Effect of Antibiotic Diversity on Ventilator-Associated Pneumonia Caused by ESKAPE Organisms

Background: The aim of this study was to test in the clinic whether antimicrobial diversity affects resistance of Enterococcus faecium, Staphylococcus aureus, Klebsiella species, Acinetobacter baumainnii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE) pathogens in ventilator-associated pneumonia (VAP). Methods: Three different strategies of empirical antimicrobial prescription for VAP were consecutively implemented in an ICU: patient specific (10 months); scheduling, including sequential quarterly prioritization (12 months) and restriction (12 months) of antimicrobials; and mixing (10 months). Periods were compared, measuring the antimicrobial heterogeneity index (AHI). Incidence and resistance patterns of VAP caused by ESKAPE were compared. Results: Overall, 127 microbiologic VAP episodes were documented. ESKAPE VAP increased significantly during scheduling (AHI, 0.65) compared with patient-specific (AHI, 0.88) and mixing (AHI, 0.87) periods (relative risk, 2.67 and 3.84, respectively). This finding was associated with a significant (P < .05) increase of carbapenem-resistant A baumannii during the scheduling period (15.0%) compared with the patient-specific (2.4%) and mixing (0%) periods. ICU mortality of resistant patients with ESKAPE VAP was doubled that of patients without ESKAPE VAP (relative risk, 2.25; 95% CI, 1.67-9.48). Thirty-day mechanical ventilation-free days was significantly increased (5 days) in patients with resistant ESKAPE VAP. Conclusions: Antibiotic strategies promoting diversity may prevent the emergence of resistance of ESKAPE organisms, improving use of health-care resources. CHEST 2011; 140(3):643-651