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Biomedical subjects

Yehuda Carmeli

Publications and source records attributed to Yehuda Carmeli.

53 records · Page 3Linked to original sources
PubMed2003

The impact of antimicrobial resistance on health and economic outcomes.

Despite an increasing prevalence of antimicrobial-resistant pathogens, the health and economic impact of colonization and infection with these organisms has not been fully elucidated. We explore how antimicrobial resistance can affect patient outcomes by enhancing virulence, causing a delay in the administration of appropriate therapy, and limiting available therapy. Next, we examine the different perspectives held by hospitals, third-party payers, patients, and society on the impact of resistance. Finally, we review methodological issues in designing and assessing studies that address the clinical outcomes for patients infected or colonized with resistant pathogens, including adjustment for important confounding variables, control group selection, and the quantification of economic outcomes.

Bacterial Infections↗
PubMed2003

Adverse clinical and economic outcomes attributable to methicillin resistance among patients with Staphylococcus aureus surgical site infection.

Data for 479 patients were analyzed to assess the impact of methicillin resistance on the outcomes of patients with Staphylococcus aureus surgical site infections (SSIs). Patients infected with methicillin-resistant S. aureus (MRSA) had a greater 90-day mortality rate than did patients infected with methicillin-susceptible S. aureus (MSSA; adjusted odds ratio, 3.4; 95% confidence interval, 1.5-7.2). Patients infected with MRSA had a greater duration of hospitalization after infection (median additional days, 5; P<.001), although this was not significant on multivariate analysis (P=.11). Median hospital charges were 29,455 dollars for control subjects, 52,791 dollars for patients with MSSA SSI, and 92,363 dollars for patients with MRSA SSI (P<.001 for all group comparisons). Patients with MRSA SSI had a 1.19-fold increase in hospital charges (P=.03) and had mean attributable excess charges of 13,901 dollars per SSI compared with patients who had MSSA SSIs. Methicillin resistance is independently associated with increased mortality and hospital charges among patients with S. aureus SSI.

Female↗
PubMed2003

Treatment with a broad-spectrum cephalosporin versus piperacillin-tazobactam and the risk for isolation of broad-spectrum cephalosporin-resistant Enterobacter species.

Receipt of a broad-spectrum cephalosporin is a strong risk factor for isolation of broad-spectrum cephalosporin-resistant Enterobacter species, and yet the risk from other broad-spectrum beta-lactams hydrolyzed by group 1 beta-lactamases has not been well characterized. We compared the risk conferred by broad-spectrum cephalosporins to that conferred by piperacillin-tazobactam, alone or in combination with an aminoglycoside or a fluoroquinolone. A retrospective cohort was monitored from treatment onset until a broad-spectrum cephalosporin-resistant Enterobacter strain was isolated or the patient was discharged. There were 447 patients in the piperacillin-tazobactam group and 2,341 patients in the broad-spectrum cephalosporin group. Groups were similar in age (mean, 62.5 years). The piperacillin-tazobactam group had a smaller percentage of men (32% versus 44%, P < 0.001) and a lower rate of intensive care unit stay (25% versus 38%, P < 0.001) but a higher rate of surgery (41% versus 26%, P < 0.001). Groups differed in the distribution of comorbidities. Resistant Enterobacter strains were isolated from 62 patients, 2% in each group (hazard ratio [RR] = 1.02 [P = 0.95]). In multivariable analysis, risk was similar among treatment groups (RR = 0.71 [P = 0.32]). Intensive care unit stay and surgery were associated with increased risk (RR = 4.53 [P < 0.001] and RR = 1.97 [P = 0.015], respectively), fluoroquinolones were protective (RR = 0.24 [P = 0.003]), and aminoglycosides did not affect risk (RR = 0.98 [P = 0.95]). The protective effect of fluoroquinolones against isolation of broad-spectrum cephalosporin-resistant Enterobacter spp. and the equivalence in risk associated with piperacillin-tazobactam and broad-spectrum cephalosporins may have important clinical and epidemiologic implications.

Anti-Bacterial Agents↗
PubMed2003

Occurrence and phenotypic characteristics of extended-spectrum beta-lactamases among members of the family Enterobacteriaceae at the Tel-Aviv Medical Center (Israel) and evaluation of diagnostic tests.

