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Extended-spectrum beta-lactamase-producing Enterobacteriaceae strains in community-acquired bacteremia in Southern Israel.

BACKGROUND: In recent years, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae have emerged in many hospitals worldwide. The increasing dissemination and long-term carriage of these organisms within the community carry tremendous implications on the empirical therapy of community-acquired infection. MATERIAL/METHODS: To evaluate the prevalence and clinical features of community-acquired bacteremia involving ESBL-producing Enterobacteriaceae in southern Israel (ESBL-P) we retrospectively studied all Enterobacteriaceae bacteremias during an 8-month period in the Negev region using medical and laboratory records. Antibiotic susceptibility was determined using the disk-diffusion method. ESBL production was determined using an E-test ESBL strip. Cases involving ESBL-P were compared to those involving non-producing strains (ESBL-NP) using the chi-square test. RESULTS: In all, 187 Enterobacteriaceae bacteremias were detected, of which 119 were community-acquired (63.6%). ESBL-P were found in six cases (5%) which are described herein in greater detail. Patients with ESBL-P bacteremia were older, and were more likely to stay in the intensive-care unit. Urinary catheterization and bed-ridden conditions were significant risk factors for ESBL-P. ESBL-P strains were significantly resistant to nearly all antibiotic agents except for imipienem and piperacillin-tazobactam as opposing to ESBL-NP. Patients with ESBL-P bacteremia were more likely to suffer from complications and had a higher mortality. CONCLUSIONS: This paper is the first to describe community-acquired Enterobacteriaceae bacteremia involving ESBL-P strains in Israel. Although the exact prevalence of these organisms in Israel is currently unknown, our findings suggest that ESBL-producers have already begun to disseminate in our community.

Adult↗

Risk factors for increasing multidrug resistance among extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species.

BACKGROUND: The importance of infections due to extended-spectrum beta -lactamase-producing Escherichia coli and Klebsiella species (ESBL-EK) has been increasingly recognized in recent years. ESBL-EK infections are of clinical concern, because few antimicrobials are available as therapeutic options. Increased reliance on carbapenems has led to increasing carbapenem resistance. Efforts to maintain current therapeutic options for ESBL-EK infections are essential. METHODS: We conducted a case-control study to identify risk factors for multidrug resistance (MDR) among ESBL-EK. All patients at our institution who had an inpatient clinical culture result positive for an ESBL-EK during the period of 1 June 1997 through 31 December 2002 were eligible for inclusion. An MDR ESBL-EK was defined as ESBL-EK demonstrating resistance to trimethoprim-sulfamethoxazole, aminoglycosides, and quinolones. All available ESBL-EK isolates were characterized by pulsed-field gel electrophoresis (PFGE). RESULTS: Of 361 total ESBL-EK isolates, 68 (18.8%) were MDR. During the study period, the prevalence of MDR among ESBL-EK isolates increased from 12.5% to 26.9%. The only independent risk factor for MDR ESBL-EK was the infecting organism (i.e., Klebsiella pneumoniae; adjusted odds ratio, 11.7; 95% confidence interval, 4.77-28.51; P < .001). Prior antibiotic use was not independently associated with MDR ESBL-EK. PFGE patterns from K. pneumoniae isolates indicated close genetic relatedness among a substantial proportion of isolates. CONCLUSIONS: The emergence of MDR among ESBL-EK has important implications for the future ability to treat these infections. The strong association between the species of infecting organism and MDR suggests that the epidemiology in K. pneumoniae may be unique. PFGE results suggest that horizontal spread is important in the emergence of MDR ESBL-EK.

Adolescent↗

Bloodstream infections by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in children: epidemiology and clinical outcome.

