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PubMed2004

Beta-lactam susceptibilities and prevalence of ESBL-producing isolates among more than 5000 European Enterobacteriaceae isolates.

In vitro susceptibility to 15 beta-lactam antibiotics was evaluated using Enterobacteriaceae isolated during the SENTRY Antimicrobial Surveillance Program. Piperacillin/tazobactam was the most active penicillin against Escherichia coli, Proteus mirabilis, Klebsiella oxytoca and Klebsiella pneumoniae (94.9%, 98.3%, 87.4% and 82.9% of isolates susceptible). Of the cephalosporins, cefepime was most effective against Escherichia coli, Proteus mirabilis and Enterobacter cloacae (99.2%, 96.3% and 95.2% of isolates susceptible, respectively) and cefoxitin against Klebsiella oxytoca and Klebsiella pneumoniae (98.6% and 95.6% of isolates susceptible). Carbapenems had excellent activity (> or =99.5% of all isolates). ESBL-production was confirmed with the ESBL-Etest and disk diffusion test in 1.3% of Escherichia coli isolates, 18.4% of Klebsiella pneumoniae, 12.6% of Klebsiella oxytoca and 5.3% of Proteus mirabilis isolates.

Aztreonam↗
PubMed1997

Transfer of antibiotic resistance and production of extended-spectrum beta-lactamase (ESBL) in nosocomial Klebsiella pneumoniae strains from two hospitals in Czech Republic.

Six Klebsiella pneumoniae strains were collected from two hospitals in Ostrava, Czech republic. Four strains (Nos. 209, 217, 218, 222) were isolated from sputa of critically ill patients from Municipal Hospital Vítkovice-Ostrava. They were resistant to cephalothin, cefotaxime, and ceftazidime (MIC > 100 mg x l-1). Strain No. 218 was intermediately resistant also to ofloxacin and aztreonam (MIC = 12.5 mg x l-1), strain No. 222 was resistant to aztreonam (MIC = 50 mg x l-1). Determinants of resistance to cephalothin, cefotaxime, aztreonam and ceftazidime were transferred to recipient strains of P. mirabilis P-38 rif+ and E. coli K-12 No. 3110 rif+ by all four strains. Synergy between clavulanate-cefotaxime, clavulanate-ceftazidime and clavulanate-aztreonam indicated production of ESBLs by these strains. Two strains, No. 214 and 224, from patients of the ICU in the University Hospital were resistant to cephalothin, cefotaxime and ceftazidime (MIC > 100 mg x l-1). Strain No. 214 was intermediately resistant to aztreonam and ofloxacin (MIC = 12.5 mg x l-1) and strain No. 224 was highly resistant to aztreonam (MIC = 50 mg x l-1). Synergy between clavulanate and cefotaxime as well as between clavulanate and aztreonam, but not between clavulanate and ceftazidime corresponds with non-transferable ceftazidime resistance in strains No. 214 and 224 and indicates different types of ESBL in strains from each of two hospitals.

Aztreonam↗
PubMed2005

Multidrug resistance in Gram-negative bacteria that produce extended-spectrum beta-lactamases (ESBLs).

In 1983, just two years after the introduction of the oxymino-beta-lactams to the market , the first extended-spectrum beta-lactamases were isolated in Germany from Klebsiella pneumoniae strains. Since then several outbreaks have been reported in many European countries and the USA, and nowadays in several places worldwide the problem seems to reach endemic dimensions, with rates exceeding 50% in some countries, such as Portugal and Turkey. On the other hand not only K. pneumoniae but also Escherichia coli strains, with Enterobacter aerogenes predominating among the other enterobacteriaceal species, are increasingly reported as ESBL producers. In this review types, molecular characteristics, detection methods, epidemiology as well as interventions for therapy and antibiotic strategies to prevent and control infections caused by ESBL-producing microorganisms, are presented and discussed.

Anti-Bacterial Agents↗
PubMed2000

[Extended-spectrum beta-lactamase (ESBL) produced by Escherichia coli and Klebsiella pneumoniae isolated from Teikyo University Hospital--the second report].

