy per 1000 inpatient-days, respectively (p < 0.001). Adverse effects occurred in 2 of the 23 patients with a positive result who received antibiotics that were not indicated. Conclusions: Appropriateness of antibiotic prescribing, as measured by concordance of decisions between the expert panel and prescribers, was more common among patients with negative urine culture results than among those with positive results. However, there is an opportunity to improve prescribing for both groups through antimicrobial stewardship initiatives. Unnecessary days of therapy and adverse effects were more common in patients with a positive culture result. PMID:23467594

Chiu, Jonathan; Thompson, G William; Austin, Thomas W; Hussain, Zafar; John, Michael; Bombassaro, Anne Marie; Connelly, Sarah E; Elsayed, Sameer

2013-01-01

386

A Gene Cluster for Macrolide Antibiotic Biosynthesis in Streptomyces venezuelae: Architecture of Metabolic Diversity  

Microsoft Academic Search

In a survey of microbial systems capable of generating unusual metabolite structural variability, Streptomyces venezuelae ATCC 15439 is notable in its ability to produce two distinct groups of macrolide antibiotics. Methymycin and neomethymycin are derived from the 12-membered ring macrolactone 10-deoxymethynolide, whereas narbomycin and pikromycin are derived from the 14-membered ring macrolactone, narbonolide. This report describes the cloning and characterization

Yongquan Xue; Lishan Zhao; Hung-Wen Liu; David H. Sherman

1998-01-01

387

Homology between Streptomyces genes coding for synthesis of different polyketides used to clone antibiotic biosynthetic genes  

Microsoft Academic Search

Many important antibiotics such as tetracyclines, erythromycin, adriamycin, monensin, rifamycin and avermectins are polyketides. In their biosynthesis, multifunctional synthases1 catalyse iterated condensation of thio-esters derived from acetate, propionate or butyrate to yield aliphatic chains of varying length and carrying different alkyl substituents. Subsequent modifications, including aromatic or macrolide ring closure or specific methylations or glycosylations, generate further chemical diversity. It

F. Malpartida; S. E. Hallam; H. M. Kieser; H. Motamedi; C. R. Hutchinson; M. J. Butler; D. A. Sugden; M. Warren; C. McKillop; C. R. Bailey; G. O. Humphreys; D. A. Hopwood

1987-01-01

388

MICROBIOLOGY: An Antibiotic Mimics Immunity  

NSDL National Science Digital Library

Access to the article is free, however registration and sign-in are required. In Carl Nathan's Perspective, he discusses a type of relationship between antimicrobial chemotherapy and host immunity: An antibacterial agent can mimic immunity by generating an important chemistry of the immune response (4) .Singh et al. find that nitroimidazoles kill Mycobacterium tuberculosis (Mtb) under hypoxic conditions at least in part by undergoing enzyme-catalyzed denitration, which generates reactive nitrogen intermediates.

Carl Nathan (Weill Cornell Medical College; Department of Microbiology and Immunology)

2008-11-28

389

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

PubMed Central

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

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

2013-01-01

390

"Pseudo" gamma-butyrolactone receptors respond to antibiotic signals to coordinate antibiotic biosynthesis.  

PubMed

In actinomycetes, the onset of secondary metabolite biosynthesis is often triggered by the quorum-sensing signal gamma-butyrolactones (GBLs) via specific binding to their cognate receptors. However, the presence of multiple putative GBL receptor homologues in the genome suggests the existence of an alternative regulatory mechanism. Here, in the model streptomycete Streptomyces coelicolor, ScbR2 (SCO6286, a homologue of GBL receptor) is shown not to bind the endogenous GBL molecule SCB1, hence designated "pseudo" GBL receptor. Intriguingly, it could bind the endogenous antibiotics actinorhodin and undecylprodigiosin as ligands, leading to the derepression of KasO, an activator of a cryptic type I polyketide synthase gene cluster. Likewise, JadR2 is also a putative GBL receptor homologue in Streptomyces venezuelae, the producer of chloramphenicol and cryptic antibiotic jadomycin. It is shown to coordinate their biosynthesis via direct repression of JadR1, which activates jadomycin biosynthesis while repressing chloramphenicol biosynthesis directly. Like ScbR2, JadR2 could also bind these two disparate antibiotics, and the interactions lead to the derepression of jadR1. The antibiotic responding activities of these pseudo GBL receptors were further demonstrated in vivo using the lux reporter system. Overall, these results suggest that pseudo GBL receptors play a novel role to coordinate antibiotic biosynthesis by binding and responding to antibiotics signals. Such an antibiotic-mediated regulatory mechanism could be a general strategy to coordinate antibiotic biosynthesis in the producing bacteria. PMID:20562102

