In vitro activity of the new ketolide telithromycin compared with those of macrolides against Streptococcus pyogenes: influences of resistance mechanisms and methodological factors.
One hundred and seven clinical isolates of Streptococcus pyogenes, 80 susceptible to macrolides and 27 resistant to erythromycin A (MIC >0.5 microgram/ml), were examined. The erythromycin A-lincomycin double-disk test assigned 7 resistant strains to the M-phenotype, 8 to the inducible macrolide, lincosamide, and streptogramin B resistance (iMLS(B)) phenotype, and 12 to the constitutive MLS(B) resistance (cMLS(B)) phenotype. MICs of erythromycin A, clarithromycin, azithromycin, roxithromycin, and clindamycin were determined by a broth microdilution method. MICs of telithromycin were determined by three different methods (broth microdilution, agar dilution, and E-test methods) in an ambient air atmosphere and in a 5 to 6% CO(2) atmosphere. Erythromycin A resistance genes were investigated by PCR in the 27 erythromycin A-resistant isolates. MICs of erythromycin A and clindamycin showed six groups of resistant strains, groups A to F. iMLS(B) strains (A, B, and D groups) are characterized by two distinct patterns of resistance correlated with genotypic results. A- and B-group strains were moderately resistant to 14- and 15-membered ring macrolides and highly susceptible to telithromycin. All A- and B-group isolates harbored erm TR gene, D-group strains, highly resistant to macrolides and intermediately resistant to telithromycin (MICs, 1 to 16 microgram/ml), were all characterized by having the ermB gene. All M-phenotype isolates (C group), resistant to 14- and 15-membered ring macrolides and susceptible to clindamycin and telithromycin, harbored the mefA gene. All cMLS(B) strains (E and F groups) with high level of resistance to macrolides, lincosamide, and telithromycin had the ermB gene. The effect of 5 to 6% CO(2) was remarkable on resistant strains, by increasing MICs of telithromycin from 1 to 6 twofold dilutions against D-E- and F-group isolates.
Bemer-Melchior
P
P
Department of Microbiology, Laënnec University Hospital, Nantes, France. pascale.bemermelchior@chu-nantes.fr
Juvin
M E
ME
Tassin
S
S
Bryskier
A
A
Schito
G C
GC
Drugeon
H B
HB
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins; D002245:Carbon Dioxide / Q000378:metabolism; D003470:Culture Media; D004352:Drug Resistance, Microbial / Q000235:genetics; D004917:Erythromycin / Q000494:pharmacology*; D006801:Humans; D048628:Ketolides; D018942:Macrolides; D008565:Membrane Proteins / Q000235:genetics; D008780:Methyltransferases / Q000235:genetics; D008826:Microbial Sensitivity Tests / Q000379:methods*; D016133:Polymerase Chain Reaction; D013297:Streptococcus pyogenes / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003470:Culture Media; D048628:Ketolides; D018942:Macrolides; C117866:MefA protein, Streptococcus; D008565:Membrane Proteins; D002245:Carbon Dioxide; D004917:Erythromycin; C111078:ErmTR protein, bacteria; D008780:Methyltransferases; C035181:rRNA (adenosine-O-2'-)methyltransferase; C106791:telithromycin