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PubMed2005

Serious consequences to the use of cephalosporins as the first line of antimicrobial therapy administered in hemodialysis units.

BACKGROUND: The dramatic spread of vancomycin-resistant enterococci (VRE) among hemodialysis (HD) patients led to the replacement of vancomycin with cephalosporins as part of the primary empiric therapy for bacterial infections in HD units. The aim of the study was to examine the effects of this new regimen on the colonization rate of resistant bacteria among HD patients. METHODS: Rectal swabs were taken from 105 HD patients and 91 control hospitalized patients. Groups were matched for age, sex, nursing home residency and background diseases. Enterococci were tested for vancomycin resistance, Staphylococcus aureus isolates were tested for methicillin resistance (MRSA), and Enterobacteriaceae were tested for extended-spectrum beta-lactamase (ESBL) activity. RESULTS: In the HD group 1 VRE, 1 MRSA and 9 ESBL-producing organisms were isolated compared to 1 MRSA and 1 ESBL organism in the control group (p = 0.018 for ESBL). In the year prior to the study, the use of cephalosporins had been enhanced in the HD group compared to the control group (p < 0.001), and in the HD ESBL-positive patients compared to the HD ESBL-negative ones (p = 0.007). The overall use of antibiotics in the control group was the same as in the HD group. In a subanalysis of the HD group alone, the ESBL carriers were older, sicker, used more antibiotics, were hospitalized frequently and had a higher mortality rate, compared to noncarriers. CONCLUSIONS: The use of cephalosporins as first-line therapy in HD patients in central Israel reduced the prevalence of VRE colonization but may have contributed to the emergence of ESBL-producing organisms through induction of selection pressure. This may lead to serious complications in the management of these patients.

Aged↗

PubMed2006

Clinical outcome and risk factors related to extended-spectrum beta-lactamase-producing Klebsiella spp. infection among hospitalized patients.

Over the past two decades, nosocomial infections caused by extended-spectrum beta-lactamase (ESBL)-producing Klebsiella spp. have become a major problem all around the world. This situation is of concern because there are limited antimicrobial options to treat patients infected with these pathogens, and also because this kind of resistance can spread to a wide variety of Gram-negative bacilli. Our objectives were to evaluate among in-patients at a public university tertiary-care hospital with documented infection due to Klebsiella spp., which were the risk factors (cross-sectional analysis) and the clinical impact (prospective cohort) associated with an ESBL-producing strain. Study subjects were all patients admitted at the study hospital between April 2002 and October 2003, with a clinically and microbiologically confirmed infection caused by Klebsiella spp. at any body site, except infections restricted to the urinary tract. Of the 104 patients studied, 47 were infected with an ESBL-producing strain and 57 with a non-ESBL-producing strain. Independent risk factors associated with infection with an ESBL-producing strain were young age, exposure to mechanical ventilation, central venous catheter, use of any antimicrobial agent, and particularly use of a 4th generation cephalosporin or a quinolone. Length of stay was significant longer for patients infected with ESBL-producing strains than for those infected with non-ESBL-producing strains, although fatality rate was not significantly affected by ESBL-production in this cohort. In fact, mechanical ventilation and bacteremia were the only variables within dependent association with death detected in this investigation.

Cross Infection↗

PubMed2005

The effect of an estrone D-lactam steroid ester derivative on breast cancer cells and its predicted binding interactions with the ligand binding domain of estrogen receptor-alpha.

In order to further improve the toxicity profile and the anticancer effect of chlorambucil (CBL), we have synthesized a new estrone D-lactam steroidal ester of CBL (ESBL). The aim of this study was to investigate the in vitro activity of ESBL against primary breast carcinoma (BC) cells of operable tumors in comparison with CBL. Cells derived from fresh tumor sections that were obtained from 28 postmenopausal women with ductal BC were treated with CBL and ESBL. Apoptotic cells were distinguished from viable ones with flow cytometric methods. ESBL generated a significantly higher rate of cell apoptosis and cytotoxicity than CBL. ESBL cytotoxic effect demonstrated a significant positive weak to moderate dose-dependent correlation with the ER expression. ESBL produced antineoplastic activity superior to CBL on primary BC tumors in vitro. Moreover, a docking study on the binding interactions of ESBL with the ligand binding domain (LBD) of estrogen receptor-alpha (ERalpha) was investigated. ESBL was found to be positioned inside the binding cavity with its steroidal moiety, whereas the alkylating moiety protruded out of receptor's pocket.