To determine the epidemiologic features and clinical outcomes of bloodstream infections caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae isolates, cases of bacteremia caused by these organisms in children were analyzed retrospectively. Among the 157 blood isolates recovered from 1993 to 1998 at the Seoul National University Children's Hospital, the prevalence of ESBL production was 17.9% among the E. coli isolates and 52.9% among the K. pneumoniae isolates. The commonest ESBLs were SHV-2a and TEM-52. A novel ESBL, TEM-88, was identified. Pulsed-field gel electrophoresis analysis of the ESBL-producing organisms showed extensive diversity in clonality. The medical records of 142 episodes were reviewed. The risk factors for bloodstream infection with ESBL-producing organisms were prior hospitalization, prior use of oxyimino-cephalosporins, and admission to an intensive care unit within the previous month. There was no difference in clinical severity between patients infected with ESBL-producing strains (the ESBL group) and those infected with ESBL-nonproducing strains (the non-ESBL group) at the time of presentation. However, the overall fatality rate for the ESBL group was significantly higher than that for the non-ESBL group: 12 of 45 (26.7%) versus 5 of 87 (5.7%) (P = 0.001). In a subset analysis of patients treated with extended-spectrum cephalosporins with or without an aminoglycoside, favorable response rates were significantly higher in the non-ESBL group at the 3rd day (6 of 17 versus 33 of 51; P = 0.035), the 5th day (6 of 17 versus 36 of 50; P < 0.05), and the end of therapy (9 of 17 versus 47 of 50; P < 0.001). In conclusion, the ESBL production of the infecting organisms has a significant impact on the clinical course and survival of pediatric patients with bacteremia caused by E. coli and K. pneumoniae.

Adolescent↗

Dramatic increase in prevalence of fecal carriage of extended-spectrum beta-lactamase-producing Enterobacteriaceae during nonoutbreak situations in Spain.

The occurrence of extended-spectrum beta-lactamase (ESBL)-producing isolates has increased worldwide. Fecal carriage of ESBL-producing isolates has mainly been detected in nosocomial outbreaks, and few studies have evaluated fecal carriage during nonoutbreak situations and among patients in the community. We have studied the prevalence of ESBLs in 1,239 fecal samples from 849 patients (64.1% of whom were ambulatory) in 1991 and have compared the prevalence data with those obtained in 2003 for 400 fecal samples from 386 patients (75.9% of whom were ambulatory) and 108 samples from independent healthy volunteers. Samples were diluted in saline and cultured in two MacConkey agar plates supplemented with ceftazidime (1 microg/ml) and cefotaxime (1 microg/ml), respectively. Colonies were screened (by the double-disk synergy test) for ESBL production. The clonal relatedness of all ESBL-producing isolates was determined by pulsed-field gel electrophoresis with XbaI digestion; and the ESBLs of all ESBL-producing isolates were characterized by isoelectric focusing, PCR, and sequencing. The rates of fecal carriage of ESBL-producing isolates increased significantly (P < 0.001) in both hospitalized patients and outpatients, from 0.3 and 0.7%, respectively, in 1991, to 11.8 and 5.5%, respectively, in 2003. The rate of occurrence of ESBL-producing isolates among healthy volunteers was 3.7%. All ESBL-producing isolates recovered in 2003 were nonepidemic clones of Escherichia coli. ESBL characterization revealed an increasing diversity of ESBL types: TEM-4 and CTX-M-10 were the only enzymes detected in 1991, whereas TEM-4, TEM-52, SHV-12, CTX-M-9, CTX-M-10, CTX-M-14, and a CTX-M-2-like enzyme were recovered in 2003. The ESBL-producing isolates recovered from outpatients in 2003 corresponded to a CTX-M-9-type cluster (62.5%) and SHV-12 (31.2%), whereas TEM-4 was detected only in hospitalized patients. The frequencies of coresistance in isolates recovered in 2003 were as follows: sulfonamide, 75%; tetracycline, 64.3%; streptomycin, 57.1%; quinolones, 53.5%; and trimethoprim, 50%. The increased prevalence of fecal carriage of ESBL-producing isolates during nonoutbreak situations in hospitalized patients and the establishment of these isolates in the community with coresistance to non-beta-lactam antibiotics, including quinolones, represent an opportunity for these isolates to become endemic.

Electrophoresis, Gel, Pulsed-Field↗

Extended spectrum beta-lactamase mediated resistance in urinary tract isolates of family Enterobacteriaceae.

