Yehuda Carmeli

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.

Prior Antimicrobial Therapy and Risk for Hospital-Acquired Candida glabrata and Candida krusei Fungemia: a Case-Case-Control Study

ABSTRACT The incidence of infections caused by Candida glabrata and Candida krusei, which are generally more resistant to fluconazole than Candida albicans, is increasing in hospitalized patients. However, the extent to which prior exposure to specific antimicrobial agents increases the risk of subsequent C. glabrata or C. krusei candidemia has not been closely studied. A retrospective case-case-control study was performed at a university hospital. From 1998 to 2003, 60 patients were identified with hospital-acquired non-C. albicans candidemia (C. glabrata or C. krusei; case group 1). For comparison, 68 patients with C. albicans candidemia (case group 2) and a common control group of 121 patients without candidemia were studied. Models were adjusted for demographic and clinical risk factors, and the risk for candidemia associated with exposure to specific antimicrobial agents was assessed. After adjusting for both nonantimicrobial risk factors and receipt of other antimicrobial agents, piperacillin-tazobactam (odds ratio [OR], 4.15; 95% confidence interval [CI], 1.04 to 16.50) and vancomycin (OR, 6.48; CI, 2.20 to 19.13) were significant risk factors for C. glabrata or C. krusei candidemia. For C. albicans candidemia, no specific antibiotics remained a significant risk after adjusted analysis. Prior fluconazole use was not significantly associated with either C. albicans or non-C. albicans (C. glabrata or C. krusei) candidemia. In this single-center study, exposure to antibacterial agents, specifically vancomycin or piperacillin-tazobactam, but not fluconazole, was associated with subsequent hospital-acquired C. glabrata or C. krusei candidemia. Further studies are needed to prospectively analyze specific antimicrobial risks for nosocomial candidemia across multiple hospital centers.

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.

Risk factors for emergence of resistance to broad-spectrum cephalosporins among Enterobacter spp.

ABSTRACT Among 477 patients with susceptible Enterobacter spp., 49 subsequently harbored third-generation cephalosporin-resistantEnterobacter spp. Broad-spectrum cephalosporins were independent risk factors for resistance (relative risk [OR] = 2.3, P = 0.01); quinolone therapy was protective (OR = 0.4, P = 0.03). There were trends toward decreased risk for resistance among patients receiving broad-spectrum cephalosporins and either aminoglycosides or imipenem. Of the patients receiving broad-spectrum cephalosporins, 19% developed resistance.

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.

Risk Factors for Recovery of Ampicillin-Sulbactam-Resistant Escherichia coli in Hospitalized Patients

ABSTRACT Ampicillin-sulbactam resistance in Escherichia coli is an emerging problem. This study determined risk factors for the recovery of ampicillin-sulbactam-resistant E. coli in hospitalized patients. A case-control design was used to compare two groups of case patients with control patients. The first group of case patients consisted of patients from whom nosocomially acquired ampicillin-sulbactam-resistant E. coli strains were isolated, and the second group of case patients consisted of patients from whom ampicillin-sulbactam-susceptible E. coli strains were isolated. Control patients were a random selection among 5% of all patients admitted during the same time period. Risk factors analyzed included antimicrobial drug exposure, comorbid conditions, and demographics. Univariate and multivariate analyses were performed. Ampicillin-sulbactam-resistant E. coli strains were isolated from 175 patients, and ampicillin-sulbactam-susceptibleE. coli strains were isolated from 577 patients. Nine hundred thirty-four control patients were selected. Exposure to penicillin antibiotics as a class and to ampicillin and ampicillin-sulbactam individually were the only significant, independent risk factors associated with the isolation of ampicillin-sulbactam-resistant E. coli (odds ratio [OR] = 2.32 [P < 0.001], OR = 3.04 [P = 0.02], and OR = 1.72 [P= 0.04], respectively), but they were not associated with the isolation of ampicillin-sulbactam-susceptible E. coli. Interestingly, exposure to piperacillin-tazobactam tended to protect against the isolation of E. coli strains resistant to ampicillin-sulbactam, but this did not reach statistical significance (OR = 0.13; P = 0.11).

Predictors of mortality in patients with bloodstream infection due to ceftazidime-resistant Klebsiella pneumoniae.