Aged↗

PubMed2004

Clinical outcome of bacteremic spontaneous bacterial peritonitis due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae.

BACKGROUND: This study was conducted to evaluate the risk factors for infection and clinical outcomes of bacteremic spontaneous bacterial peritonitis (SBP) due to ESBL-producing E. coli and K. pneumoniae, in patients with advanced liver cirrhosis. METHODS: The ESBL production was determined by NCCLS guidelines and/or double-disk synergy tests, on stored E. coil and K. pneumoniae blood isolates collected between 1998 and 2002. Of the patients with advanced liver cirrhosis, 15 case patients, with SBP due to ESBL-producers, were compared with 30 matched controls, with SBP due to non-ESBL-producers. RESULTS: There were no significant differences in age, sex, Child-Pugh scores, or APACHE II scores between the two groups. Significant factors associated with infection by ESBL-producing organisms, according to univariate analysis, were: ICU care, indwelling urinary catheter, central venous catheterization, an invasive procedure within the previous 72 hours, and prior use of antibiotics within the previous 30 days. When assessing the clinical response at 72 hours after the initial antimicrobial therapy, the treatment failure rate was significantly higher in the ESBL group (73.3% vs. 16.7%, p<0.001). Also, overall 30-day mortality rates were 60% (9/15) in the ESBL groups and 23.3% (7/30) in the control group (p=0.015). CONCLUSION: Among patients with advanced liver cirrhosis, bacteremic SBP due to ESBL-producing E. coil and K. pneumoniae was associated with adverse outcomes, and significantly higher mortality.

Bacteremia↗

PubMed2004

[Genotype of extended-spectrum beta-lactamases produced by antibiotic-resistant Escherichia coli and Klebsiella pneumoniae in surgical intensive care unit].

OBJECTIVE: To describe the antibiotic resistant mode of extended-spectrum beta-lactamases(ESBLs) producing Escherichia coli (E. coli.) and Klebsiella pneumoniae (KPn) in surgical intensive care unit(SICU), and to implore the molecular epidemiology of ESBLs coding genes of these strains. METHODS: The minimal inhibitory concentrations (MICs) at antibiotics were examined by agar dilution method. The ESBLs coding genes were amplified by TEM, SHV and CTX-M specific primers. Amplicons of such genes with conjugates' plasmids as templates were sequenced. RESULTS: In vitro susceptibility tests of ESBLs producing strains showed a high level of resistance to most of the beta-lactam biotics, especially cefotaxime. 93.5% of these ESBLs positive strains contained CTX-M group genes,and 38.7% of the strains contained SHV genes. By sequencing, some genotype were determined: TEM-1, CTX-M-1,3,14,22. CONCLUSION: ESBLs producing strains were resistant to most of the beta-lactam biotics. The most prevalent ESBLs genotype of ESBLs produced by E coli and KPn in SICU was CTX-M subgroup. The most probable reason might be the extensive use of cefotaxime.

Anti-Bacterial Agents↗

PubMed2005

[Comparison of different phenotypic methods detecting extended spectrum beta-lactamases in Pseudomonas aeruginosa and Acinetobacter baumannii strains].

