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PubMed2001

Clinical significance and impact on mortality of extended-spectrum beta lactamase-producing Enterobacteriaceae isolates in nosocomial bacteremia.

During an 8-month period, 55 episodes of nosocomial bacteremia caused by Enterobacteriaceae species were identified in a tertiary medical center, of which 26 (47%) were caused by extended-spectrum beta lactamase (ESBL)-producing organisms. ESBL production was associated with resistance to aminoglycosides, fluoroquinolones, tetracycline and co-trimoxazole compared with non-ESBL-producing organisms (p < 0.01). By multivariate analysis, infection with ESBL-producing organisms was associated with previous antibiotic therapy and central venous catheter insertion and mortality was associated with heart failure, malignancy and a prolonged hospital stay. Nineteen (73%) patients infected with ESBL-producing organisms received adequate empirical antibiotic therapy and all 26 received adequate definitive therapy. The in-hospital mortality rate did not differ between patients infected with ESBL producers and those infected by non-ESBL-producing Enterobacteriaceae species [13/26 (50%) and 11/29 (38%), respectively] (p > 0.5).

Adult↗

PubMed2006

Accelerated detection of extended-spectrum beta-lactamases in clinical isolates of Enterobacteriaceae.

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.

Anti-Bacterial Agents↗

PubMed2000

Characterization of an outbreak due to extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in a pediatric intensive care unit transplant population.

Limited information exists regarding Klebsiella pneumoniae's production of an extended-spectrum beta-lactamase (KP-ESBL) in pediatric patients, particularly solid-organ transplant recipients. This study characterized the microbiological, epidemiological, and clinical features of a KP-ESBL outbreak in children receiving a liver transplant, an intestinal transplant, or both. All children found to have microbiologically confirmed K. pneumoniae during a 21-month period were reviewed. ESBL production was defined by double-disk diffusion, and 6 distinct pulsed-field gel electrophoresis patterns were identified. Fifty-six percent of the transplant patients we studied developed KP-ESBL, representing 87% of all microbiologically confirmed cases at our institution. As compared with 16 control transplant patients who were negative for KP-ESBL, the 20 transplant patients who acquired KP-ESBL were younger (aged < or = 5 years; 80.0% vs. 43.8%, P = .038) and experienced placement of > or = 3 central venous catheters before recovery of the first K. pneumoniae isolate (73.7% vs. 18.8%, P = .002). This study suggests that children who receive liver or intestinal transplants are at high risk for KP-ESBL acquisition.

Adolescent↗

PubMed2001

Extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae: risk factors for infection and impact of resistance on outcomes.

The prevalence of antibiotic resistance among extended-spectrum beta-lactamase (ESBL)--producing Escherichia coli and Klebsiella pneumoniae has increased markedly in recent years. Thirty-three patients with infection due to ESBL-producing E. coli or K. pneumoniae (case patients) were compared with 66 matched controls. Total prior antibiotic use was the only independent risk factor for ESBL-producing E. coli or K. pneumoniae infection (odds ratio, 1.10; 95% confidence interval, 1.03--1.18; P=.006). Case patients were treated with an effective antibiotic a median of 72 hours after infection was suspected, compared with a median of 11.5 hours after infection was suspected for controls (P<.001). ESBL-producing E. coli or K. pneumoniae infection was associated with a significantly longer duration of hospital stay and greater hospital charges (P=.01 and P<.001, respectively). Finally, many ESBL-producing E. coli and K. pneumoniae isolates were closely related. ESBL-producing E. coli and K. pneumoniae infections have a significant impact on several important clinical outcomes, and efforts to control outbreaks of infection with ESBL-producing E. coli and K. pneumoniae should emphasize judicious use of all antibiotics as well as barrier precautions to reduce spread.

Adolescent↗

PubMed2004

Reduced use of third-generation cephalosporins decreases the acquisition of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae.