We assessed the prevalence and phenotypic characteristics of extended-spectrum beta-lactamase (ESBL) producers among cefuroxime-resistant (CXM-R) (MIC > or = 32 micro g/ml) members of the family Enterobacteriaceae in our institution. The 438 CXM-R clinical isolates obtained from nonurine sources among inpatients were screened. ESBL production was confirmed by disk diffusion assay using cefpodoxime (CPD), cefotaxime (CTX), and ceftazidime (CTZ) with and without clavulanate (CLAV). A difference of > or =5 mm in the size of the zone of inhibition in the presence of CLAV for at least one of the agents was considered representative of the ESBL phenotype: 186 isolates (42.5%) were confirmed as ESBL producers. The isolates tested and the rates of ESBL producers were as follows: Klebsiella spp. (n = 81), 79%; Proteus spp. (n = 58), 62%; Escherichia coli (n = 64), 53%; Enterobacter spp. (n = 69), 42%; Serratia spp. (n = 70), 14%; Citrobacter spp. (n = 25), 24%; Providencia spp. (n = 21), 24%; Morganella spp. (n = 41), 5%; and Kluyvera (n = 3), 0%. The overall sensitivity of isolated ESBL confirmatory tests was 79% for CPD-CLAV, 66% for CTZ-CLAV, and 91% for CTX-CLAV. Sensitivities of CTZ-CLAV confirmatory tests for Klebsiella spp., Proteus spp., E. coli, and Enterobacter spp. were 84, 22, 76, and 62%, respectively, and those for CTX-CLAV were 95, 97, 94, and 83%, respectively. They were 90% for CPD-CLAV and CTZ-CLAV, 95% for CPD-CLAV and CTX-CLAV, and 100% for CTZ-CLAV and CTX-CLAV. ESBL production was highly prevalent among Enterobacteriaceae. Using resistance to CXM as an ESBL screening criterion is a suitable option in high-incidence areas where Klebsiella spp. are not the dominant ESBL producers. This screening criterion may simplify the screening test and improve its sensitivity, although at the price of testing more isolates. The CTX-CLAV combination confirmed ESBL producers better than the CTZ-CLAV combination, with sensitivity varying between species. Combined CTZ-CLAV and CTX-CLAV testing detected all these strains; CPD-CLAV provided no additional benefit.

Anti-Bacterial Agents↗
PubMed2003

Infection of a ventriculoatrial shunt with phenotypically variable Staphylococcus epidermidis masquerading as polymicrobial bacteremia due to various coagulase-negative Staphylococci and Kocuria varians.

The diagnosis of bloodstream infection with coagulase-negative staphylococci is frequently based on the isolation of the same organism from more than one blood culture. Phenotypic variation is a common characteristic of pathogenic strains of Staphylococcus epidermidis which may affect species identification by the microbiology laboratory. We describe a patient with a new onset of nephritis and gram-positive bacteremia. Gram-positive cocci grew in multiple blood cultures and were identified by the Vitek 2 system as Kocuria varians, Staphylococcus hyicus, and S. epidermidis. Bacterial isolates grew on blood agar and Congo red agar plates as two distinct morphotypes and exhibited phenotypic variation. Neither morphotype could be identified by the API-Staph assay. Cellular fatty acid analysis identified one of the morphotypes as S. epidermidis but could not identify the other morphotype. All isolates were found to be identical by pulsed-field gel electrophoresis, and both colonial morphotypes were identified as S. epidermidis by 16S ribosomal gene sequencing. Phenotypic variation of S. epidermidis may affect identification to the species level by phenotype-based identification systems. Caution should be exercised when differentiating between true infection and contamination based on strain identification.

Actinomycetales↗
PubMed2003

Clinical implications of varying degrees of vancomycin susceptibility in methicillin-resistant Staphylococcus aureus bacteremia.

