The influence of metallo-β-lactamase production on mortality in nosocomial Pseudomonas aeruginosa infections

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 A 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 bla(SPM1) 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 A 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 bla(SPM-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.