OBJECTIVES: To identify risk factors for the respiratory acquisition of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae among patients admitted to a neurosurgical intensive care unit (NSICU) and to modify them without changing general infection control measures. DESIGN: Nested case-control and intervention study. SETTING: A 1,200-bed, tertiary-care teaching hospital with a 17-bed NSICU. METHODS: Sputa of all patients admitted to the NSICU were cultured weekly during the study. From October 2002 through February 2003, 29 case-patients from whose sputum ESBL-producing K. pneumoniae was isolated were detected and 59 controls-patients were randomly selected among patients without any positive isolate of ESBL-producing K. pneumoniae. After analyzing the risk factors, we intervened to modify them and compared the acquisition rate of ESBL-producing K. pneumoniae before (October 2002 to February 2003) and after (April to August 2003) the intervention. RESULTS: Multivariate analysis showed that prior exposure to third-generation cephalosporins (TGCs) (OR, 6.0; CI95, 1.9 to 18.6; P = .002) was an independent risk factor of ESBL-producing K. pneumoniae acquisition. The neurosurgical team was notified of the result, and the infectious diseases specialist visited the NSICU three times a week to regulate TGC use during the intervention period. Patients admitted before the intervention were older than patients admitted after. The respiratory acquisition of ESBL-producing K. pneumoniae per 1,000 patient-days (13.5 [CI95, 8.9 to 18.1] vs 2.7 [CI95, 0.9 to 4.6]) and the antimicrobial use density of TGCs (38.2 +/- 5.0 vs 17.3 +/- 2.6; P < .001) decreased significantly after the intervention. CONCLUSION: Prior exposure to TGCs was an independent risk factor for the respiratory acquisition of ESBL-producing K. pneumoniae, and less use of TGCs was associated with a decrease in acquisition.

Adolescent↗

PubMed2006

Limiting the emergence of extended-spectrum Beta-lactamase-producing enterobacteriaceae: influence of patient population characteristics on the response to antimicrobial formulary interventions.

BACKGROUND: Effective methods to control the emergence of extended-spectrum beta -lactamase-producing Escherichia coli and Klebsiella species (ESBL-EK) remain unclear. Variations in the patient populations at different hospitals may influence the effect of antimicrobial formulary interventions. METHODS: To examine variations across hospitals in the response to antimicrobial interventions (ie, restriction of ceftazidime and ceftriaxone) designed to curb the spread of ESBL-EK, we conducted a 5-year quasi-experimental study. This study was conducted at 2 hospitals within the same health system: Hospital A is a 625-bed academic medical center, and Hospital B is a 344-bed urban community hospital. All adult patients with a healthcare-acquired clinical culture of ESBL-EK from July 1, 1997 through December 31, 2002 were included. RESULTS: After the interventions, the use of ceftriaxone decreased by 86% at Hospital A and by 95% at Hospital B, whereas the use of ceftazidime decreased by 95% at Hospital A and by 97% at Hospital B. The prevalence of ESBL-EK at Hospital A decreased by 45% (P < .001), compared with a 22% decrease at Hospital B (P = .36). The following variables were significantly more common among ESBL-EK-infected patients at Hospital B: residence in a long-term care facility (adjusted odds ratio, 3.77 [95% confidence interval, 1.70-8.37]), advanced age (adjusted odds ratio, 1.04 [95% confidence interval, 1.01-1.06]), and presence of a decubitus ulcer (adjusted odds ratio, 4.13 [95% confidence interval, 1.97-8.65]). CONCLUSIONS: The effect of antimicrobial formulary interventions intended to curb emergence of ESBL-EK may differ substantially across institutions, perhaps as a result of differences in patient populations. Variability in the epidemiological profiles of ESBL-EK isolates at different hospitals must be considered when designing interventions to respond to these pathogens.

Adolescent↗

PubMed2006

Bacteremia due to extended-spectrum beta -lactamase-producing Escherichia coli in the CTX-M era: a new clinical challenge.

