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PubMed2005

In vitro activity of three different antimicrobial agents against ESBL producing Escherichia coli and Klebsiella pneumoniae blood isolates.

Extended spectrum beta-lactamases (ESBLs) usually associated with multiple drug resistance, including beta-lactam and non-beta-lactam antibiotics. This resistance can cause Limitation in the choice of drugs appropriate for using in clinical practice, especially in life-threatening infections. In this study we aimed to investigate in vitro activity of meropenem, ciprofloxacine and amikacin against ESBL-producing and non-producing blood isolates of Escherichia coli and Klebsiella pneumoniae strains. Fifty-eight E. coli (21 ESBL-producing, 37 non-ESBL producing) and 99 K. pneumoniae (54 ESBL-producing, 45 non-ESBL producing) strains were included in the study. The presence of ESBL was investigated by double disk synergy test and E-test methods. Antibiotic susceptibility test was done by microdilution method according to NCCLS guideline. In vitro susceptibilities of ESBL producing E. coli and K. pneumoniae strains were found as 100% for meropenem, 33.3% and 25.9% for ciprofloxacine, 94.5% and 83.3% for amikacin. It was observed that; meropenem was equally active agent in both ESBL-producing and non-producing strains, and its activity was not affected by ESBL production. Whereas amikacin activity was minimally affected and ciprofloxacine activity was markedly decreased by ESBL production. In conclusion, meropenem seems to be better choice of antibiotic should be used for ESBL positive life-threatening infections, because of remaining highest activity.

Amikacin↗
PubMed2004

Evaluation of the MicroScan ESBL plus confirmation panel for detection of extended-spectrum beta-lactamases in clinical isolates of oxyimino-cephalosporin-resistant Gram-negative bacteria.

OBJECTIVE: We aimed to assess the performance of the MicroScan ESBL plus confirmation panel using a series of 87 oxyimino-cephalosporin-resistant Gram-negative bacilli of various species. METHODS: Organisms tested included 57 extended-spectrum beta-lactamase (ESBL) strains comprising Enterobacter aerogenes (3), Enterobacter cloacae (10), Escherichia coli (11), Klebsiella pneumoniae (26), Klebsiella oxytoca (3) and Proteus mirabilis (4). Also included were 30 strains resistant to oxyimino cephalosporins but lacking ESBLs, which were characterized with other resistance mechanisms, such as inherent clavulanate susceptibility in Acinetobacter spp. (4), hyperproduction of AmpC enzyme in Citrobacter freundii (2), E. aerogenes (3), E. cloacae (3), E. coli (4), Hafnia alvei (1) and Morganella morganii (1), production of plasmid-mediated AmpC beta-lactamase in K. pneumoniae (3) and E. coli (3) or hyperproduction of K1 enzyme in K. oxytoca (6). RESULTS: The MicroScan MIC-based clavulanate synergy correctly classified 50 of 57 ESBL strains as ESBL-positive and 23 of 30 non-ESBL strains as ESBL-negative (yielding a sensitivity of 88% and a specificity of 76.7%, respectively). False negatives among ESBL producers were highest with Enterobacter spp. due to masking interactions between ESBL and AmpC beta-lactamases. False-positive classifications occurred in two Acinetobacter spp., one E. coli producing plasmid-mediated AmpC beta-lactamase and two K. oxytoca hyperproducing their chromosomal K1 beta-lactamase. CONCLUSION: The MicroScan clavulanate synergy test proved to be a valuable tool for ESBL confirmation. However, this test has limitations in detecting ESBLs in Enterobacter spp. and in discriminating ESBL-related resistance from the K1 enzyme and from inherent clavulanate susceptibility in Acinetobacter spp.

Cephalosporin Resistance↗
PubMedDate not supplied

Occurrence of extended-spectrum betalactamases (ESBL) in Dutch hospitals.

The prevalence of ESBL was determined among isolates of Escherichia coli (n = 571) and Klebsiella spp. (n = 196) collected during a 1-week study period in 8 university and 3 large regional laboratories all over the Netherlands. 18 isolates were positive for at least one of the screening tests used, i.e., VITEK-ESBL, E-test ESBL and MIC ratio of ceftazidime/ceftazidime-clavulanic acid, cefotaxime/cefotaxime-clavulanic acid. In 5 of these 18 putative ESBLs no betalactamase production was detectable. A TEM type was found in three E. coli and two Klebsiella spp. An SHV type was present in five Klebsiella spp. In one E. coli and one Klebsiella pneumoniae both enzymes were present. In one Klebsiella oxytoca neither of the two enzymes was present. Using PCR for both ESBL TEM and ESBL SHV, an SHV ESBL was found in one E. coli and four Klebsiella isolates. The mutations at position 238 and 240 were already described. In one E. coli isolate a TEM ESBL was found with three mutations, at position 21, 164 and 265. These mutations were already described in other ESBLs but not in this combination suggesting a new TEM ESBL. The overall prevalence of ESBL producing E. coli and Klebsiella spp. was less than 1% (6 out of 767).

Anti-Bacterial Agents↗
PubMed2005

Clinical implications of extended spectrum beta-lactamase (ESBL) producing Klebsiella species and Escherichia coli on cefepime effectiveness.

OBJECTIVE: To determine the affect of ESBL production among Klebsiella species and Escherichia coli on cefepime effectiveness. METHODS: This was a retrospective, case-controlled study comparing the clinical and microbiologic responses of patients receiving cefepime for ESBL producing Klebsiella species or E. coli from a non-urine source with matched controls receiving cefepime for non-ESBL strains. Cases with ESBLs were included if they received monotherapy and were clinically evaluable. Non-ESBL controls were matched in a 2:1 ratio based on age, infection site, intensive care unit (ICU) stay, pathogen species and date of hospitalization. RESULTS: Ten patients receiving cefepime for ESBLs were matched to 20 controls. Most patients received cefepime 1g q12h. Patients receiving cefepime for an ESBL infection were 9.7 (95% CI: 1.4-68.8) and 28.5 (95% CI: 2.6-306.6) times as likely to have an unsuccessful clinical and microbiological response compared with those with a non-ESBL infection. The presence of an ESBL did not have a statistically significant effect on all cause or infection-related mortality. CONCLUSION: These data indicate that ESBL production among non-urinary Klebsiella species and E. coli negatively affected cefepime effectiveness. Further studies are required to evaluate if higher doses of cefepime may improve responses in ESBLs that are initially susceptible.

Adult↗
PubMed2004

Evaluation of a new cefepime-clavulanate ESBL Etest to detect extended-spectrum beta-lactamases in an Enterobacteriaceae strain collection.

OBJECTIVES: In this study, we evaluated the performance of a new ESBL Etest configuration based on clavulanate synergy with cefepime compared with cefotaxime-clavulanate and ceftazidime-clavulanate ESBL Etest strips for the detection of extended-spectrum beta-lactamases (ESBL) in an Enterobacteriaceae strain collection, with special focus on Enterobacter spp. METHODS: Overall, a total of 54 clinical isolates of ESBL-producing Enterobacteriaceae species were evaluated: Enterobacter aerogenes (n=3), Enterobacter cloacae (n=10), Escherichia coli (n=10), Klebsiella oxytoca (n=3), Klebsiella pneumoniae (n=25) and Proteus mirabilis (n=3). To check Etest behaviour with resistance phenotypes similar to ESBL, our panel was expanded by six clinical isolates of K. oxytoca that were identified as putative producers of their chromosomal K1 beta-lactamase. RESULTS: With this panel, ESBL Etest was 98% sensitive with cefepime-clavulanate, 83% with cefotaxime-clavulanate, and 74% with ceftazidime-clavulanate strips. Concentrating on Enterobacter spp., reliable ESBL detection could only be achieved by the new cefepime-clavulanate strip since it confirmed ESBL production in all strains (100% sensitivity) whereas only 4/13 (31%) of Enterobacter strains were positive using cefotaxime-clavulanate or ceftazidime-clavulanate strips. A limitation of using the new cefepime strip was less than optimal specificity with K1 phenotypes of K. oxytoca: among six strains, four isolates were scored false-positive by Etest strips containing cefepime-clavulanate. CONCLUSION: The new Etest ESBL strip containing cefepime-clavulanate is a valuable supplement to current methods for detection of ESBLs. In our study collection, the cefepime-clavulanate strip was the best configuration for detection of ESBLs, particularly in Enterobacter spp.

Anti-Bacterial Agents↗
PubMed2002

Prevalence of extended spectrum beta-lactamase (ESBL)-producing clinical isolates in the Asia-Pacific region and South Africa: regional results from SENTRY Antimicrobial Surveillance Program (1998-99).

The frequency of occurrence of ESBL-producing clinical strains varies widely in distinct geographic areas. The objective of this study was to describe the frequency of occurrence, the preferred substrate, and the co-resistance patterns of the ESBL-producing isolates collected from the Asia-Pacific region and South Africa through the SENTRY Antimicrobial Surveillance Program between January 1998 and December 1999. A total of 1,377 Escherichia coli, 678 Klebsiella pneumoniae, and 138 Proteus mirabilis isolates were collected from diverse body sites. Using NCCLS criteria, 139 E. coli (10.1%), 171 K. pneumoniae (25.2%), and 2 P. mirabilis (1.4%) had presumptive ESBL phenotypes; 100, 146 and 1 strain respectively were confirmed to be ESBL producers on clavulanate enhancement testing. The frequency of occurrence of confirmed ESBL-producing E. coli by the medical centers varied from 0-1% for centers located in Australia to 13-35% for mainland Chinese centers. The higher prevalence rates (>20%) of ESBL K. pneumoniae phenotypes were observed in all mainland Chinese centers, one Japanese and one Taiwanese center, and in the Philippine, South African, Singaporean and medical centers. The spread of the presumptive ESBL phenotype to the Enterobacter species was observed in nine medical centers. Overall, ceftriaxone and aztreonam were the best substrates for the detection of the ESBL phenotype between both E. coli isolates and K. pneumoniae ESBL phenotypes; however, there was significant variation between countries in substrate preference. Co-resistances to gentamicin, tobramycin, tetracycline, and trimethoprim-sulfamethoxazole were common throughout isolates collected from most medical centers. Ciprofloxacin resistance rates were very high among isolates collected from Hong Kong, mainland China, Singapore, and the Philippines. The best coverage against ESBL-producing isolates was obtained with imipenem (0% resistance), followed by amikacin (6% resistance).

Asia↗
PubMed1997

Antimicrobial Susceptibility of Klebsiella pneumoniae Producing Extended-Spectrum beta-lactamase (ESBL) Isolated in Hospitals in Brazil.

The prevalence of klebsiella pneumoniae producing extended-spectrum beta-lactamase (ESBL) has been increasing all over the world. Infections caused by ESBL producing isolates are difficult to detect with current susceptibility tests, and are difficult to treat. ESBLs confer resistance to all currently available beta-lactam, except carbapenems. In addition, ESBL production is usually associated with resistance to other classes of antimicrobial agents such as aminoglycosides and quinolones. The objective of this study was to evaluate the in vitro susceptibility patterns of ESBL producing K pneumoniae isolated in Brazil. Seventy-two strains were tested using E test against 30 antimicrobial agents, including carbapenems, second and third generation cephalosporins, aminoglycosides, quinolones, and some new compounds. The most active compounds (i.e. 100% susceptibility) were meropenem (MIC90, 0.125µg/mL), imipenem (MIC90, 0.25µg/mL), and cefotetan (MIC90, 2µg/mL). Ciprofloxacin (MIC90, 1µg/mL, 94% susceptibility) and cefepime (MIC90, 6µg/mL, 92% susceptibility), were also very active against our collection of ESBL producing K pneumoniae. None of the six aminoglycosides showed good activity against these strains (16% to 41% susceptibility) and only 39% of the isolates were susceptible to piperacillin/tazobactam. The results of our study indicated that the carbapenems are the most active compounds against ESBL producing L pneumoniae in Brazil, and ciprofloxacin remains very active against these strains. Cefotetan and cefepime were also very active against ESBL producing K.pneumoniaein Brazil; however, further studies are necessary to evaluate the role of these cephalosporins in the treatment of infections due to ESBL producing strains.

Journal Article↗
PubMed2005

[Prevalence of ESBL-positive strains of Klebsiella pneumoniae in the Czech Republic and their molecular biology analysis].

BACKGROUND: One of the problems of contemporary medicine is an increasing number of bacterial strains with hazardous phenotypes of resistance. The feared bacterial pathogens include Klebsiella pneumoniae strains producing AmpA extended-spectrum beta-lactamases. The study focused on the molecular biological characteristics of ESBL-positive strains of Klebsiella pneumoniae collected in the Czech Republic. MATERIALS AND METHODS: Clinical material from patients hospitalized in 16 Czech hospitals in September and October 2004 was used to isolate and determine Klebsiella pneumoniae strains by standard identification procedures. Their susceptibility to antibiotics was tested using a dilution micromethod. A Double-Disk Synergy Test was used for phenotype determination of ESBL production. The blaTEM, blaSHV and blaOXA genes coding ESBL production were demonstrated by PCR. Molecular biological characteristics of ESBL-positive strains utilized the genomic DNA isolation, XbaI restrictase digestion and PFGE differentiation. The acquired restriction maps of individual isolates were compared using GelCompar II software and their relationship was determined. RESULTS: During the monitored period, 913 Klebsiella pneumoniae strains causing clinically detectable diseases were isolated. Of these, 234 (25.6 %) were determined as ESBL-positive strains. The prevalence of ESBL-positive strains was 38.5 % in ICUs and 15.8 % in standard wards. More than 50 % of ESBL-positive isolates were effectively treated only with meropenem (98 %), cefoperazone/sulbactam (61 %) and amikacin (54 %). Conversely, ESBL-negative strains showed high susceptibility to all tested antibiotics (76-99 %). The molecular biological analysis identified 18 clonal types containing 2-6 identical strains. 17 clones usually contained isolates from one hospital and only in one clone strains from two hospitals were identified. CONCLUSION: Based on the above mentioned results, the prevalence of ESBL-positive strains of Klebsiella pneumoniae in the Czech Republic can be perceived as relatively high, especially in the ICUs. An extensive spread of epidemic clones within Czech hospitals and, to a limited extent, between them can be demonstrated.

Czech Republic↗
PubMed2006

Comparative activities of cefepime and piperacillin/tazobactam tested against a global collection of Escherichia coli and Klebsiella spp. with an ESBL phenotype.

Cefepime exhibits more stability to hydrolysis by extended-spectrum beta-lactamases (ESBLs) compared with other cephalosporins, and piperacillin/tazobactam may be active against these pathogens because of the enzyme inhibitory activity of tazobactam. Thus, we evaluated the in vitro activity of these 2 antimicrobials against a large collection of isolates with an ESBL phenotype. A total of 50,637 clinical isolates (34,367 Escherichia coli and 16,270 Klebsiella spp.) collected from more than 80 medical centers (1998-2004) were tested by reference broth microdilution methods, and isolates with an ESBL phenotype (MIC, > or = 2 microg/mL for aztreonam or ceftazidime or ceftriaxone) were submitted to a clavulanate inhibition test (confirmation of ESBL production). Among isolates from North America, 3.9% of E. coli and 8.6% of Klebsiella spp. showed an ESBL phenotype, whereas among isolates from the rest of the world (ROW) (Europe, Latin America, and Asia), 7.7% of E. coli and 28.3% of Klebsiella spp. exhibited this pattern. Confirmation rates varied from 21.6% of E. coli in North America to 52.8% of Klebsiella spp. in the row Among E. coli from North America, cefepime (90.3% susceptibility) was generally more active than piperacillin/tazobactam (82.7%), especially among ESBL-not-confirmed (97.0% versus 85.5%). Cefepime also showed reasonable activity against Klebsiella spp. from North America (89.4% susceptibility). In general, isolates from North America exhibited higher susceptibility rates to both beta-lactams compared with isolates from the ROW, and ESBL-not-confirmed strains showed generally higher susceptibility rates than ESBL-confirmed organisms.

Anti-Bacterial Agents↗
PubMed2003

Evaluation of MicroScan ESBL confirmation panel for Enterobacteriaceae-producing, extended-spectrum beta-lactamases isolated in Japan.

We assessed use of the MicroScan ESBL confirmation panel (Dade Behring, Tokyo, Japan) for the detection of eight Enterobacteriaceae-producing extended-spectrum beta-lactamases (ESBL) species. Of 137 bacterial strains isolated from patients in 32 hospitals in the Kinki area of Japan, 91 produced ESBL and comprised 60 bacteria (of E. coli, K. oxytoca, and K. pneumoniae) targeted by the NCCLS ESBL test and 31 non-target bacteria such as chromosomal AmpC-producing bacteria (e.g., Serratia marcescens, Enterobacter spp.). Sensitivity and specificity of the MicroScan panel for the target bacteria were 92% and 93%, respectively; sensitivity and specificity for non-target bacteria were 52% and 100%, respectively. There were 20 ESBL-positive strains that were not inhibited by clavulanic acid in the MicroScan panel (3 of 32 ESBL-producing E. coli strains, 1 of 24 K. pneumoniae, 1 of 4 K. oxytoca, 8 of 13 E. cloacae, and 7 of 14 S. marcescens), and most of them were bacteria not targeted by the NCCLS test. In 19 of the 20 strains, the synergy effect of clavulanic acid was observed in the modified-double-disk synergy test using only the cefepime-disk. Because these strains had high MICs of > or = 16 microg/ml for cephamycins such as cefoxitin and cefmetazole, these strains might produce high levels of AmpC in addition to ESBL. The MicroScan ESBL confirmation panel showed excellent performance in detecting target, but not other bacteria. Addition of cefepime and clavulanic acid to the MicroScan panel may significantly improve detection of non-target bacteria.

Anti-Bacterial Agents↗
PubMed2000

Screening and confirmatory testing for extended spectrum beta-lactamases (ESBL) in Escherichia coli, Klebsiella pneumoniae, and Klebsiella oxytoca clinical isolates.

Escherichia coli and Klebsiella spp. were screened for ESBL based on routine susceptibility testing results. Isolates with intermediate or resistant susceptibilities for extended spectrum cephalosporins or aztreonam were reported as probable ESBL producers. By using the NCCLS proposed ESBL confirmatory method, we tested 61 screen-positive isolates from 42 patients, 30 randomly selected susceptible isolates, and 12 isolates with previously characterized beta-lactamases. Ceftazidime contributed to 97% of screen-positive isolates, whereas aztreonam added a single patient isolate. An ESBL was confirmed in 86% of K. pneumoniae, 100% of K. oxytoca, and 20% of E. coli screen-positive single patient isolates. None of the susceptible isolates were shown to produce ESBL. Based on these findings a comment regarding the presence of ESBL seems sufficient for Klebsiella spp. but confirmatory testing is indicated for E. coli. 0.25 microg/mL was used to indicate the presence of ESBL, the specificity of the assay increased to 100%. The NCCLS ESBL phenotypic confirmatory method was reproducible and accurate enough to be used in the clinical laboratory.

