In vitro activities of new ketolide, telithromycin, and eight other macrolide antibiotics against Streptococcus pneumoniae having mefA and ermB genes that mediate macrolide resistance.
The comparative in vitro activity of a new ketolide, telithromycin (TEL), and eight other macrolide-lincosamide antibiotics (MLS) against 215 strains, of Streptococcus pneumoniae including penicillin-resistant isolates (PRSP), was determined by the agar dilution method. These strains were isolated from patients with pneumonia, otitis media, and purulent meningitis between 1995 and 1997. Two genes, mefA and ermB, that encode MLS resistance in the strains were identified by polymerase chain reaction (PCR). Of the strains, 30.2% (n = 65) had the mefA gene, 37.7% (n = 81) had the ermB gene, and 1.4% (n = 3) had both resistant genes. The minimum inhibitory concentration (MIC90s) of TEL and 16-membered ring MLS for strains having the mefA gene were 0.063-0.25 microg/ml, which were the same level as those for MLS-susceptible strains. On the other hand, the strains with the mefA gene showed low-level resistance to 14- and 15-membered ring MLS, with MIC90s ranging from 1 to 4 microg/ml. Only the MIC90 of TEL at 0.5 microg/ml, for strains having the ermB gene was superior to that of the 14-, 15-, and 16-membered ring MLS (MIC90, > or =64 microg/ml). TEL also showed excellent activity against PRSP having abnormal pbp1a, pbp2x, and pbp2b genes. Most strains having the mefA and ermB genes were serotyped to 3, 6, 14, 19, and 23. These results suggest that TEL may be a useful chemotherapeutic agent for respiratory tract infections caused by S. pneumoniae.
D001426:Bacterial Proteins / Q000235:genetics; D017931:DNA Primers; D004269:DNA, Bacterial / Q000032:analysis; D024881:Drug Resistance, Bacterial; D004587:Electrophoresis, Agar Gel; D006801:Humans; D048628:Ketolides; D018942:Macrolides / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics; D008780:Methyltransferases / Q000235:genetics; D008826:Microbial Sensitivity Tests; D016133:Polymerase Chain Reaction; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification / Q000187:drug effects* / Q000235:genetics
D001426:Bacterial Proteins; D017931:DNA Primers; D004269:DNA, Bacterial; D048628:Ketolides; D018942:Macrolides; C117866:MefA protein, Streptococcus; D008565:Membrane Proteins; D008780:Methyltransferases; C035181:rRNA (adenosine-O-2'-)methyltransferase; C106791:telithromycin