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.

FIG. 1.

Effect of fluoroquinolone use on the isolation of fluoroquinolone-resistant Enterobacteriaceae. Results from standard case-control studies are shown. Stippled boxes, ORs for the individual studies; black regions, pooled ORs. From top to bottom, the names at the left correspond to references , , , , , , , , , and .