Pseudomonas aeruginosa and Acinetobacter baumannii which are of great concern as the frequent causative agents of nosocomial infections, frequently exhibit resistance to beta-lactam antibiotics. One of the most common causes of this resistance is the presence of extended spectrum beta-lactamases (ESBL). There is still no standardized method for the detection of ESBLs in P. aeruginosa and A.baumannii strains. The aim of this study was to compare the results of Epsilomer test (E-test), combined disk (CD) and double disk synergy (DDS) methods for the detection of ESBL in a total of 38 P. aeruginosa and 45 A.baumannii strains with ceftazidim or cefotaxime MIC > or = 1 microg/ml, isolated from different clinical samples. Cefepime was included in the group of indicator antibiotics and the distance between clavulanic acid containing disk and indicator antibiotic disks was reduced to increase the sensitivity of DDS test. Of the P. aeruginosa strains, 78.9% was detected as ESBL producers by ceftazidime/ ceftazidime-clavulanic acid and 21.1% detected by cefotaxime/cefotaxime-clavulanic acid ratio. Among this group of strains, 31.5% was positive by DDS test and 84.2% was positive by CD method. Of the A.baumannii strains, 93.3% of them was positive by ceftazidime/ceftazidime-clavulanic acid and 6.6% was positive by cefotaxime/cefotaxime-clavulanic acid ratio. DDS test detected 20% and CD method detected 53.3% of the strains positive by E-test method. The use of cefotaxime together with ceftazidime as an indicator antibiotic increased the sensitivity of detection of ESBL enzymes. Although inclusion of cefepime and reduction of the distance between disks increased the detection of ESBL by DDS method, it was still less effective than E-test. Although, 28.9% of the P. aeruginosa and 13.3% of the A. baumannii strains were susceptible to ceftazidime by in vitro tests, they were ESBL producers. In conclusion, E-test method was found to be the most sensitive phenotypic method for the detection of ESBL in our study collection.

Acinetobacter baumannii↗

PubMedDate not supplied

Risk factors and outcomes of extended-spectrum beta-lactamase-producing E. coli peritonitis in CAPD patients.

OBJECTIVE: To determine the risk factors and outcomes of peritonitis caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli in continuous ambulatory peritoneal dialysis (CAPD). PATIENTS AND METHODS: Episodes of E. coli CAPD peritonitis in our unit from October 1994 to August 2003 were reviewed. Demographic data, underlying medical conditions, recent use of gastric acid inhibitors (including H2 antagonist and proton pump inhibitor), recent antibiotic therapy, antibiotic regimen for peritonitis episodes, sensitivity test results of the E. coli isolated, and clinical outcomes were examined. RESULTS: Over a 10-year study period, 88 episodes of E. coli peritonitis were recorded; 11 of the 88 cases were caused by ESBL-producing E. coli. Recent use of cephalosporins and gastric acid inhibitor were associated with the development of ESBL-producing E. coil peritonitis. Compared with non-ESBL-producing E. coli peritonitis, more cases in the ESBL-producing E. coli group developed treatment failure (45.5% vs 13.0%, p = 0.02) and died of sepsis (27.3% vs 3.9%, p = 0.02). Peritoneal failure rate was higher in the ESBL-producing E. coli group, although the difference was not statistically significant (18.2% vs 3.9%, p = 0.12). CONCLUSION: Peritonitis caused by ESBL-producing E. coli is associated with worse clinical outcomes. The use of cephalosporins and gastric acid inhibitors may contribute to its development. Further studies are warranted to investigate and determine the predisposing factors for ESBL-producing E. coli peritonitis.

Aged↗

PubMed2006

Clinical experiences of the infections caused by extended-spectrum beta-lactamase-producing Serratia marcescens at a medical center in Taiwan.

CTX-M-3 has become the most common extended-spectrum beta-lactamase (ESBL) produced by Serratia marcescens in Taiwan. An expanded effort to detect ESBL among 123 nonrepetitive isolates of S. marcescens was made and 15 (12%) ESBL-producers were identified, all revealing CTX-M-3. Without routinely detecting the ESBL for S. marcescens in clinical laboratories, 80% of the ESBL-producers were reported to be susceptible to cefepime. The clinical spectrum of ESBL-producing S. marcescens-related infections included febrile urinary tract infection (n = 3); afebrile pyuria (n = 2); pneumonia (n = 3); spontaneous bacterial peritonitis (n = 3); secondary bacteremia (n = 2) and one each with primary bacteremia and colonization of the central catheter tip. Overall, the 30-day mortality rate was 33.3% (5/15) and the outcome depended on the severity of the underlying disorder and infection per se. In conclusion, although our case numbers were limited, due to the substantial incidence and associated mortality of ESBL-producing S. marcescens and its potential treatment failure by an apparently susceptible cephalosporin, we recommend that the detection and report of ESBL production for S. marcescens in clinical laboratories be made mandatory.

Amikacin↗

PubMed2006

[Genotype distribution of extended-spectrum beta-lactamases and AmpC beta-lactamases produced in Escherichia coli isolated from men with urinary infection].

OBJECTIVE: To study the genotype distribution of extended-spectrum p-lactamases (ESBLs) and AmpC p-lactamases produced in E. coli isolated from men with urinary infection in Nanjing. METHODS: Organisms of clinical infection were identified by automatic microbial system (Vitek-32). ESBLs were detected by disk diffusion confirmatory test, and ESBLs and AmpC p-lactamases by three-dimensional extract test (TDET) , the presence of plasmid-mediated ESBLs and ampC genes determined by PCR, and conjugal transfer assays of the ampC resistance determinants carried out by a broth mating procedure. RESULTS: ESBLs were produced in 24. 6% (46/187) of the E. coli and the 46 E. coli isolates showed p-lactamase activity in TDET, 3 positive for both ESBLs and AmpC beta-lactamases and 43 for ESBLs only. Forty-four of the 46 isolates were shown by PCR to contain at least one of the genes blaTEM, blaOXA, bla(CTX-M), but no blaSHA. AmpC specific amplication products were observed in 3 of the 46 isolates, of which 2 were of CIT type, and 1 of DHA type. All of the 3 transconjugants transferred the plasmids harbouring ampC genes to recipients. CONCLUSION: CTX-M is the most common genotype in plasmid-mediated ESBLs produced by E. coli isolated from men with urinary infection in Nanjing. Present findings indicate that AmpC-producing E. coli are present in this hospital, and ampC-encoding plasmids are transferable.

Bacterial Proteins↗

PubMed2026

Efficacy of the NMIC-150 system in identifying extended-spectrum beta-lactamases in clinical isolates.

Extended-spectrum beta-lactamases (ESBLs) are significant contributors to the growing global crisis of antimicrobial resistance. This study evaluated the performance of the NMIC-150 System for susceptibility testing of third-generation cephalosporins (3GCs) and assessed whether ceftazidime-avibactam and aztreonam-avibactam could identify ESBL-producing carbapenem-resistant Enterobacterales (CREs). A total of 278 non-duplicate clinical isolates (Klebsiella pneumoniae, E. coli, and Proteus mirabilis) were analyzed. Antimicrobial susceptibility was determined using reference broth microdilution (BMD) and the NMIC-150 System. ESBL production was defined as an ≥eight-fold reduction in the minimum inhibitory concentration (MIC) of 3GCs in the presence of clavulanic acid, according to CLSI criteria. Whole-genome sequencing was performed to characterize ESBL and carbapenemase genes among 3GC-resistant isolates. A Random Forest model was used to predict ESBL-producing isolates based on MIC values. The NMIC-150 System demonstrated over 90% categorical and essential agreement with BMD for ceftazidime and ceftriaxone, along with robust predictive performance via Random Forest analysis. These findings suggest that the NMIC-150 System is a reliable platform for 3GC susceptibility testing and that an ≥eight-fold MIC reduction with ceftazidime-avibactam or aztreonam-avibactam may serve as a phenotypic indicator of ESBL production in CRE isolates. In conclusion, the NMIC-150 System shows potential for routine antimicrobial resistance surveillance and may facilitate the rapid identification of ESBL-producing CREs in clinical settings.

Microbial Sensitivity Tests↗

PubMed2000

Use of the ligase detection reaction-polymerase chain reaction to identify point mutations in extended-spectrum beta-lactamases.

