Objective.Society for Health Care Epidemiology guidelines recommend decreasing the use of fluoroquinolone antibiotics in institutions where methicillin‐resistant Staphylococcus aureus (MRSA) is endemic. We evaluated whether an intervention to limit fluoroquinolone use was associated with a lower rate of nosocomial MRSA infection and summarized changes in antibiotic use, changes in other variables potentially correlated with a lower rate of MRSA infection, and rates of nosocomial infections due to other pathogens.

Design.Single‐center quasi‐experimental design. A time series of nosocomial MRSA infections was measured at monthly intervals from July 2001 through June of 2004; there were 80 MRSA infections recorded. Segmented regression analysis (ie, quasi‐Poisson generalized linear models) was used to evaluate variables possibly associated with the nosocomial MRSA infection rate.

Setting.An 87‐bed Veterans Affairs teaching hospital with an extended‐care facility.

Intervention.A physician‐directed computer‐generated intervention designed to limit the use of fluoroquinolone antibiotics was initiated, and institutional changes in antibiotic use and nosocomial MRSA infection rates were tracked.

Results.After the intervention, fluoroquinolone use decreased by approximately 34%, and levofloxacin use decreased by approximately 50%. Decreased fluoroquinolone use was offset by increased cephalosporin, piperacillin‐tazobactam, and trimethoprim‐sulfamethoxazole use. The nosocomial MRSA infection rate decreased from 1.37 to 0.63 episodes per 1,000 patient‐days after the study intervention ( ). Coagulase‐negative Staphylococcus and Enterococcus infection rates also decreased. However, the rate of infection with gram‐negative organisms increased. The rate of MRSA infection was positively correlated with levofloxacin use ( ) and azithromycin use ( ), whereas it was negatively correlated with summer season ( ). In a subsequent model, the rate of MRSA infection was negatively correlated with the study intervention ( ).

Conclusion.Reduction in the institutional use of fluoroquinolones may be associated with a lower nosocomial MRSA infection rate.