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Original Investigation
June 27, 2005

Impact of Inadequate Initial Antimicrobial Therapy on Mortality in Infections Due to Extended-Spectrum β-Lactamase–Producing Enterobacteriaceae: Variability by Site of Infection

Author Affiliations

Author Affiliations: Center for Clinical Epidemiology and Biostatistics (Ms Hyle, Mr Lipworth, and Drs Zaoutis, Bilker, and Lautenbach), Center for Education and Research on Therapeutics (Ms Hyle, Mr Lipworth, and Drs Zaoutis, Bilker, and Lautenbach), Departments of Pathology and Laboratory Medicine (Dr Nachamkin) and Biostatistics and Epidemiology (Drs Bilker and Lautenbach), and Division of Infectious Diseases, Department of Medicine (Dr Lautenbach), University of Pennsylvania School of Medicine, Philadelphia; and Division of Infectious Diseases, Department of Medicine, The Children’s Hospital of Philadelphia (Dr Zaoutis).

Arch Intern Med. 2005;165(12):1375-1380. doi:10.1001/archinte.165.12.1375

Background  Infections due to extended-spectrum β-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.