Activities of clindamycin, daptomycin, doxycycline, linezolid, trimethoprim-sulfamethoxazole, and vancomycin against community-associated methicillin-resistant Staphylococcus aureus with inducible clindamycin resistance in murine thigh infection and in vitro pharmacodynamic models.
Abstract
Controversy exists about the most effective treatment options for community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and about the ability of these strains to develop inducible resistance to clindamycin during therapy. Using both in vitro pharmacodynamic and murine thigh infection models, we evaluated and compared several antimicrobial compounds against CA-MRSA. Strains with inducible macrolide lincosamide-streptogramin type B (iMLS(B)) resistance and strains in which resistance was noninducible were evaluated. Two levels of inocula (10(5) and 10(7)) were evaluated for clindamycin activity in the in vivo model. In both models, the antimicrobial evaluation was performed in triplicate, and bacterial quantification occurred over 72 h, with drug doses that were designed to simulate the free drug area-under-the-concentration-time curve values (fAUCs) obtained from human samples. When the activity of clindamycin against the iMLS(B) strains was evaluated, constitutive resistance was noted at 24 h (MIC of >256), and failure was noted at an inoculum of > or =10(6) in the in vivo models. However, at a low inoculum (10(5)) in the murine thigh-infection model, clindamycin demonstrated modest activity, reducing the C...Continue Reading
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