title: In-vitro and in-vivo activity of trovafloxacin against Streptococcus pneumoniae.
abstract: Trovafloxacin had greater in-vitro activity than comparative fluoroquinolone agents against penicillin-sensitive pneumococci in studies from the USA, UK, Slovakia, Czech Republic, Sweden and South Africa. This activity was maintained against penicillin-resistant strains, with MIC90 values of < or = 0.25 mg/L observed for both groups. Bactericidal activity appeared to occur within one or two dilutions of the MIC and, in the limited number of strains studied, the MIC was independent of the medium tested and pH over the range pH 5-8. Mutation to decreased susceptibility to trovafloxacin occurred in vitro at a low frequency in the pneumococcus (< or = 8.9 x 10(-9)). Mutants with changes in the topoisomerase IV A subunit (GrlA) were still inhibited by 0.5 mg/L of trovafloxacin. Trovafloxacin was more efficacious than ciprofloxacin, temafloxacin or ofloxacin in mouse pneumonia models for both penicillin-susceptible and penicillin-resistant pneumococci. Trovafloxacin was also highly efficacious in a rabbit pneumococcal meningitis model. These data suggest that the clinical efficacy of trovafloxacin against pneumococci should be evaluated further.
authors.affiliation: Department of Medical Microbiology, South African Institute for Medical Research and University of the Witwatersrand, Johannesburg. 174klug@chiron.wits.ac.za
authors.forename: K P
authors.initials: KP
authors.lastname: Klugman
authors.forename: T D
authors.initials: TD
authors.lastname: Gootz
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D024841:Fluoroquinolones; D006863:Hydrogen-Ion Concentration; D008586:Meningitis, Pneumococcal / Q000188:drug therapy; D051379:Mice; D008826:Microbial Sensitivity Tests; D009287:Naphthyridines / Q000494:pharmacology* / Q000627:therapeutic use; D010403:Penicillin Resistance; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy; D011817:Rabbits; D013296:Streptococcus pneumoniae / Q000187:drug effects*
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; C080163:trovafloxacin