title: In vitro activity of CEM-101 against Streptococcus pneumoniae and Streptococcus pyogenes with defined macrolide resistance mechanisms.
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 <or=0.5 microg/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 microg/ml against macrolide-susceptible strains and from 0.015 to 1 microg/ml against macrolide-resistant strains. Against erm(B) strains, erythromycin, azithromycin, and clarithromycin MICs were 32 to >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 <or=1 microg/ml, and erythromycin, azithromycin, and clarithromycin MICs of 0.5 to >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.
authors.affiliation: Department of Pathology, Hershey Medical Center, P.O. Box 850, Hershey, PA 17033, USA.
authors.forename: Pamela
authors.initials: P
authors.lastname: McGhee
authors.forename: Catherine
authors.initials: C
authors.lastname: Clark
authors.forename: Klaudia M
authors.initials: KM
authors.lastname: Kosowska-Shick
authors.forename: Kensuke
authors.initials: K
authors.lastname: Nagai
authors.forename: Bonifacio
authors.initials: B
authors.lastname: Dewasse
authors.forename: Linda
authors.initials: L
authors.lastname: Beachel
authors.forename: Peter C
authors.initials: PC
authors.lastname: Appelbaum
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D018942:Macrolides / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D010400:Penicillin G / Q000494:pharmacology; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D013297:Streptococcus pyogenes / Q000187:drug effects*; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; D014230:Triazoles; C547755:solithromycin; D010400:Penicillin G