BACKGROUND: Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, particularly those producing CTX-M types of ESBL, are emerging pathogens. Bacteremia caused by these organisms represents a clinical challenge, because the organisms are frequently resistant to the antimicrobials recommended for treatment of patients with suspected E. coli sepsis. METHODS: A cohort study was performed that included all episodes of bloodstream infection due to ESBL-producing E. coli during the period from January 2001 through March 2005. Data on predisposing factors, clinical presentation, and outcome were collected. ESBLs were characterized using isoelectric focusing, polymerase chain reaction, and sequencing. RESULTS: Forty-three episodes (8.8% of cases of bacteremia due to E. coli) were included; 70% of the isolates produced a CTX-M type of ESBL. The most frequent origins of infection were the urinary (46%) and biliary tracts (21%). Acquisition was nosocomial in 21 cases (49%), health care associated in 14 cases (32%), and strictly community acquired in 8 cases (19%). Thirty-eight percent and 25% of patients had obstructive diseases of the urinary and biliary tracts, respectively, and 38% had recently received antimicrobials. Nine patients (21%) died. Compared with beta-lactam/beta-lactamase-inhibitor and carbapenem-based regimens, empirical therapy with cephalosporins or fluoroquinolones was associated with a higher mortality rate (9% vs. 35%; P=.05) and needed to be changed more frequently (24% vs. 78%; P=.001). CONCLUSIONS: ESBL-producing E. coli is a significant cause of bloodstream infection in hospitalized and nonhospitalized patients in the context of the emergence of CTX-M enzymes. Empirical treatment of sepsis potentially caused by E. coli may need to be reconsidered in areas where such ESBL-producing isolates are present.

Adult↗

PubMed2003

Evaluation of Oxoid combination discs for detection of extended-spectrum beta-lactamases.

OBJECTIVES: We evaluated the reliability of cefpirome/clavulanate (CD04) compared with ceftazidime/clavulanate (CD02) and cefotaxime/clavulanate (CD03) Oxoid combination discs for the detection of extended-spectrum beta-lactamases (ESBL) in several Enterobacteriaceae isolates, including Enterobacter spp. METHODS: Overall, a total of 105 ESBL-positive [positive double-disc synergy test (DDST)] and 94 ESBL-negative (negative DDST) Gram-negative isolates were evaluated. Ninety-eight isolates were confirmed as ESBL-positive on the basis of the sequence alignments of the blaTEM and/or blaSHV gene amplification products, which matched with previously identified ESBLs. The phenotypic detection of ESBLs was performed by the three combination discs according to the NCCLS and BSAC methods. The CD04 disc was evaluated with the manufacturer's recommended zone size difference breakpoint of > or =4 mm. RESULTS: In Escherichia coli and Klebsiella spp., the sensitivities (%)/specificities (%) of CD02, CD03 and CD04 discs, and the combination of CD02 or CD04 discs, were, respectively, 88/92, 90/92, 95/84 and 100/82, while the corresponding figures were 94/100, 4/100, 94/100 and 100/100 in Enterobacter aerogenes. NCCLS and BSAC methods yielded concordant results in 99% of the isolates. CONCLUSIONS: CD04 and CD02 discs were the best combination for detection of ESBLs in our collection of Enterobacteriaceae isolates, including E. aerogenes.

Cephalosporins↗

PubMed2006

Spread of bla(CTX-M-type) and bla(PER-2) beta-lactamase genes in clinical isolates from Bolivian hospitals.

OBJECTIVES: To assess the prevalence and types of genes encoding extended-spectrum beta-lactamases (ESBLs) in clinical isolates of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. from Bolivia. METHODS: A total of 642 clinical isolates were collected consecutively during a 4 month period (September to December 2004). Resistance or reduced susceptibility to cefotaxime and/or ceftazidime and/or aztreonam was assessed using double disc synergy tests using clavulanic acid, cefotaxime, ceftazidime and aztreonam to identify putative ESBL-producing isolates. The ESBL determinants were characterized by colony blot hybridization, PCR and DNA sequencing. RESULTS: Of the 642 isolates, 220 (34.3%) showed resistance or reduced susceptibility to cefotaxime and/or ceftazidime and/or aztreonam, and 150 (23.4%) were putative ESBL producers. A total of 106 ESBL-producing isolates contained the bla(CTX-M-2) gene, and 32 isolates had a novel allele, bla(CTX-M-43). bla(CTX-M) alleles were detected in all P. aeruginosa and Acinetobacter spp. studied. In contrast, only 12 ESBL-producing isolates had bla(PER-2), mainly Enterobacteriaceae, although it was also found in a strain of P. aeruginosa. CONCLUSIONS: This is the first study on ESBL-producing strains in Bolivia and it reveals a high prevalence of bla(CTX-M) genes. The PER-2 enzyme was less prevalent, but its gene was detected in several species, including P. aeruginosa, which is consistent with horizontal transfer.

Acinetobacter↗

PubMed2026

Genomic epidemiology of extended-spectrum beta-lactamase-producing Escherichia coli across humans, poultry and wastewater sectors in Douala, Cameroon.