The aim of this study was to detect point mutations in extended-spectrum beta-lactamase (ESBL) genes in a background of wild-type (non-ESBL-producing) bacteria using a highly sensitive and specific method developed for this purpose. The ligase detection reaction-polymerase chain reaction (LDR-PCR) method was used to test different ESBL-producing strains and clinical isolates for a specific point mutation in the bla SHV-ESBL gene (glycine to serine mutation at position 238) and was compared with the commercially available E test ESBL (AB Biodisk, Sweden). Nine of the 40 clinical isolates tested were positive for the bla SHV-ESBL point mutation when tested by the LDR-PCR method but negative when tested by the E test. In contrast to the E test or other molecular genetic tests, the LDR-PCR method is able to identify a single bacterium with a point mutation in a background of 100,000 wild-type (non-ESBL-producing) bacteria.

Amino Acid Substitution↗

PubMed1995

Decreased transmission of Enterobacteriaceae with extended-spectrum beta-lactamases in an intensive care unit by nursing reorganization.

In our gastrointestinal surgical intensive care unit (SICU), the large number of patients with multiple enterostomies enhances the risk of nosocomial transmission of gut extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) by health care workers. A control study performed in our SICU from June-August 1992 showed an ESBLE gut colonization rate of 70%. To reduce this rate, nursing procedures were intensified or modified, particularly handwashing, single-use equipment and waste control. To test the efficiency of these procedures, 64 patients hospitalized for more than two days from September 1992-March 1993 were screened for gut acquisition of ESBLE. Rectal samples were taken within 48 h after admission and then weekly. After nursing reorganization, the ESBLE colonization rate dropped significantly to 40% (P < 0.001). Twenty patients (31.7%) acquired a gut ESBLE, after a mean of 24.3 +/- 13.7 days. Each patient was colonized with one, two or three ESBLE (Klebsiella pneumoniae, Escherichia coli and Enterobacter aerogenes). Baseline characteristics of the 20 colonized and 39 non-colonized patients showed no significant difference (Student's t-test, P > 0.05). The nursing workload, estimated as a omega index, was greater in the colonized group (P < 0.001). These findings show that strict observance of nursing procedures can significantly reduce ESBLE acquisition in a high-risk surgical unit.

Aged↗

PubMed2006

Resistance in gram-negative bacteria: Enterobacteriaceae.

The emergence and spread of resistance in Enterobacteriaceae are complicating the treatment of serious nosocomial infections and threatening to create species resistant to all currently available agents. Approximately 20% of Klebsiella pneumoniae infections and 31% of Enterobacter spp infections in intensive care units in the United States now involve strains not susceptible to third-generation cephalosporins. Such resistance in K pneumoniae to third-generation cephalosporins is typically caused by the acquisition of plasmids containing genes that encode for extended-spectrum beta-lactamases (ESBLs), and these plasmids often carry other resistance genes as well. ESBL-producing K pneumoniae and Escherichia coli are now relatively common in healthcare settings and often exhibit multidrug resistance. ESBL-producing Enterobacteriaceae have now emerged in the community as well. Salmonella and other Enterobacteriaceae that cause gastroenteritis may also be ESBL producers, which is of relevance when children require treatment for invasive infections. Resistance of Enterobacter spp to third-generation cephalosporins is most typically caused by overproduction of AmpC beta-lactamases, and treatment with third-generation cephalosporins may select for AmpC-overproducing mutants. Some Enterobacter cloacae strains are now ESBL and AmpC producers, conferring resistance to both third- and fourth-generation cephalosporins. Quinolone resistance in Enterobacteriaceae is usually the result of chromosomal mutations leading to alterations in target enzymes or drug accumulation. More recently, however, plasmid-mediated quinolone resistance has been reported in K pneumoniae and E coli, associated with acquisition of the qnr gene. The vast majority of Enterobacteriaceae, including ESBL producers, remain susceptible to carbapenems, and these agents are considered preferred empiric therapy for serious Enterobacteriaceae infections. Carbapenem resistance, although rare, appears to be increasing. Particularly troublesome is the emergence of KPC-type carbapenemases in New York City. Better antibiotic stewardship and infection control are needed to prevent further spread of ESBLs and other forms of resistance in Enterobacteriaceae throughout the world.

Carbapenems↗

PubMed2006

Resistance in gram-negative bacteria: enterobacteriaceae.

Anti-Bacterial Agents↗

PubMed2004

A pragmatic approach to identify extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in Taiwan: in vitro activity of newer and established antimicrobial agents.