BACKGROUND & OBJECTIVES: Extended spectrum beta-lactamases (ESBL) hydrolyse expanded spectrum cephalosporins like ceftazidime, cefotaxime and monobactam aztreonam. ESBL producing bacteria may not be detectable in the routine disk diffusion susceptibility tests leading to inappropriate use of antibiotics and treatment failures. As information on ESBL producers causing urinary tract infection (UTI) is not available from our country, the occurrence of ESBL producing strains causing UTI was studied as also the differences between the antimicrobial susceptibility patterns of ESBL and non-ESBL producers. METHODS: Urinary isolates (233) were tested for antimicrobial susceptibility by Stoke's method and ESBL production by double disk diffusion method (ceftazidime and clavulanic acid). The clinical and demographic profile of the patients was noted. RESULTS: Sixty two of the 233 isolates tested (26.6%) were ESBL producers. Approximately 38.5 per cent of Klebsiellae, 24.7 per cent of Escherichia coli, 24 per cent of Enterobacter aerogenes, 33.3 per cent of Proteus sp. and the only Citrobacter strain produced ESBL. Recent surgery was found to be a significant (P < 0.01) risk factor for acquisition of ESBLs. Approximately 30 per cent of the ESBL producers appeared falsely sensitive or moderately sensitive to cefotaxime/ceftazidime in routine susceptibility testing. There was no difference between the ESBL producers and non-producers in the susceptibility to non-beta lactam agents except for gentamicin. INTERPRETATION & CONCLUSION: A high percentage of urinary tract isolates produced ESBL. Since they are likely to be missed in routine disk diffusion susceptibility tests, all microbiology laboratories should look for ESBL production routinely to avoid treatment failures.

Cephalosporins↗

Phenotypic characteristics of clinical isolates of Klebsiella pneumoniae & evaluation of available phenotypic techniques for detection of extended spectrum beta-lactamases.

BACKGROUND & OBJECTIVES: Identifying organisms that harbour extended spectrum beta lactamases (ESBLs) is a major challenge for a diagnostic clinical microbiology laboratory. Wide variety of ESBLs produced and lack of a sensitive phenotypic method for their detection make the detection of ESBLs difficult and is responsible for under-recognition. The present study was undertaken to evaluate phenotypic characteristics, initial screening tests and established confirmatory phenotypic methods for detection of ESBLs Klebsiella pneumoniae isolates prevalent in a hospital in north India. METHODS: One hundred, non-repeat clinical isolates of K. pneumoniae collected over a period of six months were included in the study. Susceptibilities of the isolates to 20 different antimicrobial agents were determined. Agar dilution and broth dilution methods were used to determine minimum inhibitory concentrations (MICs) of ceftazidime (CAZ) and cefotaxime (CTX). CAZ and CTX were used with and without clavulanic acid to detect ESBL harbouring isolates. Using agar dilution and broth dilution, MIC reduction of two and three doubling dilutions were evaluated as a criterion for ESBL harbouring isolates. Standard double disk synergy test (DDST) with disks placed at 30 mm and modified DDST with disks placed at 16 mm center-to-center distance, using at least two different third generation cephalosporins and combined disk method were also performed to detect ESBL harbouring isolates. RESULTS: Multi-drug resistance (resistance to three or more antimicrobials of different classes) was found among 94 per cent of the isolates. Pooling the results of all the three confirmatory techniques MIC reduction of >3 doubling dilutions using broth dilution method (using CTX and CAZ), combined disk method [(using CTX, ceftriaxone [(CRO), CAZ and aztreonam)] and standard DDST (using CTX, CRO, CAZ and aztreonam), revealed as many as 87 per cent of the isolates as ESBL producers. CTX had greater sensitivity in identifying isolates that harboured ESBLs. Modified DDST using CTX was as sensitive method as broth dilution method and combined disk method in detecting ESBL harbouring isolates. MIC reduction technique using agar dilution method and standard DDST had lowest overall sensitivity in detecting ESBLs. INTERPRETATION & CONCLUSION: Modified DDST using at least two different third generation cephalosporins was considered to be the best technique for detection of ESBL producing K. pneumoniae at our hospital. MIC reduction test with >2 doubling dilution reduction in MICs was found to be a better criterion than the presently recommended >3 doubling dilution reduction. For screening of potential ESBL producers, MIC determination using agar dilution was as good as that using broth dilution method. However, while performing MIC reduction test agar dilution method was found highly unreliable for detection of ESBL harbouring isolates.

Humans↗

Effects of phenotype and genotype on methods for detection of extended-spectrum-beta-lactamase-producing clinical isolates of Escherichia coli and Klebsiella pneumoniae in Norway.

