Impact of a hospital-wide programme of heterogeneous antibiotic use on the development of antibiotic-resistant Gram-negative bacteria.

Although antibiotic heterogeneity has been proposed as a strategy to limit the emergence of antibiotic resistance, few clinical studies have been conducted to validate the concept. This paper evaluates a hospital-wide strategy of heterogeneous antibiotic use intended to reduce infections caused by resistant Gram-negative rods (GNR). A strategy termed 'periodic antimicrobial monitoring and supervision' (PAMS) was implemented between September 2006 and February 2008. The 18 month intervention period was compared with the preceding 18 months (12 months pre-establishment and 6 months preparation). During PAMS, recommended, restricted and off-supervised classes of antibiotics active against more resistant GNR were changed every 3 months according to the antimicrobial usage density and rates of resistance to those antibiotics in Pseudomonas aeruginosa during the preceding term. Usage of five categories of antibiotics was supervised by four full-time staff. Antibiotic heterogeneity was estimated using the Peterson index (AHI). AHI estimates were 0.66 and 0.74 during the observation period but rose after the introduction of PAMS (period 1: 0.84; period 2: 0.94; period 3: 0.88). The incidence of patients from whom resistant GNR were isolated decreased significantly (P<0.001), whereas isolation of multidrug-resistant (MDR) GNR decreased from 1.7% to 0.5% (P<0.001). There was no significant difference in the incidence of extended spectrum beta-lactamase-producing organisms. Rates of imipenem resistance among Pseudomonas aeruginosa improved during PAMS2. PAMS facilitated hospital-wide heterogeneous antibiotic usage which was associated with reduced rates of resistant GNR.