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Antimicrobial Agents and Chemotherapy, September 2008, p. 3244-3252, Vol. 52, No. 9
0066-4804/08/$08.00+0     doi:10.1128/AAC.00063-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Bloodstream Infections Caused by Extended-Spectrum-β-Lactamase- Producing Escherichia coli: Risk Factors for Inadequate Initial Antimicrobial Therapy

Mario Tumbarello,^1* Michela Sali,² Enrico Maria Trecarichi,¹ Fiammetta Leone,² Marianna Rossi,¹ Barbara Fiori,² Gennaro De Pascale,¹ Tiziana D'Inzeo,² Maurizio Sanguinetti,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 16 January 2008/ Returned for modification 28 March 2008/ Accepted 21 June 2008

Extended-spectrum-β-lactamase (ESBL)-producing strains of Escherichia coli are a significant cause of bloodstream infections (BSI) in hospitalized and nonhospitalized patients. We previously showed that delaying effective antimicrobial therapy in BSI caused by ESBL producers significantly increases mortality. The aim of this retrospective 7-year analysis was to identify risk factors for inadequate initial antimicrobial therapy (IIAT) (i.e., empirical treatment based on a drug to which the isolate had displayed in vitro resistance) for inpatients with BSI caused by ESBL-producing E. coli. Of the 129 patients considered, 56 (43.4%) received IIAT for 48 to 120 h (mean, 72 h). Independent risk factors for IIAT include an unknown BSI source (odds ratios [OR], 4.86; 95% confidence interval [CI], 1.98 to 11.91; P = 0.001), isolate coresistance to 3 antimicrobials (OR, 3.73; 95% CI, 1.58 to 8.83; P = 0.003), hospitalization during the 12 months preceding BSI onset (OR, 3.33; 95% CI, 1.42 to 7.79; P = 0.005), and antimicrobial therapy during the 3 months preceding BSI onset (OR, 2.65; 95% CI, 1.11 to 6.29; P = 0.02). IIAT was the strongest risk factor for 21-day mortality and significantly increased the length of hospitalization after BSI onset. Our results underscore the need for a systematic approach to the management of patients with serious infections by ESBL-producing E. coli. Such an approach should be based on sound, updated knowledge of local infectious-disease epidemiology, detailed analysis of the patient's history with emphasis on recent contact with the health care system, and aggressive attempts to identify the infectious focus that has given rise to the BSI.

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* 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

Published ahead of print on 30 June 2008.

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Antimicrobial Agents and Chemotherapy, September 2008, p. 3244-3252, Vol. 52, No. 9
0066-4804/08/$08.00+0     doi:10.1128/AAC.00063-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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