Anti-Bacterial Agents↗
PubMed2003

ESBL-producing multidrug-resistant Providencia stuartii infections in a university hospital.

OBJECTIVES: To investigate the epidemiological and clinical findings of extended-spectrum beta-lactamase (ESBL)-producing Providencia stuartii infections in a large Italian university hospital. PATIENTS AND METHODS: All consecutive episodes of P. stuartii infection that occurred during 1999-2002 were included in the study. For each patient, we recorded the area of hospitalization and drug susceptibility of the P. stuartii strains. Patients with ESBL-producing P. stuartii infection were considered cases and those with non-ESBL-producing P. stuartii infection were used as controls. RESULTS: One hundred and sixteen (52%) out of 223 P. stuartii strains collected during the study period were found to be ESBL-producing. On the basis of PCR and DNA sequencing experiments, TEM-52 was identified in 87% of isolates and TEM-72 in 13%. All ESBL-producing P. stuartii infections were nosocomially acquired. The prevalence increased from 31% of P. stuartii infections in 1999 to 62% in 2002 (P = 0.04). All 116 strains were classified as ESBL-producing multidrug-resistant P. stuartii, since 88% of the isolates were cross-resistant to ciprofloxacin and amikacin and the other 12% were cross-resistant to ciprofloxacin and gentamicin. At logistic regression analysis, advanced age (P < 0.001), previous hospitalization (P < 0.01), neoplastic disease (P < 0.001) and previous antibiotic therapy (P < 0.001) were independent risk factors for the development of ESBL-producing infections. CONCLUSIONS: This 4 year surveillance of Providencia complaints clearly indicates that infections caused by ESBL-producing multidrug-resistant P. stuartii are an emerging problem.

Adult↗
PubMed2000

A preliminary survey of extended-spectrum beta-lactamases (ESBLs) in clinical isolates of Klebsiella pneumoniae and Escherichia coli in Japan.

We conducted a survey of extended-spectrum beta-lactamases (ESBLs) among 16805 Escherichia coli and 9794 Klebsiella pneumoniae clinical isolates recovered from 196 separate medical institutions during the period January 1997 to January 1998. Using the criteria for minimal inhibitory concentrations (MICs) of oxyimino-cephalosporins of >/=8 microg ml(-1) and confirmation by double-disk test, we detected 15 E. coli and 34 K. pneumoniae isolates producing ESBLs. Genotypes of ESBLs determined by PCR with type-specific primers included one TEM-derived and 24 SHV-derived ESBLs, in addition to 24 Toho-1-type ESBLs, one of the major types of ESBLs reported in Japan. Nucleotide sequence analysis of SHV-specific PCR products revealed that SHV-12 was the dominant type of SHV-derived ESBL. In addition, we also identified TEM-26 and SHV-2. This is the first report characterizing TEM- and SHV-derived ESBLs in Japan.

Anti-Bacterial Agents↗
PubMed2005

[Molecular biology characteristics of ESBL-positive strains of Klebsiella pneumoniae collected in the Neonatal Unit of the Teaching Hospital in Olomouc].

