Affiliation:
1. Hershey Medical Center, Hershey, Pennsylvania 17033
2. Kurume University School of Medicine, Kurume, Japan
Abstract
ABSTRACT
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, 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 μg/ml, and only for the one strain with
erm
(B) did CEM-101 MICs rise from 1 to 8 μg/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
.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
60 articles.
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