cefotaxime and Enterobacteriaceae-Infections

To summarize published studies on the prevalence of and risk factors for maternal bacterial colonization and/or infection with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) in pregnant and/or post-partum women in Africa.. A systematic review was conducted using the PubMed, Scopus, and Google Scholar databases. Bibliographies of included eligible studies were manually searched to identify additional relevant articles. No language restriction was applied. The timeframe of the search included all records from electronic database inception to July 15, 2017. A random-effects meta-analysis was performed to summarize the prevalence and the 95% confidence intervals (CI) of ESBL-E colonization or infection in pregnant or post-partum women in Africa. The meta-analysis was conducted using STATA IC 13.1 software and the metaprop function/plugin.. Ten studies (seven on pregnant women and three on post-partum women) were included, documenting a 17% prevalence of maternal colonization with ESBL-E in Africa (95% CI 10-23%). The prevalence of ESBL-E in community isolates exceeded that in isolates from the hospital setting (22% vs. 14%). The most frequently reported ESBL-encoding gene was CTX-M (cefotaxime hydrolyzing capabilities). Data on risk factors for maternal ESBL-E colonization and infection are very limited.. The prevalence of colonization and/or infection with ESBL-E in pregnant and post-partum women in Africa exceeds that reported from high- and middle-income settings, representing a risk for subsequent neonatal colonization and/or infection with ESBL-E.

Topics: Africa; beta-Lactamases; Cefotaxime; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Postpartum Period; Pregnancy; Pregnancy Complications, Infectious; Prevalence; Risk Factors

CTX-M-type enzymes are a group of class A extended-spectrum beta-lactamases (ESBLs) that are rapidly spreading among Enterobacteriaceae worldwide. More that 50 allotypes are known, clustered into six sub-lineages. The CTX-M-encoding genes have been captured from the chromosome of Kluyvera spp. on conjugative plasmids that mediate their dissemination among pathogenic enterobacteria. CTX-M-type ESBLs exhibit powerful activity against cefotaxime and ceftriaxone but generally not against ceftazidime, which has important implications for laboratory detection. However, several CTX-M variants with enhanced ceftazidimase activity have been detected. The rapid and massive spread of CTX-M-type ESBLs is rapidly changing the ESBL epidemiology and, in some geographical areas, these enzymes are now the most prevalent ESBLs in Enterobacteriaceae.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Cefotaxime; Ceftazidime; Ceftriaxone; Cephalosporins; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Models, Molecular; Prevalence

Infection by Citrobacter appears in man only in certain circumstances, since it usually acts as contaminant or colonizer. Bacteraemia by this bacillus can affect immunodeficient people, elderly people or those patients who have undergone invasive hospital processes. Although incidence of bacteraemia is low (0.3-0.9%), the death rate is very high, about 48%. This bacillus is seldom the cause of endocarditis. That is why we describe a case of endocarditis by Citrobacter freundii, in an aged person with previous valvulopathy.

Topics: Aged; Aortic Valve; Cefotaxime; Cephalosporins; Citrobacter freundii; Endocarditis, Bacterial; Enterobacteriaceae Infections; Heart Valve Diseases; Humans; Male; Mitral Valve

Cefixime, a new oral cephalosporin, is more active against enterobacteriaceae than the conventional oral cephalosporins. About 20% of the drug is excreted by the kidneys as active drug. Therefore, the treatment of urinary tract infection (UTI) by cefixime may be a good alternative. In two smaller uncontrolled and four larger, controlled (amoxicillin, co-trimoxazole) "western" studies as well as in eight Japanese studies the good efficacy of cefixime in uncomplicated UTI could be demonstrated. Because of its antibacterial spectrum in this kind of infection the therapy with cefixime can be initiated already prior to sensitivity testing. Concerning the treatment of acute pyelonephritis only few cases are reported. Good results, except in the case of Proteus mirabilis infection, could be achieved. In the treatment of complicated UTI our own controlled (norfloxacin) and 13 uncontrolled Japanese studies showed cefixime to be an effective antibiotic if infections are caused by sensitive strains. Since in complicated UTI also gram-positive and nonfermenting pathogens resistant to cefixime can be found, treatment should not be initiated without sensitivity testing. Concerning treatment of UTI in children only few, but promising, results are reported. The tolerance of cefixime was similar to that of the comparative drugs. The once daily dose (400 mg), however, showed a higher incidence of gastrointestinal adverse effects than a twice daily dose (200 mg). Therefore, the daily dose should be administered in two divided doses. In summary, cefixime proved to be a good alternative in the treatment of UTI.

Topics: Anti-Infective Agents, Urinary; Cefixime; Cefotaxime; Enterobacteriaceae Infections; Humans; Urinary Tract Infections

The new cephalosporin compounds have increased in vitro activity against gram-negative enteric bacilli and penetrate well into cerebrospinal fluid. Moreover, their pharmacokinetic properties are favorable and their safety seems adequate, although insufficiently evaluated to date. Interest has been focused on them as therapeutic agents for neonatal sepsis and meningitis caused by Enterobacteriaceae. In this review the third generation cephalosporins are evaluated for their possible use in the neonates; opinions are based on currently available data. It is concluded that moxalactam and cefotaxime and probably also ceftriaxone and ceftazidime represent valuable alternatives to aminoglycosides for therapy of severe neonatal infection.

Topics: Cefotaxime; Ceftazidime; Ceftriaxone; Cephalosporins; Enterobacteriaceae Infections; Humans; Infant, Newborn; Meningitis; Moxalactam; Sepsis

Topics: Anti-Bacterial Agents; beta-Lactams; Cefmenoxime; Cefmetazole; Cefoperazone; Cefotaxime; Cefotiam; Cefsulodin; Ceftazidime; Ceftizoxime; Ceftriaxone; Cephalosporins; Cephamycins; Drug Interactions; Drug Resistance, Microbial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Imipenem; Moxalactam

In a prospective, open clinical trial 21 patients suffering from lower respiratory tract infections were treated with the new oral cephalosporin cefixime. The antibiotic was given at a dosage of 200 mg b. i. d. for seven to eleven days. Seventeen of 18 evaluable patients were cured or distinctly improved at the end of therapy as well as two days after the end of treatment. Clinical results correlated well with the results of the lung function tests, especially with the significant decrease of resistance. At the end of therapy all initially isolated pathogens were eradicated. The tolerability of cefixime was good, only in two patients treated mild and transient side effects were noticed (1 x diarrhea, 1 x epigastric pain).

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Bronchitis; Bronchopneumonia; Cefixime; Cefotaxime; Citrobacter; Drug Resistance, Microbial; Drug Tolerance; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Haemophilus Infections; Humans; Male; Middle Aged; Pneumonia; Pneumonia, Pneumococcal; Prospective Studies; Proteus Infections

Biliary sepsis represents a major percentage of fatal complications after endoscopic retrograde cholangiopancreatography. We performed a randomized controlled study to investigate the value of antibiotic prophylaxis, and to assess the frequency and source of infectious complications associated with ERCP. Ninety-six patients who underwent 100 endoscopic retrograde cholangiopancreatographies were included in the study. Half of the patients received antibiotic prophylaxis (Cefotaxime 2 g i.v. 15 min before the procedure). Bacteremia was detected in 2% of the patients receiving antibiotic prophylaxis, as compared with 16% (p less than 0.02) in the control group. In order to determine the source of bacteremia, bile samples and irrigation fluid from the suction channel of the endo-scope were obtained for bacteriological evaluation. Several lines of evidence suggested that bacteremia associated with ERCP was essentially caused by mucosal lesions of the oropharynx. Bacteremia was asymptomatic, with the exception of two patients who subsequently developed fever, but recovered rapidly under antibiotic therapy. The frequency of cholangitis following ERCP was not significantly reduced by antibiotic prophylaxis (4% vs. 2%). Recommendations for antibiotic prophylaxis are discussed.

Topics: Cefotaxime; Cholangiopancreatography, Endoscopic Retrograde; Cholangitis; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Premedication; Prospective Studies; Sepsis

In a prospective randomized study to determine whether prevention of colonization of Gram-negative bacteria results in prevention of Gram-negative bacterial infections, 96 intensive care patients were randomly allocated into a control group and a study group. The study group received oral nonabsorbable antimicrobial agents (i.e., tobramycin, amphotericin B, and polymyxin E) in addition to parenteral antibiotics. Colonization with Gram-negative microorganisms in the oropharynx, and respiratory and digestive tracts increased in the control group during their stay, while the study group did not tend to colonize with Gram-negative bacteria. In the control group, 107 nosocomial infections were diagnosed, vs. 42 nosocomial infections in the study group. Nosocomial infections caused by Gram-negative bacteria were significantly less frequent in the study group. Mortality due to an acquired infection was significantly less frequent in the study group. We conclude that colonization, infection, and subsequent mortality by nosocomial Gram-negative bacteria can be prevented by a regime of topically applied nonabsorbable antibiotics.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Anti-Bacterial Agents; Bacteria; Cefotaxime; Child; Colistin; Cross Infection; Digestive System; Drug Therapy, Combination; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Oropharynx; Prospective Studies; Pseudomonas Infections; Random Allocation; Respiratory System; Tobramycin

In a prospective, randomized study we compared cefotaxime (C) with tobramycin plus cefazolin (C + T) in the treatment of Enterobacterial septicemia. Twenty-five patients received C and twenty two C + T. There are 8 treatment failures, in C + T group, 3 in C group. We observed 5 adverse effects, 2 in the C group (1 reversible collapse and 1 Pseudomonas aeruginosa superinfection) and 3 in the C + T group (acute renal failures). We conclude that C may be more effective and less toxic than cefazolin plus tobramycin for patients with Enterobacterial septicemia.

Topics: Aged; Cefazolin; Cefotaxime; Drug Therapy, Combination; Enterobacteriaceae Infections; Humans; Middle Aged; Prospective Studies; Random Allocation; Sepsis; Tobramycin

Topics: Amikacin; Cefotaxime; Clinical Trials as Topic; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Sepsis

93 patients were enrolled into a prospective randomised study to determine the efficacy and safety of netilmicin, cefotaxime or their combination in the treatment of sepsis caused by susceptible strains of Enterobacteriaceae or staphylococci. 83 patients were evaluable for safety, 74 for clinical efficacy and 63 for microbiological response including 36 patients (57%) with positive blood cultures. There were significantly more clinical failures with cefotaxime than with netilmicin even when urinary tract sepsis was excluded. Microbiological failures occurred more frequently in the cefotaxime arm and were associated with Klebsiella and Enterobacter spp. Four cefotaxime failures were subsequently successfully treated with netilmicin. More mixed infections were however enrolled by chance into the cefotaxime arm. The statistical difference between netilmicin and cefotaxime is not significant if mixed infections are excluded. There was no difference in efficacy between the netilmicin and combination groups although superinfection was seen in the latter group. The incidence of nephrotoxicity was greater in the netilmicin group but not significantly so. Only one minor case of ototoxicity was detected in the 41 patients receiving netilmicin who had serial audiograms. The results suggest that netilmicin is a more effective agent than cefotaxime for treating life-threatening infections with susceptible Enterobacteriaceae or staphylococci particularly with infections in non-urinary tract sites. If dosage of netilmicin is closely monitored by measuring serum concentrations, toxicity is minimal.

Topics: Adolescent; Adult; Bacterial Infections; Cefotaxime; Cross Infection; Drug Therapy, Combination; Enterobacteriaceae Infections; Humans; Netilmicin; Random Allocation; Sepsis; Staphylococcal Infections

In a prospective, randomized, double-blind study, we compared cefotaxime with nafcillin plus tobramycin in the treatment of serious bacterial infections. Of 195 patients with suspected or proven infections who were not neutropenic, definite bacterial infections were identified in 81; 34 of 38 patients given cefotaxime and 26 of 43 given nafcillin plus tobramycin (p less than 0.01) responded to treatment. The difference in response rates occurred primarily in patients with rapidly fatal underlying disease or with an infection outside the urinary tract. A logistic regression analysis showed that treatment with cefotaxime was still associated with a higher response rate after adjusting for several potential confounding factors. Among patients treated for 3 days or more, our criteria for nephrotoxicity were met in 2 of 68 (2.9%) given cefotaxime and 16 of 57 (28.1%) given nafcillin plus tobramycin (p less than 0.001). Prolongation of the prothrombin time and enterococcal colonization did not occur more frequently with cefotaxime. We conclude that cefotaxime may be more effective and less toxic than nafcillin plus tobramycin for patients with serious bacterial infections.

Topics: Adult; Aged; Bacterial Infections; Cefotaxime; Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Enterobacter; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Humans; Infusions, Parenteral; Kidney Diseases; Male; Middle Aged; Nafcillin; Penicillin Resistance; Prognosis; Pseudomonas Infections; Random Allocation; Tobramycin; Urinary Tract Infections

Ceftizoxime, a new beta-lactamase-resistant, semisynthetic antibiotic, was compared to cefamandole in a prospective randomized trial to determine its efficacy and safety in 21 patients with acute, complicated urinary tract infections. Four patients randomized initially to receive cefamandole were found to have resistant organisms and were treated with ceftizoxime. Dosage for ceftizoxime was 1 gm. administered parenterally every 12 hours, while 1 gm. cefamandole was given every 6 hours. Urine cultures were obtained before the initiation of therapy, on day 4, after completion of therapy and 4 to 6 weeks after therapy. Specified laboratory tests were obtained. Of 14 patients receiving ceftizoxime 11 (79 per cent) and of 7 patients receiving cefamandole 7 (100 per cent) had negative cultures at the completion of therapy and 4 to 6 weeks later. No patient had any adverse reaction to ceftizoxime. Ceftizoxime is a safe and effective antibiotic agent when used as a single agent for complicated urinary tract infections. However, ceftizoxime is much more expensive than cefamandole therapy. Therefore, it is recommended that ceftizoxime be reserved for treatment of urinary tract infections stemming from pathogenic species resistant to the less expensive antimicrobials.

Topics: Adolescent; Adult; Aged; Cefamandole; Cefotaxime; Ceftizoxime; Cephalosporins; Clinical Trials as Topic; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Prospective Studies; Pseudomonas Infections; Random Allocation; Urinary Tract Infections

Fecal carriage of extended-spectrum beta-lactamase and Carbapenemase-producing Enterobacteriaceae is a potential risk for the transmission of infection with resistant strains. Understanding the burden of these resistant strains in asymptomatic people is essential to reduce the chain of infection transmission. However, data on the fecal carriage of Extended-spectrum Beta-lactamase and Carbapenemase-producing Enterobacteriaceae among food handlers were limited in developing countries especially in Ethiopia. The aim of the present study is, therefore, to assess fecal carriage rate, associated factors, and antimicrobial resistance patterns of Extended-spectrum Beta-lactamase and Carbapenemase-producing Enterobacteriaceae among food handlers at the University of Gondar Cafeterias, Northwest Ethiopia.. An institution-based cross-sectional study was conducted from February to June 2021 at the University of Gondar cafeterias. A total of 290 stool samples were collected, transported using Cary Blair transport medium, and processed. All isolates were cultured and identified by using MacConkey agar, and routine biochemical tests. Antimicrobial susceptibility testing was done to each isolate following the Kirby Bauer disk diffusion method. If the zone of inhibition was ≤ 22 mm for ceftazidime, ≤25 mm for ceftriaxone, and ≤27 for cefotaxime they were considered as potential ESBL strain and selected for a further phenotypic confirmatory. Moreover, the double-disc diffusion test and the modified carbapenem inactivation method were used for confirmations of Extended-spectrum β-lactamase and Carbapenemase-producing Enterobacteriaceae respectively. If a ≥5mm difference in zone diameter for either antimicrobial agent in combination with clavulanic acid versus the zone diameter of the agent when tested alone (without B-lactamase inhibitor), was confirmed as ESBL-PE and if the zone of inhibition diameter between 6-15mm and 16- 18mm with a pinpoint colony, it was considered as carbapenem resistance Enterobacteriaceae. Data were entered using Epi-data version 4.6 and then exported to SPSS version 26 for analysis. Potential risk factors were assessed using multivariable logistic regression and a p-value less than 0.05 was considered statistically significant.. Out of 290 stool samples, 63 (21.7%) and 7 (2.4%) were confirmed as Extended-spectrum β-lactamase and Carbapenemase-producing Enterobacteriaceae. The most predominant ESBL-PE was E. coli 43 (14.8%) followed by K. pneumoniae 17 (5.9%). Most of the Extended-spectrum β-lactamase and Carbapenemase-producing isolates were resistant to tetracycline, cefotaxime, ceftazidime, and ceftriaxone (100% each). In contrast, a low resistance level was recorded for Meropenem and cefoxitin. The overall Multi-drug resistant Enterobacteriaceae (MDR) was 147 (42.3%). Antibiotics usage in the last 3 months and drinking unpasteurized milk were associated with the carriage of the Extended-spectrum beta-lactamase-Producing Enterobacteriaceae.. The high fecal carriage rate of Multi-drug resistance isolate, Extended-spectrum β-lactamase, and Carbapenemase-producing Enterobacteriaceae were recorded among food handlers. Therefore, this study gives signals in the spread of drug-resistant bacteria easily to the community. Hence, the need for adjusting and promotion of infection prevention measures to prevent the spread of drug-resistant bacteria should not be underestimated.

Topics: Anti-Bacterial Agents; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Cefotaxime; Ceftazidime; Ceftriaxone; Cross-Sectional Studies; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Ethiopia; Humans; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Prevalence

To design and assess a novel protocol that employs isothermal titration calorimetry (ITC) for rapid detection of extended-spectrum β-lactamase (ESBL)-producers in clinical pathogens.. A total of 69 clinical Enterobacteriaceae isolates were examined in the new ESBL-ITC test by examining the heat profiles associated with enzyme hydrolysis of different substrates (imipenem, cefotaxime and clavulanic acid). The presence of β-lactamase genes in the bacteria tested was confirmed by PCR and DNA sequencing. Comparative analysis between ESBL-ITC and conventional minimum inhibitory concentrations (MIC)/combined disk method (CDM) showed high agreement between the two assays. However, the ESBL-ITC test had a remarkable advantage of providing testing result within 1 h, in comparison to the 32-48 h required by MIC/CDM.. The ESBL-ITC test developed in this work offers a new option for rapid and accurate detection of ESBL-producers.. Timely detection of ESBL-producers is vital to guide the decision-making process in clinical treatment as well as in hospital-infection control. The new ESBL-ITC test provides a rapid phenotypic assay that can be further adapted for clinical diagnosis of ESBL-producing pathogens.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Calorimetry; Cefotaxime; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Hydrolysis; Imipenem; Microbial Sensitivity Tests; Polymerase Chain Reaction

Usage of cephalosporin and quinolone antibiotics has aggravated the development of extended-spectrum beta-lactamase (ESBL)-producing quinolone-resistant (QR) pathogenic Enterobacteriaceae. The present study aims to determine antimicrobial activity of cinnamaldehyde alone or in combination with cefotaxime/ciprofloxacin to reverse the drug resistance and evaluations of efficacy, and possible molecular mechanism of action of the combination was also evaluated using in vitro assays. Broth microdilution assay was used to determine minimum inhibitory concentrations (MICs) of cinnamaldehyde and antibiotics against ESBL-QR Enterobacteriaceae. Synergistic effect and dynamic interaction with antibiotics were further examined by checkerboard assay, isobologram analysis, and time-kill assay, respectively. Cellular morphology of bacteria was viewed with scanning electron microscopy (SEM). Effects of cinnamaldehyde and its combination on the expression of gene encoding-porins (ompC, ompF, ompK35, and ompK36), efflux pump genes (acrB-E. coli, acrB-K. pneumoniae), and antibiotic-resistant genes (blaTEM, blaSHV, blaCTXM, and QnrB) were evaluated using real-time quantitative PCR (RT-qPCR). Majority of the E. coli (32.1%) and K. pneumoniae (24.2%) isolates demonstrated MIC of cinnamaldehyde at 7.34 μg/mL and 0.91 g/mL, respectively. Synergism between cinnamaldehyde and cefotaxime was noted among 75% E. coli and 60.6% K. pneumoniae. Similarly, synergism with ciprofloxacin was observed among 39.6% and 42.4% of the bacteria, respectively. Thus, cinnamaldehyde reduced MIC of cefotaxime and ciprofloxacin 2-1024-fold with bactericidal and/synergistic effect after 24 h. Cinnamaldehyde and its combination altered gene expression by ~ 1.6 to ~ 400-fold. Distorted bacterial cell structures were visible after treatment with cinnamaldehyde and/or with cefotaxime/ciprofloxacin. The results indicated the potential efficacy and mode of action of cinnamaldehyde alone and in combination with antibiotics against pathogenic ESBL-QR bacteria.

Topics: Acrolein; Anti-Bacterial Agents; beta-Lactamases; Cefotaxime; Ciprofloxacin; Drug Resistance, Bacterial; Drug Synergism; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Membrane Transport Proteins; Microbial Sensitivity Tests; Multidrug Resistance-Associated Proteins

The MALDI Biotyper Selective Testing of Antibiotic Resistance-β-Lactamase (MBT STAR-BL) assay, which analyzes bacterial induced hydrolysis of cefotaxime using MALDI-TOF MS, correctly identified 100.0% of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae as positive and 94.7% of non-ESBL producers as negative in 80 strains tested.

