Laboratory and clinical evaluation of doripenem in deep-seated skin infection

We conducted a multicenter clinical trial of doripenem (DRPM), a new carbapenem for injection, to examine its skin penetration and its clinical efficacy and safety in deep-seated skin infections. The concentration in skin tissue was 2.29-3.15 μg/g and in plasma 6.48-18.1 μg/mL 30-70 minutes after a single i.v. injection of 250 mg of DRPM. The ratio of skin concentration to plasma concentration was 15.7-36.9%. The minimum inhibitory concentration (MIC) against two clinical isolates of Staphylococcus aureus was 0.05 μg/mL. DRPM was administered to 22 patients at a dose of 250 mg or 500 mg twice a day for 5-8 days. Overall clinical efficacy was 100% (19/19). Cases by diagnosis consisted of 10 of cellulitis, 3 of erysipelas, 3 of lymphangitis, 1 of lymphadenitis and 2 of carbuncle. The bacteriological response was 85.0% (17/20). Adverse reactions were observed in 13.6% (3/22) and abnormal laboratory findings in 36.4% (8/22). One developed pseudomembranous colitis after DRPM treatment followed by oral cefcapene pivoxil, and the causal relationship to the treatment with DRPM could not be ruled out. This adverse reaction disappeared rapidly after vancomycin administration. These results suggest that DRPM is a useful antibacterial agent for deep-seated skin infection.