Reappraisal of Pseudomonas aeruginosa hospital-acquired pneumonia mortality in the era of metallo-beta-lactamase-mediated multidrug resistance: a prospective observational study.

INTRODUCTION: Hospital-acquired pneumonia (HAP) due to Pseudomonas aeruginosa is associated with high mortality rates. The metallo-beta-lactamases (MBLs) are emerging enzymes that hydrolyze virtually all beta-lactams. We aimed to assess P. aeruginosa HAP mortality in a setting of high-rate MBL production METHODS: A prospective cohort study was performed at two tertiary-care teaching hospitals. A logistic regression model was constructed to identify risk factors for 30-day mortality. RESULTS: One-hundred and fifty patients with P. aeruginosa HAP were evaluated. The 30-day mortality was 37.3% (56 of 150): 57.1% (24 of 42) and 29.6% (32 of 108) for patients with HAP by MBL-producing P. aeruginosa and by non-MBL-producing P. aeruginosa, respectively (relative risk, 1.93; 95% confidence interval (CI), 1.30-2.85). The logistic regression model identified a higher Charlson comorbidity score (odds ratio, 1.21; 95% CI, 1.04-1.41), presentation with severe sepsis or septic shock (odds ratio, 3.17; 95% CI, 1.30-7.72), ventilator-associated pneumonia (odds ratio, 2.92; 95% CI, 1.18-7.21), and appropriate therapy (odds ratio, 0.24; 95% CI, 0.10-0.61) as independent factors for 30-day mortality. MBL production was not statistically significant in the final model. CONCLUSION: MBL-producing P. aeruginosa HAP resulted in higher mortality rates, particularly in patients with ventilator-associated pneumonia, most probably related to the less frequent institution of appropriate antimicrobial therapy. Therapeutic approaches should be reviewed at institutions with a high prevalence of MBL.

Risk factors for nosocomial infections due to Pseudomonas aeruginosa producing metallo-beta-lactamase in two tertiary-care teaching hospitals.

OBJECTIVES: To assess risk factors for nosocomial infections due to Pseudomonas aeruginosa producing metallo-beta-lactamase (MBL-PA) in two teaching hospitals where horizontal dissemination has been demonstrated. METHODS: A case-control study was performed in both hospitals (assigned as hospital 1 and 2). Cases were patients with MBL-PA infections and controls were those with non-MBL-PA infections. Multivariate analysis was performed to identify independent risk factors. RESULTS: A total of 86 cases and 212 controls were included in the study. A logistic regression model showed that exposure to beta-lactams [odds ratio (OR) 3.21; 95% confidence interval (CI) 1.74-5.93] or fluoroquinolones (OR 3.50; 95% CI 1.46-8.37) was associated with MBL-PA infections. Other independent risk factors were neurological disease (OR 3.00; 95% CI 1.61-5.58), urinary tract infection (OR 2.48; 95% CI 1.21-5.09) and renal failure (OR 2.29; 95% CI 1.13-4.65). Admission to hospital 1 (OR 5.97; 95% CI 3.45-14.09) and intensive care unit stay (OR 2.07; 95% CI 1.46-3.96) were also associated with increased risk for MBL-PA infections. CONCLUSIONS: beta-Lactam exposure is an important risk factor for MBL-PA infections even in a setting where patient-to-patient transmission plays a major role in the spread of the isolates. Other risk factors deserve further investigation, particularly exposure to fluoroquinolones.

The influence of metallo-beta-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 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 bla(SPM-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