BACKGROUND: The global health threat of antimicrobial resistance involves the human, animal and environmental sectors. Data from Cameroon are scarce. OBJECTIVES: This study aimed to define extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-Ec) rates and associated risk factors across the three sectors in Douala, Cameroon, and to define molecular characteristics of isolates. METHODS: From June 2022 to May 2023, we collected blood cultures from hospitalized patients, rectal swabs from healthy pregnant women, caeca from broiler chickens and environmental wastewater. Samples were screened for ESBL-Ec using CHROMAgar™ ESBL and cefotaxime-supplemented Tryptone Bile X-glucuronide agar. Antimicrobial susceptibility testing was performed by disk diffusion following EUCAST guidelines. Whole-genome sequencing was carried out using Illumina technology. RESULTS: Of 628 samples, 374 yielded ESBL-Ec. Prevalence was 54.6% (131/240) in pregnant women, 70.4% (169/240) in chickens and 93.1% (67/72) in wastewater. The proportion of ESBL-Ec among E. coli-positive-blood cultures was 9.2% (7/76). Multi-family household living was independently associated with ESBL-Ec carriage among pregnant women (adjusted odds ratio = 1.7, 95% CI 1.0-3.1, P = 0.03). High co-resistance (>70%) was observed for tetracycline, ciprofloxacin and trimethoprim/sulfamethoxazole. Sequencing of 32 isolates revealed 45 distinct resistance genes, including blaCTX-M-15 (n = 13, 40.6%), blaCTX-M-55 (n = 11, 34.4%) and last-resort antibiotic resistance genes mcr-1 and bla OXA-181. High-risk sequence types included ST131 (pregnant women) and ST10 (chickens). Notably, ST48 was shared between pregnant women and chickens, and ST155 between pregnant women and wastewater. CONCLUSION: Cross-sectoral ESBL-Ec in Douala exhibits high genomic diversity and alarming resistance. The occurrence of last-resort genes requires immediate One Health surveillance and coordinated interventions.

Journal Article↗

PubMed2005

Dissemination of transferable CTX-M-type extended-spectrum beta-lactamase-producing Escherichia coli in Korea.

AIMS: Among 365 Escherichia coli isolated in 2003, 31 cefotaxime-resistant isolates were obtained from clinical specimens taken from adults hospitalized in Busan, Korea. Six extended-spectrum beta-lactamase (ESBL)-producing isolates were investigated further to determine the mechanism of resistance. METHODS AND RESULTS: These isolates were analysed by antibiotic susceptibility testing, pI determination, plasmid profiles, transconjugation test, PCR-restriction fragment length polymorphism (RFLP), enterobacterial repetitive consensus (ERIC)-PCR and DNA sequencing. All six of these isolates were found to contain the CTX-M-type ESBL genes. Five clinical isolates and their transconjugants produced CTX-M-3. One clinical isolate (K17391) and its transconjugant (trcK17391) produced CTX-M-15. Five clinical isolates also produced another TEM-1. One clinical isolate (K12776) also contained another TEM-52. CTX-M-3 ESBL gene was responsible for the resistance to piperacillin, cephalothin, cefotaxime, cefepime and aztreonam. CTX-M-15 or TEM-52 was especially responsible for the resistance to ceftazidime. CONCLUSIONS: These results appear to represent the in vivo evolution of CTX-M-type beta-lactamase genes (bla(CTX-M-3) --> bla(CTX-M-15)) under the selective pressure of antimicrobial therapy (especially ceftazidime). PCR-RFLP is a reliable method to discriminate CTX-M-15 gene from CTX-M-3 gene. ERIC-PCR analysis revealed that dissemination of CTX-M-3 was not due to a clonal outbreak of a resistant strain but to the intra-species spread of resistance to piperacillin, cephalothin, cefotaxime, cefepime and aztreonam in Korea. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report of the occurrence of CTX-M-1 cluster ESBLs in Korea. A more comprehensive survey of these ESBL types from Korea is urgently needed because of the in vivo evolution of CTX-M-15 from CTX-M-3. The emergence of these CTX-M-type ESBLs suggests that diagnostic laboratories should screen for ESBLs with ceftazidime as well as cefotaxime; they should still perform clavulanate synergy tests on resistant isolates.

Adult↗

PubMed2004

Epidemiology and clinical features of bloodstream infections caused by AmpC-type-beta-lactamase-producing Klebsiella pneumoniae.

Cases of bacteremia caused by AmpC-type-beta-lactamase-producing Klebsiella pneumoniae isolates were retrospectively studied to determine the epidemiologic features and clinical outcomes of bloodstream infections. Among 389 blood isolates recovered from 1998 to 2002, 65 isolates (16.7%) were found to be extended-spectrum beta-lactamase (ESBL) or AmpC beta-lactamase producers. The beta-lactamases from 61 of the 65 isolates were characterized; 28 of 61 isolates produced AmpC-type enzymes (14 isolates each produced DHA-1 and CMY-1-like enzymes), 32 isolates produced TEM or SHV-related ESBLs, and 1 isolate produced a CTX-M-14-like enzyme. To compare the clinical features and outcomes of bloodstream infections caused by AmpC producers with those caused by TEM- or SHV-related ESBL producers, 27 patients infected with isolates producing AmpC-type enzymes (AmpC group) and 25 patients infected with isolates producing TEM- or SHV-related enzymes (ESBL group) were analyzed. There was no significant difference between the AmpC and the ESBL groups in terms of risk factors. When the initial response was assessed at 72 h after antimicrobial therapy, the treatment failure rate for the AmpC group was 51.9% (14 of 27 patients) and the 7- and 30-day mortality rates were 14.8 and 29.6%, respectively, which were similar to those for the ESBL group. When the mortality rate for the patients who received extended-spectrum cephalosporins as definitive treatment was assessed, all four patients in the DHA-1 group and one of three patients in the CMY-1-like group died. In summary, the prevalence of AmpC enzyme-producing K. pneumoniae was high at the Seoul National University Hospital, and the clinical features and outcomes for the patients infected with AmpC-producing organisms were similar to those for the patients infected with TEM- or SHV-related ESBL producers.

Bacteremia↗

PubMed2004

Bloodstream infections due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae: risk factors for mortality and treatment outcome, with special emphasis on antimicrobial therapy.

This study was conducted to evaluate risk factors for mortality and treatment outcome of bloodstream infections due to extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EK). ESBL production in stored K. pneumoniae and E. coli blood isolates from Jan 1998 to Dec 2002 was phenotypically determined according to NCCLS guidelines and/or the double-disk synergy test. A total of 133 patients with ESBL-EK bacteremia, including 66 patients with ESBL-producing K. pneumoniae and 67 with ESBL-producing E. coli, were enrolled. The overall 30-day mortality rate was 25.6% (34 of 133). Independent risk factors for mortality were severe sepsis, peritonitis, neutropenia, increasing Acute Physiology and Chronic Health Evaluation II score, and administration of broad-spectrum cephalosporin as definitive antimicrobial therapy (P < 0.05 for each of these risk factors). In 117 of the 133 patients, excluding 16 patients who died within 3 days after blood culture sample acquisition, the 30-day mortality rates according to definitive antibiotics were as follows: carbapenem, 12.9% (8 of 62); ciprofloxacin, 10.3% (3 of 29); and others, such as cephalosporin or an aminoglycoside, 26.9% (7 of 26). When patients who received appropriate definitive antibiotics, such as carbapenem or ciprofloxacin, were evaluated, mortality in patients receiving inappropriate empirical antimicrobial therapy was found not to be significantly higher than mortality in those receiving appropriate empirical antimicrobial therapy (18.9 versus 15.5%; P = 0.666). Carbapenem and ciprofloxacin were the most effective antibiotics in antimicrobial therapy for ESBL-EK bacteremia. A delay in appropriate definitive antimicrobial therapy was not associated with higher mortality if antimicrobial therapy was adjusted appropriately according to the susceptibility results. Our data suggest that more prudent use of carbapenem as empirical antibiotic may be reasonable.

APACHE↗

PubMed1998

Can results obtained with commercially available MicroScan microdilution panels serve as an indicator of beta-lactamase production among escherichia coli and Klebsiella isolates with hidden resistance to expanded-spectrum cephalosporins and aztreonam?