We conducted a retrospective study of the clinical aspects of bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA) with heterogeneously reduced susceptibility to vancomycin. Bloodstream MRSA isolates were screened for reduced susceptibility by using brain-heart infusion agar, including 4 mg/L vancomycin with and without 4% NaCl. Patients whose isolates exhibited growth (case-patients) were compared with those whose isolates did not (controls) for demographics, coexisting chronic conditions, hospital events, antibiotic exposures, and outcomes. Sixty-one (41%) of 149 isolates exhibited growth. Subclones from 46 (75%) of these had a higher MIC of vancomycin than did their parent isolates. No isolates met criteria for vancomycin heteroresistance. No differences in potential predictors or in outcomes were found between case-patients and controls. These data show that patients with vancomycin-susceptible MRSA bacteremia have similar baseline clinical features and outcomes whether or not their bacterial isolates exhibit growth on screening media containing vancomycin.

Bacteremia↗
PubMed2003

Pseudomonas aeruginosa and the oropharyngeal ecosystem of tube-fed patients.

We evaluated whether elderly patients fed with nasogastric tubes (NGT) are predisposed to Pseudomonas aeruginosa colonization in the oropharynx. Fifty-three patients on NGT feeding and 50 orally fed controls with similar clinical characteristics were studied. The tongue dorsum was swabbed and cultured. P. aeruginosa was isolated in 18 (34%) of the NGT-fed group but in no controls (p<0.001). Other gram-negative bacteria were cultured from 34 (64%) of NGT-fed patients as compared with 4 (8%) of controls (p<0.001). Antibiotic susceptibility of the oropharyngeal P. aeruginosa isolates was compared with that of isolates from sputum cultures obtained from our hospital's bacteriologic laboratory. The oropharyngeal isolates showed a higher rate of resistance; differences were significant for amikacin (p<0.03). Scanning electron microscope studies showed a biofilm containing P. aeruginosa organisms. The pulsed-field gel electrophoresis profile of these organisms was similar to that of P. aeruginosa isolates from the oropharynx. NGT-fed patients may serve as vectors of resistant P. aeruginosa strains.

Aged↗
PubMed2003

Fluoroquinolones and the risk for methicillin-resistant Staphylococcus aureus in hospitalized patients.

To determine whether fluoroquinolone exposure is a risk factor for the isolation of Staphylococcus aureus and whether the effect is different for methicillin-resistant S. aureus (MRSA) versus methicillin--susceptible S. aureus (MSSA), we studied two case groups. The first case group included 222 patients with nosocomially acquired MRSA. The second case group included 163 patients with nosocomially acquired MSSA. A total of 343 patients admitted concurrently served as controls. Outcome measures were the adjusted odds ratio (OR) for isolation of MRSA and MSSA after fluoroquinolone exposure. Exposure to both levofloxacin (OR 5.4; p <0.0001) and ciprofloxacin (OR 2.2; p < 0.003) was associated with isolation of MRSA but not MSSA. After adjustment for multiple variables, both drugs remained risk factors for MRSA (levofloxacin OR 3.4; p <0.0001; ciprofloxacin OR 2.5; p = 0.005) but not MSSA. Exposure to levofloxacin or ciprofloxacin is a significant risk factor for the isolation of MRSA, but not MSSA.

Aged↗
PubMed2002

Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteremia: a meta-analysis.

A meta-analysis was performed to summarize the impact of methicillin-resistance on mortality in Staphylococcus aureus bacteremia. A search of the MEDLINE database for studies published during the period of 1 January 1980 through 31 December 2000 and a bibliographic review identified English-language studies of S. aureus bacteremia. Studies were included if they contained the numbers of and mortality rates for patients with methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) bacteremia. Data were extracted on demographic characteristics of the patients, adjustment for severity and comorbid illness, source of bacteremia, and crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for in-hospital mortality. When the results were pooled with a random-effects model, a significant increase in mortality associated with MRSA bacteremia was evident (OR, 1.93; 95% CI, 1.54-2.42; P<.001); significant heterogeneity was present. We explored the reasons for heterogeneity by means of subgroup analyses. MRSA bacteremia is associated with significantly higher mortality rate than is MSSA bacteremia.

Bacteremia↗
PubMed2002

Health and economic outcomes of vancomycin-resistant enterococci.

