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Antimicrobial Agents and Chemotherapy, June 2007, p. 1987-1994, Vol. 51, No. 6
0066-4804/07/$08.00+0     doi:10.1128/AAC.01509-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Predictors of Mortality in Patients with Bloodstream Infections Caused by Extended-Spectrum-ß-Lactamase-Producing Enterobacteriaceae: Importance of Inadequate Initial Antimicrobial Treatment{triangledown}

Mario Tumbarello,1* Maurizio Sanguinetti,2 Eva Montuori,1 Enrico M. Trecarichi,1 Brunella Posteraro,2 Barbara Fiori,2 Rita Citton,1 Tiziana D'Inzeo,2 Giovanni Fadda,2 Roberto Cauda,1 and Teresa Spanu2

Institute of Infectious Diseases,1 Institute of Microbiology, Catholic University of the Sacred Heart, Largo A. Gemelli 8, 00168 Rome, Italy2

Received 30 November 2006/ Returned for modification 3 January 2007/ Accepted 18 March 2007

Bloodstream infections (BSI) caused by extended-spectrum ß-lactamase (ESBL)-producing organisms markedly increase the rates of treatment failure and death. We conducted a retrospective cohort analysis to identify risk factors for mortality in adult in-patients with BSI caused by ESBL-producing Enterobacteriaceae (ESBL-BSI). Particular attention was focused on defining the impact on the mortality of inadequate initial antimicrobial therapy (defined as the initiation of treatment with active antimicrobial agents >72 h after collection of the first positive blood culture). A total of 186 patients with ESBL-BSI caused by Escherichia coli (n = 104), Klebsiella pneumoniae (n = 58), or Proteus mirabilis (n = 24) were identified by our microbiology laboratory from 1 January 1999 through 31 December 2004. The overall 21-day mortality rate was 38.2% (71 of 186). In multivariate analysis, significant predictors of mortality were inadequate initial antimicrobial therapy (odds ratio [OR] = 6.28; 95% confidence interval [CI] = 3.18 to 12.42; P < 0.001) and unidentified primary infection site (OR = 2.69; 95% CI = 1.38 to 5.27; P = 0.004). The inadequately treated patients (89 of 186 [47.8%]) had a threefold increase in mortality compared to the adequately treated group (59.5% versus 18.5%; OR = 2.38; 95% CI = 1.76 to 3.22; P < 0.001). The regimens most commonly classified as inadequate were based on oxyimino cephalosporin or fluoroquinolone therapy. Prompt initiation of effective antimicrobial treatment is essential in patients with ESBL-BSI, and empirical decisions must be based on a sound knowledge of the local distribution of pathogens and their susceptibility patterns.

* Corresponding author. Mailing address: Istituto Malattie Infettive, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy. Phone: 39-06-30155373. Fax: 39-06-3054519. E-mail: tumbarello{at}rm.unicatt.it

{triangledown} Published ahead of print on 26 March 2007.

Antimicrobial Agents and Chemotherapy, June 2007, p. 1987-1994, Vol. 51, No. 6
0066-4804/07/$08.00+0     doi:10.1128/AAC.01509-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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