The activities of 17 antimicrobials were evaluated against 211 clinical extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae isolates from Taiwan. A pragmatic approach by sequential Etest (AB BIODISK, Solna, Sweden) ESBL screen (narrow MIC range) and/or the usual Etest method (broad MIC range) was used. Among 131 isolates with a ceftazidime MIC of > 8 microg/ml, 125 (95.4%) had a reduction of > or =3 log2 dilution steps for ceftazidime (positive test). Among 83 isolates with a ceftriaxone MIC of > 8 microg/ml and ceftazidime MIC at < or =8 microg/ml, 81 (97.5%) had a reduction of > or =3 three log2 dilution steps for ceftriaxone. Among the remaining eight isolates with nondeterminable results, additional Etest MIC method results revealed five ESBL-positive and two ESBL-negative (putative AmpC) determinations. This approach offered a cost-effective strategy to screen for ESBL among large number of isolates. The carbapenems (meropenem and imipenem) were the most active compounds (100% susceptibility) followed by newer fluoroquinolones (levofloxacin, gemifloxacin and gatifloxacin) at approximately 80% susceptible. Co-resistance to gentamicin was 96%, tobramycin 96%, and amikacin 62%. In conclusion, ESBL-producing strains of K. pneumoniae, also resistant to cefepime and aminoglycosides, are now widespread in Taiwan. The carbapenems and newer fluoroquinolones remain quite active against these ESBL strains recognized by this novel diagnostic approach.

Anti-Infective Agents↗

PubMed2005

Evolution and dissemination of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae: epidemiology and molecular report from the SENTRY Antimicrobial Surveillance Program (1997-2003).

During 2001, occurrences of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae isolates were detected in a single medical center (Hospital A) from the SENTRY Antimicrobial Surveillance Program that became endemic in long-term acute care areas and in the intensive care unit in 2002-2003. Between 2001 and 2003, 123 patients were infected or colonized with ESBL-positive K. pneumoniae. Resistance profiles were determined by reference broth microdilution methods, and automated ribotyping and pulsed-field gel electrophoresis (PFGE) were performed. The ESBL-positive K. pneumoniae isolates were resistant to aztreonam, ceftazidime, aminoglycosides, and trimethoprim/sulfamethoxazole and susceptible to ciprofloxacin and tetracycline. In 1997, 1998, and 2000, 9 ESBL-producing K. pneumoniae strains from 2 New York City hospitals shared the same antibiograms and ribotype (204.2) as the strains from Hospital A. PFGE patterns divided Hospital A isolates into 2 subtypes (A and A1) and 3 New York City strains were similar to the Hospital A isolates (A2, A3, and A4). Isoelectric focusing studies of 1 New York City isolate (A4) revealed pIs at 5.4, 7.7, and 8.2. PCR and sequencing results from 1 strain of each Hospital A and 1 New York PFGE pattern determined that TEM-1 and SHV-5 (ESBL) were present in all strains. In addition, 2 New York isolates from 1998 (A3 and A4) also had an OXA-2 enzyme. ESBL-producing K. pneumoniae isolates with ribotype 204.2 from SENTRY Program sites have been recognized in New York only since 1997 and in Hospital A beginning in 2001. The similarities of the antibiogram and epidemiological patterns suggest that these isolates have persisted over time and may have evolved into different but genetically related endemic ESBL-positive K. pneumoniae clones that have the ability to cause sustained epidemic outbreaks in US medical centers.

Adolescent↗

PubMed2005

Analysis of Salmonella spp. with resistance to extended-spectrum cephalosporins and fluoroquinolones isolated in North America and Latin America: report from the SENTRY Antimicrobial Surveillance Program (1997-2004).