We studied the high-level resistant to cefotaxime (CTX, MIC > or = 512 micrograms/ml) clinical isolates of Escherichia coli and Klebsiella pneumoniae in Teikyo University Hospital. The CTX-resistance could be transferred to E. coli K-12 chi 1037 or ML4903 strains from 30 of the 33 isolates by conjugation at a frequency of 10(-4). When the hydrolysis rate of benzylpenicillin was 100%, the beta-lactamases which were extracted from the transconjugants hydrolyzed CTX, CAZ and AZT at the rate of 38-95%, 0-8.6% and 0-56%, respectively. These results demonstrate that these enzymes should be categorized into ESBL. The nucleotide sequence of CTX-resistant gene was identified to that of the CTX-M2 gene which was first described in Argentina. It was found to have 99.9% homology to Toho-1 gene in Japan and 99.6% homology to CMY-2 gene. Using a PCR methods for the detection of one of ESBL gene such as CTX-M2, Toho-1 or CMY-2, the DNA was amplified from all strains (11 isolates of E. coli and 21 isolates of K. pneumoniae).

Cefotaxime↗
PubMed2003

Utilization of extended-spectrum beta-lactamase (ESBL) detection systems in microbiology laboratories: survey of Connecticut hospitals from 1998-2002.

There has been recent concern raised over the detection, prevalence, and clinical implications of infection with Escherichia coli and Klebsiella spp. which produce extended-spectrum beta-lactamases (ESBLs). These enzymes hydrolyze beta-lactams including the cephalosporins (i.e., ceftazidime, ceftriaxone, cefotaxime), thus frequently leading to treatment failures. Standard in vitro testing may report these isolates as susceptible when in fact they are resistant in vivo. As a result of this phenomenon, additional testing for suspected isolates is recommended nationally. We surveyed 28 Connecticut hospitals from 1998-2002 to determine if these institutions utilized screening and confirmation methods for suspected isolates. The number of hospitals which have implemented ESBL detection systems doubled from 11 to 22 over the study period. Currently, 15 of the 22 laboratories conduct both screening and confirmatory testing. This expanded testing will be of great assistance to clinicians in optimizing the clinical care of patients with Gramnegative infections.

Aztreonam↗
PubMed2003

[Detection of novel nucleotide substitutions resulting amino acid substitutions in TEM type beta-lactamase gene isolated from a clinically isolated extended spectrum beta-lactamases (ESBLs) productive Escherichia coli].

We screened Escherichia coli (E. coli) from specimens submitted to the Showa University hospital clinical laboratory that showed an advanced resistance to third generation cephems (Cefotaxime or Ceftazidime), as candidate extended spectrum beta-lactamases(ESBLs) producing strains. Among the candidates, two strains showed the characteristics of class A ESBLs in their susceptibility to Cefmetazole, a second generation cephem, and their resistance was inhibited by the addition of clavulanic acid. Further, we detected the TEM-type gene in one of the two E. coli strains. By determining the nucleotide sequence of the whole coding region of the TEM gene, two nucleotide substitutions with amino acid substitutions 82Val-->Ile, and 182Ala-->Val were identified.

Adult↗
PubMed2004

[Incidence of extended spectrum beta-lactamase (ESBL)-producing Enterobacteria in the area of Caltagirone (Sicily)].

The authors report the incidence of extended spectrum b-lactamases (ESBL)- producing strains in 1,602 enterobacteria consecutively isolated, from April 2002 to December 2003, in Caltagirone (CT) Hospital, and their in vitro susceptibility to several antimicrobial agents. The incidence of ESBL-producing Enterobacteria was equal to 1.5%, mainly among Escherichia coli, Klebsiella spp and Citrobacter koseri, isolated by emergency and medicine wards. In vitro, the enterobacteria were fully susceptible to carbapenems and highly susceptible to third-generation cephalosporin, aztreonam, piperacillin, amikacin, and ciprofloxacin.

