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  • Title: Synergy between gemifloxacin and trimethoprim/sulfamethoxazole against community-associated methicillin-resistant Staphylococcus aureus.
    Author: Leonard SN, Kaatz GW, Rucker LR, Rybak MJ.
    Journal: J Antimicrob Chemother; 2008 Dec; 62(6):1305-10. PubMed ID: 18801920.
    Abstract:
    OBJECTIVES: The rapid emergence of methicillin-resistant Staphylococcus aureus from the community (CA-MRSA) presents difficulties in making treatment choices. We evaluated whether combining another orally available agent commonly used to treat CA-MRSA with gemifloxacin would enhance gemifloxacin activity against CA-MRSA. METHODS: Fifty strains of SCCmec IV, agr group 1, Panton-Valentine leucocidin-positive CA-MRSA were evaluated for susceptibilities to gemifloxacin, trimethoprim/sulfamethoxazole, doxycycline, levofloxacin, rifampicin, clindamycin and erythromycin. Twenty of these strains were evaluated for the potential for synergy between gemifloxacin and trimethoprim/sulfamethoxazole, clindamycin and rifampicin by time-kill analysis. Two strains were further evaluated in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model. RESULTS: In time-kill analyses, gemifloxacin combined with trimethoprim/sulfamethoxazole produced additivity (6/20) or synergy (11/20) in 85% of the isolates tested. The addition of clindamycin to gemifloxacin showed additivity (3/20) or synergy (2/20) in 25% of the isolates. All isolates displayed indifference to the combination of gemifloxacin and rifampicin. In the PK/PD model, combining gemifloxacin and trimethoprim/sulfamethoxazole provided potent and sustained bactericidal activity to detection limits of 2 log(10) cfu/mL by 48 h; gemifloxacin combined with clindamycin or with rifampicin killed to detection limits by 56 h or later. One isolate developed efflux-mediated resistance to gemifloxacin at 96 h with gemifloxacin monotherapy. All combinations prevented the emergence of this resistance. CONCLUSIONS: Synergy or additivity was demonstrated by time-kill analysis between gemifloxacin and trimethoprim/sulfamethoxazole in most isolates tested. In the PK/PD model, the addition of trimethoprim/sulfamethoxazole, clindamycin and rifampicin enhanced the activity of gemifloxacin against CA-MRSA and suppressed the emergence of resistance to gemifloxacin.
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