BACKGROUND: The health and economic impact of vancomycin-resistant enterococci has not been quantified. METHODS: A retrospective matched cohort study was conducted comparing the outcomes of patients with vancomycin-resistant enterococci (cases) with those of control subjects matched for length of hospital stay until inclusion in the cohort, hospital location, and calendar date. The propensity to be a vancomycin-resistant enterococci case was modeled based on patient characteristics, and included in multivariable models to adjust for confounding. Analyses included the following: (1) conditional logistic regression for mortality, surgery, intensive care unit admission, and discharge to long-term care; (2) linear regression for the logarithm of cost; and (3) accelerated failure time model for length of stay. RESULTS: A total of 233 cases were compared with 647 controls. Groups were similar in age (mean, 62 years), sex (female, 47%), and length of stay before inclusion in the cohort (mean, 8.1 days), but differed in primary diagnosis and comorbidities, past infection or colonization with methicillin sodium-resistant Staphylococcus aureus or Clostridium difficile, and treatment with cephalosporins or metronidazole. These variables were included in the propensity score, which had good to excellent prediction. Outcomes for cases vs controls and adjusted risks (relative risks [RRs]) were as follows: (1) case fatality rate, 17% vs 6% (RR, 2.13; P =.04); (2) length of stay after inclusion in the cohort, 15.1 vs 8.5 days (RR, 1.73; P<.001); (3) hospital costs, $52 449 vs $31 915 (RR, 1.40; P<.001); (4) surgery after inclusion in the cohort, 18% vs 10% (RR, 2.74; P =.001); (5) intensive care unit admission after inclusion in the cohort, 25% vs 14% (RR, 3.47; P<.001); and (6) transfer to an institution, 51% vs 35% (RR, 2.01; P =.001). CONCLUSION: Compared with a matched hospital population, a population with vancomycin-resistant enterococci was associated with severe adverse outcomes: increased mortality, morbidity, and costs.

Cohort Studies↗
PubMed2002

Control-group selection importance in studies of antimicrobial resistance: examples applied to Pseudomonas aeruginosa, Enterococci, and Escherichia coli.

We aimed to illustrate the importance of control-group selection on the results of risk factor analysis for (1) imipenem-resistant Pseudomonas aeruginosa, (2) vancomycin-resistant enterococci (VRE), and (3) ampicillin-sulbactam-resistant Escherichia coli. Case patients were compared with 2 different control groups: patients with the susceptible form of the organism (type 1), and control patients among whom the case patients arose during the same period as the case patients (type 2). Comparison of case patients who had imipenem-resistant P. aeruginosa with type-1 control patients identified use of imipenem (odds ratio [OR], 27.1) and quinolones (OR, 3.25) as a risk factor for selection of antimicrobial resistance, and comparison of the same case patients with type-2 control patients identified imipenem (OR, 6.34). When case patients with VRE were compared with type-1 and with type-2 control patients, use of vancomycin was identified as a risk factor (OR, 4.38 and 2.77, respectively). Comparison of case patients who had ampicillin-sulbactam-resistant E. coli compared with type-1 control patients identified ampicillin-sulbactam (OR, 2.71) and quinolones (OR, 2.72), and comparison with type-2 control patients identified ampicillin-sulbactam (OR, 1.68). The selection of control patients from the potentially suboptimal control type 1 can falsely identify certain antibiotics and overestimate the OR of the resistance-defining antibiotic.

Anti-Bacterial Agents↗
PubMed2002

Health and economic outcomes of the emergence of third-generation cephalosporin resistance in Enterobacter species.

BACKGROUND: This study evaluated the clinical and economic impact of the emergence of third-generation cephalosporin-resistant Enterobacter species. METHODS: Mortality, length of hospitalization, and hospital charges were examined in a cohort that was selected from a group of 477 patients with initial cultures that yielded a third-generation cephalosporin-susceptible Enterobacter species. Case patients (n = 46) had subsequent cultures yielding a third-generation cephalosporin-resistant Enterobacter species. Control patients (n = 113) who did not develop resistance were matched to cases on site of Enterobacter infection and length of hospitalization prior to isolation of the initial susceptible organism. Multivariable analyses were used to adjust for confounding. RESULTS: Twenty-six percent of cases died vs 13% of controls (P =.06). The median total hospital stay for cases was 29.5 days (interquartile range [IQR], 20-60) and 19 days for controls (IQR, 13-27; P<.001). The median hospital charge for cases was $79 323 (IQR, $34 546-$161 384) and for controls was $40 406 (IQR, $18 470-$79 005; P<.001). After adjusting for comorbidities, severity of illness, intensive care unit admission, surgery, transfer from another hospital, sex, and age, emergence of resistance was associated with increased mortality (relative risk, 5.02; P =.01), hospital stay (1.5-fold, P<.001), and hospital charges (1.5-fold, P<.001). Emergence of resistance had a median attributable hospital stay of 9 days and an average attributable hospital charge of $29 379. CONCLUSIONS: Emergence of antibiotic resistance in Enterobacter species results in increased mortality, hospital stay, and hospital charges. Minimizing resistance in Enterobacter species should be a priority.

