Mechanisms of resistance to telithromycin in Streptococcus pneumoniae.
Reports of ketolide resistance remain scarce, however, a few laboratory-derived and clinical isolates of resistant Streptococcus pneumoniae have been documented. Mutations in key telithromycin-binding sites such as domains II and V of the 23S rRNA and ribosomal proteins L4 and L22, as well as mutations of the resistance determinant erm(B) are associated with elevated telithromycin MICs. Mutations in the secondary binding site of domain II coupled with ribosomal methylation may have serious resistance consequences should the domain II binding site be lost. Although ketolides are purported to maintain excellent activity against efflux-positive isolates, laboratory-derived telithromycin-resistant strains have been generated. As telithromycin usage increases, ketolide-resistant isolates of S. pneumoniae may well increase.
Hisanaga
Tamiko
T
Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada. thisanga@shaw.ca
Hoban
Daryl J
DJ
Zhanel
George G
GG
D001665:Binding Sites; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D048628:Ketolides / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009154:Mutation; D012338:RNA, Ribosomal, 23S / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics*
D048628:Ketolides; C506765:L22 protein, Streptococcus pneumoniae; D012338:RNA, Ribosomal, 23S; D012269:Ribosomal Proteins; C056368:ribosomal protein L4; C106791:telithromycin