Topics: beta-Lactam Resistance; Cefotaxime; Enterobacteriaceae Infections; Escherichia coli; Hospitals, University; Japan; Klebsiella pneumoniae; Mass Screening; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefotaxime; Ceftriaxone; Cross Infection; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Intensive Care Units; Microbial Sensitivity Tests

Ceftaroline fosamil was approved by the United States Food and Drug Administration in 2010 and by the European Medicines Agency in 2012. As of April 2017, only one commercial antimicrobial susceptibility testing device offered a Gram-negative panel that included ceftaroline. This circumstance is unfortunate, as many clinical microbiology laboratories rely solely on commercial devices to generate

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactams; Cefotaxime; Ceftazidime; Ceftriaxone; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests

AmpC β-lactamases are encoded on the chromosomes of certain Enterobacterales and lead to clinical resistance to various β-lactams in case of high-level expression. In WT bacteria with inducible AmpC, the expression is low, but selection of stably ampC-derepressed mutants may occur during β-lactam therapy. Thus, for Enterobacter spp., Citrobacter freundii complex, Serratia spp. and Morganella morganii that test susceptible in vitro to oxyimino-cephalosporins, the EUCAST expert rules recommend suppressing susceptibility testing results for these agents or noting that their use in monotherapy should be discouraged, owing to the risk of selecting resistance. However, clinical observations suggest that emergence of resistance is not equally common in all species with inducible AmpC.. To determine species-specific mutation rates, which are more accurate and reproducible than previously described mutant frequencies, for ampC derepression in Enterobacterales with inducible AmpC.. Mutation rates were determined using a protocol based on Luria-Delbrück fluctuation analyses. Overall, 237 isolates were analysed.. Mutation rates were high in Enterobacter cloacae complex, Enterobacter aerogenes, C. freundii complex and Hafnia alvei isolates, with a mean mutation rate of 3 × 10-8. In contrast, mean mutation rates were considerably lower in Providencia spp., Serratia spp. and especially M. morganii isolates. Furthermore, we observed species-specific variations in the resistance patterns of ampC-derepressed mutants.. Our data might help to predict the risk of treatment failure with oxyimino-cephalosporins in infections by different Enterobacterales with inducible AmpC. Moreover, we make a proposal for optimization of the current EUCAST expert rule.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; beta-Lactams; Cefotaxime; Chromosomes, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Microbial Sensitivity Tests; Mutation Rate; Species Specificity

The aim of the study was to validate whether rapid antimicrobial susceptibility testing (AST) by very early reading of disc diffusion tests would provide reliable results in daily routine work. A total of 264 positive blood culture bottles were examined, of which 178 were examined as part of the daily routine workflow. Enterobacterales were evaluated for resistance to cefotaxime, ceftazidime, gentamicin and ampicillin. Staphylococcus aureus (S. aureus) was tested for resistance to cefoxitin as a marker of methicillin-resistant S. aureus (MRSA). The zones were read after 3 h, and if there was insufficient growth, 30 and 60 min later. The results were compared to standard overnight AST. For ampicillin, gentamicin and cefoxitin, there were no errors. For cefotaxime, there were three minor (1.5%), three major (1.5%) and no very major errors. For ceftazidime, there were 13 minor (6.5%) errors only. With the exception of one minor error, all errors were ESBL-A- or AmpC-producing isolates where rapid AST showed a higher degree of resistance than standard AST. This low-cost method may contribute to early effective antibacterial treatment by providing reliable results of AST within 3-4 h. Special breakpoints for early reading are a prerequisite.

Topics: Ampicillin; Anti-Bacterial Agents; Bacteremia; Blood Culture; Cefotaxime; Cefoxitin; Ceftazidime; Diagnostic Errors; Disk Diffusion Antimicrobial Tests; Drug Resistance, Bacterial; Early Diagnosis; Enterobacteriaceae; Enterobacteriaceae Infections; Gentamicins; Humans; Methicillin-Resistant Staphylococcus aureus; Staphylococcal Infections; Time Factors

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Carbapenem-Resistant Enterobacteriaceae; Cefotaxime; Ceftazidime; Disk Diffusion Antimicrobial Tests; Enterobacteriaceae Infections; Ertapenem; Fluoroquinolones; Humans; Nigeria; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

β-Lactamases (BLs) able to hydrolyze β-lactam antibiotics and more importantly the last resort carbapenems, represent a major mechanism of resistance in Gram-negative bacteria showing multi-drug or extensively drug resistant phenotypes. The early detection of BLs responsible of resistant infections is challenging: approaches aiming at the identification of new BLs inhibitors (BLI) can thus serve as the basis for the development of highly needed diagnostic tools. Starting from benzo-[b]-thiophene-2-boronic acid (BZB), a nanomolar inhibitor of AmpC β-lactamase (K

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Proteins; beta-Lactamase Inhibitors; beta-Lactamases; Boronic Acids; Cefotaxime; Ceftazidime; Computational Biology; Drug Resistance, Bacterial; Enterobacteriaceae Infections; Microbial Sensitivity Tests

Cefotaxime plays an important role in the treatment of patients with bacteremia due to Enterobacteriaceae, although cefotaxime resistance is reported to be increasing in association with extended-spectrum β-lactamase (ESBL) and AmpC β-lactamase (AmpC).. We conducted a case-control study in a Japanese university hospital between 2011 and 2012. We assessed the risk factors and clinical outcomes of bacteremia due to cefotaxime-non-susceptible Enterobacteriaceae (CTXNS-En) and analyzed the resistance mechanisms.. Of 316 patients with Enterobacteriaceae bacteremia, 37 patients with bacteremia caused by CTXNS-En were matched to 74 patients who had bacteremia caused by cefotaxime-susceptible Enterobacteriaceae (CTXS-En). The most common CTXNS-En was Escherichia coli (43%), followed by Enterobacter spp. (24%) and Klebsiella spp. (22%). Independent risk factors for CTXNS-En bacteremia included previous infection or colonization of CTXNS-En, cardiac disease, the presence of intravascular catheter and prior surgery within 30 days. Patients with CTXNS-En bacteremia were less likely to receive appropriate empirical therapy and to achieve a complete response at 72 h than patients with CTXS-En bacteremia. Mortality was comparable between CTXNS-En and CTXS-En patients (5 vs. 3%). CTXNS-En isolates exhibited multidrug resistance but remained highly susceptible to amikacin and meropenem. CTX-M-type ESBLs accounted for 76% of the β-lactamase genes responsible for CTXNS E. coli and Klebsiella spp. isolates, followed by plasmid-mediated AmpC (12%). Chromosomal AmpC was responsible for 89% of CTXNS Enterobacter spp. isolates.. CTXNS-En isolates harboring ESBL and AmpC caused delays in appropriate therapy among bacteremic patients. Risk factors and antibiograms may improve the selection of appropriate therapy for CTXNS-En bacteremia. Prevalent mechanisms of resistance in CTXNS-En were ESBL and chromosomal AmpC.

Topics: Adult; Aged; Aged, 80 and over; Bacteremia; Bacterial Proteins; beta-Lactamases; Case-Control Studies; Cefotaxime; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Japan; Male; Microbial Sensitivity Tests; Middle Aged; Plasmids; Treatment Outcome

Third-generation cephalosporins (3GCs) [ceftriaxone (CRO) and cefotaxime (CTX)] have remarkable potency against Enterobacteriaceae and are commonly prescribed for the treatment of community-onset bacteraemia. However, clinical evidence supporting the updated interpretive criteria of the Clinical and Laboratory Standards Institute (CLSI) is limited. Adults with community-onset monomicrobial Enterobacteriaceae bacteraemia treated empirically with CRO or CTX were recruited. Clinical information was collected from medical records and CTX MICs were determined using the broth microdilution method. Eligible patients (n=409) were categorised into de-escalation (260; 63.6%), no switch (115; 28.1%) and escalation (34; 8.3%) groups according to the type of definitive antibiotics. Multivariate regression revealed five independent predictors of 28-day mortality: fatal co-morbidities based on McCabe classification [odds ratio (OR)=19.96; P<0.001]; high Pitt bacteraemia score (≥4) at bacteraemia onset (OR=13.91; P<0.001); bacteraemia because of pneumonia (OR=5.45; P=0.007); de-escalation after empirical therapy (OR=0.28; P=0.03); and isolates with a CTX MIC≤1mg/L (OR=0.17; P=0.02). Of note, isolates with a CTX MIC≤8mg/L (indicated as susceptible by previous CLSI breakpoints) were not associated with mortality. Furthermore, clinical failure and 28-day mortality rates had a tendency to increase with increasing CTX MIC (γ=1.00; P=0.01). Conclusively, focusing on patients with community-onset Enterobacteriaceae bacteraemia receiving empirical 3GC therapy, the present study provides clinically critical evidence to validate the proposed reduction in the susceptibility breakpoint of CTX to MIC≤1mg/L.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Cefotaxime; Ceftriaxone; Community-Acquired Infections; Enterobacteriaceae Infections; Female; Humans; Male; Microbial Sensitivity Tests; Retrospective Studies; Survival Analysis; Treatment Outcome

Dissemination of antibiotic resistance in Enterobacteriaceae mediated by AmpC β-lactamase, extended-spectrum β-lactamase (ESBL) and metallo-β-lactamase (MBL) is clinically significant. A simple and relatively quick method for the detection of these resistance phenotypes would greatly improve chemotherapeutic recommendation. This technology would provide valuable input in our surveillance of resistance on a global stage, particularly if the methodology could be applicable to resource-poor settings. A resazurin microtitre plate (RMP) assay incorporating cloxacillin, clavulanic acid and EDTA for the rapid phenotypic identification of AmpC, ESBL and MBL and the co-existence of β-lactamases has been developed. A total of 47 molecularly characterized Enterobacteriaceae clinical isolates producing AmpCs, ESBLs, co-producers of ESBL and AmpC, MBLs and co-producers of ESBL and MBL were phenotypically examined using the RMP assay. The ceftazidime- and cefotaxime-based RMP assays successfully detected all 16 AmpC, 14 ESBL and 9 MBL producers, 6 ESBL-AmpC co-producers and 2 ESBL-MBL co-producers without false-positive results. The ceftazidime-based assay was more reliable in detecting AmpC alone, while the cefotaxime-based assay performed better in identifying co-producers of ESBL and AmpC. There was no difference in the detection of ESBL and MBL producers. The findings of the present study suggest that use of the RMP assay with particular β-lactamase inhibitors explicitly detects three different β-lactamases, as well as co-existence of β-lactamases, within 6 h of initial isolation of the pathogen. This assay is applicable to carry out in any laboratory, is cost-effective and is easy to interpret. It could be implemented in screening patients and controlling infection and for surveillance purposes.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cefotaxime; Ceftazidime; Coloring Agents; Enterobacteriaceae; Enterobacteriaceae Infections; Enzyme Assays; Enzyme Inhibitors; Humans; Microbial Sensitivity Tests; Oxazines; Phenotype; Xanthenes

Resistance to third generation cephalosporins is widely disseminated in Enterobacteriaceae mainly due to extended-spectrum-β-lactamases, plasmid AmpC β-lactamases, and hyperproduction of chromosomal AmpC β-lactamases. Here we evaluated the performance of a novel fluorogenic probe rapid test and compared the results with the phenol red assay using a total of 77 characterized organisms (44 extended-spectrum-β-lactamases, 33 chromosomal or plasmid AmpC β-lactamases) and 46 susceptible organisms. The fluorescent assay showed higher sensitivity than the phenol red assay in cefotaximase type extended-spectrum-β-lactamases, non- cefotaximase type extended-spectrum-β-lactamases, chromosomal AmpC β-lactamases, and plasmid AmpC β-lactamases (96.7% vs. 90.0%, p=0.157; 71.4% vs. 7.1%, p=0.003; 100.0% vs. 64.7%, p<0.001; 100.0% vs. 6.3%, p<0.001). The fluorescent assay had a positive correlation with the exponents of cefotaxime and ceftazidime minimum inhibitory concentrations (p<0.001 for both). The new fluorescent assay will be very useful for the rapid detection of resistance to third generation cephalosporins that originates from various β-lactamases.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cefotaxime; Ceftazidime; Cephalosporin Resistance; Cephalosporins; Drug Combinations; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Fluorescent Dyes; Microbial Sensitivity Tests; Phenolsulfonphthalein; Plasmids; Sensitivity and Specificity

The data on susceptibility of important cephalosporins against four Enterobacteriaceae members producing potential extended-spectrum β-lactamase (ESBL) collected from Taiwanese intensive care units are lacking.. Minimum inhibitory concentrations (MICs) of cefotaxime, ceftazidime, and cefepime were determined using agar dilution method, against Escherichia coli (n = 344), Klebsiella pneumoniae (n = 359), Enterobacter cloacae (n = 103), and Proteus mirabilis (n = 78). Susceptibilities of these isolates to three cephalosporins were assessed according to MIC breakpoints recommended by the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in 2013. The double-disk synergy test using disks containing cefepime (30 μg) with or without clavulanate (10 μg) was applied to confirm production of ESBL for isolates with cephalosporin MIC ≥ 2 μg/mL.. A total of 175 isolates were verified as ESBL producers. The rates of cefepime susceptibility among the ESBL-producing isolates, according to CLSI (EUCAST) criteria, were 56.7% (22.4%) for E. coli, 61.3% (12.0%) for K. pneumoniae, 57.9% (31.6%) for E. cloacae, and 71.4% (7.1%) for P. mirabilis. Using different cefepime MIC breakpoints (MICs ≥ 16 μg/mL recommended by CLSI criteria and ≥ 2 μg/mL by EUCAST criteria) to define nonsusceptibility, we found that both criteria were poorer at predicting ESBL producers among K. pneumoniae and E. cloacae than among the other two species. In addition, we also found that the cefepime MIC level of 1.0 μg/mL best distinguished non-ESBL- from ESBL-producing K. pneumoniae and E. cloacae.. To detect ESBLs, CLSI should revise the cefepime MIC breakpoint against Enterobacteriaceae.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefepime; Cefotaxime; Ceftazidime; Cephalosporin Resistance; Cephalosporins; Enterobacteriaceae; Enterobacteriaceae Infections; Epidemiological Monitoring; Humans; Intensive Care Units; Microbial Sensitivity Tests; Taiwan

This study was performed to compare the therapeutic efficacy of cefuroxime with that of cefotaxime as initial antimicrobial therapies in women with complicated nonobstructive acute pyelonephritis (APN) caused by Enterobacteriaceae infections. The clinical characteristics and outcomes of a cefuroxime-treated group (n = 156) were compared with those of a cefotaxime-treated group (n = 166). Of these 322 women, 90 from each group were matched by propensity scores. The defervescence rates were not significantly different in the cefuroxime and cefotaxime groups at 72 h after the start of antimicrobial therapy (81.1% versus 78.9%, P = 0.709). The clinical and microbiological cure rates during the follow-up visits that were 4 to 14 days after the end of the antimicrobial therapies were not significantly different in the cefuroxime versus cefotaxime groups, which were 97.8% (87/89) versus 97.8% (87/89) (P > 0.999) and 89.5% (68/76) versus 90.7% (68/75) (P = 0.807), respectively. The median hospital stay duration and the median times to defervescence in the cefuroxime versus cefotaxime groups were 8 days (interquartile range [IQR], 7 to 10 days) versus 9 days (IQR, 7 to 11 days), respectively, and 55 h (IQR, 37 to 70 h) versus 55 h (IQR, 35 to 69 h), respectively. Bacteremia, extended-spectrum-β-lactamase-producing Enterobacteriaceae, C-reactive protein levels of ≥ 15 mg/dl, and white blood cell counts of ≥ 15,000/mm(3) of blood had independent effects on the rates of early clinical failure. Our data suggest that the effects of cefuroxime are not different from those of cefotaxime when they are used as an initial antimicrobial treatments for community-onset complicated nonobstructive APN in women.

Topics: Acute Disease; Aged; Anti-Bacterial Agents; Cefotaxime; Cefuroxime; Community-Acquired Infections; Enterobacteriaceae Infections; Female; Humans; Middle Aged; Pyelonephritis; Retrospective Studies; Treatment Outcome

Resistance to third-generation cephalosporins in Gram-negative bacteria is emerging in Asia. We report the prevalence and distribution of extended-spectrum beta-lactamase (ESBL), AmpC beta-lactamase and carbapenemase-coding genes in cefotaxime-resistant Enterobacteriaceae isolates from bloodstream infections (BSI) in Cambodia. All Enterobacteriaceae isolated from BSI in adult patients at Sihanouk Hospital Centre of HOPE, Phnom Penh, Cambodia (2007-2010) were assessed. Antimicrobial susceptibility testing was carried out by disc diffusion and MicroScan according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Screening for ESBL, plasmidic AmpC and carbapenemase-coding genes was performed by multiplex polymerase chain reaction (PCR) sequencing assays. Identification of the ST131 clone was performed in all CTX-M-positive Escherichia coli, using PCR targeting the papB gene. Out of 183 Enterobacteriaceae, 91 (49.7 %) isolates (84 BSI episodes) were cefotaxime-resistant: E. coli (n = 68), Klebsiella pneumoniae (n = 17) and Enterobacter spp. (n = 6). Most episodes were community-acquired (66/84; 78.3 %). ESBLs were present in 89/91 (97.8 %) cefotaxime-resistant isolates: 86 (96.6 %) were CTX-M, mainly CTX-M-15 (n = 41) and CTX-M-14 (n = 21). CTX-M of group 1 were frequently associated with TEM and/or OXA-1/30 coding genes and with phenotypic combined resistance to ciprofloxacin, sulphamethoxazole-trimethoprim and gentamicin (39/50, 78.0 %). Plasmidic AmpC (CMY-2 and DHA-1 types) were found alone (n = 2) or in combination with ESBL (n = 4). Eighteen E. coli isolates were identified as B2-ST131-O25B: 11 (61.1 %) carried CTX-M-14. No carbapenemase-coding genes were detected. ESBL among Enterobacteriaceae from BSI in Cambodia is common, mainly associated with CTX-M-15 and CTX-M-14. These findings warrant urgent action for the containment of antibiotic resistance in Cambodia.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; beta-Lactamases; Cambodia; Cefotaxime; Cephalosporins; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Female; Humans; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Multiplex Polymerase Chain Reaction; Prevalence; Prospective Studies; Sequence Analysis, DNA; Young Adult

The study aimed to characterize beta-lactam resistance mechanisms of Enterobacteriaceae isolates recovered from diseased dogs and cats between 2008 and 2010 in a European surveillance program (ComPath I) for the antibiotic susceptibility of bacterial pathogens. A total of 608 non-duplicated Enterobacteriaceae isolates were obtained prior antibiotic treatment from diseased dogs (n=464) and cats (n=144). Among the 608 Enterobacteriaceae isolates, 22 presented a minimal inhibitory concentration against cefotaxime above EUCAST breakpoints of susceptibility. All the 22 isolates remained susceptible to carbapenems. Ten isolates were confirmed as extended-spectrum-beta-lactamase (ESBL) producers by PCR-sequencing of bla coding genes including 9 blaCTX-M (CTX-M-1, 14, 15, 32,…) and 1 blaTEM-52 and 12 were AmpC-producing isolates (10 plasmidic CMY-2 group and 2 isolates overexpressing their chromosomal AmpC). ESBLs and plasmid-mediated AmpC (pAmpC)-producing isolates were mainly recovered from dogs (n=17) suffering from urinary tract infections (n=13) and originated from eight different countries. ESBL-bearing plasmids were mostly associated with IncFII incompatibility groups while CMY-2 was predominantly associated with plasmid of the IncI1 group. ESBL/pAmpC-producing Escherichia coli belonged to phylogroup A (n=5), B2 (n=4), and D (n=5). Multilocus sequence typing analysis revealed that among three CTX-M-15-producing E. coli, two belong to sequence type (ST) 131 and one to ST405. The presence of CTX-M-15 including on IncFII plasmids in E. coli ST131-B2 has also been described in isolates of human origin. This suggests the possibility of exchanges of these isolates from humans to companion animals or vice-versa.

