Mechanisms of resistance to telithromycin in Streptococcus pneumoniae

Reports of ketolide resistance remain scarce, however, a few laboratory-derived and clinical isolates of resistantStreptococcuspneumoniaehavebeendocumented.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. pneumoniaemay well increase