BACKGROUND: One of the problems of contemporary medicine is an increasing number of bacterial strains with hazardous phenotypes of resistance. This is also true for neonatal units where nosocomial infections caused by multiresistant bacteria pose a serious threat to newborns. The feared bacterial pathogens include Klebsiella pneumoniae strains producing AmpA Extended-Spectrum Beta-Lactamases. The study focused on the molecular biology characteristics of ESBL-positive strains of K. pneumoniae collected in the Neonatal Unit of the Teaching Hospital in Olomouc (THO). MATERIALS AND METHODS: Clinical material from newborns hospitalized in the THO Neonatal Unit between January and June 2004 was used to isolate and determine K. pneumoniae strains by standard identification procedures. Their susceptibility to antibiotics was tested using a dilution micromethod. A Double-Disk Synergy Test was used for phenotype determination of ESBL production. The bla gene coding ESBL production was demonstrated by PCR. Molecular biology characteristics of ESBL-positive strains utilized the genomic DNA isolation, XbaI restrictase digestion and PFGE differentiation. The acquired restriction maps of individual isolates were compared using the GelCompare software and their relationship was determined. The selection pressure of antimicrobial agents was assessed according to the absolute number of defined daily doses of individual antibiotics. RESULTS: During the monitored period, 112 K. pneumoniae strains were isolated in total. In 22 of them (19.6%), the TEM-type ESBL production was determined. ESBL-positive strains were only observed in upper respiratory tract and rectal swabs collected from newborns with no signs of infection. The molecular biology analysis showed that 21 ESBL-positive strains had an identical restriction profile, i.e. they were very likely to be identical. The selection pressure of third- and fourth-generation cephalosporins was very low over the observed period and their consumption accounted for 1.9 % of all administered antimicrobial agents. CONCLUSION: The results presented above suggest that ESBL-positive strains of K. pneumoniae occurred in the THO Neonatal Unit due to clonal and horizontal spread from an unidentified source.

Cross Infection↗
PubMed2005

[Application of four variants of the diagnostic disc test (CD01, CD02, CD03, CD04) for detection of ESBL-positive strains of gram-negative rods].

The aim of this study was to evaluate the usefulness of four variants of the diagnostic disc test (DD) to detect extended-spectrum beta-lactamases (ESBLs) in nosocomial strains of gram-negative rods. Also, the diagnostic disc test (DD) was compared with the double-disc synergy test (DDST) for the effectivity of ESBLs identification. A total number of 111 ESBL-positive (DDST-positive) strains of gram-negative rods isolated from hospitalized patients in 2004 was examined. Ninety nine strains belonged to enteric rods (89.2%) and twelve strains--to nonfermentative rods (10.8%). Two reference strains: E. coli ATCC 25922 (ESBL-negative one) and K. pneumoniae ATCC 700603 (ESBL-positive one) were included in the study. Four variants of the diagnostic disc test (DD, Oxoid Ltd, UK) were applied for ESBLs detection: CPD/CD01, CAZ/CD02, CTX/CD03 and CPO/CD04. All examined strains (111) were DDST-positive. Positive results in the DD test (Oxoid Ltd) were as follows: CPD/CD01--59 strains (53.2%), CAZ/CD02--80 strains (72.1%), CTX/CD03--92 strains (82.9%) and CPO/CD04--110 strains (99.1%). Discs containing cefpirome (CPO) and cefpirome with clavulanic acid (CD04) were the best set for detection of ESBLs in our collection of clinical gram-negative rods. Results of this variant of the DD test were the most consistent with the results of the DDST. Application of several disc diffusion methods to detect ESBL producers increases the probability of proper identification of these strains.

Anti-Bacterial Agents↗
PubMed2004

Survey of CTX-M-3 extended-spectrum beta-lactamase (ESBL) among cefotaxime-resistant Serratia marcescens at a medical center in middle Taiwan.

