title: Comparative in vitro and bactericidal activities of telithromycin against penicillin-nonsusceptible, levofloxacin-resistant, and macrolide-resistant Streptococcus pneumoniae by time-kill methodology.
abstract: Broth microdilution MICs were determined for 14 antimicrobial agents against 296 clinical, non-duplicate isolates of Streptococcus pneumoniae collected at Methodist Hospital (Indianapolis, Indiana, USA) from January 2001 to December 2003. Isolates were categorized as susceptible, intermediate, or resistant using Clinical and Laboratory Standards Institute breakpoints. Time-kill studies were performed to evaluate the bactericidal activity of telithromycin at 1, 2, 4, and 8x MIC against 10 penicillin-nonsusceptible, levofloxacin-resistant, and macrolide-resistant (7 M-phenotype, 3 MLS(B)-phenotype) strains. Bactericidal activity was defined as a >/=3-log(10) reduction in CFU/mL. The prevalence of resistance was highest for the macrolides (32%), followed by penicillin (16.2%), clindamycin (10.8%), amoxicillin+/-clavulanate (4.4%), levofloxacin (3.0%), gatifloxacin and moxifloxacin (2.4%), ceftriaxone and cefotaxime (2.0%), and gemifloxacin (1.4%). None of the isolates tested were resistant to telithromycin. At 24h, telithromycin was bactericidal for 0/10, 2/10, 7/10, and 7/10 isolates at 1x MIC, 2x MIC, 4x MIC, and 8x MIC, respectively. At 4-8x MIC, telithromycin was bactericidal for 7/7 M-phenotype isolates and 0/3 MLS(B)-phenotype isolates. For the MLS(B)-phenotype isolates, colony counts were decreased by 1.3-2.1log(10) colony-forming units/mL after 24h at 8x MIC. Overall, telithromycin was highly active against 296 isolates of S. pneumoniae from our institution and demonstrated bactericidal activity at clinically achievable concentrations for 7 of 10 penicillin-nonsusceptible, levofloxacin-resistant, and macrolide-resistant S. pneumoniae. However, telithromycin was bacteriostatic for the MLS(B)-phenotype isolates.
authors.affiliation: Purdue University School of Pharmacy and Pharmaceutical Sciences, Department of Pharmacy Practice, W7555 Myers Building, WHS, 1001 West Tenth Street, Indianapolis, IN 46202, USA. mkays@iupui.edu
authors.forename: Michael B
authors.initials: MB
authors.lastname: Kays
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Lisek
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Denys
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D048628:Ketolides / Q000494:pharmacology*; D064704:Levofloxacin; D018942:Macrolides / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D015242:Ofloxacin / Q000494:pharmacology; D010403:Penicillin Resistance; D011008:Pneumococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000302:isolation & purification
chemical_list: D000900:Anti-Bacterial Agents; D048628:Ketolides; D018942:Macrolides; D064704:Levofloxacin; D015242:Ofloxacin; C106791:telithromycin