Aged↗
PubMed2002

Antibacterial properties of dermaseptin S4 derivatives with in vivo activity.

Derivatives of the cytotoxic peptide dermaseptin S4 have recently emerged as potential antimicrobial agents. Here, we report on the antibacterial properties of three derivatives with improved toxicity profiles: a 28-residues K4K20-S4 and two shorter versions, K4-S4(1-16) and K4-S4(1-13). The range of MICs of K4K20-S4 against clinical isolates of Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli were, respectively, 1 to 4, 1 to 4, and 1 to 16 microg/ml. MICs of the short derivatives were rather similar or two to fourfold higher. Each of the three peptides was rapidly bactericidal in vitro, reducing the number of viable CFU of either E. coli or S. aureus by 6 log units in 30 min or less. Compared with MSI-78 or PG-1, K4-S4(1-13) was at least as potent against bacteria (assessed at two MIC multiples) but displayed lesser toxicity against human erythrocytes. Serial passage in subinhibitory concentrations led to emergence of resistance to commercial antibiotics but not to the L- or D isomer of either of the dermaseptin derivatives. The short derivatives were further investigated for antibacterial activity in vivo, using a peritonitis model of mice infected with P. aeruginosa. Naive mice in the vehicle control group exhibited 75% mortality, compared to 18 or 36% mortality in mice that received a single intraperitoneal injection (4.5 mg/kg) of K4-S4(1-16) or K4-S4(1-13), respectively. In vivo bactericidal activity was confirmed in neutropenic mice, where intraperitoneal administration of K4-S4(1-16) reduced the number of viable CFU in a dose-dependent manner by >3 log units within 1 h of exposure, and this was sustained for at least 5 h. Overall, the data suggest that dermaseptin S4 derivatives could be useful in treatment of infections, including infections caused by multidrug-resistant bacteria.

Amino Acid Sequence↗
PubMed2002

Use of insurance claims data to assess outpatient antimicrobial therapy for gram-positive infections.

With the increasing frequency of antibiotic-resistant gram-positive infections in the United States, many patients are being treated outside the hospital setting. The majority of studies on the cost of outpatient antimicrobial therapy involve retrospective medical record review or prospective data collection. These methods tend to be expensive and time consuming, and often fail to produce a sufficiently large sample size. Analysis of insurance claims data offers a convenient approach for studying the costs associated with outpatient therapy for gram-positive infections. To demonstrate this approach, a study of the cost of intravenous vancomycin home care therapy was conducted using claims data from a large insurance company.

Adolescent↗
PubMed2002

Antecedent treatment with different antibiotic agents as a risk factor for vancomycin-resistant Enterococcus.

We conducted a matched case-control study to compare the effect of antecedent treatment with various antibiotics on subsequent isolation of vancomycin-resistant Enterococcus (VRE); 880 in-patients; 233 VRE cases, and 647 matched controls were included. After being matched for hospital location, calendar time, and duration of hospitalization, the following variables predicted VRE positivity: main admitting diagnosis; a coexisting condition (e.g., diabetes mellitus, organ transplant, or hepatobiliary disease); and infection or colonization with methicillin-resistant Staphylococcus aureus or Clostridium difficile within the past year (independent of vancomycin treatment). After controlling for these variables, we examined the effect of various antibiotics. Intravenous treatment with third-generation cephalosporins, metronidazole, and fluoroquinolones was positively associated with VRE. In our institution, when we adjusted the data for temporo-spatial factors, patient characteristics, and hospital events, treatment with third-generation cephalosporins, metronidazole, and fluoroquinolones was identified as a risk factor for VRE. Vancomycin was not a risk factor for isolation of VRE.

Adolescent↗