Xu, Gangming; Wang, Juan; Wang, Linqi; Tian, Xiuyun; Yang, Haihua; Fan, Keqiang; Yang, Keqian; Tan, Huarong

2010-08-27

391

Urine Antibiotic Activity in Patients Presenting to Hospitals in Laos: Implications for Worsening Antibiotic Resistance  

PubMed Central

Widespread use of antibiotics may be important in the spread of antimicrobial resistance. We estimated the proportion of Lao in- and outpatients who had taken antibiotics before medical consultation by detecting antibiotic activity in their urine added to lawns of Bacillus stearothermophilus, Escherichia coli, and Streptococcus pyogenes. In the retrospective (N = 2,058) and prospective studies (N = 1,153), 49.7% (95% confidence interval [CI] = 47.4–52.0) and 36.2% (95% CI = 33.4–38.9), respectively, of Vientiane patients had urinary antibiotic activity detected. The highest frequency of estimated antibiotic pre-treatment was found in patients recruited with suspected central nervous system infections and community-acquired septicemia (both 56.8%). In Vientiane, children had a higher frequency of estimated antibiotic pre-treatment than adults (60.0% versus 46.5%; P < 0.001). Antibiotic use based on patients histories was significantly less frequent than when estimated from urinary antibiotic activity (P < 0.0001). PMID:21813851

Khennavong, Manisone; Davone, Viengmon; Vongsouvath, Manivanh; Phetsouvanh, Rattanaphone; Silisouk, Joy; Rattana, Olay; Mayxay, Mayfong; Castonguay-Vanier, Josée; Moore, Catrin E.; Strobel, Michel; Newton, Paul N.

2011-01-01

392

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

PubMed

The aim of this study was to develop and evaluate an enzyme immunoassay (EIA) for the cephalosporin antibiotic in milk, in combination with a new microbiological test system (brilliant black reduction test, BRT-P). Polyclonal antibodies against cefquinome were produced in rabbits, using cefquinome-keyhole limpet hemocyanine as the immunogen. These antibodies and a cefquinome-glucose oxidase conjugate were used in a competitive indirect EIA. The detection limit for cefquinome in milk was 1.5 ng ml(-1), recoveries were 80-128% at 4-40 ng ml(-1). Cross-reactivities with other cephalosporins/penicillins were all <1%. The EIA was used to determine cefquinome in incurred raw milk, the BRT-P (detection limit ? 20 ng ml(-1)) and a receptor assay (ßeta-s.t.a.r., detection limit ? 15 ng ml(-1)) were used in parallel. Five lactating cows, suffering from clinical mastitis, were treated with cefquinome by simultaneous intramammary and intramuscular injection. Cefquinome residues (maximum 10-27 ?g?ml(-1)) were most exclusively found in the udder quarter which was treated intramammary, residue levels in the other three quarters were low (<20 ng ml(-1)). Even in milk from intramammary-dosed quarters, residue levels fell below European Union maximum residue level (MRL, 20 ?g kg(-1)) 2 days before the end of the withdrawal period. EIA, BRT-P, and ßeta-s.t.a.r. results showed acceptable agreement for milk samples, but the newly developed EIA is superior in aspects of sensitivity. In conclusion, this is the first one description of immunoassay and microbiological tests capable to determine cefquinome in milk at the MRL in incurred sample material. PMID:21103866

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

2011-01-01

393

Hospital outbreak of Klebsiella pneumoniae resistant to broad-spectrum cephalosporins and beta-lactam-beta-lactamase inhibitor combinations by hyperproduction of SHV-5 beta-lactamase.  