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Cats; Cefotaxime; Dogs; Enterobacteriaceae; Enterobacteriaceae Infections; Europe; Gene Expression Regulation, Bacterial; Humans; Microbial Sensitivity Tests; Multilocus Sequence Typing; Pets; Plasmids; Urinary Tract Infections

Considering the hypothesis that the high biliary elimination of ceftriaxone could be responsible for the selection of Enterobacteriaceae harbouring high-level AmpC β-lactamase (HL-CASE), the use of ceftriaxone was discontinued in our hospital in 2006 and replaced with cefotaxime.. Antibiotic consumption, expressed as defined daily dose (DDD)/1000 patient-days (PD), and HL-CASE incidence, expressed as the number of patients carrying HL-CASE/1000 PD, were compared between the pre-intervention period (Period 1, 2001-05) and the post-intervention period (Period 2, 2006-12) using an interrupted time series analysis.. The incidence of HL-CASE increased significantly from 0.32 to 0.69/1000 PD during Period 1 (coefficient = 0.082, P < 0.01). A significant inflection of the slope in the incidence curve occurred in Period 2 (coefficient = -0.061, P = 0.05), mainly owing to the stabilization of the HL-CASE incidence of Enterobacteriaceae harbouring chromosomally inducible cephalosporinase (Period 1, 0.27 to 0.64/1000 PD; Period 2, 0.58 to 0.61/1000 PD) and especially for Enterobacter cloacae (Period 1, 0.09 to 0.30/1000 PD; Period 2, 0.26 to 0.27/1000 PD). This deceleration was observed despite a significant increase in the slope of cefotaxime consumption over Period 2 (coefficient = 2.97, P < 0.01).. Despite the disadvantages of using cefotaxime compared with ceftriaxone (administration three times daily versus once a day), the ecological benefits of this substitution seem sufficiently convincing to preferentially use cefotaxime. Control of HL-CASE incidence is crucial to limiting carbapenem use and preventing the selection of carbapenemase-producing Enterobacteriaceae.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cefotaxime; Ceftriaxone; Drug Utilization; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Incidence; Retrospective Studies

The worldwide dissemination of Enterobacteriaceae producing AmpC β-lactamases and carbapenemases makes difficult the phenotypic detection of extended-spectrum β-lactamases (ESBLs), as they may be masked by these additional enzymes. A modification of the CLSI ESBL confirmatory test was developed and evaluated in a comparative study for its ability to successfully detect ESBLs among Enterobacteriaceae producing various carbapenemases (Klebsiella pneumoniae carbapenemase [KPC], VIM, NDM, and OXA-48) and plasmidic or derepressed AmpCs. The modified CLSI ESBL confirmatory test was performed with cefotaxime and ceftazidime disks with and without clavulanate, on which both boronic acid (BA) and EDTA were dispensed. A total of 162 genotypically confirmed ESBL-positive Enterobacteriaceae isolates (83 carbapenemase/ESBL producers, 25 AmpC/ESBL producers, and 54 ESBL-only producers) were examined. For comparison, 139 genotypically confirmed ESBL-negative Enterobacteriaceae isolates (94 of them possessed carbapenemases and 20 possessed AmpCs) were also tested. The standard CLSI ESBL confirmatory test was positive for 106 of the 162 ESBL producers (sensitivity, 65.4%) and showed false-positive results for 4 of the 139 non-ESBL producers (specificity, 97.1%). The modified CLSI ESBL confirmatory test detected 158 of 162 ESBL producers (sensitivity, 97.5%) and showed no false-positive results for non-ESBL producers (specificity, 100%). The findings of the study demonstrate that the modified CLSI ESBL confirmatory test using antibiotic disks containing both BA and EDTA accurately detects ESBLs in Enterobacteriaceae regardless of the coexistence of additional β-lactam resistance mechanisms.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Cefotaxime; Ceftazidime; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests

The Clinical and Laboratory Standards Institute (CLSI) updated its antimicrobial susceptibility testing interpretation criteria for Enterobacteriaceae. This study assessed the effects of clinical breakpoint changes in the CLSI 2009 to 2012 guidelines on antibiotic susceptibility testing reports.. In total, 2,076 non-duplicate clinical isolates of Enterobacteriaceae were analyzed. The disk diffusion method was used for susceptibility testing. The CLSI 2009-12 clinical breakpoints were applied to determine susceptibility of cefotaxime and ertapenem. Combined-disk testing was used for phenotypic confirmation of extended-spectrum beta-lactamase (ESBL) production.. In total, Enterobacteriaceae resistance rates to cefotaxime increased from 13.1% using the CLSI 2009 guidelines to 23.6% with the CLSI 2010-12 guidelines, and the resistance rates to ertapenem were 0.4%, 1.0% and 0.8% with CLSI 2009, 2011 and 2012, respectively. Based on the 2010-12 CLSI criteria, all ESBL-producing Escherichia coli and Klebsiella pneumoniae were resistant to cefotaxime. Marked differences in susceptibility to ertapenem between the 2009 CLSI criteria and 2012-12 CLSI criteria were noted in ESBL-producing K. pneumoniae.. Breakpoints changes in the updated CLSI guidelines resulted in higher resistance rates to cefotaxime and ertapenem. In addition, the effects were different in individual Enterobacteriaceae species. As a result, clinicians may opt to use alternative antimicrobial agents. Upon implementation of the newer CLSI guidelines, laboratories should be aware of the possible consequences and closely monitor the effects.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactams; Cefotaxime; Enterobacteriaceae; Enterobacteriaceae Infections; Ertapenem; Humans; Microbial Sensitivity Tests

Febrile infants under 3 months of age are often treated with broad-spectrum intravenous antibiotics while awaiting culture results, to prevent mother-to-child bacterial infections. Human parechoviruses (HPeV) have recently been described as etiologic agents of meningitis and severe sepsis in neonates and young infants. They are rarely investigated and are therefore probably underestimated. They cause acute clinical symptoms that can incorrectly suggest a bacterial infection. In the present case, a 6-week-old infant infected with HPeV developed severe sepsis, complicated by hepatic cytolysis, meningitis, acute renal failure, and mild hemophagocytic lymphohistiocytosis. HPeV type 3 was found by routine specific RT-PCR in cerebrospinal fluid, stools, and plasma. The outcome was spontaneously favorable after 4 days. Early diagnosis of the HPeV infection by routine specific RT-PCR reduces unnecessary antibiotic use and extended hospitalization in febrile young infants.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Cefotaxime; Citrobacter freundii; Drug Therapy, Combination; Early Diagnosis; Enterobacteriaceae Infections; Gentamicins; Humans; Infant; Male; Meningitis, Viral; Parechovirus; Picornaviridae Infections; Reverse Transcriptase Polymerase Chain Reaction; Risk Factors; Severity of Illness Index; Treatment Outcome; Viremia

The aim of this study was to compare the current screening methods and to evaluate confirmation tests for phenotypic plasmidal AmpC (pAmpC) detection.. For this evaluation we used 503 Enterobacteriaceae from 18 Dutch hospitals and 21 isolates previously confirmed to be pAmpC positive. All isolates were divided into three groups: isolates with 1) reduced susceptibility to ceftazidime and/or cefotaxime; 2) reduced susceptibility to cefoxitin; 3) reduced susceptibility to ceftazidime and/or cefotaxime combined with reduced susceptibility to cefoxitin. Two disk-based tests, with cloxacillin or boronic acid as inhibitor, and Etest with cefotetan-cefotetan/cloxacillin were used for phenotypic AmpC confirmation. Finally, presence of pAmpC genes was tested by multiplex and singleplex PCR.. We identified 13 pAmpC producing Enterobacteriaceae isolates among the 503 isolates (2.6%): 9 CMY-2, 3 DHA-1 and 1 ACC-1 type in E. coli isolates. The sensitivity and specificity of reduced susceptibility to ceftazidime and/or cefotaxime in combination with cefoxitin was 97% (33/34) and 90% (289/322) respectively. The disk-based test with cloxacillin showed the best performance as phenotypic confirmation method for AmpC production.. For routine phenotypic detection of pAmpC the screening for reduced susceptibility to third generation cephalosporins combined with reduced susceptibility to cefoxitin is recommended. Confirmation via a combination disk diffusion test using cloxacillin is the best phenotypic option. The prevalence found is worrisome, since, due to their plasmidal location, pAmpC genes may spread further and increase in prevalence.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Bacterial Typing Techniques; beta-Lactam Resistance; beta-Lactamases; Cefotaxime; Cefotetan; Cefoxitin; Ceftazidime; Cloxacillin; Disk Diffusion Antimicrobial Tests; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Netherlands; Plasmids; Prevalence

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cefotaxime; Ceftriaxone; Enterobacteriaceae; Enterobacteriaceae Infections; Humans

We present the first case of Raoultella planticola bacteria in human infections with a direct relationship between fish intake and enteric infection. The patient was treated with antibiotherapy (cefotaxime). It is important to consider this organism in the differential diagnosis of enteric fever and even more with previous ingestion of fish.

Topics: Anti-Bacterial Agents; Bacteremia; Cefotaxime; Enterobacteriaceae; Enterobacteriaceae Infections; Foodborne Diseases; Gastroenteritis; Humans; Male; Middle Aged

To characterize the naturally occurring β-lactamase gene identified from a clinical isolate belonging to a novel enterobacterial species that is closely related to Rahnella spp. and Ewingella spp.. Shotgun cloning and expression in Escherichia coli were performed in order to characterize this resistance determinant. Enzymatic activities were measured by UV spectrophotometry after an ion-exchange chromatography purification procedure.. A chromosomal gene coding for the extended-spectrum β-lactamase (ESBL) SMO-1 was identified from a novel enterobacterial species that is taxonomically related to Rahnella aquatilis and Ewingella americana. The β-lactamase efficiently hydrolysed penicillins and cefotaxime, and shared 75% amino acid identity with the plasmid-mediated β-lactamase SFO-1 from Serratia fonticola, 74% amino acid identity with the plasmid-mediated ESBL CTX-M-2 originating from Kluyvera spp. and 72% amino acid identity with the chromosomally encoded and intrinsic RAHN-1 from R. aquatilis.. We have identified a novel enterobacterial species recovered from a clinical specimen, constituting another potential source of acquired ESBL. The ESBL shared significant similarities with the CTX-M-type enzymes.

Topics: beta-Lactamases; Cefotaxime; Chromatography, Ion Exchange; Cloning, Molecular; DNA, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Gene Expression; Humans; Hydrolysis; Molecular Sequence Data; Penicillins; Sequence Analysis, DNA; Sequence Homology, Amino Acid; Spectrophotometry, Ultraviolet

The aim of this study was to determine the prevalence of vaginal Escherichia coli colonization and perianal carriage of Enterobacteriaceae resistant to third generation cephalosporins in pregnant women. Vaginal and perianal samples from 259 pregnant women were studied. Vaginal swabs were inoculated onto MacConkey agar plates and perianal swabs were inoculated onto CHROMagar extended-spectrum beta-lactamase (ESBL) plates. The minimal inhibitory concentration of the isolates was determined using the Epsilometer test method. The phenotypic detection of ESBLs was performed by the combined disc method using cefotaxime versus cefotaxime plus clavulanate. The prevalence of vaginal E. coli colonization during pregnancy was 14.3%. The resistance rate to ampicillin, gentamicin, and cefotaxime was 48.6, 10.8, and 0.8%, respectively. Enterobacteriaceae resistant to third generation cephalosporins were recovered in 7.3% of all perianal specimens. Among them, 5.4% of pregnant women were colonized with E. coli ESBL-producer strains. The present study revealed that colonization with Enterobacteriaceae resistant to third generation cephalosporins is significant in pregnancy. ESBL-producing E. coli were the most prevalent organisms. Screening strategies designed to monitor for ESBL-producing E. coli could be useful in endemic areas to prevent perinatal transmission and the introduction of multiresistant strains to the maternity ward.

Topics: Anti-Bacterial Agents; Argentina; beta-Lactamases; Cefotaxime; Cephalosporins; Clavulanic Acid; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Female; Gestational Age; Humans; Maternal Exposure; Microbial Sensitivity Tests; Pregnancy; Prevalence; Vagina

The rapid detection of extended-spectrum beta-lactamases (ESBLs) is a challenge for most clinical microbiology laboratories because inaccurate identification of ESBL producers has important clinical implications for both antibiotic treatment and infection control. The aim of our study was to develop a rapid detection assay of ESBL producers based upon flow cytometric analysis. Antimicrobial susceptibility testing followed by molecular characterization of bla(TEM) , bla(SHV) or bla(CTX-M) genes was performed on clinical isolates (41 ESBL positive and 20 ESBL negative) and isolates expressing well-characterized beta-lactamases, including ESBLs (n = 13), plasmid AmpCs (n = 3), oxacillinases (n = 5) and carbapenemases (n = 3). Additionally, two ATCC strains recommended by CLSI for susceptibility testing were used as controls. The flow cytometry analysis protocol involved an incubation of bacterial cells with different concentrations of ceftazidime (1, 2 and 4 mg/L) and cefotaxime (4, 8 and 16 mg/L) for 1 and 2 hours, in the presence and absence of clavulanic acid; subsequently, cells were stained with the fluorescent dye Bis-(1,3-dibutylbarbituric acid) trimethine oxonol [DiBAC(4) (3)], a lipophilic anion able to diffuse across depolarized membranes. Additionally, CFU counts were performed. Susceptible isolates displayed increased fluorescence after 1 hour of incubation; conversely, the increase of the depolarized population was only observed after incubation with clavulanic acid associated with ceftazidime or cefotaxime in ESBL producers. An excellent correlation was obtained between the number of non-depolarized bacteria quantified by flow cytometry and by conventional CFU assays. A novel, accurate and fast flow cytometric assay is available to detect the presence of ESBLs.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefotaxime; Ceftazidime; Colony Count, Microbial; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Flow Cytometry; Genes, Bacterial; Humans; Microbial Sensitivity Tests; Microbial Viability; Phenotype

Topics: Age Factors; Aged; Aged, 80 and over; Aging; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Carrier State; Cefotaxime; Chi-Square Distribution; Disease Reservoirs; Disk Diffusion Antimicrobial Tests; Enterobacteriaceae; Enterobacteriaceae Infections; Feces; Female; France; Homes for the Aged; Humans; Long-Term Care; Male; Middle Aged; Prevalence; Urine

To determine the prevalence of CTX-M β-lactamase-producing Enterobacteriaceae and to study the risk factors associated with faecal carriage in asymptomatic rural Thai people.. In all, 417 stool samples were obtained from rural Thai people and screened for extended-spectrum β-lactamases (ESBLs) using MacConkey agar supplemented with 2 mg/L cefotaxime. Results were confirmed using cefotaxime and ceftazidime with and without clavulanic acid. The bla(CTX-M) genes were identified and genotyped using PCR with bacterial DNA samples. Multivariate analysis was performed to investigate risk factors associated with the faecal carriage of CTX-M producers.. The prevalence of CTX-M-type ESBL-producing Enterobacteriaceae was 65.7%. The CTX-M-9 group (60.6%) was dominant, followed by the CTX-M-1 group (38.7%). Most of the bacteria were Escherichia coli (85.4%) and Klebsiella pneumoniae (4.7%). Of a total of 234 E. coli strains, 48.7% belonged to phylogenetic group A, 28.6% to group B1, 15.8% to group D and 6.8% to group B2. Most CTX-M producers were susceptible to carbapenems and amikacin, but resistant to tetracycline and gentamicin. In a multivariate logistic regression model, better education status (OR 2.245; 95% CI 1.297-3.884), history of hospitalization (OR 1.643; 95% CI 1.036-2.603) and the use of antibiotics within the last 3 months (OR 1.883; 95% CI 1.221-2.903) were independently associated with faecal carriage.. Faecal carriage of CTX-M-type ESBL-producing Enterobacteriaceae among asymptomatic individuals in rural Thailand remains alarmingly high, and previous antibiotic use and a history of hospitalization may contribute to its dissemination.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Carrier State; Cefotaxime; Ceftazidime; Culture Media; DNA, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Feces; Female; Humans; Male; Middle Aged; Polymerase Chain Reaction; Prevalence; Risk Factors; Rural Population; Thailand; Young Adult

Very little is known about the prevalence and composition of various types of extended-spectrum β-lactamases (ESBL) in pediatric patients. The aims of this study were the following: (i) to determine the prevalence of ESBLs among Enterobacteriaceae in a tertiary-care pediatric population; (ii) to characterize the genetic composition of the identified ESBL enzymes; and (iii) to determine the relative prevalence of CTX-M enzymes and Escherichia coli ST131 strains among ESBL-producing isolates in the same pediatric patient population. Among the 1,430 Enterobacteriaceae isolates screened for elevated MICs to cefotaxime and/or ceftazidime from pediatric patients during a 1-year period, 94 isolates possessed at least one ESBL gene. CTX-M was the most commonly isolated ESBL type, consisting of 74% of all ESBLs versus 27% TEM and 24% SHV enzymes. Sequence analysis and probe-specific real-time PCR revealed that the majority (80%) of the CTX-M-type ESBLs were CTX-M-15 enzymes, followed by CTX-M-14 (17%) and CTX-M-27(2.8%). Multilocus sequence typing (MLST) and repetitive PCR analyses revealed that the relative prevalence of ST131 among ESBL-producing E. coli isolates is 10.2%. This study highlights the growing problem of ESBL resistance in pediatric Enterobacteriaceae isolates and demonstrates a transition toward the predominance of CTX-M-type enzymes among ESBL-producing Enterobacteriaceae organisms causing pediatric infections.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefotaxime; Ceftazidime; Child; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Isoenzymes; Male; Microbial Sensitivity Tests; Multilocus Sequence Typing; Phylogeny; Prevalence; Real-Time Polymerase Chain Reaction; Tertiary Care Centers; Texas

The aim of this work was to evaluate the fecal carriage of third generation cephalosporins resistant Enterobacteriaceae in nonhospitalized asymptomatic young adults.. A total of 517 normal fecal samples were spread onto plates agar containing cefotaxime. Isolated strains were identified and studied with agar disk diffusion antibiogram, minimal inhibition concentration in liquid medium and phenotypic and molecular study. Data were compared with a previous study realised in the same conditions in 1999.. In 2009, the prevalence of cefotaxime resistant enterobacteria was 4.2%. Of these 22 Enterobacteriaceae, 11 harboured overexpressed cephalosporinase and 11 produced extended-spectrum-betalactamase (ESBL). Among ESBL, six E. coli produced CTX-M from group 1 (n=6), group 2 (n=1), group 9 (n=2), one E. coli produced SHV-12 and one Klebsiella pneumoniae produced CTX-M from group 1. All ESBL were multiresistant. In 1999, all the CTX resistant isolates recovered produced a cephalosporinase and no ESBL was found.. This study highlights the increasing prevalence of fecal carriage of ESBL-producing enterobacteria in asymptomatic young patients in the community (0% in 1999 versus 2.1% in 2009; P<0.001). E. Coli with CTX-M from group 1 was the most frequent ESBL identified, while fecal carriage of Enterobacteteriaceae overproducing cephalosporinase was similar (2.1%).

Topics: Anti-Bacterial Agents; beta-Lactamases; Carrier State; Cefotaxime; Cephalosporin Resistance; Cephalosporinase; DNA, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Feces; France; Humans; Intestines; Military Personnel; Phenotype; Prevalence; Prospective Studies; Young Adult

Extended-spectrum β-lactamase (ESBLs) production is still the most frequent mechanism of resistance to cephalosporins in gram-negative bacteria. The aim of the study was to identify the types of ESBL-producing Enterobacteriaceae clinical isolates causing nosocomial infections in Mexico.. ESBL production was performed using a disk diffusion method. The MIC for several antibiotics was performed by agar dilution on Mueller-Hinton. PFGE typing was carried out on all enterobacteria assayed. The β-lactamase pattern was obtained by IEF and bioassay. Genes of β-lactamases were amplified by PCR with specific primers and products were sequenced and analyzed using informatics programs. Plasmid isolation and conjugation experiments were carried out using standard methodologies.. There were 134 isolates of Enterobacteriaceae included from a retrospective and multicenter study that included eight Mexican hospitals from 1999 to 2005. The most prevalent species were K. pneumoniae (56%), Enterobacter cloacae (29%), and Escherichia coli (15%). Molecular analysis identified the underlying endemic and polyclonal spread of enterobacterials in each hospital. The most frequent ESBLs identified were SHV-type (84%), TLA-1 (11%), and CTX-M-15 (5%). Successful matings were detected in 68.4% (71/104) isolates.. ESBL-producer K. pneumoniae remains the most frequent bacterial species obtained in nosocomial infections. The SHV-type and TLA-1 ESBLs were disseminated in most hospitals analyzed and CTX-M-15 was emerging in one of the studied hospitals. This work highlights the proper use of antibiotics to avoid the selection of these types of multiresistant bacteria.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefotaxime; Congresses as Topic; Cross Infection; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Isoelectric Point; Mexico; Microbial Sensitivity Tests; R Factors; Retrospective Studies

The resistance mechanism of 49 Enterobacteriaceae isolates with decreased susceptibility to carbapenems collected from 2004 to 2008 at 16 teaching hospitals in China was investigated. Moderate- to high-level carbapenem resistance in most isolates was more closely associated with loss or decreased expression of both major porins combined with production of AmpC or extended-spectrum beta-lactamase enzymes, while KPC-2, IMP-4, and IMP-8 carbapenemase production may lead to a low to moderate level of carbapenem resistance in Enterobacteriaceae in China.

Topics: Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; Bacterial Proteins; beta-Lactamases; Carbapenems; China; Cross Infection; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Enterobacteriaceae; Enterobacteriaceae Infections; Genotype; Integrons; Microbial Sensitivity Tests; Phenotype; Population Surveillance; Porins; Reverse Transcriptase Polymerase Chain Reaction

Five different strains of bacteria belonging to the family Enterobacteriaceae were isolated from two patients hospitalized in the intensive care unit of the Central Military Hospital of Algiers, Algeria. All five strains, one Providencia stuartii strain, two Escherichia coli strains, and two Klebsiella pneumoniae strains, were intermediate or resistant to all beta-lactams, including carbapenems. Synergy between imipenem and EDTA was observed for all five strains. The results of the PCR experiment confirmed the presence of a bla(VIM) gene in all five strains. The bla(VIM) genes were located as part of a class 1 integron on a 180-kb conjugative plasmid. They encoded a novel metallo-beta-lactamase designated VIM-19, which differed from the parental enzyme VIM-1 by only two substitutions: Ser228Arg, previously observed in the closely related enzyme VIM-4, and Asn215Lys, not previously observed in other VIM-type carbapenemases. VIM-19 was further characterized after purification through determination of its kinetic constants. This enzyme was inhibited by EDTA and hydrolyzed penicillins, cephalosporins, and carbapenems, as observed for other VIM-type carbapenemases but with greater catalytic efficiency against penicillins than VIM-1. VIM-19 is the first carbapenemase enzyme identified from an isolate from Algeria. These results confirm the emergence of VIM-4-like enzymes in members of the family Enterobacteriaceae from Mediterranean countries.

Topics: Algeria; Anti-Bacterial Agents; Base Sequence; beta-Lactamases; beta-Lactams; Carbapenems; DNA, Bacterial; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Genome, Bacterial; Hospitals, Military; Imipenem; Isoelectric Focusing; Kinetics; Microbial Sensitivity Tests; Molecular Sequence Data; Penicillins; Phenotype

Eighteen carbapenem-resistant, OXA-48-positive enterobacterial isolates recovered from Turkey, Lebanon, Egypt, France, and Belgium were analyzed. In most isolates, similar 70-kb plasmids carrying the carbapenemase gene bla(OXA-48) were identified. That gene was located within either transposon Tn1999 or transposon Tn1999.2, which was always inserted within the same gene. This work highlights the current plasmid-mediated dissemination of the OXA-48 carbapenemase worldwide.

