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In Vitro Activity of CEM-101 against Streptococcus pneumoniae and Streptococcus pyogenes with Defined Macrolide Resistance Mechanisms ▿

McGhee, Pamela; Clark, Catherine; Kosowska-Shick, Klaudia M.; Nagai, Kensuke; Dewasse, Bonifacio; Beachel, Linda; Appelbaum, Peter C.
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
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CEM-101 had MIC ranges of 0.002 to 0.016 μg/ml against macrolide-susceptible pneumococci and 0.004 to 1 μg/ml against macrolide-resistant phenotypes. Only 3 strains with erm(B), with or without mef(A), had CEM-101 MICs of 1 μg/ml, and 218/221 strains had CEM-101 MICs of ≤0.5 μg/ml. CEM-101 MICs were as much as 4-fold lower than telithromycin MICs against all strains. For Streptococcus pyogenes, CEM-101 MICs ranged from 0.008 to 0.03 μg/ml against macrolide-susceptible strains and from 0.015 to 1 μg/ml against macrolide-resistant strains. Against erm(B) strains, erythromycin, azithromycin, and clarithromycin MICs were 32 to >64 μg/ml, while 17/19 strains had telithromycin MICs of 4 to 16 μg/ml; CEM-101 MICs were 0.015 to 1 μg/ml. By comparison, erm(A) and mef(A) strains had CEM-101 MICs of 0.015 to 0.5 μg/ml, clindamycin and telithromycin MICs of ≤1 μg/ml, and erythromycin, azithromycin, and clarithromycin MICs of 0.5 to >64 μg/ml. Pneumococcal multistep resistance studies showed that although CEM-101 yielded clones with higher MICs for all eight strains tested, seven of eight strains had clones with CEM-101 MICs that rose from 0.004 to 0.03 μg/ml (parental strains) to 0.06 to 0.5 μg/ml (resistant clones); for only one erm(B) mef(A) strain with a parental MIC of 1 μg/ml was there a resistant clone with a MIC of 32 μg/ml...