Thirty-four clinical isolates of Serratia marcescens nonsusceptible to cefotaxime were collected from a medical center in middle Taiwan. Confirmatory tests for extended-spectrum beta-lactamases (ESBLs) by cefotaxime and ceftazidime +/- clavulanic acid using Etest ESBL Screen identified only one ESBL producer; the remaining 33 isolates revealed nondeterminable results, because of off-scale minimum inhibitory concentration (MIC) levels for cefotaxime +/- clavulanic acid. Agar microdilution method using broader MIC ranges confirmed 21 ESBL-producers and one non-determinable result, achieving a highly predicting value compared to golden standard by PCR and DNA sequencing analysis, which identified 22 (65%) isolates containing blaCTX-M-3 genes. Only one strain carried concurrent CTX-M-3 and SHV-5 conferring high-level MICs to both cefotaxime (128 microg/mL) and ceftazidime (64 microg/mL). Other enzymatic mechanisms, such as chromosome-encoded AmpC including a novel SRT-2 enzyme, may confer resistance to cefotaxime on the remaining 12 isolates without ESBL bla genes. Thus, it is unreliable to predict the resistance mechanism by antibiogram, and current Etest ESBL Screen tests. Our study highlights expanding efforts to detect ESBLs in S. marcescens are urgently needed in Taiwan.

Anti-Bacterial Agents↗
PubMed2004

Extended-spectrum beta-lactamases (ESbLs): characterization, epidemiology and detection.

Beta-lactamases of Enterobacteriaceae are the most important mechanism of resistance against beta-lactam drugs. Two types of beta-lactamases can confer resistance against 3rd generation cephalosporins. Chromosomally mediated beta-lactamases are inducible and are not inhibited by clavulanic acid. Resistance due to these enzymes is non-transferable. The 2nd type of enzyme is plasmid-mediated beta-lactamases, which are inhibited by clavulanic acid. These enzymes are more important clinically as these can be transferred between various species of Enterobacteriaceae. These enzymes are called extended-spectrum beta-lactamases (ESBLs). ESBL-producing Enterobacteriaceae have been responsible for numerous outbreaks of infection throughout the world and pose challenging infection control issues. Antibacterial choice is often complicated by multi-resistance. ESBLs can confer resistance against all beta-lactam drugs except carbapenems and cephamycins. Nursing home patients may be an important reservoir of ESBL-containing multiple antibiotic-resistant organisms. Use of broad-spectrum oral antibiotics and probably poor infection control practices may facilitate spread of this plasmid-mediated resistance. In addition to known populations at risk, ambulatory patients with chronic conditions represent another patient population that may harbor ESBL-producing organisms. Various methods can be used for detection of ESBLs in the laboratory. These tests include double disc diffusion test, Vitek ESBL test, E Tests, MIC Determination, genetic method, and isoelectric focusing (IEF).

Anti-Bacterial Agents↗
PubMed2006

Treatment of ESBL-producing Klebsiella pneumoniae bacteraemia with carbapenems or flomoxef: a retrospective study and laboratory analysis of the isolates.

OBJECTIVES: To better understand the clinical outcomes of patients with extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) bacteraemia treated with either flomoxef or a carbapenem, and to evaluate the in vitro activities of these antibiotics against ESBL-KP. METHODS: Retrospective analyses to identify risk factors for mortality in patients with flomoxef-susceptible ESBL-KP, especially addressing the therapeutic roles of flomoxef and carbapenem. In vitro activities of flomoxef and carbapenem against flomoxef-susceptible ESBL-KP isolates were evaluated by susceptibility testing and time-kill study. RESULTS: Twenty-seven patients (flomoxef group, n=7; carbapenem group, n=20) were included. Clinical severity reflected by high Pitt bacteraemia score (>or=6) was an independent risk factor for mortality (OR 13.43; 95% CI, 1.08-166.73; P=0.043), while use of flomoxef or a carbapenem was not. The MICs of flomoxef and carbapenem indicated that the tested ESBL-KP were susceptible to these antibiotics regardless of the inoculum size of 10(5) or 10(7) cfu/mL. Time-kill study showed that these antibiotics (flomoxef 8 mg/L and meropenem 4 mg/L) each acted actively against and inhibited the regrowth of the tested ESBL-KP for at least 24 h. CONCLUSIONS: Flomoxef might be as clinically effective as a carbapenem in treating flomoxef-susceptible ESBL-KP bacteraemia.

Adolescent↗