Topics: Anti-Bacterial Agents; Belgium; beta-Lactam Resistance; beta-Lactamases; Carbapenems; DNA Transposable Elements; Egypt; Enterobacteriaceae; Enterobacteriaceae Infections; France; Humans; Lebanon; Microbial Sensitivity Tests; Plasmids; Turkey

A central nervous system infection due to Morganella morganii is uncommon. We report a case diagnosed at the neurological department of Fann teaching hospital in Dakar, Senegal. A 12-year-old boy was hospitalized for acute meningoencephalitis. The CT scan was normal and the study of cerebrospinal fluid (CSF) revealed cytological and biochemical abnormalities and M. morganii. HIV and syphilitic serologies were negative and blood CD4 lymphocyte count showed 354 per mm(3). The treatment with cefotaxime associated with gentamicin for 6 weeks was successful. The outcome of infection depends on many factors such as the onset and quality of treatment, the virulence of the germ and the status of immune system.

Topics: Anti-Bacterial Agents; CD4-Positive T-Lymphocytes; Cefotaxime; Child; Drug Therapy, Combination; Enterobacteriaceae Infections; Gentamicins; Humans; Male; Meningoencephalitis; Morganella morganii; Senegal; Treatment Outcome

Because of the strong association between qnr genes and plasmids carrying β-lactamase genes, we screened 176 clinical isolates of Enterobacter cloacae with cefotaxime MICs of ≥16 μg/mL for qnr genes. The qnrA, qnrB, and qnrS genes were detected in 18 (10.2%), 11 (6.2%), and 1 (0.56%) of the isolates, respectively. The genetic environments of the plasmids encoding these qnr genes were analyzed.

Topics: Anti-Bacterial Agents; Bacterial Typing Techniques; beta-Lactamases; Cefotaxime; DNA Fingerprinting; DNA Gyrase; DNA, Bacterial; Electrophoresis, Gel, Pulsed-Field; Enterobacter cloacae; Enterobacteriaceae Infections; Gene Order; Genes, Bacterial; Humans; Microbial Sensitivity Tests; Plasmids; Republic of Korea

Three kinds of plasmid-mediated quinolone resistance (PMQR) determinants have been discovered and have been shown to be widely distributed among clinical isolates: qnr genes, aac(6')-Ib-cr, and qepA. Few data on the prevalence of these determinants in strains from animals are available. The presence of PMQR genes in isolates from animals was determined by PCR amplification and DNA sequencing. The production of extended-spectrum beta-lactamases (ESBLs) and AmpC beta-lactamases in the strains was detected, and their genotypes were determined. The genetic environment of PMQR determinants in selected plasmids was analyzed. All samples of ceftiofur-resistant (MICs > or = 8 microg/ml) isolates of the family Enterobacteriaceae were selected from 36 companion animals and 65 food-producing animals in Guangdong Province, China, between November 2003 and April 2007, including 89 Escherichia coli isolates, 9 Klebsiella pneumoniae isolates, and isolates of three other genera. A total of 68.3% (69/101) of the isolates produced ESBLs and/or AmpC beta-lactamases, mainly those of the CTX-M and CMY types. Of the 101 strains, PMQR determinants were present in 35 (34.7%) isolates, with qnr, aac(6')-Ib-cr, and qepA detected alone or in combination in 8 (7.9%), 19 (18.8%), and 16 (15.8%) strains, respectively. The qnr genes detected included one qnrB4 gene, four qnrB6 genes, and three qnrS1 genes. Five strains were positive for both aac(6')-Ib-cr and qepA, while one strain was positive for qnrS1, aac(6')-Ib-cr, and qepA. qnrB6 was flanked by two copies of ISCR1 with an intervening dfr gene downstream and sul1 and qacEDelta1 genes upstream. In another plasmid, aac(6')-Ib-cr followed intI1 and arr-3 was downstream. PMQR determinants are highly prevalent in ceftiofur-resistant Enterobacteriaceae strains isolated from animals in China. This is the first report of the occurrence of PMQR determinants among isolates from companion animals.

Topics: Acetyltransferases; Adolescent; Adult; Aged; Animals; Animals, Domestic; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cambodia; Cephalosporins; China; Conjugation, Genetic; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli Proteins; Female; Humans; Male; Mali; Microbial Sensitivity Tests; Middle Aged; Nasal Cavity; Plasmids; Quinolones; Young Adult

Since the discovery of qnrA in 1998, two additional qnr genes, qnrB and qnrS, have been described. These three plasmid-mediated genes contribute to quinolone resistance in gram-negative pathogens worldwide. A clinical strain of Proteus mirabilis was isolated from an outpatient with a urinary tract infection and was susceptible to most antimicrobials but resistant to ampicillin, sulfamethoxazole, and trimethoprim. Plasmid pHS10, harbored by this strain, was transferred to azide-resistant Escherichia coli J53 by conjugation. A transconjugant with pHS10 had low-level quinolone resistance but was negative by PCR for the known qnr genes, aac(6')-Ib-cr and qepA. The ciprofloxacin MIC for the clinical strain and a J53/pHS10 transconjugant was 0.25 microg/ml, representing an increase of 32-fold relative to that for the recipient, J53. The plasmid was digested with HindIII, and a 4.4-kb DNA fragment containing the new gene was cloned into pUC18 and transformed into E. coli TOP10. Sequencing showed that the responsible 666-bp gene, designated qnrC, encoded a 221-amino-acid protein, QnrC, which shared 64%, 42%, 59%, and 43% amino acid identity with QnrA1, QnrB1, QnrS1, and QnrD, respectively. Upstream of qnrC there existed a new IS3 family insertion sequence, ISPmi1, which encoded a frameshifted transposase. qnrC could not be detected by PCR, however, in 2,020 strains of Enterobacteriaceae. A new quinolone resistance gene, qnrC, was thus characterized from plasmid pHS10 carried by a clinical isolate of P. mirabilis.

Topics: Amino Acid Sequence; Anti-Infective Agents; Bacterial Proteins; Base Sequence; Conjugation, Genetic; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests; Molecular Sequence Data; Plasmids; Polymerase Chain Reaction; Proteus Infections; Proteus mirabilis; Quinolones; Sequence Analysis, DNA

The aim of this study was to determine the steady-state plasma and peritoneal concentrations of cefotaxime and its metabolite desacetyl-cefotaxime administered by continuous infusion to critically ill patients with secondary peritonitis.. In 11 patients, a continuous infusion of 4 g/24 h of cefotaxime following a bolus of 2 g was evaluated. Plasma and peritoneal levels of cefotaxime and desacetyl-cefotaxime were measured at steady state on days 2 and 3 (plasma) and on day 3 (peritoneal) by HPLC. Results are expressed as means +/- SD.. Total and unbound plasma levels of cefotaxime were 24.0 +/- 21.5 and 20.3 +/- 19.8 mg/L on day 2 and 22.1 +/- 20.7 and 18.9 +/- 19.2 mg/L on day 3, respectively. Total and unbound levels of cefotaxime in the peritoneal fluids were 16.2 +/- 11.5 and 14.3 +/- 10.4 mg/L, respectively. The unbound fraction of plasma cefotaxime was 81.8 +/- 5.9% on day 2 and 82.6 +/- 7.7% on day 3, and the unbound fraction at the peritoneal site was 87.0 +/- 5.5% on day 3. Total and unbound plasma levels of desacetyl-cefotaxime were 9.0 +/- 8.1 and 8.4 +/- 8.1 mg/L on day 2 and 7.6 +/- 7.6 and 7.2 +/- 7.6 mg/L on day 3, respectively. Total and unbound levels of desacetyl-cefotaxime in the peritoneal fluids were 11.9 +/- 11.5 and 10.9 +/- 10.8 mg/L, respectively. The MICs for the enterobacteria recovered ranged from 0.016 to 0.25 mg/L.. Continuous infusion of 4 g/24 h of cefotaxime provided a peritoneal concentration >5x MIC for the recovered Enterobacteriaceae and the susceptibility breakpoint of cefotaxime for facultative Gram-negative bacilli.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Ascitic Fluid; Cefotaxime; Critical Illness; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Infusions, Intravenous; Male; Microbial Sensitivity Tests; Middle Aged; Peritonitis; Plasma

Preterm premature rupture of the membranes is associated with a high risk of neonatal sepsis. An increase in the incidence of early-onset neonatal sepsis due to ampicillin-resistant Escherichia coli in premature infants has been observed in the past few years. Intrapartum prophylaxis with ampicillin has proven to be efficient for the prevention of early neonatal sepsis due to group B streptococci. To date, there is no strategy for the prevention of early neonatal sepsis due to ampicillin-resistant E. coli. Our aim was to investigate whether a standardized dosage regimen of intrapartum cefotaxime could provide concentrations in the cord blood greater than the cefotaxime MIC(90) for E. coli. Seven pregnant women hospitalized with preterm premature rupture of the membranes and colonized with ampicillin-resistant isolates of the family Enterobacteriaceae were included. Cefotaxime was given intravenously during delivery, as follows: 2 g at the onset of labor and then 1 g every 4 h until delivery. Blood specimens were collected from the mother 30 min after the first injection and just before the second injection, and at birth, blood specimens were simultaneously collected from the mother and the umbilical cord. The concentrations of cefotaxime in the cord blood ranged from 0.5 to 8.5 mg/liter. The MIC(90) of cefotaxime for E. coli strains (0.125 mg/liter) was achieved in all cases. This preliminary study supports the use of cefotaxime for intrapartum prophylaxis in women colonized with ampicillin-resistant isolates of Enterobacteriaceae. The effectiveness of this regimen for the prevention of neonatal sepsis needs to be evaluated with a larger population.

Topics: Ampicillin Resistance; Anti-Bacterial Agents; Bacteremia; Cefotaxime; Enterobacteriaceae Infections; Female; Fetal Blood; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Microbial Sensitivity Tests; Pregnancy

Topics: Acquired Immunodeficiency Syndrome; Anti-Bacterial Agents; Antiretroviral Therapy, Highly Active; Cambodia; Cefotaxime; Child; Drug Resistance, Bacterial; Enterobacter; Enterobacteriaceae Infections; HIV Infections; Humans; Klebsiella; Klebsiella Infections; Opportunistic Infections

Extended-spectrum beta-lactamases (ESBLs) may not always be detected in routine susceptibility tests. This study reports the performance of the cefepime-clavulanate ESBL Etest for the detection of ESBLs in Enterobacteriaceae, including those producing AmpC enzyme.. Consecutive non-duplicate isolates of Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis isolated from bloodstream infections from January to June 2008 were tested for ESBL by both the standard CLSI double-disk diffusion method using ceftazidime and cefotaxime disks and Etests using ceftazidime/ceftazidime-clavulanate, cefotaxime/cefotaxime-clavulanate and cefepime/cefepime-clavulanate gradients. Isolates were also tested for the presence of transferable AmpC beta-lactamase by AmpC disk test and the efficacies of the different Etests in detecting ESBL production were compared.. A total of 113 bacterial isolates (61 K. pneumoniae, 50 E. coli, and 2 P. mirabilis) were recovered. Respectively, 42 (37.2%) and 55 (48.7%) isolates were positive for ESBL by the ceftazidime-clavulanate and cefotaxime-clavulanate combined disk tests. The cefepime/cefepime-clavulanate Etest strip detected the maximum number of isolates (70/113, 61.9 %) as ESBL-positive compared to the ceftazidime/ceftazidime-clavulanate and cefotaxime/cefotaxime-clavulanate strips, which detected 57 (50.4%) isolates each as ESBL-positive. All three ESBL Etest strips were equally effective in detecting ESBL in the isolates that were AmpC negative. In the 66 (58.4%) isolates that co-produced AmpC in addition to the ESBL enzymes, cefepime/cefepime-clavulanate Etest strip detected ESBL in an additional 13 (11.4%) isolates as compared to the other ESBL Etest strips.. Cefepime-clavulanate ESBL Etest is a suitable substitute to test for ESBL production, especially in organisms producing AmpC beta-lactamases.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cefepime; Cefotaxime; Ceftazidime; Cephalosporins; Clavulanic Acid; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Proteus mirabilis; Sensitivity and Specificity

The IMP-4 metallo-beta-lactamase, originally recognized in Acinetobacter spp. from Hong Kong, more recently appeared simultaneously in isolates of the family Enterobacteriaceae from Sydney and Melbourne, Australia. The bla(IMP-4)-qacG2-aacA4-catB3 cassette array was found in isolates from both cities, but in different wider genetic contexts and on different plasmids, suggesting movement of this array by homologous recombination.

Topics: Australia; Bacterial Proteins; beta-Lactamases; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Molecular Sequence Data; Polymerase Chain Reaction; Sequence Analysis, DNA

Two clinical strains of Escherichia coli (2138) and Enterobacter cloacae (7506) isolated from the same patient in France and showing resistance to extended-spectrum cephalosporins and low susceptibility to imipenem were investigated. Both strains harbored the plasmid-contained bla(TEM-1) and bla(KPC-2) genes. bla(KLUC-2), encoding a mutant of the chromosomal beta-lactamase of Kluyvera cryocrescens, was also identified at a plasmid location in E. cloacae 7506, suggesting the ISEcp1-assisted escape of bla(KLUC) from the chromosome. Determination of the KPC-2 structure at 1.6 A revealed that the binding site was occupied by the C-terminal (C-ter) residues coming from a symmetric KPC-2 monomer, with the ultimate C-ter Glu interacting with Ser130, Lys234, Thr235, and Thr237 in the active site. This mode of binding can be paralleled to the inhibition of the TEM-1 beta-lactamase by the inhibitory protein BLIP. Determination of the 1.23-A structure of a KPC-2 mutant in which the five C-ter residues were deleted revealed that the catalytic site was filled by a citrate molecule. Structure analysis and docking simulations with cefotaxime and imipenem provided further insights into the molecular basis of the extremely broad spectrum of KPC-2, which behaves as a cefotaximase with significant activity against carbapenems. In particular, residues 104, 105, 132, and 167 draw a binding cavity capable of accommodating both the aminothiazole moiety of cefotaxime and the 6 alpha-hydroxyethyl group of imipenem, with the binding of the former drug being also favored by a significant degree of freedom at the level of the loop at positions 96 to 105 and by an enlargement of the binding site at the end of strand beta 3.

Topics: Aged; Base Sequence; beta-Lactam Resistance; beta-Lactamases; beta-Lactams; Catalytic Domain; Cephalosporin Resistance; Crystallography, X-Ray; DNA Primers; DNA, Bacterial; Enterobacter cloacae; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; France; Genes, Bacterial; Humans; Imipenem; Kinetics; Male; Models, Molecular; Mutation

A novel gene, bla(KHM-1), encoding a metallo-beta-lactamase, KHM-1, was cloned from a clinical isolate of Citrobacter freundii resistant to most beta-lactam antibiotics. Escherichia coli expressing bla(KHM-1) was resistant to all broad-spectrum beta-lactams except for monobactams and showed reduced susceptibility to carbapenems. Recombinant KHM-1 exhibited EDTA-inhibitable hydrolytic activity against most beta-lactams, with an overall preference for cephalosporins.

Topics: Amino Acid Sequence; Base Sequence; beta-Lactam Resistance; beta-Lactamases; Citrobacter freundii; Conjugation, Genetic; DNA Primers; DNA, Bacterial; Enterobacteriaceae Infections; Escherichia coli K12; Genes, Bacterial; Humans; Microbial Sensitivity Tests; Molecular Sequence Data; Phylogeny; Plasmids; Recombinant Proteins; Sequence Homology, Amino Acid

Quinolone resistance is an emerging problem in China. To investigate the prevalence of the plasmid-mediated quinolone resistance genes qnr and aac(6')-Ib-cr, a total of 265 clinical isolates of Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, and Enterobacter cloacae with ciprofloxacin MICs of > or =0.25 microg/ml were screened at nine teaching hospitals in China. The qnrA, qnrB, qnrS, and aac(6')-Ib genes were detected by PCR. The aac(6')-Ib-cr gene was further identified by digestion with BtsCI and/or direct sequencing. The qnr gene was present in significantly smaller numbers of isolates with cefotaxime MICs of <2 microg/ml than isolates with higher MICs (> or =2.0 microg/ml) (20.6% and 42.1%, respectively; P < 0.05). aac(6')-Ib-cr was present in 17.0% of the isolates tested, and 7.9% of the isolates carried both the qnr and the aac(6')-Ib-cr genes. Among the isolates with cefotaxime MICs of > or =2.0 microg/ml, qnr and aac(6')-Ib-cr were present in 65.7% and 8.6% of E. cloacae isolates, respectively; 65.5% and 21.8% of K. pneumoniae isolates, respectively; 63.3% and 26.7% of C. freundii isolates, respectively; and 6.5% and 16.9% of E. coli isolates, respectively. The 20 transconjugants showed 16- to 128-fold increases in ciprofloxacin MICs, 14 showed 16- to 2,000-fold increases in cefotaxime MICs, and 5 showed 8- to 32-fold increases in cefoxitin MICs relative to those of the recipient due to the cotransmission of bla(CTX-M-14), bla(CTX-M-3), bla(DHA-1), bla(SHV-2), and bla(SHV-12) with the qnr and aac(6')-Ib-cr genes. Southern hybridization analysis showed that these genes were located on large plasmids of different sizes (53 to 193 kb). These findings indicate the high prevalence of qnr and aac(6')-Ib-cr in members of the family Enterobacteriaceae and the widespread dissemination of multidrug resistance in China.

Topics: Acetyltransferases; Anti-Bacterial Agents; Bacterial Proteins; China; Conjugation, Genetic; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Hospitals, Teaching; Humans; Microbial Sensitivity Tests; Plasmids; Polymerase Chain Reaction; Prevalence; Quinolones

To report a case of successful treatment of Citrobacter koseri infection in a preterm infant as a means of challenging the current treatment recommendations on the basis of pharmacodynamic and pharmacokinetic considerations.. A premature infant was diagnosed with C. koseri sepsis after 3 weeks in intensive care. Concern for meningitis was based on the propensity for central nervous system (CNS) involvement with Citrobacter infection along with new findings of ventriculomegaly and hydrocephalus shown on cranial ultrasound (CUS). The infant was treated with ciprofloxacin 10-20 mg/day and cefotaxime 100 mg/day for 21 days. After treatment, lumbar puncture was normal, follow-up CUS returned to baseline, and the infant passed a hearing screen after discharge. A favorable outcome was achieved in this case.. Approximately 76% of neonatal patients infected with C. koseri develop brain abscesses. The mortality rate for meningitis due to Citrobacter spp. is approximately 30%, and of the infants who survive, more than 80% have some degree of mental retardation. Third-generation cephalosporins and aminoglycosides are traditional therapies against this infection. The current antibiotic strategies have failed to prevent the high rates of morbidity and mortality associated with Citrobacter infections. A possible basis for these poor outcomes is failure to apply appropriate pharmacokinetic and pharmacodynamic principles in selecting antibiotics that will achieve adequate concentrations to kill the bacteria in granulocytes within the CNS. Based on favorable sensitivity data, penetration into neutrophils and the CNS, and favorable toxicity profiles, ciprofloxacin and meropenem would appear to be the most appropriate antibiotic treatment options for systemic infection or meningitis caused by C. koseri.. Ciprofloxacin and meropenem should be considered antibiotic treatment options for systemic infection or meningitis caused by C. koseri.

Topics: Anti-Bacterial Agents; Cefotaxime; Ciprofloxacin; Citrobacter koseri; Drug Therapy, Combination; Enterobacteriaceae Infections; Female; Humans; Infant, Newborn; Infant, Premature

Topics: Adult; Amikacin; Anti-Bacterial Agents; Bacteremia; Cefotaxime; Drug Resistance, Microbial; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Epididymitis; Humans; Male; Microbial Sensitivity Tests; Opportunistic Infections; Orchitis; Paraplegia

The distribution of conjugative-plasmid-mediated 16S rRNA methylase genes among amikacin-resistant Enterobacteriaceae collected between 1995 and 1998 and between 2001 and 2006 at a university hospital in South Korea was examined, and conjugative plasmids carrying the 16S rRNA methylase genes were characterized by PCR-based replicon typing and by determination of their antimicrobial resistance pattern. Among the 7,127 isolates, 463 isolates showed a high level of resistance to amikacin, and 218 of the 463 isolates transferred amikacin resistance by conjugation. Among the 218 isolates, armA was detected in 153 isolates (88 Klebsiella pneumoniae, 28 Escherichia coli, 19 Enterobacter cloacae, and 6 Serratia marcescens isolates and 12 isolates of other organisms), and rmtB was detected in 51 isolates (32 K. pneumoniae isolates, 18 E. coli isolates, and 1 Citrobacter freundii isolate). The first appearance of armA was in 1997. The armA gene was carried by conjugative plasmids of replicon groups IncL/M, IncFIIAs, IncF, IncA/C, IncHI2, and Inc(unidentified) in 38, 20, 7, 9, 4, and 75 strains, respectively. The rmtB gene was carried by conjugative plasmids of groups IncA/C, IncF, and IncI1-Igamma in 43 strains, 7 strains, and 1 strain, respectively. Transconjugants that received the IncL/M plasmid carrying armA or the IncA/C plasmid carrying rmtB showed an additional resistance to cefotaxime. Transconjugants that received the IncFIIA plasmid or Inc(unidentified) plasmid carrying the armA gene showed an additional resistance to cefoxitin and a high MIC(50) (0.25 mg/liter) of ciprofloxacin. In conclusion, this study demonstrated that the dissemination of 16S rRNA methylase genes among the Enterobacteriaceae is mediated by conjugative plasmids of various incompatibility groups that confer resistance to multiple drugs, including aminoglycosides, extended-spectrum beta-lactams, and/or quinolones.

