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Yehuda Carmeli

Publications and source records attributed to Yehuda Carmeli.

At least 37 records · Page 2Linked to original sources

CTX-M-2 and a new CTX-M-39 enzyme are the major extended-spectrum beta-lactamases in multiple Escherichia coli clones isolated in Tel Aviv, Israel.

The rate of occurrence of the extended-spectrum beta-lactamase (ESBL)-producing phenotype among Escherichia coli isolates in Tel Aviv is 12% (22). The aim of this study was to understand the molecular epidemiology of E. coli ESBL producers and to identify the ESBL genes carried by them. We studied 20 single-patient ESBL-producing E. coli clinical isolates. They comprised 11 distinct nonrelated pulsed-field gel electrophoresis (PFGE) genotypes: six isolates belonged to the same PFGE clone, four other clones included two isolates each, and six unrelated clones included only one isolate. All isolates produced various beta-lactamases with pIs ranging from 5.2 to 8.2, varying within similar PFGE clones. The most prevalent ESBL gene was bla(CTX-M); 16 isolates carried bla(CTX-M-2) and three carried a new ESBL gene designated bla(CTX-M-39). Three strains carried bla(SHV) (two bla(SHV-12) and one bla(SHV-5)), and two strains carried inhibitor-resistant ESBL genes, bla(TEM-33) and bla(TEM-30); 18 strains carried bla(TEM-1) and eight strains carried bla(OXA-2). Plasmid mapping and Southern blot analysis with a CTX-M-2 probe demonstrated that bla(CTX-M-2) is plasmid borne. The wide dissemination of ESBLs among E. coli isolates in our institution is partly related to clonal spread, but more notably to various plasmid-associated ESBL genes, occurring in multiple clones, wherein the CTX-M gene family appears almost uniformly. We report here a new CTX-M gene, designated bla(CTX-M-39), which revealed 99% homology with bla(CTX-M-26), with a substitution of arginine for glutamine at position 225.

Escherichia coli↗

Extended-spectrum beta-lactamases among Enterobacter isolates obtained in Tel Aviv, Israel.

The extended-spectrum beta-lactamase (ESBL)-producing phenotype is frequent among Enterobacter isolates at the Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. We examined the clonal relatedness and characterized the ESBLs of a collection of these strains. Clonal relatedness was determined by pulsed-field gel electrophoresis. Isoelectric focusing (IEF) and transconjugation experiments were performed. ESBL gene families were screened by colony hybridization and PCR for bla(TEM), bla(SHV), bla(CTX-M), bla(IBC), bla(PER), bla(OXA), bla(VEB), and bla(SFO); and the PCR products were sequenced. The 17 Enterobacter isolates studied comprised 15 distinct genotypes. All isolates showed at least one IEF band (range, one to five bands) whose appearance was suppressed by addition of clavulanate; pIs ranged from 5.4 to > or = 8.2. Colony hybridization identified at least one family of beta-lactamase genes in 11 isolates: 10 harbored bla(TEM) and 9 harbored bla(SHV). PCR screening and sequence analysis of the PCR products for bla(TEM), bla(SHV), and bla(CTX-M) identified TEM-1 in 11 isolates, SHV-12 in 7 isolates, SHV-1 in 1 isolate, a CTX-M-2-like gene in 2 isolates, and CTX-M-26 in 1 isolate. In transconjugation experiments with four isolates harboring bla(TEM-1) and bla(SHV-12), both genes were simultaneously transferred to the recipient strain Escherichia coli HB101. Plasmid mapping, PCR, and Southern analysis with TEM- and SHV-specific probes demonstrated that a single transferred plasmid carried both the TEM-1 and the SHV-12 genes. The widespread presence of ESBLs among Enterobacter isolates in Tel Aviv is likely due not to clonal spread but, rather, to plasmid-mediated transfer, at times simultaneously, of genes encoding several types of enzymes. The dominant ESBL identified was SHV-12.

Anti-Bacterial Agents↗

High levels of antimicrobial coresistance among extended-spectrum-beta-lactamase-producing Enterobacteriaceae.

We compared the susceptibility of 312 extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae isolates with that of 1,216 ESBL nonproducers. Of ESBL producers, 25% were susceptible to gentamicin, 30% to trimethoprim-sulfamethoxazole, 41% to ciprofloxacin, and 60% to piperacillin-tazobactam. ESBL nonproducers were more often susceptible to these agents. ESBL-producing Enterobacteriaceae represent a major source of resistance to various antibiotics.

Cross Infection↗

Effect of various antibacterial preparations on the pathogenic oral flora in elderly patients fed via nasogastric tube.