Consecutive clinical isolates of Escherichia coli (n = 87) and Klebsiella pneumoniae (n = 25) with reduced susceptibilities to oxyimino-cephalosporins (MICs > 1 mg/liter) from 18 Norwegian laboratories during March through October 2003 were examined for bla(TEM/SHV/CTX-M) extended-spectrum-beta-lactamase (ESBL) genes, oxyimino-cephalosporin MIC profiles, ESBL phenotypes (determined by the ESBL Etest and the combined disk and double-disk synergy [DDS] methods), and susceptibility to non-beta-lactam antibiotics. Multidrug-resistant CTX-M-15-like (n = 23) and CTX-M-9-like (n = 15) ESBLs dominated among the 50 ESBL-positive E. coli isolates. SHV-5-like (n = 9) and SHV-2-like (n = 4) ESBLs were the most prevalent in 19 ESBL-positive K. pneumoniae isolates. Discrepant ESBL phenotype test results were observed for one major (CTX-M-9) and several minor (TEM-128 and SHV-2/-28) ESBL groups and in SHV-1/-11-hyperproducing isolates. Negative or borderline ESBL results were observed when low-MIC oxyimino-cephalosporin substrates were used to detect clavulanic acid (CLA) synergy. CLA synergy was detected by the ESBL Etest and the DDS method but not by the combined disk method in SHV-1/-11-hyperproducing strains. The DDS method revealed unexplained CLA synergy in combination with aztreonam and cefpirome in three E. coli strains. The relatively high proportion of ESBL-producing E. coli organisms with a low ceftazidime MIC in Norway emphasizes that cefpodoxime alone or both cefotaxime and ceftazidime should be used as substrates for ESBL detection.

Drug Resistance, Multiple, Bacterial↗

Impairment of respiratory burst in polymorphonuclear leukocytes by extended-spectrum beta-lactamase-producing strains of Klebsiella pneumoniae.

The ability of extended-spectrum beta-lactamase (ESBL)-producing and non-ESBL-producing Klebsiella pneumoniae strains to induce a respiratory burst in polymorphonuclear leukocytes (PMNLs) was investigated. Ninety ESBL-producing and 178 non-ESBL-producing Klebsiella pneumoniae isolates were serotyped and their ability to induce a respiratory burst in PMNLs tested by monitoring the cells' chemiluminescence (CL) response. The percentage of isolates inducing high levels of CL response (CL>75%) was significantly higher among non-ESBL producers (52%) than among ESBL producers (32.2%) ( P<0.0001; OR=3.396; 95%CI=2.036-5.664). The median CL response was significantly higher among the non-ESBL producers (76.9%) than among the ESBL producers (52.6%) ( P=0.034). The two groups did not differ in their ability to resist intracellular killing by PMNLs ( P>0.05), with strains inducing high levels of CL response having significantly lower survival rates (31.8% vs. 42.4%) than strains inducing low levels of CL response (164% vs. 200%) ( P<0.01). The frequencies of the K2 and the K25 serotypes were significantly higher among ESBL-producing strains (17.8% and 22.2%, respectively) than among the non-ESBL producers (6.2% and 1.7%, respectively) ( P=0.0057 and P<0.0001). Of the 77 Klebsiella K serotypes, 71 were detectable among the non-ESBL producers, but only 24 were detectable among the ESBL producers. ESBL-producing Klebsiella pneumoniae strains might have a greater pathogenic potential by virtue of their ability to escape the phagocytic activity of PMNLs.

Anti-Bacterial Agents↗

Influx of extended-spectrum beta-lactamase-producing enterobacteriaceae into the hospital.

