Background . We investigated the possible association between fluoroquinolone use and the rate of methicillin-resistant Staphylococcus aureus (MRSA) recovery from consecutive hospitalized patients.

Methods . We conducted a nonrandomized, prospective, controlled interventional “fluoroquinolone-free” study at 4 large teaching hospitals in northwest France, catering to a total of 5,882,600 persons. During the intervention period (January through December 2001), fluoroquinolone use was prohibited at 1 of the 4 hospitals (Caen Hospital), unless no effective alternative was available. Three university hospitals were used as controls because they had similar preintervention rates of MRSA.

Results . During the intervention period (2001), the annual rate of fluoroquinolone use decreased from 54 to 5 defined daily doses per 1000 patients per day at Caen Hospital and remained stable in the control hospitals. At the end of the intervention, the rate of MRSA isolation was significantly lower at Caen Hospital than at the control hospitals (353 [32.3%] of 1093 S. aureus isolates were MRSA, compared with 2495 [36.8%] of 6787 isolates; odds ratio, 0.82; 95% confidence interval, 0.69–0.99; P = .036), as determined on the basis of a marginal model that took into account within-hospital clustering. In a before-after time series analysis, compared with forecasted rates, there was a significant downward trend in observed monthly rates of MRSA isolation at Caen Hospital at the end of the intervention.

Conclusion . This quasi experimental study confirms the association between fluoroquinolone use and MRSA isolation among hospitalized patients.