In vitro activity of CEM-101 against Streptococcus pneumoniae and Streptococcus pyogenes with defined macrolide resistance mechanisms.

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McGhee P, Clark C, Kosowska-Shick KM, Nagai K, Dewasse B, Beachel L, Appelbaum PC

In vitro activity of CEM-101 against Streptococcus pneumoniae and Streptococcus pyogenes with defined macrolide resistance mechanisms.

Antimicrob Agents Chemother. 2010 Jan;54(1):230-8. doi: 10.1128/AAC.01123-09. Epub 2009 Nov 2.

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19884376 [ View in PubMed
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Abstract

CEM-101 had MIC ranges of 0.002 to 0.016 microg/ml against macrolide-susceptible pneumococci and 0.004 to 1 microg/ml against macrolide-resistant phenotypes. Only 3 strains with erm(B), with or without mef(A), had CEM-101 MICs of 1 microg/ml, and 218/221 strains had CEM-101 MICs of 64 microg/ml, while 17/19 strains had telithromycin MICs of 4 to 16 microg/ml; CEM-101 MICs were 0.015 to 1 microg/ml. By comparison, erm(A) and mef(A) strains had CEM-101 MICs of 0.015 to 0.5 microg/ml, clindamycin and telithromycin MICs of 64 microg/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 microg/ml (parental strains) to 0.06 to 0.5 microg/ml (resistant clones); for only one erm(B) mef(A) strain with a parental MIC of 1 microg/ml was there a resistant clone with a MIC of 32 microg/ml, with no detectable mutations in the L4, L22, or 23S rRNA sequence. Among two of five S. pyogenes strains tested, CEM-101 MICs rose from 0.03 to 0.25 microg/ml, and only for the one strain with erm(B) did CEM-101 MICs rise from 1 to 8 microg/ml, with no changes occurring in any macrolide resistance determinant. CEM-101 had low MICs as well as low potential for the selection of resistant mutants, independent of bacterial species or resistance phenotypes in pneumococci and S. pyogenes.

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