BACKGROUND: The prevalence of infections caused by extended-spectrum beta -lactamase (ESBL)-producing Enterobacteriaceae is increasing worldwide. The influx of these bacteria into hospitals has major implications for infection-control and empirical treatment strategies. METHODS: Isolates from 2 patient cohorts--patients with gram-negative bacteremia within 2 days after admission and patients screened for fecal colonization at admission--were assessed for ESBL production. ESBL phenotype was confirmed according to Clinical and Laboratory Standards Institute guidelines. Predictors of ESBL phenotype were examined by univariate and multivariate analyses. RESULTS: Of 80 Enterobacteriaceae isolates from blood samples obtained at admission to the hospital, 13.7% produced ESBL. Thirty-eight patients with ESBL-positive isolates and 72 with ESBL-negative isolates were included in a case-control study. Predictors of ESBL production were male sex and nursing home residence (area under receiver operator characteristic curve, 0.7). Of 241 persons screened at admission, 26 (10.8%) had fecal carriage of ESBL-producing Enterobacteriaceae. Predictors of fecal carriage were poor functional status, antibiotic use, chronic renal insufficiency, liver disease, and use of histamine2 blockers (area under receiver operator characteristic curve, 0.8). Four (15.4%) of the 26 individuals with fecal carriage had subsequent bacteremia with ceftazidime-resistant Enterobacteriaceae, compared with 1 (0.5%) noncarrier (odds ratio, 38.9; P<.001). Of 80 ESBL-producing Enterobacteriaceae isolates obtained at admission, 65 were health care associated, and 15 were community acquired. The 15 community-acquired ESBL-producing Enterobacteriaceae belonged to diverse clones. The most prevalent ESBL gene among these isolates was CTX-M-2 (found in 53.3% of the isolates). CONCLUSIONS: We report high rates of bacteremia and colonization with ESBL-producing Enterobacteriaceae at admission to our institution, which may undermine infection-control measures and complicate the selection of empirical treatment.

Aged↗

Proteus mirabilis bloodstream infections: risk factors and treatment outcome related to the expression of extended-spectrum beta-lactamases.

Bloodstream infection (BSI) due to Proteus mirabilis strains is a relatively uncommon clinical entity, and its significance has received little attention. This study was initiated to evaluate risk factors and treatment outcome of BSI episodes due to P. mirabilis producing extended-spectrum beta-lactamases (ESBLs). Twenty-five BSI episodes caused by P. mirabilis occurred at our hospital (Ospedale di Circolo e Fondazione Macchi, Varese, Italy) over a 7.5-year period. Phenotypic and molecular methods were used to assess ESBL production. Clinical records of BSI patients were examined retrospectively. Demographic data, underlying diseases (according to McCabe and Jackson classification and Charlson weighted index), risk factors, and treatment outcome were investigated by comparing cases due to ESBL-positive strains to cases due to ESBL-negative strains. Eleven isolates were found to express ESBLs (TEM-52 or TEM-92). The remaining 14 isolates were ESBL negative and were uniformly susceptible to extended-spectrum cephalosporins and monobactams. Comparison of the two groups showed that previous hospitalization in a nursing home (P = 0.04) and use of bladder catheter (P = 0.01) were significant risk factors for infections due to ESBL-positive strains. In addition, cases due to ESBL-positive strains showed a significantly higher mortality attributable to BSI (P = 0.04). BSI cases due to ESBL-negative isolates uniformly responded to therapy, whereas 5/11 cases due to ESBL-positive isolates failed to respond (P < 0.01). Use of carbapenems was associated with complete response independently of ESBL production. Therapeutic failure and mortality may occur in BSI episodes caused by ESBL-positive P. mirabilis isolates. Thus, recognition of ESBL-positive strains appears to be critical for the clinical management of patients with systemic P. mirabilis infections.

Aged↗

Extended-spectrum beta-lactamases: a clinical update.

Extended-spectrum beta-lactamases (ESBLs) are a rapidly evolving group of beta-lactamases which share the ability to hydrolyze third-generation cephalosporins and aztreonam yet are inhibited by clavulanic acid. Typically, they derive from genes for TEM-1, TEM-2, or SHV-1 by mutations that alter the amino acid configuration around the active site of these beta-lactamases. This extends the spectrum of beta-lactam antibiotics susceptible to hydrolysis by these enzymes. An increasing number of ESBLs not of TEM or SHV lineage have recently been described. The presence of ESBLs carries tremendous clinical significance. The ESBLs are frequently plasmid encoded. Plasmids responsible for ESBL production frequently carry genes encoding resistance to other drug classes (for example, aminoglycosides). Therefore, antibiotic options in the treatment of ESBL-producing organisms are extremely limited. Carbapenems are the treatment of choice for serious infections due to ESBL-producing organisms, yet carbapenem-resistant isolates have recently been reported. ESBL-producing organisms may appear susceptible to some extended-spectrum cephalosporins. However, treatment with such antibiotics has been associated with high failure rates. There is substantial debate as to the optimal method to prevent this occurrence. It has been proposed that cephalosporin breakpoints for the Enterobacteriaceae should be altered so that the need for ESBL detection would be obviated. At present, however, organizations such as the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) provide guidelines for the detection of ESBLs in klebsiellae and Escherichia coli. In common to all ESBL detection methods is the general principle that the activity of extended-spectrum cephalosporins against ESBL-producing organisms will be enhanced by the presence of clavulanic acid. ESBLs represent an impressive example of the ability of gram-negative bacteria to develop new antibiotic resistance mechanisms in the face of the introduction of new antimicrobial agents.