Topics: Amikacin; Anti-Bacterial Agents; Bacterial Proteins; Cefotaxime; Ciprofloxacin; Conjugation, Genetic; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli Proteins; Hospitals, University; Humans; Korea; Methyltransferases; Microbial Sensitivity Tests; Plasmids; Polymerase Chain Reaction

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Carrier State; Cattle; Cattle Diseases; Cefotaxime; Ceftazidime; Cephalosporin Resistance; Enterobacteriaceae; Enterobacteriaceae Infections; Feces; France; Microbial Sensitivity Tests; Prevalence

The prevalence of three plasmid-mediated quinolone resistance determinants, QnrA, QnrB, and QnrS, among 526 nonreplicate clinical isolates of Enterobacter cloacae collected at a Taiwanese university hospital in 2004 was determined by PCR and colony hybridization, and the association of Qnr with the IMP-8 metallo-beta-lactamase was investigated. Eighty-six (16.3%) of all isolates were qnr positive, and the qnrA1-like, qnrB2-like, and qnrS1-like genes were detected alone or in combination in 3 (0.6%), 53 (10.1%), and 34 (6.5%) isolates, respectively. Among 149 putative extended-spectrum-beta-lactamase-producing isolates, 59 (39.6%) isolates, all of which were SHV-12 producers, harbored qnrA (0.7%; 1 isolate), qnrB (28.9%; 43 isolates), or qnrS (12.1%; 18 isolates). Forty-four (78.6%) of 56 IMP-8 producers carried qnrB (58.9%; 33 isolates), qnrS (25.0%; 14 isolates), or both. PCR and sequence analysis revealed that qnrA1 was located in a complex sul1-type integron that contains dhr15, aadA2, qacEDelta1, sul1, orf513, qnrA1, ampR, and qacEDelta1. Conjugation experiments revealed the coexistence of qnrB and bla(IMP-8) on the transferred plasmids and the absence of beta-lactamase content on the transferred qnrS-positive plasmids. The transferred bla(IMP-8)-positive plasmids with and without qnrB had very similar restriction patterns, suggesting the horizontal mobility of qnrB. Pulsed-field gel electrophoresis showed six major patterns among the 44 qnr-positive IMP-8-producing isolates. Thus, the extremely high prevalence of qnr among the metallo-beta-lactamase-producing E. cloacae isolates in the hospital may be due mainly to the intrahospital spread of a few clones and the dissemination of plasmids containing both qnrB and blaIMP-8.

Topics: Anti-Bacterial Agents; beta-Lactamases; Drug Resistance, Bacterial; Enterobacter cloacae; Enterobacteriaceae Infections; Genes, Bacterial; Hospitals; Microbial Sensitivity Tests; Molecular Sequence Data; Plasmids; Prevalence; Quinolones; Taiwan

Bloodstream infections (BSI) caused by extended-spectrum beta-lactamase (ESBL)-producing organisms markedly increase the rates of treatment failure and death. We conducted a retrospective cohort analysis to identify risk factors for mortality in adult in-patients with BSI caused by ESBL-producing Enterobacteriaceae (ESBL-BSI). Particular attention was focused on defining the impact on the mortality of inadequate initial antimicrobial therapy (defined as the initiation of treatment with active antimicrobial agents >72 h after collection of the first positive blood culture). A total of 186 patients with ESBL-BSI caused by Escherichia coli (n = 104), Klebsiella pneumoniae (n = 58), or Proteus mirabilis (n = 24) were identified by our microbiology laboratory from 1 January 1999 through 31 December 2004. The overall 21-day mortality rate was 38.2% (71 of 186). In multivariate analysis, significant predictors of mortality were inadequate initial antimicrobial therapy (odds ratio [OR] = 6.28; 95% confidence interval [CI] = 3.18 to 12.42; P < 0.001) and unidentified primary infection site (OR = 2.69; 95% CI = 1.38 to 5.27; P = 0.004). The inadequately treated patients (89 of 186 [47.8%]) had a threefold increase in mortality compared to the adequately treated group (59.5% versus 18.5%; OR = 2.38; 95% CI = 1.76 to 3.22; P < 0.001). The regimens most commonly classified as inadequate were based on oxyimino cephalosporin or fluoroquinolone therapy. Prompt initiation of effective antimicrobial treatment is essential in patients with ESBL-BSI, and empirical decisions must be based on a sound knowledge of the local distribution of pathogens and their susceptibility patterns.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Cross Infection; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Female; Humans; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Predictive Value of Tests; Proteus mirabilis; Risk Factors; Survival Analysis; Treatment Outcome

A prospective observational study was conducted to identify factors associated with bloodstream infections (BSIs) caused by integron-carrying Enterobacteriaceae and to evaluate the clinical significance of integron carriage. Consecutive patients with Enterobacteriaceae BSIs were identified and followed up until discharge or death. Identification of blood isolates and susceptibility testing were performed by the Wider I automated system. int-1-specific PCR, conserved-segment PCR, and DNA sequencing were used to determine the presence, length, and content of integrons. The relatedness among the isolates was examined by pulsed-field gel electrophoresis. Two hundred fifty episodes of Enterobacteriaceae BSI occurred in 233 patients; 109 (43.6%) were nosocomial, 82 (32.8%) were community acquired, and 59 (23.6%) were health care associated. Integrons were detected in 11 (13.4%) community-acquired, 24 (40.7%) health care-associated, and 46 (42.2%) nosocomial isolates. Integron-carrying organisms were more likely to exhibit resistance to three or more classes of antimicrobials (odds ratio [OR], 9.84; 95% confidence interval [95% CI], 5.31 to 18.23; P < 0.001) or to produce extended-spectrum beta-lactamases (OR, 5.75; 95% CI, 2.38 to 13.89; P < 0.001) or a VIM-type metallo-beta-lactamase (P, 0.003). Inter- or intraspecies integron transfer and cross-transmission of integron-carrying clones were observed. Use of cotrimoxazole (OR, 4.77; 95% CI, 1.81 to 12.54; P < 0.001) and a nosocomial or other health care setting (OR, 3.07; 95% CI, 1.30 to 7.22; P, 0.01) were independently associated with BSIs caused by integron-carrying Enterobacteriaceae. Patients with a nonurinary source of bacteremia (OR, 9.46; 95% CI, 2.77 to 32.32; P < 0.001) and a Pitt bacteremia score of > or =4 (OR, 23.36; 95% CI, 7.97 to 68.44; P < 0.001) had a significantly higher 14-day mortality rate, whereas integron carriage did not affect clinical outcomes. These findings may have implications affecting antibiotic policies and infection control measures.

Topics: Bacteremia; Community-Acquired Infections; Cross Infection; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Enterobacteriaceae Infections; Gene Transfer, Horizontal; Humans; Infectious Disease Transmission, Professional-to-Patient; Integrons; Microbial Sensitivity Tests; Nucleic Acid Amplification Techniques; Polymerase Chain Reaction; Prospective Studies; Risk Factors; Sequence Analysis, DNA; Treatment Outcome

The epidemiology of clavulanic acid-inhibited extended-spectrum beta-lactamases (ESBLs) was investigated among infection-associated enterobacterial isolates at the University Hospital in Lausanne, Switzerland, from January 2004 to June 2005. Out of 57 nonrepetitive ESBL producers (prevalence rate of 0.7%), 45 produced CTX-M-like ESBLs. CTX-M enzymes were mostly from clonally nonrelated Escherichia coli isolates, from urinary infections and community-acquired infections. Pediatric patients (20 out of 57) accounted for a large number of CTX-M producers. CTX-M-15 was the most frequent CTX-M-type enzyme. The plasmid-located bla(CTX-M) genes were associated with either ISEcp1 or ISCR1 insertion sequences. This study is the first published report of CTX-M-type beta-lactamases in Switzerland.

Topics: Anti-Bacterial Agents; beta-Lactamases; Community-Acquired Infections; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Hospitals, University; Humans; Microbial Sensitivity Tests; Molecular Epidemiology; Polymerase Chain Reaction; Prevalence; Switzerland

During a 2004 survey, 49 extended-spectrum-beta-lactamase-producing enterobacteria were collected in 20 French private health care centers and one local hospital. They included 12 CTX-M-producing Escherichia coli strains (1.8% versus 0.3% in a 1999 survey). Most of them belonged to the same clone and contained a bla(CTX-M-15) gene on similar conjugative plasmids.

Topics: Anti-Bacterial Agents; beta-Lactamases; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; France; Health Surveys; Hospitals, Private; Molecular Sequence Data; Plasmids

Enterobacter cloacae is an emerging clinical pathogen that may be responsible for nosocomial infections. Management of these infections is often difficult, owing to the high frequency of strains that are resistant to disinfectants and antimicrobial agents in the clinical setting. Multidrug efflux pumps, especially those belonging to the resistance-nodulation-division family, play a major role as a mechanism of antimicrobial resistance in gram-negative pathogens. In the present study, we cloned and sequenced the genes encoding an AcrAcB-TolC-like efflux pump from an E. cloacae clinical isolate (isolate EcDC64) showing a broad antibiotic resistance profile. Sequence analysis showed that the acrR, acrA, acrB, and tolC genes encode proteins that display 79.8%, 84%, 88%, and 82% amino acid identities with the respective homologues of Enterobacter aerogenes and are arranged in a similar pattern. Deletion of the acrA gene to yield an AcrA-deficient EcDC64 mutant (EcDeltaacrA) showed the involvement of AcrAB-TolC in multidrug resistance in E. cloacae. However, experiments with an efflux pump inhibitor suggested that additional efflux systems also play a role in antibiotic resistance. Investigation of several unrelated isolates of E. cloacae by PCR analysis revealed that the AcrAB system is apparently ubiquitous in this species.

Topics: Bacterial Proteins; Base Sequence; beta-Lactamases; Carrier Proteins; Cloning, Molecular; DNA, Bacterial; Drug Resistance, Bacterial; Enterobacter cloacae; Enterobacteriaceae Infections; Genes, MDR; Genetic Vectors; Humans; Microbial Sensitivity Tests; Molecular Sequence Data; Plasmids; Porins

Topics: Brazil; Cefotaxime; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Enterobacter cloacae; Enterobacteriaceae Infections; Humans; Molecular Sequence Data; Outpatients; Plasmids; Quinolones; Sequence Analysis, DNA

From January 2002 to December 2003, 12 patients in a tertiary teaching hospital in northern Taiwan had bloodstream infections caused by Citrobacter freundii. Seven of the 12 isolates were resistant to cefotaxime. Using polymerase chain reaction and DNA sequencing, 3 of the 7 cefotaxime-resistant C. freundii isolates were found to carry extended-spectrum beta-lactamase (ESBL). AmpC beta-lactamase genes were also detected in all strains of C. freundii. All strains of C. freundii with MICs >or=4 mg/L for cefepime were positive for ESBL. Rather than performing PCR on all cefotaxime-resistant C. freundii isolates, assessment of the MIC for cefepime might be a practical way to choose between treatment with cefepime or with carbapenems.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Cefotaxime; Citrobacter freundii; Drug Resistance, Bacterial; Enterobacteriaceae Infections; Female; Hospitals, Teaching; Humans; Infant; Male; Middle Aged; Polymerase Chain Reaction; Sequence Analysis, DNA; Taiwan

We present a diabetic patient with necrotizing fasciitis caused by Citrobacter freundii associated with an injury from the fish fin. Two isolates recovered six days after cefotaxime treatment had a cefotaxime minimum inhibitory concentration (MIC) of 0.12 and 256 mg/L, respectively, and a cefepime MIC of 0.03 and 0.25 mg/L, respectively. The two isolates both possessed bla(CMY-2) gene. The patient responded unsatisfactorily to cefotaxime and cefepime therapy and surgical debridement but recovered completely after ertapenem treatment for 42 days.

Topics: Anti-Bacterial Agents; beta-Lactams; Cefepime; Cefotaxime; Cephalosporin Resistance; Cephalosporins; Citrobacter freundii; Enterobacteriaceae Infections; Ertapenem; Fasciitis, Necrotizing; Female; Humans; Middle Aged; Osteomyelitis; Wounds and Injuries

A preterm infant with early onset Morganella morganii sepsis was treated with cefotaxime and gentamicin after confirmation of antimicrobial susceptibility. The infant developed persistent ventriculitis caused by the emergence of a cefotaxime-resistant Morganella variant with derepression of its AmpC beta-lactamase. When choosing antibiotic therapy, the risk of development of resistance to cephalosporins should be considered in infections caused by M. morganii and other Gram-negative organisms with inducible AmpC beta-lactamases.

Topics: Bacteremia; Bacterial Proteins; beta-Lactamases; Cefotaxime; Cephalosporin Resistance; Enterobacteriaceae Infections; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Meningitis, Bacterial; Microbial Sensitivity Tests; Morganella morganii

Topics: beta-Lactam Resistance; beta-Lactamases; Cefotaxime; Ceftriaxone; Colombia; Enterobacteriaceae; Enterobacteriaceae Infections; Genes, Bacterial; Humans

Increasing resistance to third generation cephalosporins has become a cause for concern especially among Enterobacteriaceae that cause nosocomial infections. The prevalence of extended spectrum beta-lactamases (ESBLs) among members of Enterobacteriaceae constitutes a serious threat to current beta-lactam therapy leading to treatment failure and consequent escalation of costs. A detailed study was initiated to identify the occurrence of ESBLs among the Enterobacteriaceae isolates at a tertiary care hospital using the double disk potentiation technique. Antibiogram profiles were determined to commonly used antibiotics and confirmation of ESBLs production was carried out by the disk diffusion assay using ceftazidime and cefotaxime in the presence and absence of clavulanic acid. Our results indicate that the majority of ESBLs were expressed in Escherichia coli.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Cefotaxime; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests

A prospective study is carried out to evaluate the performance of a protocol for the accelerated detection of extended-spectrum beta-lactamases (ESBLs) in clinical isolates of Escherichia coli, Klebsiella pneumoniae and other Gram-negative bacteria. A modified double-disc test (MDDT) is incorporated in a Gram-negative template for routine susceptibility testing. The MDDT identified accurately ESBLs in all isolates subsequently confirmed as ESBL-producers by the standard Clinical Laboratory Standards Institute (CLSI) combined disc method. Of 1213 isolates tested, 98 (8%) were positive for ESBLs by MDDT and 95 (7.8%) were positive by the CLSI method. ESBLs were detected in 48 (7.8%) E. coli, 21 (8%) K. pneumoniae, 12 (5.8%) Proteus mirabilis, 13 (18.8%) Providencia stuartii and four (6.8%) Enterobacter cloacae isolates. Time required for ESBL detection by the MDDT method was one day. The protocol described provides a simple, rapid and low-cost method for early detection of ESBLs in Gram-negative bacteria.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Cefotaxime; Ceftazidime; Disk Diffusion Antimicrobial Tests; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Prospective Studies; Saudi Arabia

To determine the prevalence of the plasmid-mediated quinolone resistance qnrA gene in a selected collection of blood culture isolates of Enterobacteriaceae resistant to both ciprofloxacin and cefotaxime.. Over a 29 month period, a total of 47 non-repetitive isolates of Enterobacteriaceae resistant to both ciprofloxacin and cefotaxime were identified. Isolates were screened for the presence of the qnrA gene, class I integrons and bla(ESBL) by PCR. Transferability was examined by conjugation with the sodium azide-resistant Escherichia coli J53. All qnrA-positive isolates were examined for DNA-relatedness by PFGE.. A total of 15 of the 47 test isolates (32%) were positive for the qnrA gene, and included single isolates of E. coli and Citrobacter freundii, 4 Klebsiella pneumoniae and 9 Enterobacter cloacae. All 15 qnrA-positive isolates carried class 1 integrons, and 11 the extended-spectrum beta-lactamase gene bla(SHV-12). By PFGE two K. pneumoniae and three E. cloacae, respectively, were considered clonally but not temporally related. Plasmid transfer of quinolone resistance was only achieved with single isolates of K. pneumoniae and E. cloacae. Both plasmids carried class 1 integrons with a pSAL-1-like gene cassette arrangement intl1-aadA2-qacEDelta-sul1.. In this selected group of ciprofloxacin- and cefotaxime-resistant bacteria, carriage of the qnrA gene was high (32%). This compares with <2.0% as demonstrated in worldwide studies of laboratory collections of ciprofloxacin-resistant bacteria. The majority of qnrA-positive isolates in our study originated from high-dependency care units within our hospital, but were shown not to be clonal by PFGE. This is the first report of qnrA-positive Enterobacteriaceae in the United Kingdom.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Blood; Cefotaxime; Conjugation, Genetic; DNA Fingerprinting; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; England; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli Proteins; Gene Transfer, Horizontal; Humans; Integrons; Plasmids; Quinolones

Expanded-spectrum betalactamases (ESBLs) are the main source of resistance to oxyimino cephalosporins and monobactams in Enterobacteriaceae. Most of them derive from TEM or SHV, however the incidence of other families like CTX-M, OXA and PER has increased. In Argentina, the most frequent ESBL in Enterobacteriaceae is CTX-M-2. This specific circumstance, which differs from the situation in the Northern Hemisphere, motivated us to study new diagnostic strategies for the detection of ESBLs in our region.. Microbiological ESBL detection was performed by double-disk synergy tests, cefotaxime and ceftazidime disks with and without clavulanic acid (NCCLS), and cefotaxime and ceftazidime disks in Müeller-Hinton agar supplemented with lithium clavulanate (MH-cla). Betalactamases were characterized by isoelectric focusing, hydrolysis profile and PCR amplification.. Among 575 clinical isolates of Enterobacteriaceae, 14% were oxyimino cephalosporin-resistant. Two different ESBLs were detected in 31 resistant strains: CTX-M-2 (28) and PER-2 groups (3). The double-disk synergy test was the least sensitive method for ESBL detection. ESBLs were detected by the other two methods in all isolates with the use of cefotaxime disks, but not with ceftazidime disks.. The microbiological method employing MH-cla with cefotaxime disks had a sensitivity and specificity comparable to the referral test using the same antibiotic proposed by the NCCLS for the detection of ESBLs.

Topics: Argentina; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Cefotaxime; Ceftazidime; Cephalosporins; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Hydrolysis; Isoelectric Focusing; Microbial Sensitivity Tests; Monobactams; Polymerase Chain Reaction; Sensitivity and Specificity; Substrate Specificity

With antibiotics and an increasing dental care and hygiene, the profound neck spaces infections have decreased their incidence. Nevertheless we can found them in the clinical practice, and they present a big morbidity and severe complications. We present in this paper a case of profound cervical abscess in a diabetic patient, discussing the clinical and therapeutics aspects.

Topics: Abscess; Aged; Anti-Bacterial Agents; Cefotaxime; Diabetes Complications; Diabetes Mellitus; Enterobacteriaceae Infections; Humans; Male; Streptococcal Infections; Submandibular Gland Diseases; Tomography, X-Ray Computed

To investigate the potential correlation between the use of extended-spectrum cephalosporins (ESCs) and resistance to this antibiotic class among clinical isolates of Enterobacter cloacae in a university-affiliated hospital.. Data on antimicrobial resistance and antimicrobial use concerning E. cloacae and ESCs were collected over a 4 year period. Various statistical tools were used to explore the potential relationship.. From 1999 to 2002, the proportion of E. cloacae isolates resistant to ESCs increased from 24.3% to 29.6%. (P=0.04), and the quantity of ESCs prescribed and given did not change. Within the subclass constituted by first-line ESCs, the proportion of ceftriaxone increased from 64.3% to 77.6% and the proportion of cefotaxime decreased accordingly, from 35.7% to 22.4%. Statistical analyses showed that E. cloacae resistance to ESCs correlated with ceftriaxone use regardless of the other ESCs. For every defined daily dose of ceftriaxone per 1000 patient days used in our hospital, resistance of E. cloacae isolates to ESCs increased by 1.36%.. This study demonstrates a specific correlation between ceftriaxone use and the development of resistance in E. cloacae clinical isolates. The high biliary elimination of ceftriaxone compared with other ESCs may be responsible for a greater impact of this antibiotic on the digestive flora.

Topics: Cefotaxime; Ceftriaxone; Cephalosporin Resistance; Cephalosporins; Data Interpretation, Statistical; Drug Utilization; Enterobacter cloacae; Enterobacteriaceae Infections; Hospitals, University; Humans; Microbial Sensitivity Tests; Spain

The incidence of infection due to extended spectrum beta-lactamases (ESBLs) producing Enterobacteriaceae has markedly increased in recent years. The traditional susceptibility methods lack sensitivity and/or specificity and this issue has prompted the search for an accurate test to detect the presence of ESBL. The present study included 300 bacterial strains and was undertaken to determine the prevalence of ESBL-producing strains. Here, compared three tests: a double disk synergy test (DDS), a three-dimensional test (3-D), and an inhibitor potentiated disk diffusion test (IPT); each test employed three different antibiotic discs, i.e., ceftazidime, ceftriaxone, and cefotaxime, in order to screen for ESBL strains. A strain was said to be an ESBL producer if it showed positive result(s) on any one of the three tests. The prevalence rate of ESBL in our hospital was 12.6% (38/300). IPT detected the most strains (34/38), followed by 3-D (23/38), and then DDS (15/38). The ceftriaxone disc was found to detect more ESBLs than either the ceftazidime or the cefotaxime disc.