Oropharyngeal colonization by pathogenic gram-negative bacilli (GNB) and Staphylococcus aureus is associated with aspiration pneumonia. Decolonization in high-risk populations may be important. We prospectively evaluated six antiseptic compounds in nasogastric tube-fed frail elderly patients; only polymixine reduced oropharyngeal colonization with GNB. None had an effect on S. aureus colonization.

Aged↗

Evaluation of an accelerated protocol for detection of extended-spectrum beta-lactamase-producing gram-negative bacilli from positive blood cultures.

We evaluated a protocol for the accelerated detection of extended-spectrum beta-lactamases (ESBLs) in gram-negative bloodstream pathogens. Two hundred eighty-three blood culture bottles were subjected to direct ESBL testing by inoculating samples directly from blood culture bottles onto agar plates containing cefotaxime and ceftazidime disks, with and without clavulanate. Standard ESBL testing in accordance with the NCCLS guidelines after subculturing on agar plates was performed in parallel. Results of the direct ESBL testing were reported 2.3 days sooner and were comparable to those of the standard NCCLS method with sensitivity, specificity, and positive and negative predictive values of 100, 98, 94, and 100%, respectively.

Anti-Bacterial Agents↗

Multidrug-resistant Acinetobacter baumannii.

To understand the epidemiology of multidrug-resistant (MDR) Acinetobacter baumannii and define individual risk factors for multidrug resistance, we used epidemiologic methods, performed organism typing by pulsed-field gel electrophoresis (PFGE), and conducted a matched case-control retrospective study. We investigated 118 patients, on 27 wards in Israel, in whom MDR A. baumannii was isolated from clinical cultures. Each case-patient had a control without MDR A. baumannii and was matched for hospital length of stay, ward, and calendar time. The epidemiologic investigation found small clusters of up to 6 patients each with no common identified source. Ten different PFGE clones were found, of which 2 dominated. The PFGE pattern differed within temporospatial clusters, and antimicrobial drug susceptibility patterns varied within and between clones. Multivariate analysis identified the following significant risk factors: male sex, cardiovascular disease, having undergone mechanical ventilation, and having been treated with antimicrobial drugs (particularly metronidazole). Penicillins were protective. The complex epidemiology may explain why the emergence of MDR A. baumannii is difficult to control.

Acinetobacter Infections↗

Methicillin-resistant Staphylococcus aureus in neonatal intensive care unit.

A neonatal intensive care unit outbreak was caused by a strain of methicillin-resistant Staphylococcus aureus previously found in the community (ST45-MRSA-IV). Fifteen infected neonates were identified, 2 of whom died. This outbreak illustrates how a rare community pathogen can rapidly spread through nosocomial transmission.

Anti-Bacterial Agents↗

Antibodies raised against N'-terminal Pseudomonas aeruginosa flagellin prevent mortality in lethal murine models of infection.

The goal of this study was to investigate if antibodies raised against N'-terminal Pseudomonas aeruginosa (Pa) flagellin could afford protection in two lethal mouse models of Pa infection. To that end, rabbit polyclonal antibodies were generated against the N'-terminal domains (amino acids 1-156) of recombinant Pa01 or Salmonella muenchen flagellins, termed anti-N'-fla-b and anti-N'-fla-Sm, respectively. In vitro, anti-N'-fla-b but not anti-N'-fla-Sm IgG specifically recognized recombinant and Pa endogenous flagellin type b proteins, total bacterial lysates of Pa type b, and inhibited Pa01 invasion into A549 cells. In vivo, administration of anti-N'-fla-b afforded a remarkable improvement in survival in lethal peritonitis (90% vs. 12% in control; p<0.001) and burn infection (83% vs. 8-17% in control groups; p<0.005) Pa models. These findings would suggest that the N'-terminal domain of Pa flagellin harbors critically important bioactive domains and that an antibody-targeted, neutralization approach directed at this region could provide a novel therapeutic strategy to combat Pa infection.

Amino Acid Sequence↗

Association between carriage of Streptococcus pneumoniae and Staphylococcus aureus in Children.