PubMed Central

An aminoglycoside- and ceftazidime-resistant strain of Klebsiella pneumoniae K2 producing the extended-spectrum beta-lactamase SHV-5 infected or colonized 14 pediatric patients at Guy's Hospital. The patients were mostly neonates recovering from cardiac surgery for congenital defects. The organism was also isolated from a nurse and from the father of one of the children. Four patients had septicemia, and two septicemic neonates with postoperative renal failure died. Aminoglycoside and cephalosporin resistance transferred to Escherichia coli in vitro on a 160-kb plasmid, and a similar resistant E. coli strain was isolated from the stools of one of the affected children. The epidemic organism colonized the bowel and skin and was probably transmitted via staff hands. Five wards were involved because of extensive patient movements. The outbreak was controlled by patient isolation and attention to handwashing. All of the isolates of the outbreak strain were identical by phage typing, ribotyping, plasmid profiling, and biochemical and serological testing, but they varied in their production of SHV-5. Some isolates produced normal amounts of SHV-5 and were susceptible to beta-lactam-beta-lactamase inhibitor combinations. Others, including the single isolate of multiresistant E. coli, produced up to five times as much enzyme as "normal" isolates. This hyperproduction resulted in increased resistance to several penicillins and cephalosporins and to the beta-lactam-beta-lactamase inhibitor combinations amoxicillin-clavulanic acid, ampicillin-sulbactam, piperacillin-tazobactam, and ceftazidime-clavulanic acid. The hyperproduction of SHV-5 by K. pneumoniae and E. coli seen in this outbreak suggests that beta-lactam-beta-lactamase inhibitor combinations may be unreliable for the treatment of organisms producing extended-spectrum beta-lactamases. PMID:8789016

French, G L; Shannon, K P; Simmons, N

1996-01-01

394

Effective treatment of cephalosporin-rifampin combinations against cryptic methicillin-resistant beta-lactamase-producing coagulase-negative staphylococcal experimental endocarditis.  

PubMed Central

The efficacy of cefazolin or cefpirome alone or combined with rifampin was compared with that of vancomycin alone or combined with rifampin in an experimental model of methicillin-resistant, beta-lactamase-producing, coagulase-negative staphylococcal endocarditis. Phenotypically, the mecA gene-positive strain used in vivo did not exhibit methicillin resistance by the agar dilution or disk susceptibility method but was resistant in vitro (oxacillin MIC, 64 micrograms/ml) by the microtiter dilution method with 2% NaCl supplementation. Macrodilution broth susceptibilities of standard inocula failed to demonstrate cross-resistance of staphylococci to cefazolin (MIC, 8 micrograms/ml) or cefpirome (MIC, 4 micrograms/ml). In vivo, vancomycin and cefpirome had similar activities, and both regimens were more effective than was cefazolin alone. While the MIC of rifampin was low (0.031 micrograms/ml), monotherapy with rifampin resulted in a bimodal distribution of outcomes due to the expected emergence of resistant mutants. The results in vitro of time-kill synergy studies using rifampin in combination with cefazolin or cefpirome varied with the antimicrobial concentrations tested and did not reliably predict activities in vivo of rifampin-beta-lactam combination therapies. Cefpirome, but not cefazolin or vancomycin, in combination with rifampin was synergistic in vivo. Cefpirome in combination with rifampin was more effective than was cefazolin in combination with rifampin. Both cephalosporin-rifampin regimens were significantly more effective than was cephalosporin or vancomycin monotherapy and were as effective as vancomycin combined with rifampin. These data support further evaluation of rifampin-beta-lactam combinations as possible alternative therapies to vancomycin-containing regimens for selected methicillin-resistant coagulase-negative staphylococcal infections. PMID:7486924

Brandt, C M; Rouse, M S; Tallan, B M; Laue, N W; Wilson, W R; Steckelberg, J M

1995-01-01

395

Concentration-dependent activity of antibiotics in natural environments  

PubMed Central

Bacterial responses to antibiotics are concentration-dependent. At high concentrations, antibiotics exhibit antimicrobial activities on susceptible cells, while subinhibitory concentrations induce diverse biological responses in bacteria. At non-lethal concentrations, bacteria may sense antibiotics as extracellular chemicals to trigger different cellular responses, which may include an altered antibiotic resistance/tolerance profile. In natural settings, microbes are typically in polymicrobial communities and antibiotic-mediated interactions between species may play a significant role in bacterial community structure and function. However, these aspects have not yet fully been explored at the community level. Here we discuss the different types of interactions mediated by antibiotics and non-antibiotic metabolites as a function of their concentrations and speculate on how these may amplify the overall antibiotic resistance/tolerance and the spread of antibiotic resistance determinants in a context of polymicrobial community. PMID:23422936

Bernier, Steve P.; Surette, Michael G.