ABSTRACT Bloodstream infection (BSI) due to multidrug-resistant Klebsiella is associated with high rates of morbidity and mortality. The aim of this study was to identify predictors of in-hospital mortality among patients with BSI due to ceftazidime-resistant (CAZ-R) Klebsiella pneumoniae at a tertiary care medical center. Patients with CAZ-R K. pneumoniae BSI were identified by our microbiology laboratory between January 1995 and June 2003. Clinical data were collected retrospectively. Logistic regression was used to identify independent predictors of all causes of in-hospital mortality. Of 779 patients with K. pneumoniae BSI, 60 (7.7%) had BSI due to CAZ-R K. pneumoniae; 43 (72%) of these were nosocomial infections. Pulsed-field gel electrophoresis identified a single predominant strain in 17 (28%) patients. The in-hospital mortality rate was 43% (n = 26). Among patients with CAZ-R K. pneumoniae BSI, those who died were similar to survivors with respect to demographic, clinical, and antimicrobial susceptibility characteristics. Only 43 (72%) patients received effective therapy within 5 days of BSI. In bivariable analysis, delay in initiation of effective therapy for >72 h after diagnosis of BSI was associated with death (P = 0.03). Strain genotype was not predictive of outcome. In multivariable analysis, delay in initiation of effective therapy for >72 h after diagnosis of BSI was an independent predictor of death (odds ratio, 3.32; 95% confidence interval, 1.07 to 10.3). Thus, among patients with BSI due to CAZ-R K. pneumoniae, a delay in the initiation of effective therapy of greater than 72 h after BSI was associated with a >3-fold increase in mortality risk.

Differential Effects of Levofloxacin and Ciprofloxacin on the Risk for Isolation of Quinolone-Resistant Pseudomonas aeruginosa

ABSTRACT Due to the greater in vitro activity of ciprofloxacin than that of levofloxacin against Pseudomonas aeruginosa, the likelihood of isolating a clinical strain of quinolone-resistant (QR) P. aeruginosa might be greater after exposure to levofloxacin than ciprofloxacin. We examined the risk of isolating QR P. aeruginosa in association with prior levofloxacin or ciprofloxacin exposure. A case-case-control study was conducted. Two groups of cases, one with nosocomial QR P. aeruginosa infections and one with nosocomial quinolone-susceptible (QS) P. aeruginosa infections, were compared to a control group of hospitalized patients without P. aeruginosa infections. Bivariable and multivariable analyses were used to determine risk factors for isolation of QR P. aeruginosa and QS P. aeruginosa. One hundred seventeen QR P. aeruginosa and 255 QS P. aeruginosa cases were identified, and 739 controls were selected. Exposures to ciprofloxacin were similar among all three groups (8% for controls, 9.4% for QR P. aeruginosa cases, and 7.5% for QS P. aeruginosa cases; P ≥ 0.6). Levofloxacin use was more frequent in the QR P. aeruginosa cases than in the controls (35.9% and 22.1%, respectively; odds ratio [OR] = 2.0; 95% confidence interval [CI] = 1.3 to 3.0) and less frequent in QS P. aeruginosa cases (14.1% of QS P. aeruginosa cases; OR = 0.6; 95% CI = 0.4 to 0.9). In multivariable analysis, levofloxacin, but not ciprofloxacin, was a significant risk factor for isolation of QR P. aeruginosa (OR for levofloxacin = 1.7 [95% CI = 1.0 to 2.9]; OR for ciprofloxacin = 1.2 [95% CI = 0.6 to 2.5]). Levofloxacin was associated with a reduced risk of isolation of QS P. aeruginosa (OR = 0.6; 95% CI = 0.4 to 0.9), whereas ciprofloxacin had no significant effect (OR = 1.0; 95% CI = 0.6 to 1.8). In conclusion, the use of levofloxacin, but not ciprofloxacin, was associated with isolation of QR P. aeruginosa.

The Magnitude of the Association between Fluoroquinolone Use and Quinolone-Resistant Escherichia coli and Klebsiella pneumoniae May Be Lower than Previously Reported

ABSTRACT 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.

Case–control study to identify factors associated with mortality among patients with methicillin-resistant Staphylococcus aureus bacteraemia

Methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia is associated with increased mortality. Delay in appropriate antimicrobial therapy (DAAT) is an important risk factor for death, although confounding between carriage of MRSA and DAAT has not been resolved. We studied the association of risk factors with mortality and searched for specific populations vulnerable to DAAT. We conducted a case-control study comparing patients with MRSA bacteraemia who died during hospitalization (cases) with patients with MRSA bacteraemia who survived (controls) in three medical centres in two states. Patients were identified using computerized hospital databases for the years 2001-2005. Medical records were retrieved and various epidemiological data extracted. Bivariate and multivariate logistic regression analyses were performed. Overall, 388 patients with MRSA bacteraemia were included, 164 cases and 224 controls. According to bivariate analyses, cases were significantly more likely than controls to (i) be older (>65 years), (ii) have transferred from an institution, (iii) have stayed in an ICU, (iv) have had more invasive devices, (v) have a poorer prognosis on admission, (vi) have higher disease severity at the time of bacteraemia, and (vii) have a DAAT of > or = 2 days. Upon multivariate analysis, among patients >65 years, DAAT was significantly associated with increased mortality (p 0.04). Furthermore, patients >65 years with severe sepsis were much more likely to experience DAAT (p 0.02). In elderly patients with MRSA bacteraemia, DAAT is associated with increased mortality. Moreover, advanced age is a predictor for DAAT. These significant epidemiological associations mandate early coverage of MRSA in septic elderly patients.