Anti-Bacterial Agents↗

[Detection of extended-spectrum beta-lactamases and drug sensitivity test in clinical isolates of the family Enterobacteriaceae in Shanghai].

OBJECTIVE: To investigate extended-spectrum beta-lactamases (ESBLs) production in clinical isolates of the family Enterobacteriaceae in Shanghai, and compare the resistant rates of ESBLs-producing strains and non-ESBLs-producing strains to 11 antibiotics. METHODS: Double-disk synergy test was used to detect ESBLs in 1,026 strains of the family Enterobacteriaceae; Kirby-bauer agar diffusion method was used to judge drug sensitivity. RESULTS: 34.31% of strains of the family Enterobacteriaceae were considered ESBLs producers by double-disk synergy test. The prevalences of ESBLs in isolates of Klebsiella pneumoniae, Escherichia coli and Enterobacter cloacae were 37.40%, 30.21% and 41.82% respectively. Except Imipinem and Cefmetazole, the resistant rates of ESBLs-producing strains to other 9 antibiotics were much higher than that of non-ESBLs-producing strains(P < 0.01). The resistant rates of Imipinem to ESBLs-producing strains were the lowest. CONCLUSIONS: The prevalence of ESBLs in clinical isolates of the family Enterobacteriaceae in Shanghai was high; it is necessary for clinical laboratory to detect ESBLs in clinical isolates of the family Enterobacteriaceae routinely. The resistant rates of ESBLs-producing strains to most antibiotics were high. Imipinem and Cefmetazole were the effective antibiotics to infections caused by ESBLs-producing strains.

Anti-Bacterial Agents↗

[Extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in spanish hospitals (GEIH-BLEE Project 2002)].

INTRODUCTION: To describe demographic aspects of a prospective multicentric nationwide study on Escherichia coli and Klebsiella pneumoniae producing extended spectrum b -lactamases (ESBL) in Spain, between March and June 2000. METHODS: 352 E. coli and K. pneumoniae strains showing a phenotype compatible to ESBL production were collected from 40 Spanish Hospitals. A form with demographic and clinical data was filled for every isolate. Identification and susceptibility testing (microdilution, NCCLS guidelines) were performed in a reference centre. RESULTS. 240 strains (170 E. coli and 70 K. pneumoniae) produced ESBL. E. coli ESBL (+) strains were isolated in 33 out of 40 participating hospitals, whereas K. pneumoniae were isolated in 17 hospitals. E. coli ESBL (+) prevalence ranged from 0% to 2.4% and K. pneumoniae ESBL (+) from 0% to 16.7%. Fifty-one percent of E. coli ESBL (+) were from outpatients, whereas 93% of K. pneumoniae ESBL (+) were from inpatients. E. coli ESBL (+) were mainly collected from Medicine and Surgery wards and K. pneumoniae from ICU and Paediatrics. ESBL (+) strains were isolated more frequently from urine samples. Patients' ages ranged from 0 to 93 years for E. coli (median 58 years) and 0 to 83 years for K. pneumoniae (median: 1 year). Paediatric cases excluded, these median values were 64 and 53 years, respectively. CONCLUSIONS: E. coli and K. pneumoniae ESBL (+) were identificated in 90% of the participating hospitals. Although E. coli was more frequently isolated than K. pneumoniae, production of ESBL was more prevalent in K. pneumoniae. Fifty-one percent of ESBL producing E. coli were isolated from outpatients.

Adolescent↗

Evaluation of extended spectrum beta lactamase in urinary isolates.