Bacterial Proteins↗
PubMedDate not supplied

The rising incidence of antibiotic-resistant ESBL-producing E. coli.

Extended-spectrum beta-lactamase (ESBL) Escherichia coil produces enzymes that enable it to develop resistance to antibiotics. Its prevalence in the UK is increasing, and the Health Protection Agency is investigating whether it has contributed to a number of deaths. While many people may be asymptomatic carriers of ESBL-producing E. coli it can be extremely harmful to the very young, the very old and those with compromised health and other risk factors. Excellent infection control is necessary to prevent its spread in health care facilities, while restrictions on the use of antibiotics may be necessary to prevent its increasing resistance.

Cross Infection↗
PubMed2005

[Susceptibility of ESBL-producing Escherichia coli and Klebsiella pneumoniae to various antibacterial agents].

With the increasing use of broad-spectrum antibacterial agents, the increase in various drug-resistant bacterial strains has become a concern in recent years. Especially, the development of drug-resistance by Enterobacteriaceae which significantly affects therapy and prognosis in sepsis and lower gastrointestinal post-operative infection. The extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae strains isolated in the Surveillance Program of Bacterial Resistance in Kinki region of Japan (SBRK) were supplied between November 2000 and March 2003. The susceptibilities of them to 16 kinds of antimicrobial agents were investigated. The number of them was 48 strains consisting of 36 Escherichia coli strains (75%) and 12 Klebsiella pneumoniae strains (25%). Our focus was on carbapenem and the new quinolone antibacterial agents. Among the 16 major antibacterial agents examined, carbapenem had low MIC50/90 values. Meropenem had a MIC50/90 of 0.03/0.06microg/ml, followed by biapenem (0.12/0.5), imipenem (0.25/0.5) and panipenem (0.25/0.5). Among cephem, ceftazidime had the lowest MIC50 at 4 microg/ml. All four of the cephem agents had a MIC90 of greater than 128microg/ml. Among beta-lactamase inhibitors, tazobactam/piperacillin had the lowest MIC50 at 4 microg/ml, and sulbactam/cefoperazone had a MIC50 of 32 microg/ml. Among the new quinolones, prulifloxacin had the lowest MIC50 at 1 microg/ml, and the other drugs had a MIC50 of 2 microg/ml. The resistance rate of ciprofloxacin was 61.1% in E. coli and 16.6% in K. pneumoniae. Comparison of drug-sensitivity to cephem by ESBL-gene type revealed that cefpirome, cefepime and cefozopran had higher MIC50/90 values against the CTX-M group with a MIC50 of greater than 128microg/ml. Ceftazidime and aztreonam had higher MIC50/90 values against the TEM/SHV group than those against the CTX-M group. In the CTX-M group, the MIC50 was 4 and 16microg/ml, respectively.

Anti-Bacterial Agents↗
PubMed1997

beta-Lactamase bioassay: a simplified method to determine extended-spectrum beta-lactamases (ESBL) in enterobacteria.

With the simultaneous use of an isoelectric focusing gel (IEF) and a nitrocefin/cefotaxime bioassay, it is possible to identify the Extended-Spectrum beta-lactamases (ESBL) with precision. A mixture of soft agar and susceptible bacterial cells are layered over the gel following overnight incubation and areas of cell growth are detected where the antibiotic has been hydrolyzed by specific enzymes. This innovative method improves sensitivity and specificity for the identification of ESBLs in those enterobacteria strains producing more than one beta-lactamase and are resistant to third generation cephalosporines.

Bacterial Proteins↗
PubMed1997

Cefuroxime resistance in Klebsiella pneumoniae. Susceptibility to cefotaxime and ceftazidime despite production of ESBLs.

