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 baumannii, 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.