Topics: Anti-Bacterial Agents; beta-Lactamases; beta-Lactams; Cefotaxime; Ceftazidime; Ceftriaxone; Enterobacteriaceae; Enterobacteriaceae Infections; Hospitals; Humans; India; Microbial Sensitivity Tests; Prevalence

Enterobacter species have become increasingly important nosocomial pathogens. However, resistance to cephalosporins often complicates the treatment of Enterobacter infection. This study was conducted to evaluate the predictors of mortality and the impact of cephalosporin resistance on outcome in patients with Enterobacter bacteremia.. A total of 183 patients with Enterobacter bacteremia were retrospectively analyzed. Broad-spectrum cephalosporin resistance was defined as in vitro resistance to cefotaxime or ceftazidime. The main outcome measure was the 30-day mortality rate.. Of 183 patients, 86 (47%) had bacteremia caused by broad-spectrum cephalosporin-resistant Enterobacter species, and their infections were classified as resistant. The 30-day mortality rate of patients with resistant infections (the resistant group) was significantly higher than that of patients with susceptible infections (the susceptible group) (33.7% vs. 18.6%; P=.021). When the 30-day mortality rates were compared according to the primary sites of infection and underlying conditions, the 30-day mortality rates of the resistant group were significantly higher than those of the susceptible group, in patients with an unknown primary site of infection, or in patients with septic shock. Multivariate analysis showed that broad-spectrum cephalosporin resistance was one of the independent risk factors associated with 30-day mortality (odds ratio [OR], 3.69; 95% confidence interval [CI], 1.01-13.52; P=.049). Presentation with septic shock and an increasing Acute Physiology and Chronic Health Evaluation II score were also independent risk factors for mortality (OR, 59.91 [95% CI, 14.93-240.15; P<.001] and 1.52 [95% CI, 1.24-1.86; P<.001], respectively).. Broad-spectrum cephalosporin resistance adversely affects the outcome of patients with Enterobacter bacteremia, especially those with an unknown primary site of infection and those with septic shock.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; APACHE; Bacteremia; Cefotaxime; Ceftazidime; Cephalosporin Resistance; Cross Infection; Enterobacter; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Survival Analysis

To study the growing trend of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in pediatric intensive care units (PICUs), 88 nonrepetitive ESBL-producing isolates were prospectively collected and analyzed by molecular methods during a 16-month period. The emergence and dissemination of ESBL-producing Enterobacteriaceae in PICUs are the consequence of the clonal dissemination of a few epidemic strains along with the horizontal transmission of resistance gene-carrying plasmids among bacterial organisms.

Topics: Adolescent; Anti-Bacterial Agents; beta-Lactamases; Cefotaxime; Ceftazidime; Cephalosporin Resistance; Child; Child, Preschool; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Intensive Care Units, Pediatric; Microbial Sensitivity Tests; Polymerase Chain Reaction

Topics: Anti-Bacterial Agents; Cefotaxime; Cephalosporins; Citrobacter koseri; Enterobacteriaceae Infections; Gentamicins; Humans; Infant, Newborn; Lung Abscess; Male; Meningitis, Bacterial; Pneumonia, Bacterial

Of 15 extended-spectrum beta-lactamase (ESBL)-producing isolates of the family Enterobacteriaceae collected from the First Municipal People's Hospital of Guangzhou, in the southern part of the People's Republic of China, 9 were found to produce CTX-M ESBLs, 3 produced SHV-12, and 3 produced both CTX-M and SHV-12. Eleven isolates produced either TEM-1B or SHV-11, in addition to an ESBL. Nucleotide sequence analysis of the 12 isolates carrying bla(CTX-M) genes revealed that they harbored three different bla(CTX-M) genes, bla(CTX-M-9) (5 isolates), bla(CTX-M-13) (1 isolate), and bla(CTX-M-14) (6 isolates). These genes have 98% nucleotide homology with bla(Toho-2). The bla(CTX-M) genes were carried on plasmids that ranged in size from 35 to 150 kb. Plasmid fingerprints and pulsed-field gel electrophoresis showed the dissemination of the bla(CTX-M) genes through transfer of different antibiotic resistance plasmids to different bacteria, suggesting that these resistance determinants are highly mobile. Insertion sequence ISEcp1, found on the upstream region of these genes, may be involved in the translocation of the bla(CTX-M) genes. This is the first report of the occurrence of SHV-12 and CTX-M ESBLs in China. The presence of strains with these ESBLs shows both the evolution of bla(CTX-M) genes and their dissemination among at least three species of the family Enterobacteriaceae, Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae, isolated within a single hospital. The predominance of CTX-M type enzymes seen in this area of China appears to be similar to that seen in South America but is different from those seen in Europe and North America, suggesting different evolutionary routes and selective pressures. A more comprehensive survey of the ESBL types from China is urgently needed.

Topics: beta-Lactamases; Blotting, Southern; Cefotaxime; Ceftazidime; Cephalosporin Resistance; Cephalosporins; China; DNA, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli Proteins; Genes, Bacterial; Humans; In Situ Hybridization; Isoelectric Focusing; Microbial Sensitivity Tests; Molecular Sequence Data; Phenotype; Plasmids; Reverse Transcriptase Polymerase Chain Reaction

Topics: Amoxicillin; Cefotaxime; Drug Resistance, Bacterial; Drug Therapy, Combination; Enterobacter; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Length of Stay; Molecular Epidemiology; Penicillins; Risk Factors; Tobramycin

Data on the incidence of Enterobacter infections in neonates over prolonged periods of time are scant. We determined the epidemiology of Enterobacter sepsis and/or meningitis and the trends of infection in a neonatal unit.. Retrospective review of sepsis and/or meningitis in inborn neonates admitted to Son Dureta University Hospital during a 22-year period. Molecular study by ribotyping of the Enterobacter strains isolated from 1995 to 1997.. There were 513 cases of culture-proved sepsis and/or meningitis in neonates. In late onset infections Klebsiella pneumoniae and Staphylococcus epidermidis were the most frequent isolates in the period 1977 through 1991. Enterobacter was the most common isolate in the period 1992 through 1998. During this latter period Candida infections also increased, and the resistance rate of Enterobacter to cefotaxime was higher (59.2%). Decrease in early onset infections and increase in late onsets (4.6/1,000 live births) were observed in the second period. From 1977 to 1998, 45 episodes of sepsis and/or meningitis by Enterobacter species were identified in 44 patients (8.7% of all neonatal bacteremias). Three patients with Enterobacter bacteremia died (6.6%, 0.03/1,000 live births). During 1995 through 1997 5 different clones causing sepsis were identified and 3 were predominant. In 1997 there was an outbreak of Enterobacter disease. After cleaning, cohort nursing and hygiene reinforcement, Enterobacter was not isolated in the next 2 years. No change in the antibiotic policy was made.. We observed a resurgence of Enterobacter infections in our neonatal intensive care unit. The sudden disappearance of this microorganism after reinforcement of hygienic measures, without withdrawing cefotaxime, confirms the importance of patient-to-patient transmission of this nosocomial infection. Further studies are needed to establish the role of antibiotics in the emergence of microorganisms in neonatal intensive care units.

Topics: Cefotaxime; Cross Infection; Drug Resistance, Bacterial; Enterobacter; Enterobacteriaceae Infections; Female; Humans; Hygiene; Infant, Newborn; Intensive Care Units, Neonatal; Longitudinal Studies; Male; Meningitis, Bacterial; Retrospective Studies; Ribotyping; Sepsis

Topics: Aged; Bacteremia; Cefotaxime; Citrobacter; Discitis; Drug Therapy, Combination; Electrodes, Implanted; Endocarditis, Bacterial; Enterobacteriaceae Infections; Equipment Contamination; Humans; Imipenem; Lumbar Vertebrae; Male; Pacemaker, Artificial; Sacrum; Tobramycin

Neonatal Citrobacter koseri (diversus) meningitis is often complicated by the formation of brain abscesses and has a poor neurological outcome with seizures, mental retardation and paresis as sequelae in 50% of the cases. As there is emerging resistance to ampicillin, gentamicin and third-generation cephalosporins, we attempted to treat this infection with carbapenems. Carbapenems in combination with cefotaxime and surgical drainage may play an important role in treating C. koseri meningitis.

Topics: Carbapenems; Cefotaxime; Cephalosporins; Citrobacter; Combined Modality Therapy; Drainage; Enterobacteriaceae Infections; Female; Humans; Infant, Newborn; Meningitis, Bacterial; Prognosis; Treatment Outcome

A group of cefotaxime-resistant Citrobacter freundii and Escherichia coli isolates were collected by a clinical laboratory in a hospital in Warsaw, Poland, in July 1996. Detailed analysis has shown that all of these produced a beta-lactamase (pI, 8.4) belonging to the CTX-M family, one of the minor extended-spectrum beta-lactamase families with a strong cefotaxime-hydrolyzing activity. Sequencing has revealed that C. freundii isolates produced a new CTX-M-3 enzyme which is very closely related to the CTX-M-1/MEN-1 beta-lactamase, sporadically identified in Europe over a period of 6 years. Amino acid sequences of these two beta-lactamases differ at four positions: Val77Ala, Asp114Asn, Ser140Ala, and Asn288Asp (the first amino acid of each pair refers to CTX-M-1/MEN-1 and second refers to CTX-M-3). The partial sequence of the E. coli CTX-M gene was identical to the corresponding region of bla(CTX-M-3), but a transconjugant of the E. coli isolate expressed higher levels of resistance to beta-lactams than did C. freundii transconjugants. These resistance differences correlated with differences in plasmid DNA restriction patterns. Our results suggest that CTX-M genes have been spread among different species of the family Enterobacteriaceae in the hospital and that the CTX-M-3-expressing C. freundii strain causing routine urinary tract infections has been maintained for a relatively long time in the hospital environment.

Topics: Amino Acid Sequence; Base Sequence; beta-Lactamases; Cefotaxime; Cephalosporin Resistance; Cephalosporins; DNA, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Isoelectric Focusing; Microbial Sensitivity Tests; Molecular Sequence Data; Plasmids; Poland; Polymerase Chain Reaction

Two successive outbreaks of colonization and infection with Enterobacter cloacae resistant to third generation cephalosporins (cephalosporin-resistant E. cloacae, CREC) and involving 15 infants occurred within 12 months in a neonatal special care unit. Isolates of clinical significance were obtained from four infants (urine 2 cases, blood, pleural drainage). According to epidemiological typing using computerized biochemical fingerprinting and pulsed-field gel electrophoresis (PFGE) the same CREC strain was found in both outbreaks. The origin of the strain and its reservoir between the two outbreaks remained unknown. Emphasizing strict barrier nursing of the infants had little or no impact on the presence and transmission of the strain in the unit. In contrast, replacing ampicillin plus cefotaxime as standard empiric therapy with penicillin G plus netilmicin plus consequent cohorting of newborns and staff promptly halted both the outbreaks. During a 5-y follow-up after the last episode, the choice of antibiotics for empirical treatment has varied, and no further outbreaks of CREC have been seen, with the exception of two sporadic cases.

Topics: Ampicillin; Cefotaxime; Cephalosporin Resistance; Cephalosporins; Cross Infection; Disease Outbreaks; Enterobacter cloacae; Enterobacteriaceae Infections; Female; Gentamicins; Humans; Infant; Infant, Newborn; Intensive Care Units, Neonatal; Male; Penicillin G; Penicillins; Sweden

Topics: Aged; Alcohol Drinking; Ascites; Cefotaxime; Cephalosporins; Citrobacter; Diagnosis, Differential; Diuretics; Enterobacteriaceae Infections; Fever; Humans; Jaundice; Male; Peritonitis; Spironolactone

We developed an experimental model of pneumonia to evaluate the efficacy of new antibiotic regimens against Enterobacter cloacae. Rats were infected by administering 8.5 log10 cfu E. cloacae intratracheally, and therapy was initiated 24 h later. At that time, animals' lungs showed bilateral pneumonia containing more than 7 log10 cfu/g of tissue. Because rats eliminate amikacin and cefepime much more rapidly than humans, renal impairment was induced in all animals to simulate the pharmacokinetic parameters in humans. Using this model, we compared the bactericidal activities of cefepime and amikacin alone or in combination against the same cefotaxime-susceptible E. cloacae strain. The MICs of cefepime and amikacin for this strain were 0.5 and 2 mg/L, respectively. In-vitro killing studies showed that antibiotic combinations were synergic only at intermediate concentrations. At peak concentrations, the combination was only as effective as amikacin alone. At trough concentrations, a non-significant trend towards the superiority of the combination over cefepime alone was found. In-vivo studies showed that each antibiotic alone failed to decrease bacterial counts in the lungs except at 6 h, whereas the combination of both antibiotics induced a significant decrease in the lung bacterial count 6, 12 and 24 h after the onset of therapy when compared with tissue bacterial numbers in untreated animals or animals treated with either antibiotic alone. In-vivo synergy between cefepime and amikacin was observed at the three time points studied. No resistant clones emerged during treatment with any of the antibiotic regimens studied.

Topics: Amikacin; Animals; Anti-Bacterial Agents; Cefepime; Cefotaxime; Cephalosporins; Drug Resistance, Microbial; Drug Synergism; Enterobacter cloacae; Enterobacteriaceae Infections; Kidney; Male; Microbial Sensitivity Tests; Pneumonia, Bacterial; Rats; Rats, Wistar

This case report reviews the clinical course of an 11-day-old boy who developed late-onset neonatal sepsis secondary to a rare neonatal pathogen, Morganella morganii. This gram-negative enteric bacterium, within the Enterobacteriaceae family, has most commonly been a nosocomial pathogen in debilitated, postsurgical patients. Like many other Enterobacteriaceae, M. morganii has an inducible beta-lactamase and is resistant to multiple antibiotics. When caring for neonates with culture-proven M. morganii sepsis, the authors recommend administering both a third-generation cephalosporin and an aminoglycoside to ensure that both antibiotics are bactericidal and to reduce the induction of resistance.

Topics: Aminoglycosides; Ampicillin; Anti-Bacterial Agents; Cefotaxime; Cephalosporins; Drug Resistance, Multiple; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Infant, Newborn; Male; Microbial Sensitivity Tests; Penicillins; Sepsis

Topics: Abscess; Bacteremia; beta-Lactam Resistance; beta-Lactamases; Cefepime; Cefotaxime; Ceftazidime; Cephalosporin Resistance; Cephalosporins; Drug Resistance, Microbial; Enterobacter; Enterobacteriaceae Infections; Humans; Mutation; Pneumonia, Bacterial

During the second quarter each of 1988, 1989, and 1990, a French collaborative study group, including 12 university hospital laboratories, surveyed the resistance to beta-lactams of clinical isolates from hospitalized patients: consecutively, 10,641, 10,692, and 9,382 isolates were tested. The distribution of bacterial species over time was similar in each laboratory. The susceptibilities of microorganisms to amoxicillin, ticarcillin, cephalothin, cefoxitin, cefotaxime (CTX), ceftazidime (CAZ), aztreonam (ATM), and imipenem (IPM) were measured by the disk diffusion method in accordance with the recommendations of the Antibiogram Committee of the French Society for Microbiology. Five reference strains were included for quality control. Extended-spectrum beta-lactamases were detected by the synergistic effect of the combination of clavulanic acid-amoxicillin with CTX, CAZ, and ATM in the double-diffusion test. A synergistic effect with CTX, CAZ, and ATM was detected for 1.5% of all strains, mainly those of Klebsiella pneumoniae (13.3%). For this species, the synergy test enabled the detection of roughly 50% of the resistant strains misclassified as susceptible on the basis of interpretative standards. Extended-spectrum beta-lactamases disseminated in 1990 in most enterobacterial species but at a low frequency. Important variations in the percentages of resistant strains were observed in terms of bacterial species, hospitals, and wards. However, when the total number of strains was considered, the percentages of resistance to newer beta-lactams remained low.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefotaxime; Drug Resistance, Microbial; Enterobacteriaceae; Enterobacteriaceae Infections; France; Humans; Microbial Sensitivity Tests

Susceptibilities to cefotaxime (Ctx) and ceftazidime (Caz) were examined for 90 recent clinical isolates of Enterobacter cloacae from Greek hospitals. Most (68%) of the isolates were resistant to both drugs, and all were resistant to cefoxitin. beta-Lactamase activities against cephaloridine in crude extracts from Ctx-Caz-resistant isolates were high, irrespective of whether or not the cells were grown with cefoxitin as an inducer of the chromosomal beta-lactamase, indicating stable derepression of the gene for the enzyme. On the other hand, double disk antagonism tests showed that all the Ctx-Caz-sensitive isolates possessed inducible expression of this beta-lactamase. Iso-electric focusing revealed the presence of five forms of the chromosomal beta-lactamase, randomly distributed amongst the Ctx-Caz-resistant and -sensitive isolates. Plasmid-mediated beta-lactamases of TEM and PSE types also were found in many isolates. These data indicate that the extremely high prevalence of Ctx-Caz-resistant E. cloacae isolates in Greek hospitals is attributed to the dissemination of mutants which constitutively overproduce the class-I chromosomal beta-lactamase. Over 90% of these isolates exhibited cross-resistance to aminoglycosides, suggesting the accumulation of unrelated antibiotic resistance mechanisms.

Topics: Cefotaxime; Ceftazidime; Drug Resistance, Microbial; Enterobacter cloacae; Enterobacteriaceae Infections; Enzyme Induction; Enzyme Repression; Greece; Humans; Isoelectric Focusing; Microbial Sensitivity Tests; Penicillinase; Prevalence

Topics: Aged; Cefixime; Cefotaxime; Discitis; Enterobacter; Enterobacteriaceae Infections; Humans; Male

In 1983 our antibiotic regimen for suspected neonatal septicemia was changed from amoxicillin-gentamicin to cefotaxime-amoxicillin. During the subsequent 5-year period we studied the effect of this change in regimen on the bacterial flora of the infants in the unit and the occurrence of serious infections. This was done with bacteriologic surveillance and analysis of the positive blood cultures from 1978 through 1987. A change in the relative numbers of isolated pathogens was observed; Klebsiella sp. and Escherichia coli decreased whereas Enterobacter sp. increased. The susceptibility of the Enterobacter isolates to cefamandole decreased from 85.3% in 1982 to 52.9% in 1983. The susceptibility of these bacteria to cefotaxime was 55.2% in 1983 and 55.0% in 1987. No change in susceptibilities to cefotaxime, amoxicillin or gentamicin was found in other pathogens. Although colonization with Enterobacter strains has increased and the susceptibility of these bacteria to the cephalosporins has decreased, the incidence of serious infections with Gram-negative bacteria decreased.

Topics: Amoxicillin; Cefotaxime; Drug Resistance, Microbial; Enterobacter; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Gentamicins; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Klebsiella Infections; Male; Sepsis

We reviewed cases of Gram-negative enteric bacillary meningitis in infants and children treated with cefotaxime at Texas Children's Hospital from January, 1984, through June, 1989. Seventeen of 20 children had an underlying condition predisposing to the development of meningitis. The etiologic organisms in these 20 children (2 days to 12 years old; median, 12 days old) were Klebsiella sp, 9; Escherichia coli, 4; Enterobacter cloacae, 3; Citrobacter diversus, 2; other, 2. With the exception of one isolate of Acinetobacter, all isolates were susceptible to cefotaxime. In addition to cefotaxime 17 children received an aminoglycoside intravenously. Children with meningitis caused by Klebsiella sp. or non-Klebsiella organisms received cefotaxime for 31 +/- 14 and 37 +/- 17 days, respectively. Aminoglycosides were administered for 16 +/- 10 days in both groups. Five children in each group also received intraventricular doses (1 to 25) of an aminoglycoside (9) or colistimethate (1). The mean durations of positive lumbar, ventricular cerebrospinal fluid or brain abscess cultures were 5.8 +/- 4.7 and 7.2 +/- 5.0 days after start of therapy in the Klebsiella and non-Klebsiella meningitis patients, respectively. Only three children were normal at the time of discharge or follow-up. Gram-negative enteric meningitis remains difficult to treat despite the excellent in vitro activity of cefotaxime against Gram-negative enterics, in part as a result of the predisposing conditions resulting in the development of this infection.

Topics: Aminoglycosides; Anti-Bacterial Agents; Cefotaxime; Child; Child, Preschool; Citrobacter; Drug Therapy, Combination; Enterobacter; Enterobacteriaceae Infections; Escherichia coli Infections; Humans; Infant; Infant, Newborn; Klebsiella Infections; Meningitis; Retrospective Studies

Topics: Adult; Anti-Bacterial Agents; beta-Lactamases; Cefotaxime; DNA, Bacterial; Drug Resistance, Microbial; Enterobacter; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Infant; Male; Meningitis; Plasmids

In systemic and local infections, the therapeutic efficacy of cefpirome was compared to that of imipenem and cefotaxime. Murine septicemia induced with methicillin-sensitive and methicillin-resistant Staphylococcus aureus strains responded well to cefpirome and imipenem therapy, the ED50 values ranged from 0.8 to 28.40 mg/kg and 0.5 to 15.58 mg/kg, respectively. The carbapenem also displayed high efficacy against Enterococci and was more potent than cefpirome. Cefotaxime, however, exhibited lower activity or proved to be inactive against these strains. With ED50 values of 0.03 to 31.33 mg/kg, cefpirome was the most active of the three antibiotics in protecting mice challenged with Enterobacteriaceae. The corresponding ED50 values of imipenem and cefotaxime ranged from 0.72 to 70.95 mg/kg and 0.06 to 66.30 mg/kg, respectively. Despite distinctly lower in vitro activity against the infecting organism, cefpirome showed efficacy similar to imipenem in the treatment of subcutaneous S. aureus abscesses in mice. It was more effective than imipenem and cefotaxime against experimental Klebsiella pneumonia in mice and the Escherichia coli infected granuloma pouch in rats.