BACKGROUND & OBJECTIVES: Urinary tract infection (UTI) remain the common infections diagnosed in outpatients as well as in hospitalized patients. Current knowledge on antimicrobial susceptibility pattern of uropathogens is mandatory for appropriate therapy. Extended spectrum beta lactamases (ESBL) hydrolyse expanded spectrum cephalosporins like ceftazidime, cephotaxime which are used in the treatment of UTI. ESBL producing bacteria may not be detectable by routine disk diffusion susceptibility test, leading to inappropriate use of antibiotics and treatment failure. Not much information on ESBL producing organisms causing UTI is available from India. An effort was therefore made to study the ESBL producing uropathogens and also the susceptibility patterns of ESBL and nonESBL producers. METHODS: Urinary isolates from symptomatic UTI cases attending or admitted to the Indira Gandhi Medical College and Hospital, Nagpur were identified by conventional methods. Antimicrobial susceptibility testing was done by Kirbey Bauer's disc diffusion method. Isolates resistant to cephotaxime were tested for ESBL production by double disc synergy test method. RESULTS: Of the 217 isolates, 87 were cephotaxime resistant Gram-negative bacilli. Of these, 42 (48.3%) were found to be ESBL producers. Escherichia coli, Klebsiella pnuemoniae and Acinetobacter were ESBL producing species. Multidrug resistance was found to be significantly (P<0.05) more in ESBL producing isolates (90.5%) than non ESBL producers (68.9%). INTERPRETATION & CONCLUSION: In the present study a large number of uropathogens were found to be ESBL producers. Most of the ESBL producing isolates were multidrug resistant. Monitoring of ESBL production and antimicrobial susceptibility testing are necessary to avoid treatment failure in patients with UTI.

Drug Resistance, Multiple, Bacterial↗

Regional variation in the prevalence of extended-spectrum beta-lactamase-producing clinical isolates in the Asia-Pacific region (SENTRY 1998-2002).

We examined the prevalence of extended-spectrum beta-lactamase (ESBL)-producing strains of Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, Proteus mirabilis, Citrobacter koseri, and Salmonella spp. that were isolated as part of the SENTRY Asia-Pacific Surveillance Program between 1998 and 2002. During the study period, a total of 6,388 strains were gathered from 17 medical centers in 7 countries and examined for ESBL production and hyperproduction of K. oxytoca chromosomal K1 beta-lactamase enzyme. High rates of confirmed ESBL-producing isolates were found in K. pneumoniae strains from Singapore (35.6%), followed by those from mainland China (30.7%), South Africa (28.1%), and the Philippines (21.9%), whereas the rates were less than 10% in Japan and Australia. ESBL-producing E. coli strains were also prominent in mainland China (24.5%), Hong Kong (14.3%), and Singapore (11.3%). ESBL-producing K. oxytoca were common in the Philippines (38.5%), Singapore (33.3%), and China (30.0%). Hyperproduction of K. oxytoca chromosomal K1 beta-lactamase enzyme was common in Australia and Japan. P. mirabilis strains from Singapore produced ESBL (17.9%) despite the low prevalence (0-8.1%) in other countries. Few ESBL-producing C. koseri and Salmonella spp. strains were found in Japan, Singapore, Taiwan, and South Africa. Although there was variation among countries in substrate preference, ceftazidime was more likely to detect presumptive ESBL phenotype in K. pneumoniae and aztreonam more likely in E. coli, whereas ceftriaxone was the best substrate for the confirmation of ESBL production. ESBL-producing strains showed high levels of co-resistance to aminoglycosides, tetracycline, trimethoprim-sulfamethoxazole, and ciprofloxacin. Imipenem retained activity against all ESBL-producing strains. Organisms expressing ESBLs are widely distributed in the Asia-Pacific region, although prevalence rates vary significantly.

Anti-Bacterial Agents↗

Epidemiology of urinary tract infections caused by extended-spectrum beta-lactamase-producing Escherichia coli.