CONTEXT: Widespread pneumococcal conjugate vaccination may bring about epidemiologic changes in upper respiratory tract flora of children. Of particular significance may be an interaction between Streptococcus pneumoniae and Staphylococcus aureus, in view of the recent emergence of community-acquired methicillin-resistant S aureus. OBJECTIVE: To examine the prevalence and risk factors of carriage of S pneumoniae and S aureus in the prevaccination era in young children. DESIGN, SETTING, AND PATIENTS: Cross-sectional surveillance study of nasopharyngeal carriage of S pneumoniae and nasal carriage of S aureus by 790 children aged 40 months or younger seen at primary care clinics in central Israel during February 2002. MAIN OUTCOME MEASURES: Carriage rates of S pneumoniae (by serotype) and S aureus; risk factors associated with carriage of each pathogen. RESULTS: Among 790 children screened, 43% carried S pneumoniae and 10% carried S aureus. Staphylococcus aureus carriage among S pneumoniae carriers was 6.5% vs 12.9% in S pneumoniae noncarriers. Streptococcus pneumoniae carriage among S aureus carriers was 27.5% vs 44.8% in S aureus noncarriers. Only 2.8% carried both pathogens concomitantly vs 4.3% expected dual carriage (P =.03). Risk factors for S pneumoniae carriage (attending day care, having young siblings, and age older than 3 months) were negatively associated with S aureus carriage. CONCLUSIONS: Streptococcus pneumoniae carriage, specifically of vaccine-type strains, is negatively associated with S aureus carriage in children. The implications of these findings in the pneumococcal vaccine era require further investigation.

Carrier State↗

Glycopeptides are no more effective than beta-lactam agents for prevention of surgical site infection after cardiac surgery: a meta-analysis.

A meta-analysis was performed to investigate whether a switch from beta-lactams to glycopeptides for cardiac surgery prophylaxis should be advised. Results of 7 randomized trials (5761 procedures) that compared surgical site infections (SSIs) in subjects receiving glycopeptide prophylaxis with SSIs in those who received beta -lactam prophylaxis were pooled. Neither agent proved to be superior for prevention of the primary outcome, occurrence of SSI at 30 days (risk ratio [RR], 1.14; 95% confidence interval [CI], 0.91-1.42). In subanalyses, beta-lactams were superior to glycopeptides for prevention of chest SSIs (RR, 1.47; 95% CI, 1.11-1.95) and approached superiority for prevention of deep-chest SSIs (RR, 1.33; 95% CI, 0.91-1.94) and SSIs caused by gram-positive bacteria (RR, 1.36; 95% CI, 0.98-1.91). Glycopeptides approached superiority to beta-lactams for prevention of leg SSIs (RR, 0.77; 95% CI, 0.58-1.01) and were superior for prevention of SSIs caused by methicillin-resistant gram-positive bacteria (RR, 0.54; 95% CI, 0.33-0.90). Standard prophylaxis for cardiac surgery should continue to be beta-lactams in most circumstances.

Anti-Bacterial Agents↗

Hospital-acquired infective endocarditis: should the definition be broadened?

Hospital-acquired infective endocarditis (IE) is a growing health-care problem. Hospital-acquired IE, according to the commonly used definition, is IE manifesting > or =72 h after admission to the hospital or within several weeks after a hospital-based invasive procedure. To assess the validity of this definition, we evaluated 87 episodes of IE, with special attention to recent hospitalizations. The incidence rate of IE in the 6-month period after discharge from the hospital was 27 cases per 100,000 person-years, compared with 1.1 cases per 100,000 person-years in a population with no recent hospitalizations. Furthermore, episodes of IE manifesting during this 6-month period were notable for a high proportion of typically hospital-acquired pathogens (26% vs. 0%; P=.001) and a low proportion of viridans streptococci (0% vs. 36%; P<.001), compared with community-acquired episodes that did not involve recent hospitalization. We conclude that characteristics of hospital-acquired IE extend to episodes arising within 6 months after discharge from the hospital and suggest that the definition of hospital-acquired IE be broadened to include these episodes.

Aged↗

Epidemiological interpretation of antibiotic resistance studies - what are we missing?

Antimicrobial resistance is an emerging public-health threat. Studies of the relationship between antibiotic use and resistance, as well as surveillance programmes, examine changes in the proportion of isolates that are resistant. Although proportions are helpful to the clinician prescribing empirical therapy, proportion-based analyses can be misleading to the public-health professional as they can yield biased estimates. Proportions do not adequately reflect the burden of resistance, a measure often of interest in public health. A more appropriate measure of this burden is the rate of isolation of resistant organisms, that is, the absolute number of resistant isolates in a population over time.

Anti-Bacterial Agents↗

The magnitude of the association between fluoroquinolone use and quinolone-resistant Escherichia coli and Klebsiella pneumoniae may be lower than previously reported.

