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JAC Advance Access published online on June 3, 2006

Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl239
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Received February 8, 2006
Accepted May 12, 2006

Original article

The influence of metallo-{beta}-lactamase production on mortality in nosocomial Pseudomonas aeruginosa infections

Alexandre Prehn Zavascki 1 *, Afonso Luís Barth 2, Ana Lúcia Saraiva Gonçalves 3, Ana Lúcia Didonet Moro 4, Juliana Fernandez Fernandes 5, Andreza Francisco Martins 3, Fabiano Ramos 6, and Luciano Zubaran Goldani 7

1 Infectious Diseases Service, Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil; Medicine: Medical Sciences Postgraduate Program, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
2 Medicine: Medical Sciences Postgraduate Program, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Microbiology Unit, Clinical Pathology Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
3 Microbiology Unit, Clinical Pathology Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
4 Medical School, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil
5 Medical School, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
6 Infectious Diseases Service, Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil
7 Medicine: Medical Sciences Postgraduate Program, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Division of Infectious Diseases, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil

* To whom correspondence should be addressed.
Alexandre Prehn Zavascki, E-mail: apzavascki{at}terra.com.br


   Abstract

Objectives: To assess the effect of metallo-{beta}-lactamase (MBL) production on Pseudomonas aeruginosa nosocomial infection mortality and to identify the determinants of such effect.

Methods: A cohort study of patients with P. aeruginosa nosocomial infections was conducted at two teaching hospitals. MBL was detected by ceftazidime/2-mercaptopropionic disc approximation test and selected isolates were submitted to PCR using blaSPM-1 primer. Molecular typing was performed by DNA macrorestriction. To evaluate the influence of MBL on mortality a Cox proportional hazards model was performed using a hierarchized framework of the variables.

Results: A total of 298 patients with P. aeruginosa infections were included. Infections by MBL-carrying Pseudomonas aeruginosa (MBL-PA) resulted in higher in-hospital mortality than those by non-MBL-PA (51.2% versus 32.1%, respectively; relative risk 1.60, 95% CI 1.20-2.12) and higher mortality rates [17.3 per 1000 versus 11.8 per 1000 patient-days, respectively; hazard ratio (HR) 1.55, 95% CI 1.06-2.27]. In the final multivariate model, severe sepsis or septic shock [adjusted HR (AHR) 3.62, 95% CI 2.41-5.43], age (AHR 1.02, 95% CI 1.01-1.03) and use of appropriate therapy ≤72 h (AHR 0.49, 95% CI 0.32-0.76) were significantly associated with mortality. Fourteen MBL-PA tested carried the blaSPM-1 gene. Clonal dissemination was documented in both hospitals.

Conclusions: MBL-PA infections resulted in higher mortality rates most likely related to the severity of these infections and less frequent early institution of appropriate antimicrobial therapy. Empirical treatments should be reviewed at institutions with high prevalence of MBL.

Keywords: P. aeruginosa; resistance; {beta}-lactamases; nosocomial infections.
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