The production of beta-lactamases, the outer membrane protein (OMP) patterns, some clinical impacts and the prevalence of resistance among cefuroxime-resistant Danish clinical isolates of Klebsiella pneumoniae were investigated. Fifteen resistant and five susceptible strains were collected from 14 patients during 1991-1994. Isolates from five patients produced extended-spectrum beta-lactamases (ESBLs). Cefuroxime resistance was accompanied by a 10-fold elevation of ciprofloxacin minimal inhibitory concentration (MIC), and for some isolates by an alteration of the OMP pattern. The relationship between alterations of the OMP patterns and cross-resistance to ciprofloxacin and the other antibiotics tested was not universal. Ten of the cefuroxime-resistant strains had elevated MICs of cefotaxime or ceftazidime, but the MICs were still below the breakpoint for susceptibility. The MICs of imipenem were not affected. Nosocomial infection or long-term colonization with resistant strains may be of importance since five patients were not treated with cefuroxime prior to isolation of the resistant strain, and all patients had either serious diseases or stayed at the hospital for a long period of time. The prevalence of cefuroxime and ciprofloxacin resistance among clinical isolates from Copenhagen county during 1990-1995 was 8.3% and 7.5%, respectively, but higher for urinary tract specimens. A greater consumption of cefuroxime as compared to cefotaxime and ceftazidime in this study, as seen generally in Denmark, indicated that ESBLs produced by the investigated strains of K. pneumoniae may be selected with cefuroxime.

Bacterial Outer Membrane Proteins↗
PubMed2003

Sustained activity and spectrum of selected extended-spectrum beta-lactams (carbapenems and cefepime) against Enterobacter spp. and ESBL-producing Klebsiella spp.: report from the SENTRY antimicrobial surveillance program (USA, 1997-2000).

Enterobacter spp. and Klebsiella spp. are important clinical pathogens that frequently exhibit resistance to third-generation cephalosporins. In Enterobacter spp. strains, resistance is usually due to derepression of the Amp C locus, whereas plasmid-encoded extended-spectrum beta-lactamases (ESBLs) are primarily responsible for resistance in Klebsiella spp. Here we report the results from the SENTRY Antimicrobial Surveillance Program concerning the rates and trends of resistance to extended-spectrum beta-lactams and other antimicrobial agents in Enterobacter spp. and Klebsiella spp. isolated between 1997 and 2000 in participating hospitals in the United States. Among Enterobacter spp., resistance (MIC>or=32 mg/l) to aztreonam, ceftazidime and ceftriaxone ranged from 12.3 to 21.2% over the 4 years, whereas resistance in Klebsiella (MIC>or=2 mg/l) ranged from 5.9 to 6.8%. There was no trend toward increased resistance to these beta-lactam agents over the monitored period. Carbapenems (imipenem, meropenem) and cefepime had excellent activity against both ceftazidime-susceptible and -resistant Enterobacter spp. and Klebsiella spp. (>99% susceptible), although the minimum inhibitory concentration values of cefepime were higher in ceftazidime-resistant isolates compared with ceftazidime-susceptible isolates. Co-resistance to other antimicrobial agents was common in both tested genus groups.

Carbapenems↗
PubMed2004

Extended-spectrum beta-lactamase (ESBL) CTX-M-15-producing Escherichia coli and Klebsiella pneumoniae in Sofia, Bulgaria.

During a survey of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in Bulgaria in 2001-2002, three isolates from Sofia (two Escherichia coli, one Klebsiella pneumoniae) showed cefotaxime MICs that were decreased in the presence of clavulanate and were 2-8-fold higher than those of ceftazidime. Resistance was transferred to a sensitive recipient strain of E. coli. Both wild-type and transconjugant strains produced a cefotaxime-hydrolysing beta-lactamase of pI 8.8. Sequencing of the PCR product obtained with oligonucleotide primers binding outside the coding region identified this beta-lactamase as CTX-M-15. To our knowledge, this is the first report of CTX-M-15 in Bulgaria.

Anti-Bacterial Agents↗
PubMed2004

Extended-Spectrum beta-lactamase (ESBL) producing Enterobacter aerogenes phenotypically misidentified as Klebsiella pneumoniae or K. terrigena.