Case-control analyses of resistant versus susceptible isolates have implicated fluoroquinolone exposure as a strong risk factor for fluoroquinolone-resistant isolates of Enterobacteriaceae. We suspect that such methodology may overestimate this association. A total of 84 cases with fluoroquinolone-resistant isolates and 578 cases with fluoroquinolone-susceptible isolates of Escherichia coli or Klebsiella pneumoniae were compared with 608 hospitalized controls in parallel multivariable analyses. For comparison of previous estimates, the results of 10 published case-control studies of risk for fluoroquinolone resistance in isolates of Enterobacteriaceae were pooled by using a random-effects model. Exposure to fluoroquinolones was significantly positively associated with fluoroquinolone resistance (odds ratio [OR], 3.17) and negatively associated with fluoroquinolone susceptibility (OR, 0.18). Multivariable analyses yielded similar estimates (ORs, 2.04 and 0.10, respectively). As data on antibiotic exposure were limited to inpatient prescriptions, misclassification of fluoroquinolone exposure in persons who received fluoroquinolones as outpatients may have led to an underestimation of the true effect size. Pooling the results of previously published studies in which a direct comparison of fluoroquinolone-resistant and fluoroquinolone-susceptible cases was used resulted in a markedly higher effect estimate (OR, 18.7). Had we directly compared resistant and susceptible cases, our univariate OR for the association between fluoroquinolone use and the isolation of resistant Enterobacteriaceae would have been 19.3, and the multivariate OR would have been 16.5. Fluoroquinolone use is significantly associated with the isolation of fluoroquinolone-resistant Enterobacteriaceae; however, previous studies likely exaggerated the magnitude of this association.

Aged↗

Fluoroquinolones protective against cephalosporin resistance in gram-negative nosocomial pathogens.

In a matched case-control study, we studied the effect of prior receipt of fluoroquinolones on isolation of three third-generation cephalosporin-resistant gram-negative nosocomial pathogens. Two hundred eighty-two cases with a third-generation cephalosporin-resistant pathogen (203 with Enterobacter spp., 50 with Pseudomonas aeruginosa, and 29 with Klebsiella pneumoniae) were matched on length of stay to controls in a 1:2 ratio. Case-patients and controls were similar in age (mean 62 years) and sex (54% male). Variables predicting third-generation cephalosporin resistance were surgery (p = 0.005); intensive care unit stay (p < 0.001); and receipt of a b-lactam/b-lactamase inhibitor (p < 0.001), a ureidopenicillin (p = 0.002), or a third-generation cephalosporin (p < 0.001). Receipt of a fluoroquinolone was protective against isolation of a third-generation cephalosporin-resistant pathogen (p = 0.005). Interventional studies are required to determine whether replacing third-generation cephalosporins with fluoroquinolones will be effective in reducing cephalosporin resistance and the effect of such interventions on fluoroquinolone resistance.

Case-Control Studies↗

Reference group choice and antibiotic resistance outcomes.

Two types of cohort studies examining patients infected with methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) were contrasted, using different reference groups. Cases were compared to uninfected patients and patients infected with the corresponding, susceptible organism. VRE and MRSA were associated with adverse outcomes. The effect was greater when uninfected control patients were used.

Cohort Studies↗

Mupirocin prophylaxis to prevent Staphylococcus aureus infection in patients undergoing dialysis: a meta-analysis.

A systematic review of the English-language literature was performed to determine the overall benefit of mupirocin therapy in reducing the rate of Staphylococcus aureus infection among patients undergoing hemodialysis (HD) or peritoneal dialysis (PD). Included studies met the following criteria: they were randomized clinical trials or cohort studies; cohorts consisted of adults (age, > or =18 years) requiring HD or PD; mupirocin therapy was administered to the treatment group, and placebo or no therapy was administered to the control group; and the primary outcome of interest was the difference in the number of S. aureus infections among mupirocin-treated and -untreated patients. Ten studies described in 9 articles were analyzed. A total of 2445 patients were included in the analysis. Use of mupirocin reduced the rate of S. aureus infections by 68% (95% confidence interval [CI], 57%-76%) among all patients undergoing dialysis; risk reductions were 80% (95% CI, 65%-89%) among patients undergoing HD and 63% (95% CI, 50%-73%) among patients undergoing PD. When data were stratified by type of infection, S. aureus bacteremia was found to be reduced by 78% among patients undergoing HD, and peritonitis and exit-site infections were found to be reduced by 66% and 62%, respectively, among patients undergoing PD. Mupirocin prophylaxis substantially reduces the rate of S. aureus infection in the dialysis population. Optimal regimens that minimize the emergence of mupirocin resistance need to be explored.

Adult↗