We determined whether clarithromycin (CAM) had the ability to eliminate glycocalyx and biofilm produced by methicillin-resistant Staphylococcus aureus (MRSA) using an in-vitro experimental system (consisting of a bladder model and a kidney model) simulating complicated urinary tract infection (UTI). We also examined whether a combination of CAM and vancomycin (VCM) was effective for eliminating the MRSA biofilm. VCM (urinary concentration simulating drip infusion of 500 mg twice a day for 5 days; minimum inhibitory concentration (MIC) 0.5 &mgr;g/ml) eliminated MRSA from the bladder model medium at 48 h, but reproliferation occurred immediately after withdrawal of the agent. No disappearance of MRSA biofilm was noted, and this appeared to be the cause of the bacterial regrowth. CAM (urinary concentration simulating oral administration of 200 mg twice a day for 5 days; MIC, 128 &mgr;g/ml) allowed microbial recovery to the initial level within 48 h, but led to the disappearance of the glycocalyx-forming biofilm. A combination of VCM and CAM caused microbial elimination from the bladder model medium at 46 h with no regrowth after withdrawal of the antimicrobial agents. Scanning electron microscopy confirmed that the MRSA biofilm disappeared completely and no microbial adhesion was noted. These results suggest that CAM has an inhibitory action on glycocalyx and biofilm of MRSA, and that the combined use of VCM and CAM may be efficacious for the treatment of MRSA UTI