Emerging antimicrobial-resistant Salmonella spp. requires increased efforts to appropriately test susceptibility. The SENTRY Antimicrobial Surveillance Program monitored Salmonella spp. and detected nalidixic acid-resistant strains with elevated fluoroquinolone minimum inhibitory concentration (MIC) results and strains with extended-spectrum beta-lactamase (ESBL) "phenotypes" over the last 8 years. A total of 786 stool and bloodstream isolates from North American and Latin American medical centers (2001-2003) were tested by reference broth microdilution methods. Genetic analysis was used to further characterize the resistance mechanisms. Twenty-one sites forwarded 89 (11.3%) nalidixic acid-resistant (MIC, > or =32 microg/mL) strains. Nineteen of these isolates were studied to determine mutations in the quinolone resistance-determining region (QRDR). Among the nalidixic acid-resistant Salmonella spp. isolates, fluoroquinolone MIC values were also elevated (8- to 32-fold) compared with "wild-type" strains. Ciprofloxacin and gatifloxacin (MIC(90), 0.5 microg/mL) were more potent than levofloxacin and garenoxacin (1 microg/mL) against nalidixic acid-resistant strains. Single gyrA mutations were responsible for elevated fluoroquinolone MIC values and included D87Y (5), S83F (7), D87N (5), and S83Y (2). During 2001, 9 sites contributed 11 (2.9%) strains that met ESBL screening criteria (> or =2 microg/mL) for aztreonam or ceftazidime or ceftriaxone. ESBL confirmation was evaluated by Etest (AB BIODISK, Solna, Sweden) ESBL strips and the enzymes were characterized by polymerase chain reaction and gene sequencing. The ESBL phenotype isolates had the following MIC patterns: ceftazidime (> or =16 microg/mL), aztreonam (4 to >16 microg/mL), and ceftriaxone (8-32 microg/mL). All strains were susceptible to cefepime, carbapenems, gentamicin, and fluoroquinolones. No strains were inhibited by clavulanic acid consistent with all isolates producing the identified CMY-2, AmpC-like enzyme. Fluoroquinolones may be compromised among isolates with QRDR mutations detected using nalidixic acid as a screening agent. Salmonella spp. with ESBL phenotypes were likely to harbor CMY-2 (not an ESBL) and remain susceptible to cefepime, carbapenems, and fluoroquinolones, which can be used for serious invasive Salmonella spp. infections. Compared with the stool culture isolates, the blood culture isolates had higher QRDR mutations, but remained susceptible to the fluoroquinolones. The blood culture isolates were more susceptible to penicillins (ampicillin and ticarcillin) and not significantly different for ceftriaxone or trimethoprim/sulfamethoxazole susceptibility patterns. No QRDR trends over time were detected in North America, but increased resistance was observed in Latin America.

Anti-Bacterial Agents↗

PubMed2006

Epidemiology of infections caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella spp.: a nested case-control study from a tertiary hospital in London.

Information on risk factors for acquisition of extended-spectrum ss-lactamase (ESBL)-producing organisms and their outcomes in patients with invasive infections is scant. The objectives of this study were to evaluate risk factors and all-cause mortality associated with infection due to ESBL-producing organisms using a nested case-control design, and to document transmission within a hospital employing molecular and conventional epidemiological methods. From December 2003 to April 2005, 50 patients with bloodstream infections (BSIs) due to ESBL-producing E. coli and Klebsiella spp. were recruited. Controls (N=50) were chosen, within the same period, from patients with non-ESBL-producing BSIs by simple random sampling; account was taken of potential confounding factors. Cases and controls were followed-up until November 2005, and outcomes were recorded as discharged or deceased. Molecular methods, supported by conventional epidemiology, were used to study the transmission of organisms. Logistic regression analyses showed prior ss-lactam antibiotics [odds ratio (OR) 11.57; 95% confidence intervals (CI) 2.31-51.15; P=0.003], hospital stay >15 days (OR 2.63; 95% CI 1.01-6.89; P=0.04) and prior admission to the intensive care unit (OR 13.98; 95% CI 1.88-19.15; P=0.006) to be independent risk factors for the acquisition of ESBL-producing organisms. In the first 15 days of follow-up, a significant proportion of patients with ESBL-producing organisms died; however, there was no difference in mortality between cases and controls at the end of the follow-up period. Molecular epidemiology identified five clusters amongst the ESBL-producing isolates. Conventional epidemiological analyses supported the evidence of transmission in three of these clusters.

Adolescent↗