BACKGROUND: Enterobacter aerogenes and Klebsiella pneumoniae are common isolates in clinical microbiology and important as producers of extended spectrum beta-lactamases (ESBL). The discrimination between both species, which is routinely based on biochemical characteristics, is generally accepted to be straightforward. Here we report that genotypically unrelated strains of E. aerogenes can be misidentified as K. pneumoniae by routine laboratories using standard biochemical identification and using identification automates. RESULTS: Ten clinical isolates, identified as K. pneumoniae or K. terrigena with the routinely used biochemical tests and with API-20E, were identified as E. aerogenes by tDNA-PCR - an identification that was confirmed by 16S rRNA gene sequencing for five of these isolates. Misidentification also occurred when using the automated identification systems Vitek 2 and Phoenix, and was due to delayed positivity for ornithine decarboxylase and motility. Subculture and prolonged incubation resulted in positive results for ornithine decarboxylase and for motility. It could be shown by RAPD-analysis that the E. aerogenes strains belonged to different genotypes. CONCLUSIONS: Clinical E. aerogenes isolates can be easily misidentified as Klebsiella due to delayed positivity for ornithine decarboxylase and motility. The phenomenon may be widespread, since it was shown to occur among genotypically unrelated strains from different hospitals and different isolation dates. A useful clue for correct identification is the presence of an inducible beta-lactamase, which is highly unusual for K. pneumoniae. In several instances, the use of genotypic techniques like tDNA-PCR may circumvent problems of phenotypic identification.

Bacterial Typing Techniques↗
PubMed2000

[Drug-resistant bacteria of current topics and their resistance mechanisms--ESBL].

Under the influence of antimicrobial agents, bacteria that primarily produce TEM-Type or SHV-Type beta-lactamases developed point mutations in structural genes which served to extend the substrate specificity of the enzymes. Undoubtedly, CTX-resistance rates increased in E. coli and K. pneumoniae in the recent years. It is strongly suggested that a survey of ESBL-producing clinical isolates of E. coli and K. pneumoniae should also be required for rigorous detection methods.

Escherichia coli↗
PubMed2003

The molecular characterisation of the extended spectrum beta-lactamase (ESBL) producing strain of Salmonella enterica serovar Mbandaka isolated in Poland.

The molecular attributes of the first ESBL producing isolate 267/99 of Salmonella enterica serovar Mbandaka isolated in 1999 in Poland were characterised. Tested strain produced CTX-M-3 and TEM-1 beta-lactamases, encoded by genes localised on the about 80 kb self-transferable plasmid, harbouring the 2 kb class 1 integron carrying aadA2 gene.

Anti-Bacterial Agents↗
PubMed2006

[Sanfetrinem, the member of trinems--in vitro activity against Klebsiella pneumoniae producing ESBL].

Sanfetrinem is the first member of tricyclic beta-lactams (trinems) which can be administered orally as a hexatil ester. His chemical structure is related to carbapenems. High stability to many beta-lactamases and human renal dehydropeptydase were described. The investigation was performed on 43 strains of Klebsiella pneumoniae producing ESBL isolated from hospitalized patients. The MICs of sanfetrinem and imipenem were determined by E-test. Additionaly, susceptibility to antibiotics was tested by disc diffusion method. Klebsiella pneumoniae ATCC 700603, Escherichia coli ATCC 25922 and Escherichia coli ATCC 35218 were used as a control strains. MIC50 and MIC90 of sanfetrinem and imipenem amounted respectively 0,38/3 mg/1 and 0,19/0,25 mg/l. Range of MIC value was from 0,064 mg/l to 4 mg/l for sanfetrinem, and from 0,094 mg/l to 0,38 mg/l for imipenem. Additionaly, geometric and aritmetic means were calculated to both antibiotics. All results of study were compared using correlation factor and "Student" t-test. None of these 43 Klebsiella pneumoniae strains was resistant to imipenem and cefepime. Majority of isolates demonstrated susceptibility to ciprofloxacin and cefoxitin--90,7% and 74,4% respectively All strains were resistant to gentamicin, amikacin and trimethoprim/sulfamethoxazole.

Anti-Bacterial Agents↗