Among clinical isolates of Escherichia coli, Klebsiella pneumoniae, and Klebsiella oxytoca, there is an ever-increasing prevalence of beta-lactamases that may confer resistance to newer beta-lactam antibiotics that is not detectable by conventional procedures. Therefore, 75 isolates of these species producing well-characterized beta-lactamases were studied using two MicroScan conventional microdilution panels, Gram Negative Urine MIC 7 (NU7) and Gram Negative MIC Plus 2 (N+2), to determine if results could be utilized to provide an accurate indication of beta-lactamase production in the absence of frank resistance to expanded-spectrum cephalosporins and aztreonam. The enzymes studied included Bush groups 1 (AmpC), 2b (TEM-1, TEM-2, and SHV-1), 2be (extended spectrum beta-lactamases [ESBLs] and K1), and 2br, alone and in various combinations. In tests with E. coli and K. pneumoniae and the NU7 panel, cefpodoxime MICs of >/=2 microg/ml were obtained only for isolates producing ESBLs or AmpC beta-lactamases. Cefoxitin MICs of >16 microg/ml were obtained for all strains producing AmpC beta-lactamase and only 1 of 33 strains producing ESBLs. For the N+2 panel, ceftazidime MICs of >/=4 microg/ml correctly identified 90% of ESBL producers and 100% of AmpC producers among isolates of E. coli and K. pneumoniae. Cefotetan MICs of >/= 8 microg/ml were obtained for seven of eight producers of AmpC beta-lactamase and no ESBL producers. For tests performed with either panel and isolates of K. oxytoca, MICs of ceftazidime, cefotaxime, and ceftizoxime were elevated for strains producing ESBLs, while ceftriaxone and aztreonam MICs separated low-level K1 from high-level K1 producers within this species. These results suggest that microdilution panels can be used by clinical laboratories as an indicator of certain beta-lactamases that may produce hidden but clinically significant resistance among isolates of E. coli, K. pneumoniae, and K. oxytoca. Although it may not always be possible to differentiate between strains that produce ESBLs and those that produce AmpC, this differentiation is not critical since therapeutic options for patients infected with such organisms are similarly limited.

Aztreonam↗

PubMed2000

Detection of extended-spectrum beta-lactamases in clinical isolates of Enterobacter cloacae and Enterobacter aerogenes.

The aim of the present study was to investigate the frequency of extended-spectrum beta-lactamases (ESBLs) in a consecutive collection of clinical isolates of Enterobacter spp. The abilities of various screening methods to detect ESBLs in enterobacters were simultaneously tested. Among the 68 consecutive isolates (56 Enterobacter cloacae and 12 Enterobacter aerogenes isolates) that were analyzed for beta-lactamase content, 21 (25 and 58%, respectively) possessed transferable ESBLs with pIs of 8.2 and phenotypic characteristics of SHV-type enzymes, 8 (14.3%) of the E. cloacae isolates produced a previously nondescribed, clavulanate-susceptible ESBL that exhibited a pI of 6.9 and that conferred a ceftazidime resistance phenotype on Escherichia coli transconjugants, and 2 E. cloacae isolates produced both of these enzymes. Among the total of 31 isolates that were considered ESBL producers, the Vitek ESBL detection test was positive for 2 (6.5%) strains, and the conventional double-disk synergy test (DDST) with amoxicillin-clavulanate and with expanded-spectrum cephalosporins and aztreonam was positive for 5 (16%) strains. Modifications of the DDST consisting of closer application of the disks (at 20 instead of 30 mm), the use of cefepime, and the use of both modifications increased the sensitivity of this test to 71, 61, and 90%, respectively. Of the 37 isolates for which isoelectric focusing failed to determine ESBLs, the Vitek test was false positive for 1 isolate and the various forms of DDSTs were false-positive for 3 isolates.

Bacterial Typing Techniques↗

PubMed2001

Outcome of cephalosporin treatment for serious infections due to apparently susceptible organisms producing extended-spectrum beta-lactamases: implications for the clinical microbiology laboratory.

