Person:

Carmeli, Yehuda

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 (\beta)-lactam/(\beta)-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.

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.

Antibiotic exposure exerts strong selective pressure and is an important modifiable risk factor for antibiotic resistance. We aimed to identify the role of various antibiotics as risk factors for the isolation of extended-spectrum-β-lactamase (ESBL)-producing Klebsiella spp. in hospitalized patients at a tertiary-care hospital. A parallel multivariable model was created to compare two groups of cases with either nosocomially acquired ESBL- or non-ESBL-producing Klebsiella spp. to a common control group of hospitalized patients (a case-case-control design). Seventy-eight ESBL cases, 358 non-ESBL cases, and 444 controls were analyzed. Significant factors associated with the isolation of Klebsiella spp. were an age of >65 years, transfer from a health care facility, an intensive care unit (ICU) stay, and the presence of a comorbid malignancy or lung, hepatic, or renal disease. A propensity score was generated from the above, and our ability to discriminate between Klebsiella cases and controls (area under the receiver-operating-characteristic [ROC] curve, 0.78) was good. The ESBL phenotype was tightly linked with fluoroquinolone resistance (95% versus 18%, P < 0.001). Factors associated with isolation of ESBL Klebsiella spp. in a multivariable analysis, adjusting for the propensity score, included exposure to β-lactam-β-lactamase inhibitor combinations (odds ratio [OR], 10.17; 95% confidence interval [CI], 1.19 to 86.92) and to fluoroquinolones (OR, 2.86; 95% CI, 1.37 to 5.97). Exposure to broad-spectrum cephalosporins was statistically associated with ESBL Klebsiella spp. only among the subgroup of patients not treated with fluoroquinolones. In our institution, where the ESBL-producing-Klebsiella phenotype is coselected with fluoroquinolone resistance, fluoroquinolone and β-lactam-β-lactamase inhibitor combinations, rather than cephalosporins, are the main risk factors for ESBL isolates. Formulary interventions to limit the spread of ESBL-producing isolates should be tailored to each setting.