title: Association between fluoroquinolone resistance and mortality in Escherichia coli and Klebsiella pneumoniae infections: the role of inadequate empirical antimicrobial therapy.
abstract: BACKGROUND
  The prevalence of fluoroquinolone (FQ) resistance among Escherichia coli and Klebsiella pneumoniae has increased markedly in recent years. However, the impact of FQ resistance on mortality remains unknown.
  
  
  METHODS
  To identify the association between FQ resistance and mortality, we conducted a retrospective cohort study of hospitalized patients with infections due to FQ-resistant strains and FQ-susceptible strains of E. coli and K. pneumoniae between 1 January 1998 and 30 June 1999.
  
  
  RESULTS
  Of 123 patients with FQ-resistant infection, 16 (13.0%) died, compared with 4 (5.7%) of 70 patients with FQ-susceptible infection (odds ratio [OR], 2.47; 95% confidence interval [CI], 0.75-10.53). After adjustment for other significant risk factors and confounders, there remained an independent association between FQ-resistant infection and mortality (adjusted OR, 4.41; 95% CI, 1.03-18.81). Patients with FQ-resistant infection were significantly less likely to have received antimicrobial therapy with activity against the infecting pathogen within the first 24 h and 48 h of infection (P=.002 and P<.001, respectively). The association between FQ resistance and mortality was no longer significant, after adjusting for inadequate empirical therapy.
  
  
  CONCLUSIONS
  FQ resistance is an independent risk factor for mortality in patients with health care-acquired E. coli and K. pneumoniae infections. This may be explained, at least in part, by a delay in the initiation of appropriate antimicrobial therapy in patients with FQ-resistant infection. These results highlight the grave clinical consequences of FQ resistance and emphasize the importance of efforts designed to curb the increase in the prevalence of resistance to these agents.
authors.affiliation: Division of Infectious Diseases, Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, USA. elautenb@cceb.med.upenn.edu
authors.forename: Ebbing
authors.initials: E
authors.lastname: Lautenbach
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Metlay
authors.forename: Warren B
authors.initials: WB
authors.lastname: Bilker
authors.forename: Paul H
authors.initials: PH
authors.lastname: Edelstein
authors.forename: Neil O
authors.initials: NO
authors.lastname: Fishman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D024901:Drug Resistance, Multiple, Bacterial; D004363:Drug Utilization; D004926:Escherichia coli / Q000187:drug effects*; D004927:Escherichia coli Infections / Q000382:microbiology / Q000401:mortality*; D005260:Female; D024841:Fluoroquinolones / Q000627:therapeutic use*; D006801:Humans; D007710:Klebsiella Infections / Q000382:microbiology / Q000401:mortality*; D007711:Klebsiella pneumoniae / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones