Impact of inadequate initial antimicrobial therapy on mortality in infections due to extended-spectrum beta-lactamase-producing enterobacteriaceae: variability by site of infection

Arch Intern Med. 2005 Jun 27;165(12):1375-80. doi: 10.1001/archinte.165.12.1375.

Abstract

Background: Infections due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species (ESBL-EK) have increased markedly in recent years. Risk factors for mortality among ESBL-EK infections have not been studied.

Methods: This retrospective cohort study was conducted in a 625-bed tertiary care medical center and a 344-bed urban community hospital to determine whether inadequate initial antimicrobial therapy (IIAT) (>48 hours between the time a culture was obtained and initiation of an agent to which the infecting organism was susceptible) is associated with mortality in ESBL-EK infections. All hospitalized patients with an ESBL-EK infection between June 1, 1997, and December 31, 2002, were eligible for inclusion. Subsequently, we conducted a nested case-control study to identify risk factors for IIAT.

Results: Of 187 subjects, 32 (17.1%) died while in the hospital. Clinical site of infection was a significant effect modifier in the association between IIAT and mortality. The presence of IIAT was an independent risk factor for mortality, but only for nonurinary ESBL-EK infections (adjusted odds ratio [95% confidence interval], 10.04 [1.90-52.96]). Independent risk factors for IIAT were (1) infection with a multidrug-resistant ESBL-EK (ie, resistant to sulfamethoxazole-trimethoprim, aminoglycosides, and quinolones) (14.58 [1.91-111.36]) and (2) health care-acquired ESBL-EK infection (4.32 [1.49-12.54]).

Conclusions: Inadequate initial antimicrobial therapy is an independent risk factor for mortality in ESBL-EK infections, but only among nonurinary infections. Multidrug resistance was a strong risk factor for IIAT.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Anti-Bacterial Agents / administration & dosage*
  • Cohort Studies
  • Drug Administration Schedule
  • Escherichia coli Infections / drug therapy
  • Escherichia coli Infections / mortality*
  • Female
  • Humans
  • Infections / drug therapy
  • Infections / microbiology
  • Infections / mortality
  • Klebsiella Infections / drug therapy
  • Klebsiella Infections / mortality*
  • Klebsiella oxytoca / enzymology*
  • Klebsiella pneumoniae / enzymology*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Treatment Failure
  • beta-Lactamases / biosynthesis*

Substances

  • Anti-Bacterial Agents
  • beta-Lactamases