title: Evaluation of telithromycin against Streptococcus pneumoniae with ribosomal mutations utilizing in vitro time-kill methodology.
abstract: In a recent study, our in vivo data suggested that clinically achievable levels of telithromycin are more effective than azithromycin against selected Streptococcus pneumoniae isolates with ribosomal mutations in 23S rRNA gene alleles and L22 region mutations. In the current study, we attempt to investigate further the antibacterial activity of telithromycin against these isolates to better delineate the disparity between isolates based on allelic differences. Four isolates of S. pneumoniae with ribosomal mutations were tested using in vitro time-kill methodology. Isolates were exposed to telithromycin at concentrations of 0.5-8 x the minimum inhibitory concentration (MIC). At these exposures, telithromycin demonstrated concentration-dependent killing for three of the four isolates. Against the fourth isolate, telithromycin affected only a 1 log decrease in colony-forming units/mL despite exposures of 8 x MIC. These data demonstrate the in vitro killing profile of telithromycin against S. pneumoniae isolates with ribosomal and L22 mutations. Whilst telithromycin did not demonstrate bactericidal activity against all isolates in these time-kill studies, the in vivo human-simulated exposures did result in a high degree of bacterial kill. Full evaluation of the potential utility of new antimicrobial agents against these emerging genotypic profiles requires both in vitro and in vivo assessments.
authors.affiliation: Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT 06102, USA.
authors.forename: Prachi K
authors.initials: PK
authors.lastname: Dandekar
authors.forename: Pamela R
authors.initials: PR
authors.lastname: Tessier
authors.forename: David J
authors.initials: DJ
authors.lastname: Farrell
authors.forename: Charles H
authors.initials: CH
authors.lastname: Nightingale
authors.forename: David P
authors.initials: DP
authors.lastname: Nicolau
mesh_terms: D048628:Ketolides / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009154:Mutation; D011008:Pneumococcal Infections / Q000382:microbiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D012338:RNA, Ribosomal, 23S / Q000235:genetics; D012270:Ribosomes / Q000235:genetics; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics; D013997:Time Factors
chemical_list: D048628:Ketolides; D011500:Protein Synthesis Inhibitors; D012338:RNA, Ribosomal, 23S; C106791:telithromycin