Topics: Abscess; Animals; Bacterial Infections; Cefotaxime; Cefpirome; Cephalosporins; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Granuloma; Imipenem; Male; Mice; Mice, Hairless; Mice, Inbred C3H; Pneumonia; Rats; Rats, Inbred Strains; Sepsis; Staphylococcal Skin Infections; Staphylococcus aureus; Streptococcal Infections

Topics: Administration, Oral; Cefotaxime; Enterobacter; Enterobacteriaceae Infections; Humans; Male; Middle Aged; Phosphates; Renal Dialysis; Tobramycin

Thirty-two patients were included in this trial: 22 with staphylococcal meningitis (including 5 methicillin-resistant) and 10 with enterobacterial meningitis. Mean duration of treatment was 14.5 and 15.9 days respectively. The combination was synergistic in vitro against 10 of the 12 strains of Staphylococcus and 5 of the 6 strains of Enterobacteriaceae studied. Bacteriological sterilization occurred in all cases which could be evaluated, and clinical recovery was obtained in 95.2% of patients with staphylococcal meningitis (4 unrelated deaths) and 100% of patients with enterobacterial meningitis (2 deaths). Bactericidal power of the cerebro-spinal fluid, often less than 1/8, was not correlated with effectiveness against Staphylococci. Mean CSF concentrations of cefotaxime, desacetylcefotaxime and fosfomycin on the 2nd and 15th days of treatment were 4, 3.5 and 39.8 mg/l and 2.2, 2.1 and 28.0 mg/l, respectively. Clinical and biological acceptability was satisfactory. There were three cases of superinfection or colonization, by Pseudomonas and Enterobacter.

Topics: Adolescent; Adult; Aged; Cefotaxime; Drug Evaluation; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Fosfomycin; Humans; Male; Meningitis; Microbial Sensitivity Tests; Middle Aged; Prospective Studies; Staphylococcal Infections; Staphylococcus

A case of Enterobacter cloacae meningitis in a postoperative patient is reported. A slow response to cefotaxime necessitated the use of gentamicin and trimethoprim-sulfamethoxazole for cure. Two types of resistance in the strain of E. cloacae isolated to cefotaxime were demonstrated: an inducible beta-lactamase that likely was the cause of the poor response to cefotaxime and a constitutive beta-lactamase in a mutant strain detected by a disc susceptibility test.

Topics: Aged; Cefotaxime; Drug Resistance, Microbial; Enterobacter; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Male; Meningitis; Mutation

Cefixime, a broad-spectrum, orally active cephalosporin, was more active in vitro than ampicillin, cefaclor, cephalothin, and trimethoprim/sulfamethoxazole against 194 nosocomial pathogens of the family Enterobacteriaceae. Activity was especially good against Klebsiella spp, Proteus spp, Serratia spp, and Providencia stuartii. Although gentamicin had equivalent or better activity against Citrobacter spp, Enterobacter spp, Escherichia coli, and Morganella morganii, all 23 of the gentamicin-resistant strains studied were susceptible to cefixime. Isolates tested were from urinary tract infections, abdominal infections, wounds, vascular infections, and respiratory infections; they were sequentially collected nosocomial pathogens from a single institution. This orally active cephalosporin should be considered for therapy of a variety of nosocomial infections involving gram-negative bacillary pathogens.

Topics: Ampicillin; Anti-Bacterial Agents; Cefaclor; Cefixime; Cefotaxime; Cephalothin; Cross Infection; Drug Combinations; Enterobacteriaceae; Enterobacteriaceae Infections; Gentamicins; Humans; Microbial Sensitivity Tests; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Despite the apparent success of several new cephalosporins in the treatment of Gram-negative bacterial meningitis, four treatment failures with cefotaxime or latamoxef were encountered (two caused by Enterobacter and two by Serratia spp.) In-vitro parameters of susceptibility of these clinical isolates were compared with those of a meningeal Ent. cloacae isolate from a successfully treated patient. The MIC and MBC values, degrees of inoculum effect, and amounts of beta-lactamase produced correlated poorly with the observed clinical outcome. However, the extent to which an isolate was killed by the cephalosporin used for treatment, in a 6-h in-vitro incubation, showed good correlation. We suggest that such a test should be used to predict clinical outcome of therapy because the other parameters such as the MIC and MBC values are not sufficiently discriminatory.

Topics: Adult; beta-Lactamases; Cefotaxime; Drug Resistance, Microbial; Enterobacter; Enterobacteriaceae Infections; Humans; Male; Meningitis; Middle Aged; Moxalactam; Serratia

Topics: Cefotaxime; Enterobacteriaceae Infections; Humans; Meningitis

Ciprofloxacin, azlocillin, ceftizoxime, and amikacin were studied alone and in combination against six Enterobacteriaceae and six strains of Pseudomonas aeruginosa in an infected chamber model in rabbits simulating a closed space infection. In-vivo results were compared with in-vitro tests of inhibition, killing and synergy. Ciprofloxacin was the most effective single agent, with efficacy against five of the six Enterobacteriaceae when used in low doses, and two of the six pseudomonads when used in high doses. The development of in-vitro resistance to ciprofloxacin was observed during therapy in strains which failed to be eradicated. Ciprofloxacin and azlocillin together was the most effective regimen, with efficacy against eleven of the twelve strains. Synergy, as determined by chequerboard testing, did not correlate with in-vivo outcome. Unlike mezlocillin, azlocillin, ceftizoxime or amikacin, MIC testing of ciprofloxacin was predictive of in-vivo success.

Topics: Amikacin; Animals; Azlocillin; Cefotaxime; Ceftizoxime; Ciprofloxacin; Drug Synergism; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Gram-Negative Bacteria; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Rabbits

The clinical efficacy of the combination therapy with cefmenoxime plus cefsulodin was studied in patients with complicated urinary tract infections caused by Pseudomonas aeruginosa. Patients received 1 g of CMX and 1 g of CFS concomitantly twice a day by 1-hour intravenous drip infusion. Of a total of 127 patients who received medication, 82 patients were evaluated on the 5th day. The overall clinical efficacy of treatment was evaluated by the criteria proposed by the UTI Committee, Japan, as excellent, moderate or poor. It was excellent in 15%, moderate in 55% and poor in 30%. Of the 143 strains isolated from 82 patients, 115 strains (80%) were eradicated. The eradication rate of P. aeruginosa was 83%. Subjective side effects were observed in 3 (2.4%) of the patients. Drug-related aggravations in laboratory test results were observed in 8 (7.5%), but most of them were minimal and reversible. The results of this study suggest that a combination of cefmenoxime and cefsulodin might be useful in the treatment of complicated urinary tract infections caused by P. aeruginosa.

Topics: Candidiasis; Cefmenoxime; Cefotaxime; Cefsulodin; Drug Therapy, Combination; Enterobacteriaceae Infections; Humans; Pseudomonas Infections; Urinary Tract Infections

Topics: Aged; Anti-Bacterial Agents; Cardiac Surgical Procedures; Cefotaxime; Cephalosporins; Drug Resistance, Microbial; Enterobacter; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Mutation

Topics: Adult; Aged; Cefotaxime; Child; Enterobacteriaceae Infections; Female; Humans; Infant; Infant, Newborn; Male; Meningitis; Middle Aged

The incidence of preoperative and postoperative infections among 46 patients who underwent transurethral prostatectomy (TUR-P) was studied. Perioperative antibacterial schedule was as follows: one gram of cefotaxime (CTX) was intravenously injected just before the beginning of TUR-P, One gram of the antibiotic was intravenously infused once more on the day after TUR-P, twice on the next day, and once during each of the succeeding 2 days. Thirteen cases out of 46 (28.3%) had significant preoperative bacteriuria (greater than or equal to 1 X 10(4)/ml), but the postoperative eradication of the bacteria was observed for 10 of the 13 cases (76.9%). Among the 33 cases that did not have significant preoperative bacteriuria, only one case developed significant bacteriuria. In this case, a non-significant bacterial contamination of the urine had been observed before TUR-P.

Topics: Aged; Bacteriuria; Cefotaxime; Enterobacteriaceae Infections; Humans; Male; Middle Aged; Postoperative Complications; Prostatectomy; Prostatic Neoplasms; Surgical Wound Infection

Topics: Adolescent; Adult; Aged; Amphotericin B; Bacterial Infections; Cefotaxime; Child; Child, Preschool; Drug Therapy, Combination; Enterobacteriaceae Infections; Humans; Infant; Middle Aged; Thoracic Injuries; Tobramycin

Intestinal colonization by members of the family Enterobacteriaceae resistant to cefotaxime was surveyed for 3 years in a hematology-oncology unit. Of 416 patients, 66 (15.9%) were colonized, each with a different strain. The incidence of intestinal carriage was not correlated with cefotaxime consumption in the ward but was strongly associated with individual exposure to cefotaxime.

Topics: Agranulocytosis; Cefotaxime; Drug Resistance, Microbial; Enterobacteriaceae; Enterobacteriaceae Infections; Feces; Hospital Units; Humans; Intestines; Neutropenia; Sepsis

An in vitro study of the sensitivity of three cephalosporins of the third generation was performed on 119 wild strains of enterobacteriae selected because of their resistance to cefalotine and cefoxitine. Cefotaxime, latamoxef and cetriaxone remain very active on such strains since almost all of the strains were inhibited by a dose of 4 micrograms/ml and CI 50 p. cent was below 0.20 micrograms/ml. The activity of these three cephalosporins was comparable on groups E. coli, Klebsiella-Enterobacter-Serratia and C. freudii. Ceftriaxone appeared clearly more active than latamoxef and cefotaxime on Proteus stains.

Topics: Cefotaxime; Cefoxitin; Ceftriaxone; Cephalosporins; Cephalothin; Drug Resistance, Microbial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests; Moxalactam; Species Specificity

Topics: Adult; Cefotaxime; Drug Resistance, Microbial; Enterobacter; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans

In the course of a study to determine the nature and type of secondary bacterial infection in dracunculiasis. The most common organisms cultured from lesions were Escherichia coli, Enterobacter and Staphylococcus aureus. E. coli and Enterobacter which were found to carry high morbidity were sensitive to Gentamycin, Claforan and Septrin.

Topics: Cefotaxime; Dracunculiasis; Drug Combinations; Enterobacter; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; Female; Gentamicins; Humans; Skin Diseases, Infectious; Skin Ulcer; Staphylococcal Skin Infections; Staphylococcus aureus; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

An outbreak of serious infections due to gentamicin-resistant Klebsiella pneumoniae occurred in a neonatal intensive care unit in which the combination of gentamicin sulfate and ampicillin sodium had been used for standard initial therapy for suspected sepsis for nearly 11 years. After institution of control measures that included the substitution of cefotaxime sodium for gentamicin in the standard regimen, the outbreak promptly subsided. Nevertheless, a second outbreak of serious infections due to cefotaxime-resistant Enterobacter cloacae began ten weeks later. Sequential stool cultures from patients in the unit confirmed the disappearance of gentamicin-resistant K pneumoniae and the emergence of cefotaxime-resistant E cloacae after the change in antibiotic policy. These observations suggest that routine use of newer cephalosporins for therapy of suspected sepsis may lead to the emergence of drug-resistant microorganisms more rapidly than has occurred with the aminoglycosides.

Topics: Ampicillin; Cefotaxime; Cross Infection; Disease Outbreaks; Drug Therapy, Combination; Enterobacter; Enterobacteriaceae Infections; Gentamicins; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Penicillin Resistance; South Carolina; Time Factors

One hundred sequential Gram-negative rod isolates from patients with hospital-acquired bloodstream infections were tested against seven new cephalosporins. Duplicate broth microdilution tests indicated superior activity for ceftazidime with 97% of strains susceptible to 16 mg/l. Less in-vitro activity was demonstrated cefotaxime (91% susceptible to 16 mg/l, P = 0.07), latamoxef (moxalactam) (90%, P = 0.04), cefoperazone (90%, P = 0.04), ceftriaxone (87%, P = 0.008), cefmenoxime (80%, P = 0.0001), and ceftizoxime (79%, P less than 0.0001). With the exception of cefoperazone, the newer drugs had mean MICs of less than or equal to 0.6 mg/l against Enterobacteriaceae. Ceftazidime and cefoperazone had highest activities against Pseudomonas aeruginosa with MIC90S of 4 and 16 mg/l, respectively. A comparison of recently published data shows important geographic differences in MIC90 data for the new cephalosporins against specific species.

Topics: Cefmenoxime; Cefoperazone; Cefotaxime; Ceftazidime; Ceftizoxime; Ceftriaxone; Cephalosporins; Cross Infection; Enterobacteriaceae; Enterobacteriaceae Infections; Gram-Negative Bacteria; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis

The synergistic activity of cefotaxime and amikacin against 21 highly resistant Pseudomonas aeruginosa and Serratia marcescens isolates was evaluated in-vitro by the checkerboard tube dilution method and in-vivo in five patients with serious infections caused by these organisms. All isolates were resistant to gentamicin, tobramycin, amikacin, and cefotaxime. Synergy was observed in 90% of isolates and occurred when the MIC of amikacin was less than 256 mg/l and of cefotaxime less than 1024 mg/l. A clinical response occurred in 100% and bacteriological cure in 80% of patients. Our results demonstrate a high degree of synergism between amikacin and cefotaxime in-vitro and clinical efficacy in the treatment of infections due to multiply-resistant Pseudomonas and Serratia species.

Topics: Aged; Amikacin; Aminoglycosides; Cefotaxime; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; Enterobacteriaceae Infections; Humans; Kanamycin; Male; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Serratia marcescens

Topics: Adult; Aged; Cefotaxime; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Pseudomonas Infections; Urinary Tract Infections

During 1981-1984, nine patients were treated with second or third generation cephalosporins for deep post-operative wound, respiratory, and blood infections with Enterobacter. In at least 50-60% of cases, therapy failed due to emergence of broad-spectrum cephalosporin resistance. Laboratory testing of two strains that became resistant showed that they were more likely to develop high level resistant mutants, which had greater ability to bind cefotaxime. Although these surgery patients represent an extreme case, spread of their resistant strains to other patients in hospital could lead to wide-spread nosocomial resistance.

Topics: Cardiac Surgical Procedures; Cefotaxime; Drug Resistance, Microbial; Enterobacter; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Middle Aged; Postoperative Complications

The inhibitory combination effect of cefmenoxime with gentamicin, tobramycin, netilmicin and amikacin against 148 Enterobacteriaceae was compared using the checkerboard agar dilution technique. On average 41% of cefmenoxime-moderately susceptible (MIC between 2 and 32 micrograms/ml) or cefmenoxime-resistant (MIC greater than 32 micrograms/ml) strains were inhibited by synergistic, and 23,5% by partial synergistic cefmenoxime-aminoglycosides combinations. Against cefmenoxime-susceptible strains, these rates of synergy or partial synergy were twofold lower, but only one isolate was not susceptible to these combinations. The amikacin-cefmenoxime interaction was the most performant.

Topics: Amikacin; Aminoglycosides; Anti-Bacterial Agents; Cefmenoxime; Cefotaxime; Drug Resistance, Microbial; Drug Synergism; Enterobacteriaceae; Enterobacteriaceae Infections; Gentamicins; Humans; Netilmicin; Species Specificity; Tobramycin

Cefotaxime treatment eliminates normally susceptible strains of enterobacteria from the digestive tract, and increases intestinal carriage of resistant enterobacteria in individuals. However the global rate of such carriage remains low in hospitalized patients and resistant strains are exceptionally isolated from bacteraemia in spite of an intensive use of this antibiotic. The epidemiology of resistant strains of enterobacteria has to be carefully monitored. The results obtained by the control of faecal carriage shows that this technique is a means of surveying evolution in this area.

Topics: Carrier State; Cefotaxime; Drug Resistance, Microbial; Enterobacteriaceae; Enterobacteriaceae Infections; Feces; Humans; Inpatients; Microbial Sensitivity Tests; Patients

We treated 12 adult patients who had gram-negative bacillary meningitis with cefotaxime administered intravenously at a dose of 2 g every 4 hours. The etiological organisms included Haemophilus influenzae (3 cases), Serratia marcescens (3 cases), Klebsiella pneumoniae (3 cases), Escherichia coli (2 cases), and Enterobacter (1 case). The infection followed a neurosurgical procedure in 6 cases. The mean inhibitory and bactericidal concentrations of cefotaxime for the isolates ranged from 0.125 to 0.25 microgram/ml. The cerebrospinal fluid (CSF) concentrations of cefotaxime ranged from 5.0 to 15.2 micrograms/ml, and the CSF bactericidal titers were 1:64 to 1:128. The CSF in all patients was sterilized within 96 hours. All 12 patients recovered, and there were no relapses.

Topics: Adult; Bacterial Infections; Cefotaxime; Enterobacteriaceae Infections; Escherichia coli Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meningitis; Meningitis, Haemophilus; Middle Aged; Serratia marcescens

Cefmenoxime was evaluated in an open trial consisting of 41 patients. Forty infections in 36 patients could be evaluated. Thirteen patients had pyelonephritis due to Escherichia coli (two bacteremic), Pseudomonas aeruginosa, Klebsiella pneumoniae, or Streptococcus faecalis; all improved and 12 of 13 were clinically cured, but one relapse (S. faecalis) occurred at two weeks. Six patients with cystitis due to E. coli, Citrobacter freundii, Serratia marcescens, P. aeruginosa, or S. faecalis all improved, but relapse or reinfection, or both, occurred in five due to P. aeruginosa, S. faecalis, C. fruendii, or E. coli. Neurogenic bladder or other complications were present in five of 13 patients with pyelonephritis and five of six with cystitis. Ten patients with pneumonia and one with tracheobronchitis due to Hemophilus influenzae, S. pneumoniae, S. agalactiae, or Neisseria meningitidis all improved and seven had resolution without relapse, but P. aeruginosa emerged in two patients, one of whom died. Eight soft tissue infections due to Staphylococcus aureus, Peptococcus prevotti, Streptococcus species, or infections of mixed origin resolved in six. Sterility of blood cultures was obtained in one patient with endocarditis due to S. anginosus, but other therapy was substituted. Clinical resolution of the toxic shock syndrome and subsequent negative endocervical cultures for S. aureus occurred in one. Granulocytopenia of unverified cause in four (with less than 1,500 mm3) and two (with less than 2,000 mm3) was reversible. Headache during treatment occurred in six patients and a possible disulfiram-like effect in three. Elevations of serum glutamic oxalacetic transaminase and alkaline phosphatase occurred in five, Coombs' positivity in two, and diarrhea in three. Clinical efficacy of cefmenoxime was significant. Possible side effects require further study.

Topics: Abscess; Adolescent; Adult; Aged; Bacterial Infections; Cefmenoxime; Cefotaxime; Cellulitis; Cystitis; Drug Resistance, Microbial; Enterobacteriaceae Infections; Female; Humans; Leukopenia; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia; Urinary Tract Infections

Sixty patients (23 men and 37 women) with a median age of 56.7 years (range 20 to 80) and a median weight of 69 kg were treated with cefmenoxime as short-term perioperative prophylaxis. Patients were undergoing surgery for an infected gallbladder, bile duct, or colon or were being treated for local or diffuse peritonitis and soft tissue infections. Overall clinical efficacy including very good and good results could be achieved in 88.3 percent. Moderate clinical efficacy was achieved in six cases, two of which were due to Pseudomonas aeruginosa. In 38 of 60 patients an antibiogram could be performed before and after therapy. Of the isolated 46 strains, 40 pathogens (86.95 percent) were eradicated during cefmenoxime treatment and in two cases a replacement was observed. After one hour, peak concentrations in serum could be reached with over 70 micrograms/ml.

Topics: Adult; Aged; Ascitic Fluid; Body Fluids; Cefmenoxime; Cefotaxime; Enterobacteriaceae Infections; Female; Humans; Kinetics; Male; Middle Aged; Premedication; Surgical Wound Infection

Topics: Cefotaxime; Enterobacteriaceae Infections; Gentamicins; Humans; Infant, Newborn; Infant, Newborn, Diseases; Intestines; Parenteral Nutrition, Total; Time Factors

MIC of ceftriaxone, moxalactam and cefotaxime is determined for 827 strains of Enterobacteriaceae isolated in the Central Laboratory of the Pitié-Salpêtrière Hospital between december 1981 and september 1982. Results are distributed according to the species involved and the pattern of sensitivity (S) and resistance (R) to ampicillin (A), carbenicilline (Ca) and cephalotin (Ct). Among the strains ASCaSCtS and ARCaRCtS cefotaxime and ceftriaxone have the lowest MICs. Among the most sensitive strains ARCaSCtR and ARCaRCtR cefotaxime, ceftriaxone and moxalactam have the similar MICs, whereas among the less sensitive ones moxalactam has the lowest MICs. The latter might be the cephalosporin of choice for the treatment of serious infection due to the less sensitive Enterobacteriaceae. On the other hand, cefotaxime and ceftriaxone might be the cephalosporins of choice for the treatment of serious infections due to the most sensitive Enterobacteriaceae.

Topics: Anti-Bacterial Agents; Cefotaxime; Ceftriaxone; Cross Infection; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests; Moxalactam; Phenotype

An outbreak of colonisation and infection with a netilmicin resistant strain of Serratia marcescens occurred in a special care baby unit. S marcescens was isolated from a total of 13 babies; significant infection occurred in five, of whom two died. Epidemiological investigation failed to detect a common source but gastrointestinal colonisation of babies formed a prolonged and possibly important reservoir for infection. Containment proved difficult until the unit was closed to new admissions, and even then spread to a temporary unit ensued. O Serotyping and bacteriophage typing disclosed a single epidemic strain. This produced an aminoglycoside acetylating enzyme (AAC(6')) conferring resistance to netilmicin and tobramycin and moderate resistance to amikacin. Use of gentamicin resulted in the isolation of serratia with increased resistance to all aminoglycosides, and, similarly, increased resistance to third generation cephalosporins emerged with their use.