2013-01-01

396

Characterization of daptomycin-loaded antibiotic cement.  

PubMed

Antibiotics are commonly mixed with polymethylmethacrylate (PMMA) cement to suppress severe periprosthetic infections associated with total joint arthroplasty. The relationship between antibiotic concentration and the resulting elution kinetics remains unclear. The purpose of this study was to characterize the release of daptomycin from PMMA cement and the subsequent effects on mechanical properties.Varying concentrations of daptomycin and tobramycin were vacuum mixed in commercially available PMMA and subjected to an in vitro elution period. High-performance liquid chromatography was used to quantify the concentration of the amount of daptomycin eluted at predetermined time points. Samples were subjected to compressive loading to analyze the effect of antibiotic concentration on cement mechanical properties. Daptomycin elution increased when initial tobramycin concentration was increased. Furthermore, the addition of antibiotics increased the compressive strength of the cement in the postelution period. The binary addition of tobramycin with daptomycin antibiotics modifies the elution and mechanical properties of PMMA bone cement. Based on the findings of our study, 2 g of daptomycin and 3.6 g of tobramycin per 40-g packet of cement should be used to promote daptomycin elution without sacrificing PMMA mechanical properties. PMID:22495850

Kaplan, Lige; Kurdziel, Michael; Baker, Kevin C; Verner, James

2012-04-01

397

Antibiotic susceptibility profiles of oral pathogens.  

PubMed

Periodontitis is a bacterial disease that can be treated with systemic antibiotics. The aim of this study was to establish the antibiotic susceptibility profiles of five periodontal pathogens to six commonly used antibiotics in periodontics. A total of 247 periodontal bacterial isolates were tested for susceptibility to the six antibiotics using the Etest method. MIC(50) and MIC(90) values (minimum inhibitory concentrations for 50% and 90% of the organisms, respectively) were calculated. Both European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Clinical and Laboratory Standards Institute (CLSI) breakpoints were used in the study to interpret results. ?-Lactamase production was tested when amoxicillin resistance was found. MIC(90) values of the anaerobic bacteria were all well below breakpoint values, except for three isolates of Prevotella intermedia and one isolate of Fusobacterium nucleatum that were resistant to amoxicillin (CLSI breakpoints); these isolates were ?-lactamase-positive. Two isolates of the capnophilic Aggregatibacter actinomycetemcomitans appeared to be amoxicillin-resistant but failed to show ?-lactamase activity. Comparison with a previous study from The Netherlands showed minor differences in susceptibility profiles, but the MIC(90) values of A. actinomycetemcomitans for amoxicillin, clindamycin, azithromycin and tetracycline were higher. Geographical differences in the susceptibility profiles of Porphyromonas gingivalis and A. actinomycetemcomitans between European countries were noted. Comparison of European susceptibility profiles with that of a South American country (Colombia) revealed a much higher resistance in the latter. Owing to these differences in susceptibility profiles, it is of concern to regularly perform surveillance studies on antibiotic resistance. PMID:22890195

Veloo, A C M; Seme, K; Raangs, E; Rurenga, P; Singadji, Z; Wekema-Mulder, G; van Winkelhoff, A J

2012-11-01

398

Gastrointestinal Colonization with a Cephalosporinase-Producing Bacteroides Species Preserves Colonization Resistance against Vancomycin-Resistant Enterococcus and Clostridium difficile in Cephalosporin-Treated Mice  

PubMed Central

Antibiotics that are excreted into the intestinal tract may disrupt the indigenous intestinal microbiota and promote colonization by health care-associated pathogens. ?-Lactam, or penicillin-type, antibiotics are among the most widely utilized antibiotics worldwide and may also adversely affect the