Although extended-spectrum beta-lactamases (ESBLs) hydrolyze cephalosporin antibiotics, some ESBL-producing organisms are not resistant to all cephalosporins when tested in vitro. Some authors have suggested that screening klebsiellae or Escherichia coli for ESBL production is not clinically necessary, and when most recently surveyed the majority of American clinical microbiology laboratories did not make efforts to detect ESBLs. We performed a prospective, multinational study of Klebsiella pneumoniae bacteremia and identified 10 patients who were treated for ESBL-producing K. pneumoniae bacteremia with cephalosporins and whose infecting organisms were not resistant in vitro to the utilized cephalosporin. In addition, we reviewed 26 similar cases of severe infections which had previously been reported. Of these 36 patients, 4 had to be excluded from analysis. Of the remaining 32 patients, 100% (4 of 4) patients experienced clinical failure when MICs of the cephalosporin used for treatment were in the intermediate range and 54% (15 of 28) experienced failure when MICs of the cephalosporin used for treatment were in the susceptible range. Thus, it is clinically important to detect ESBL production by klebsiellae or E. coli even when cephalosporin MICs are in the susceptible range (<or = 8 microg/ml) and to report ESBL-producing organisms as resistant to aztreonam and all cephalosporins (with the exception of cephamycins).

Adolescent↗

PubMed2004

Utility of NCCLS guidelines for identifying extended-spectrum beta-lactamases in non-Escherichia coli and Non-Klebsiella spp. of Enterobacteriaceae.

NCCLS screening and confirmation methods for detecting extended-spectrum beta-lactamases (ESBLs) apply only to Escherichia coli and Klebsiella spp., yet ESBLs have been found in other members of the family Enterobacteriaceae. We evaluated the effectiveness of NCCLS methods for detecting ESBLs in 690 gram-negative isolates of Enterobacteriaceae that excluded E. coli, Klebsiella pneumoniae, and Klebsiella oxytoca. Isolates were collected between January 1996 and June 1999 from 53 U.S. hospitals participating in Project ICARE (Intensive Care Antimicrobial Resistance Epidemiology). The antimicrobial susceptibility patterns of the isolates were determined by using the NCCLS broth microdilution method (BMD), and those isolates for which the MIC of ceftazidime, cefotaxime, ceftriaxone, or aztreonam was >or=2 microg/ml or the MIC of cefpodoxime was >or=8 microg/ml (positive ESBL screen test) were further tested for a clavulanic acid (CA) effect by BMD and the disk diffusion method (confirmation tests). Although 355 (51.4%) of the isolates were ESBL screen test positive, only 15 (2.2%) showed a CA effect. Since 3 of the 15 isolates were already highly resistant to the five NCCLS indicator drugs, ESBL detection would have an impact on the reporting of only 1.7% of the isolates in the study. Only 6 of the 15 isolates that showed a CA effect contained a bla(TEM), bla(SHV), bla(CTX-M), or bla(OXA) beta-lactamase gene as determined by PCR (with a corresponding isoelectric focusing pattern). Extension of the NCCLS guidelines for ESBL detection to Enterobacteriaceae other than E. coli and Klebsiella spp. does not appear to be warranted in the United States at present, since the test has poor specificity for this population and would result in changes in categorical interpretations for only 1.7% of Enterobacteriaceae tested.

Diffusion↗

PubMed2005

[Expanded-spectrum beta-lactamase-producing strains of E. coli: origin, characteristics and incidence in Southern Alicante (Spain) in the period 1999-2003].

INTRODUCTION: In the last years, we have verified the increasing emergence of bacteria, specially Escherichia coli, that produce expanded spectrum beta-lactamases (ESBL), enzymes which confer resistance to all cephalosporins (except cephamycins) and aztreonam. These bacteria are frequently resistant also to non-beta-lactam antibiotics, a fact which poses an important clinical problem. METHODS: Descriptive study of ESBL-producing strains of E. coli isolated in all kind of specimens in two hospitals of Southern Alicante (Spain), throughout a period of 57 months (January 1999 to September 2003), paying a close attention to their origin (outpatients or admitted patients), co-resistance to non beta-lactam antibiotics and evolution of their incidence. RESULTS: Respectively, 3% and 2.25% of E. coli strains isolated in each hospital produce ESBL (3.83% and 2.85% of strains from admitted and 2.74% and 2.1% from outpatients). 30.73% and 24.58% of strains ESBL were isolated in admitted patients. We found in both hospitals much higher percentages of co-resistance to ciprofloxacin, gentamicin and trimetoprim-sulfamethoxazole in ESBL-producing strains. CONCLUSION: The percentage of ESBL-producing E. coli is high in our environment, but it is even more noteworthy its clear trend to increase. It is very remarkable the high percentage of ESBL-producing strains isolated from outpatients. Finally, we emphasize the high percentages of co-resistance to non-beta-lactam antibiotics.

Community-Acquired Infections↗