Topics: Acetyltransferases; Amikacin; Cefotaxime; Cross Infection; Disease Outbreaks; Drug Resistance, Microbial; Enterobacteriaceae Infections; Gentamicins; Humans; Infant, Newborn; Netilmicin; Nurseries, Hospital; Serratia marcescens; Tobramycin

Bacterial infections are frequent events in premature and newborn infants. The reason is a defective specific and nonspecific defence of bacterial organisms. Some immunoglobulins like IgM and IgA including secretory IgA are absent. Premature infants also show a decreased level of IgG. Cellular immunity is anatomically intact but functionally defective. A number of complement factors are lacking, the activation of the alternative pathway is impaired. Newborn infants with perinatal problems like asphyxia or difficult delivery, show defects of leucocyte function like decreased deformability, defective chemotaxis and defective killing of ingested bacteria. Certain diseases, like hypoxia and malformations of immature organ functions in this age group (decreased acid production in the stomach), facilitate bacterial colonization of surface epithelia and the invasion of tissues. Consequences of these pathogenetic mechanisms are an unimpaired propagation of bacterial organisms into the blood and meninges without localization of the infecting organisms at the entry site. Bacterial meningitis is not considered a separate disease entity but a complication of bacteremia and sepsis. Clinical symptoms are nonspecific at the onset of the infection. Fever is frequently absent; decreased appetite, vomiting, a bloated abdomen, diarrhea, tachycardia, tachypnea are early signs of a bacterial infection, a grey mottled appearance, cyanosis, jaundice, petechiae, apneic spells, seizure activity and a metabolic acidosis are symptoms of advanced infection. Successful treatment at this stage is often not possible. Every sign of a decreased well being of a newborn of premature infant warrants laboratory and bacteriologic work up for septicemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Cefotaxime; Cephalosporins; Clindamycin; Drug Therapy, Combination; Enterobacteriaceae Infections; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Infant, Premature, Diseases; Meningitis; Metronidazole; Penicillin G; Pseudomonas Infections; Streptococcal Infections

Our clinical experience with new antibiotics giving special consideration to the individual cephalosporin groups is discussed. Although newer cephalosporins from cefamandol and cefoxitin to cefotiam and cefoperazon already showed increased effectiveness (for example, cefoxitin in bacteroides infection) in comparison to older ones, the real breakthrough regarding enterobacteriaceae was only made with cephalosporins of the cefotaxime group. This group's main indication is non-specific initial therapy of severe nosocomial infections, especially processes in which the presence of resistant enterobacteriaceae must be assumed. Because of its broad spectrum of action, cefotaxime can to a large extent replace the combinations with aminoglycosides which were used previously. When required, cefotaxime proves to be a good partner for combinations with pseudomonas antibiotics.

Topics: Bacteroides Infections; Cefotaxime; Cefoxitin; Cephalosporins; Cross Infection; Drug Therapy, Combination; Enterobacteriaceae Infections; Gentamicins; Humans; Pseudomonas Infections; Staphylococcal Infections; Structure-Activity Relationship

From 1979 to 1982, a large number of freshly isolated strains of bacteria were investigated at our institute with regard to their sensitivity to cefotaxime in comparison to other antibiotics. The isolates came from 42 clinics in the Rhine-Main region. The results of the investigations demonstrate that cefotaxime, due to its high stability against beta-lactamases, has advantages over to older cephalosporins, and even cefoperazon and cefoxitin. Despite increased use of cefotaxime, there was no change in the sensitivity of the organisms from 1979 to 1982.

Topics: Cefotaxime; Cefoxitin; Cephalosporins; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Moxalactam; Penicillin Resistance; Penicillins; Streptococcal Infections; Streptococcus

Cefamandole resistance in five patients was studied. Microorganisms emerged resistant to cefamandole during therapy with the drug in three patients with complicated infections. This resistance was associated with an enhanced production of beta-lactamase and/or with a change in the substrates and the isoelectric focusing patterns of the enzymes. Cross-resistance to other beta-lactam antibiotics developed concurrently in isolates from these patients. Disk diffusion tests did not detect resistance to cefamandole in the pretreatment isolate from the fourth patient; this isolate produced inactivating enzymes, and resistance was detected only in broth dilution tests. In the fifth patient, infection with a cefamandole-resistant Enterobacter developed during postoperative therapy with the drug. Resistance to cefamandole in the isolate from this patient was unstable and was associated with inducible beta-lactamase activity. These examples emphasize the need for close monitoring of patients who are given cefamandole and for thorough in vitro evaluation of isolates from the patients both before and after treatment.

Topics: Adult; Aged; Bacteroides Infections; beta-Lactamases; Cefamandole; Cefotaxime; Cefoxitin; Cephalosporins; Cephamycins; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Humans; Isoelectric Focusing; Male; Middle Aged; Moxalactam; Penicillin Resistance; Penicillins

We studied the pharmacokinetics and efficacy of cefotaxime in 32 neonates with severe gram-negative infections. Many of these patients had been treated unsuccessfully with combinations of antibiotics. Eighty-one percent of these patients were cured, 6% improved, and 13% had treatment failures; there were three deaths. Eighteen patients received cefotaxime alone; 16 were cured and two improved. These data indicate an efficacy of cefotaxime sufficient to warrant more rigorous future trials. The elimination half-life of cefotaxime ranged from 2.0 +/- 0.4 hours in term neonates more than one week of age to 5.7 +/- 0.8 hours in preterm neonates less than one week of age. A volume of distribution of approximately 0.63 L was similar for all infants irrespective of age and maturity. These kinetic data can be used in design of future therapeutic regimens in more rigidly controlled trials assessing indications for cefotaxime therapy in neonates. We recommend dosing as follows, using a dose of 25 mg/kg: every 12 hours for preterm infants less than one week of age, every 8 hours for preterm infants one to four and term infants less than one week of age, and every 6 hours for term infants more than one week of age.

Topics: Bacterial Infections; Cefotaxime; Enterobacteriaceae Infections; Humans; Infant, Newborn; Infant, Newborn, Diseases; Kinetics; Models, Biological; Pseudomonas Infections; Staphylococcal Infections; Streptococcal Infections

A transpapillary indwelling catheter was inserted to prevent stone impaction in six female patients who were suffering from choledocholithiasis. The bile withdrawn via the catheter was infected on six occasions with Escherichia coli. In one of these cases Klebsiella sp. and in another Salmonella sp. were also identified. All bacteria were sensitive to ceftizoxime (the MIC was between 0.007 and 0.06 mg/l). The bacterial counts in the bile were determined before and during treatment by means of membrane filtration. In all six cases there was a rapid decline in the colony count. The concentration of ceftizoxime in bile samples was several times higher than the MIC of ceftizoxime for the corresponding pathogens. Overall, the therapeutic results with ceftizoxime were good. Three of eight pathogens were eliminated from the bile within eight to 24 hours. In one case a change of pathogen was seen after 24 hours. Forty-eight hours after beginning treatment, four of eight pathogens had been eliminated from the bile. After 72 hours the colony count in six patients was less than 10 pathogens/ml. In two patients a change of pathogen occurred; in one patient treatment had to be stopped after the first injection because of urticaria.

Topics: Aged; Bile; Bile Duct Diseases; Cefotaxime; Ceftizoxime; Cholestasis; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Gallstones; Humans; Middle Aged

The clinical significance of a concomitant, non-specific influence of antibiotics on immune defence mechanisms was studied by evaluating the death rate in mice experimentally infected with highly resistant or primarily resistant microorganisms. It could be shown that the mortality rate of mice infected with Enterobacter cloacae or Candida albicans significantly increased under treatment with cefoxitin, whereas treatment with cefotaxine or lamoxactam either had no effect, or even resulted in a better survival rate in comparison to controls. These results run parallel to an inhibition (cefoxitin) or stimulation (cefotaxime and lamoxactam) of antibody production. The effect of cefoxitin on the course of experimental infections could be compensated for by the concomitant application of sodium-8-chlorotheophyllinate which promotes antibody formation. None of these antibiotics showed any additional effect in animals treated with cyclophosphamide. From these observations it was concluded that the influence of antibiotics on certain immunological parameters assayed in vitro may be reflected in comparable effects on the course of infections in vivo; this implies that under certain clinical conditions, the immunological side-effects of antibiotics may be of practical therapeutic significance.

Topics: Animals; Anti-Bacterial Agents; Antibody Formation; Candidiasis; Cefotaxime; Cefoxitin; Cephamycins; Cyclophosphamide; Drug Therapy, Combination; Enterobacter; Enterobacteriaceae Infections; Infections; Male; Mice; Mice, Inbred BALB C; Moxalactam; Theophylline

Topics: Aged; Bacterial Infections; Cefotaxime; Ceftriaxone; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged

Topics: Bacterial Infections; Cefotaxime; Cephalosporins; Cephamycins; Enterobacteriaceae Infections; Humans; Moxalactam

Cefotaxime concentrations obtained in the C.S.F. of twelve children suffering from bacterial meningitis and undergoing monotherapy with this antibiotic are reported. Among these 12 patients, 4 infants (aged 3 to 28 days) had neonatal meningitis (due to Serratia marcescens, Proteus mirabilis, Enterobacter cloacae, Escherichia coli); one infant (2 months old) had meningitis due to Salmonella panama; 5 children (aged 5 to 11 months) had meningitis due to Haemophilus; and 2 children had belated superinfection caused by a ventriculo-peritoneal shunt due to Klebsiella pneumoniae and Pseudomonas aeruginosa. Cefotaxime concentration reached a high level as early as one hour after the injection (3 to 19 mcg/ml), remained at this level until the fifth hour (1,8 to 14,3 mcg/ml) and decreased without significant proportionality with the disappearance of the inflammatory symptoms. Compared to the M.I.C. of the bacteria which caused the twelve cases of meningitis, these results show that the concentrations in the C.S.F. are much higher than the M.I.C.'s. These results are comparable to those of previous studies. Cefotaxime diffuses in the C.S.F. and gives concentrations which ensures an antibacterial activity that ampicillin could not reach: in particular against Haemophilus influenzae and enterobacteriaceae.

Topics: Cefotaxime; Cephalosporins; Child; Enterobacteriaceae Infections; Humans; Infant; Infant, Newborn; Meningitis; Meningitis, Haemophilus

10 patients with septicaemia caused by enterobacteriaceae were successfully treated with cefotaxime. 9 patients had previously received unsuccessful antimicrobial therapy. The pathogen was resistant in vitro to other antibiotics. Cefotaxime was administered alone or in combination with an aminoglycoside. No severe side-effects were noted.

Topics: Adult; Aged; Cefotaxime; Cephalosporins; Enterobacteriaceae Infections; Female; Humans; Injections, Intramuscular; Injections, Intravenous; Male; Middle Aged; Sepsis

Cefotaxime was given to 26 patients with serious infections resistant to other antibiotics. 15 patients were suffering from septicaemia due to Gram-negative bacilli, which were caused either by a single organism (13 cases:" of which Serratia in 6, Klebsiella in 3) or by several organisms (2 cases); 7 had upper urinary tract infections (caused by Serratia in 4 patients), and 6 had miscellaneous infections (two of these were purulent post-operative meningitis). The pathogens were usually resistant to ampicillin and cephalothin. Cefotaxime was administered at a daily dose of 3 g in 22 patients, irrespective of the renal function, and of 6 g in 4 patients (2 meningitis). Treatment included an aminoglycoside in 12 cases. The efficacy of cefotaxime was very satisfactory in 23 of the 26 patients.

Topics: Adult; Aged; Cefotaxime; Cephalosporins; Drug Resistance, Microbial; Enterobacteriaceae Infections; Female; Humans; Male; Meningitis; Middle Aged; Pseudomonas Infections; Respiratory Tract Infections; Sepsis; Urinary Tract Infections

Sixteen patients, 9 to 81 years old, with Gram-negative septicaemia have been treated with cefotaxime. In all cases, the patients were hospitalised in an intensive care unit for a severe infection distinct from septicaemia. Cefotaxime was given alone to 11 patients and was administered by infusion over 20 to 30 minutes, every 4 or 6 hours, in a daily dose of 67 to 94 mg/kg to patients with normal of subnormal renal function. Gram-negative pathogens were sensitive to cefotaxime (MIC less than 1 mcg/ml in most cases). A clinical cure was obtained in 14 patients. In all the cases, tolerance was good. The very low MIC's of cefotaxime and the results in severe Gram-negative septicaemia justify the use of cefotaxime in monotherapy, in patients with severe life-threatening infections, when blood cultures appear to be positive for Gram-negative pathogens, even without awaiting antibiograms.

Topics: Adolescent; Adult; Aged; Cefotaxime; Cephalosporins; Child; Enterobacteriaceae Infections; Humans; Middle Aged; Sepsis

Topics: Adolescent; Adult; Aged; Cefotaxime; Cephalosporins; Critical Care; Enterobacteriaceae Infections; Humans; Infusions, Parenteral; Middle Aged

Cefotaxime was used to treat 33 patients with serious Gram-negative bacillary infections. The dosage varied between 1.5 g and 4 g/day in patients without renal failure. Eighteen patients had urinary tract infections, 6 had pulmonary infections and 10 had miscellaneous infections. Sixteen patients were also bacteremic. Twenty-five infections were due to pathogens resistant to ampicillin, cephalothin, gentamicin and/or tobramycin, in vitro. Fifteen infections had failed to resolve during ampicillin, cefazolin, gentamicin or tobramycin therapy. Thirty-two patients responded favourably (cure or improvement). Four patients developed superinfection with cefotaxime-resistant bacteria. One patient developed mild reversible renal insufficiency. Cefotaxime is a very active cephalosporin with potential use in serious multi-resistant enterobacteria infections.

Topics: Acinetobacter Infections; Cefotaxime; Cephalosporins; Drug Resistance, Microbial; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Pneumonia; Urinary Tract Infections

In this study, 63 patients with various urinary tract infections were treated with cefotaxime in different dosages. They were aged from 10 to 82 years (mean: 59). The cases included 33 cystitis, 25 pyelonephritis, 4 chronic prostatitis and 1 orchiepididymitis. 85 strains of enterobacteria were identified: 20 E. coli, 2 Citrobacter freundi, 5 Proteus mirabilis, 12 indole positive Proteus, 1 Providentia, 11 Klebsiella, 3 Enterobacter cloacae and 31 Serratia marescens and liquefaciens. 80 of these strains had MIC less than or equal to 1 mcg/ml (median: 0,12 mcg/ml). More than 2/3 of the patients were treated with a daily dose of 1.50 to 2 g, and 52 (median: 0.12 mcg/ml). More than 2/3 of the patients results showed 43 cures (9 of these with reinfection) and 20 relapses. Isolated enterobacteria strains were sensitive to cefotaxime in patients with recurrence. Relapses were due to underlying urological pathology. Among reinfection organisms, only one, an Enterobacter cloacae, was resistant to cefotaxime. The clinical, local, systemic and biological tolerance was good. Cefotaxime has been very effective in the treatment of severe urinary tract infections, especially in chronic pyelonephritis and cystitis, at an average daily dose of 2 g.

Topics: Adolescent; Adult; Aged; Cefotaxime; Cephalosporins; Child; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Urinary Tract Infections

Five meningitis due to Haemophilus influenzae and 6 meningitis due to Enterobacteria were treated with cefotaxime. The antibiotic was administered at a dose of 150 to 200 mg/kg/day in four 1 hour infusions. The pathogens were eradicated in all patients. Cefotaxime activity was efficient either against resistant pathogens (Haemophilus, Enterobacter) or against organism susceptible to ampicillin. Because cefotaxime is active at low concentration and has a good diffusion in the CSF, it provides a particularly effective treatment in Gram-negative meningitis in children. The initial use of cefotaxime should result in rapid eradication of the pathogen, with consequent improvement in the prognosis.

Topics: Cefotaxime; Cephalosporins; Enterobacteriaceae Infections; Female; Humans; Infant; Infant, Newborn; Male; Meningitis; Meningitis, Haemophilus; Pseudomonas Infections; Salmonella Infections

Twenty-six children, aged from 15 days to 14 years, were treated with cefotaxime. 5 were suffering from septicaemia, 14 from respiratory tract infection and were ventilated (intensive care unit), 4 from urinary tract infection and 3 from otitis media complicated with renal failure (nephrology unit). The choice of cefotaxime treatment was based upon the bacterial activity. The daily dose was 50 to 100 mg/kg by the i.m. route, or by slow intravenous injection every 8 hours. In 17 patients, cefotaxime was combined with an aminoglycoside (gentamicin or amikacin). The results were evaluated on the basis of clinical, radiological and bacteriological criteria and, whenever possible, were correlated to the serum levels of antibiotic. The antibiotic was clinically effective in 25 out of 26 patients. The three deaths that occurred, were due to the nature of the initial disease. Tolerance was good in all the patients studied. The efficacy of cefotaxime correlated well with the favorable in vitro bacteriological results and with serum concentrations. Cefotaxime is well tolerated as shown in newborn babies. Cefotaxime is markedly different from previous cephalosporins, because of its high antibacterial activity on most Gram-negative bacilli.

Topics: Adolescent; Cefotaxime; Cephalosporins; Child; Child, Preschool; Enterobacteriaceae Infections; Fusobacterium Infections; Haemophilus Infections; Humans; Infant; Infant, Newborn; Injections, Intramuscular; Injections, Intravenous

Cefotaxime was administered alone to 25 patients, with serious infectious diseases secondary to a gastrointestinal lesion. The largest group consisted of pancreatic and biliary infections, or infectious complication in cirrhotic patients. The daily dose was 2 or 3 g, sometime 4 g of cefotaxime. In the 15 cases where the infecting organisms could be identified: E. coli: 6, Staphylococcus aureus: 4, Klebsiella: 2, Haemophilus: 1, Proteus: 1 and Pseudomonas: 1, the pathogen was eradicated bacteriologically within two to six days after the onset of therapy. The infection was controlled in all 25 cases within 2 to 8 days even though, in 11 cases, previous antibiotic therapy had been insufficient, no complementary antibiotic treatment was associated and 8 of the cases with very severe infection were a serious problem to the intensive care unit. The use of cefotaxime is justified in the treatment of gastrointestinal infection even though pathogens are identified with difficulty in these diseases.

Topics: Adult; Aged; Cefotaxime; Cephalosporins; Digestive System Diseases; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Pseudomonas Infections; Staphylococcal Infections

Thirty-nine patients, 17 to 80 years old, were admitted to a pneumology department. The diagnosis was acute serious or severe respiratory tract infection in 25 patients, exacerbation of chronic bronchopulmonary infection in 6, purulent pneumonia in 4, purulent bronchitis in 4. 28 infecting organisms were identified: Gram-positive cocci (Pneumococcus: 6, Streptococcus: 8. Staphylococcus: 1) and 6 Haemophilus influenzae (3 of which were associated with 1 Pneumococcus) 7 Enterobacteria (isolated or associated). Local, biological and systemic tolerance was generally very good in the majority of patients. Cefotaxime at a daily dose of 2 g intramuscularly for 12 days, showed very good efficacy in the treatment of various bacterial infections of the lower respiratory tract. The activity was evident against a variety of organisms in respiratory infections. The in vitro results of the antibiogram which indicated a superiority of cefotaxime in some cases on other antibiotics currently used in these indications were confirmed by the clinical results.

Topics: Adolescent; Adult; Aged; Bronchitis; Cefotaxime; Cephalosporins; Enterobacteriaceae Infections; Female; Haemophilus Infections; Humans; Male; Middle Aged; Pneumonia; Staphylococcal Infections; Streptococcal Infections

Topics: Burns; Cefotaxime; Cephalosporins; Child; Drug Resistance, Microbial; Endocarditis, Bacterial; Enterobacteriaceae Infections; Female; Humans; Sepsis; Serratia marcescens; Tricuspid Valve

The in vitro activity of moxalactam, a new semisynthetic 1-oxa-beta-lactam, was compared to those cefotaxime, cefuroxime, cephalothin, piperacillin and tobramycin against more than 500 clinical isolates of Enterobacteriaceae and non-fermenters. The geometric mean MIC against 450 Enterobacteriaceae in microgram/ml was 0.09 for moxalactam, 0.08 for cefotaxime, 5.3 for cefuroxime, 22.9 for cephalothin, 3.5 for piperacillin and 0.72 for tobramycin. The geometric mean MIC in microgram/ml against 60 P. aeruginosa strains was 12.7 for moxalactam, 22.9 for cefotaxime, 6.8 for piperacillin, 1.5 for tobramycin and 2.9 for cefsoludin. The minimum inhibitory and the bactericidal concentrations of moxalactam were almost the same in most species. The effect of the inoculum on the bactericidal concentration was slight, between 10(3) and 10(7) CFU/ml for the E. coli and the Klebsiella strains. In isolates of S. marcescens and P. aeruginosa the bactericidal concentrations increased by 4 to 5 log2 and in isolates of P. mirabilis the increased by 9 log2 with the largest inoculum.

Topics: Anti-Bacterial Agents; beta-Lactams; Cefotaxime; Cephalosporins; Cephamycins; Enterobacteriaceae; Enterobacteriaceae Infections; Fermentation; Humans; Microbial Sensitivity Tests; Moxalactam

Topics: Adult; Anti-Bacterial Agents; Cefotaxime; Cephalosporins; Cephamycins; Enterobacteriaceae Infections; Humans; Meningitis; Meningitis, Haemophilus; Moxalactam

Cefotaxime is a new cephalosporin with a spectrum of activity which may make it appropriate for use in pediatric patients. In 33 infants and children, administration of cefotaxime resulted in cure or improvement in 97% of patients, with eradication of 94% of isolated pathogens. Toxicity was minimal. The disposition of cefotaxime in this age group was similar to that reported for adults, with an elimination half-life of approximately 1.5 h, a volume of distribution of 1 liter/kg, a total serum clearance of 10 ml/min per kg, and a renal clearance of 6 ml/min per kg.

Topics: Bacterial Infections; Cefotaxime; Child; Child, Preschool; Enterobacteriaceae Infections; Humans; Infant; Injections, Intramuscular; Injections, Intravenous; Pseudomonas Infections