OBJECTIVES: To describe the epidemiology of urinary tract infections caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli. METHODS: We performed three studies: a trend study (1999 to 2004) to assess the evolution and origin of ESBL-producing E. coli isolates from urine samples; a comparison of the susceptibility patterns of ESBL-producing E. coli and a random sample of non-ESBL-producing E. coli isolated in the same interval, and a retrospective chart review to determine the risk factors for acquisition of, and outcomes from, urinary tract infections caused by ESBL-producing E. coli (n = 61) compared with a random sample of non-ESBL-producing E. coli urinary tract infections (n = 61) from patients attending our institution and matched by temporal occurrence. RESULTS: ESBL-producing E. coli significantly increased from 2 (0.20%) to 89 (5.52%) isolates per year (P value for trend = 0.000). Of the 161 patients with urinary tract infections caused by ESBL-producing E. coli, 100 (62%) were attending ambulatory health centers, and 61 (38%) were attending the hospital. ESBL-producing E. coli showed a significant reduction in the susceptibility to most antimicrobials, although carbapenems and fosfomycin retained significant activity. The chart review study showed that previous treatment with fluoroquinolones (odds ratio 12.98, 95% confidence interval 1.81 to 106.51, P = 0.017) and the presence of a urinary catheter (odds ratio 2.64, 95% confidence interval 1.01 to 6.88, P = 0.047) were independent risk factors associated with infections caused by ESBL-producing E. coli. CONCLUSIONS: ESBL-producing E. coli is a problem of increasing importance. Our study results may help physicians select appropriate antimicrobial therapy in patients suspected of having urinary tract infections caused by ESBL-producing E. coli.

Aged↗

An outbreak of hospital-acquired Klebsiella pneumoniae bacteraemia, including strains producing extended-spectrum beta-lactamase.

This study describes the clinical outcome of an outbreak of extended-spectrum beta-lactamase producing Klebsiella pneumoniae (ESBL-KP) bacteraemia. Ninety-two episodes of hospital-acquired K. pneumoniae bacteraemia were studied, 49 ESBL-KP and 43 non-ESBL-KP, from May 1993 to June 1995. Of these, 44 (90%) episodes of ESBL-KP vs. 20 (46%) episodes of non-ESBL-KP occurred in intensive care unit (ICU) patients. The incidence of K. pneumoniae bacteraemia (mainly due to ESBL-KP) increased in the ICU during the outbreak. A significant association was found between intravascular catheter-related bacteraemia and isolation of ESBL-KP [27 (56%) in the ESBL-KP group vs. 13 (30%) in the non-ESBL-KP group;P= 0.01]. The worst prognostic features were identified as age > 65 years (P= 0.02), septic shock (P< 0.001) and secondary bacteraemia (P= 0.04). High rates of resistance to beta-lactam/beta-lactamase inhibitors observed in our ESBL-KP isolates, as well as variable activity of aminoglycosides, restricts the empirical use of these antibiotics. Carbapenems should be the treatment of choice since they are uniformly active against these strains. Our study shows that ESBL-KP bacteraemia occurring in an epidemic ICU setting is mainly catheter-related. We did not find ESBL strains to be associated with a significantly poor outcome.

Age Distribution↗

Extended-spectrum beta-lactamases in Klebsiella pneumoniae bloodstream isolates from seven countries: dominance and widespread prevalence of SHV- and CTX-M-type beta-lactamases.

A huge variety of extended-spectrum beta-lactamases (ESBLs) have been detected during the last 20 years. The majority of these have been of the TEM or SHV lineage. We have assessed ESBLs occurring among a collection of 455 bloodstream isolates of Klebsiella pneumoniae, collected from 12 hospitals in seven countries. Multiple beta-lactamases were produced by isolates with phenotypic evidence of ESBL production (mean of 2.7 beta-lactamases per isolate; range, 1 to 5). SHV-type ESBLs were the most common ESBL, occurring in 67.1% (49 of 73) of isolates with phenotypic evidence of ESBL production. In contrast, TEM-type ESBLs (TEM-10 type, -12 type, -26 type, and -63 type) were found in just 16.4% (12 of 73) of isolates. The finding of TEM-10 type and TEM-12 type represents the first detection of a TEM-type ESBL in South America. PER (for Pseudomonas extended resistance)-type beta-lactamases were detected in five of the nine isolates from Turkey and were found with SHV-2-type and SHV-5-type ESBLs in two of the isolates. CTX-M-type ESBLs (bla(CTX-M-2) type and bla(CTX-M-3) type) were found in 23.3% (17 of 73) of isolates and were found in all study countries except for the United States. We also detected CTX-M-type ESBLs in four countries where they have previously not been described-Australia, Belgium, Turkey, and South Africa. The widespread emergence and proliferation of CTX-M-type ESBLs is particularly noteworthy and may have important implications for clinical microbiology laboratories and for physicians treating patients with serious K. pneumoniae infections.

Bacterial Proteins↗