title: Pharmacodynamics of moxifloxacin against Streptococcus pyogenes in an in vitro kinetic model.
abstract: The aim of the present study was to investigate the pharmacodynamics of moxifloxacin against strains of Streptococcus pyogenes with different susceptibilities to erythromycin by using an in vitro kinetic model simulating human pharmacokinetics of moxifloxacin at oral doses of 400 and 200 mg, respectively. When the different strains of S. pyogenes were exposed to the higher dose, the number of bacteria was reduced below the detection limit after 12 h and no regrowth was noted during the following 12 h. At the lower dose there was regrowth of the strains with constitutive and inducible erythromycin resistance of the MLS(B) phenotype. Replication assays of the regrowing bacteria indicated that the failure of moxifloxacin to kill the MLS(B) strains at the lower dose was likely caused by the emergence of preexisting resistant subpopulations. Thus, the present study indicates that the presently used 400-mg dose seems to have an advantage over the lower dose in that the risk for selection of resistant subpopulations is minimized.
authors.affiliation: Antibiotic Research Unit, Department of Infectious Diseases and Clinical Microbiology, University Hospital, Uppsala, Sweden. inga.odenholt@inf.mas.lu.se
authors.forename: Inga
authors.initials: I
authors.lastname: Odenholt
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Löwdin
authors.forename: Ingegerd
authors.initials: I
authors.lastname: Gustafsson
authors.forename: Otto
authors.initials: O
authors.lastname: Cars
mesh_terms: D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D001372:Aza Compounds; D003470:Culture Media; D004352:Drug Resistance, Microbial; D024841:Fluoroquinolones; D006801:Humans; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D000077266:Moxifloxacin; D011804:Quinolines; D013297:Streptococcus pyogenes / Q000187:drug effects* / Q000254:growth & development
chemical_list: D000890:Anti-Infective Agents; D001372:Aza Compounds; D003470:Culture Media; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin