title: Activity of moxifloxacin, administered once a day, against Streptococcus pneumoniae in an in vitro pharmacodynamic model of infection.
abstract: The antibacterial effect of moxifloxacin was studied by using an in vitro pharmacodynamic model of infection with dosing simulations of 400 mg every 24 h for 48 h. Streptococcus pneumoniae was tested by using four wild-type strains for which the moxifloxacin MICs were 0. 008, 0.12, 0.14, and 3.6 mg/liter. In addition, two isogenic mutants, generated from the strains for which the moxifloxacin MICs were </=0.12 mg/liter and for which the MICs were 1.0 and 1.6 mg/liter, were also used. Antibacterial efficacy was measured by the following indices: log change in viable count at 12, 24, 36, and 48 h; area under the bacterial kill curve (AUBKC); and time to kill 99.9% of the initial inoculum. With the three strains for which the moxifloxacin MICs were </=0.14 mg/liter, there was a marked reduction in viable count over 12 to 36 h; in contrast, with strains for which the MICs were >/=1.0 mg/liter, little killing occurred over 48 h. A sigmoid dose-response model indicated that the area under the curve/MIC ratio was strongly related to the log change in viable count at 24 and 48 h and to the AUBKC. These data indicate that moxifloxacin may have a role in management of S. pneumoniae infection.
authors.affiliation: Bristol Centre for Antimicrobial Research and Evaluation, Southmead Health Services NHS Trust and University of Bristol, Bristol, United Kingdom. MACGOWAN_A@southmead.swest.nhs.uk
authors.forename: A P
authors.initials: AP
authors.lastname: MacGowan
authors.forename: K E
authors.initials: KE
authors.lastname: Bowker
authors.forename: M
authors.initials: M
authors.lastname: Wootton
authors.forename: H A
authors.initials: HA
authors.lastname: Holt
mesh_terms: D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001372:Aza Compounds; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D024841:Fluoroquinolones; D008826:Microbial Sensitivity Tests; D000077266:Moxifloxacin; D011804:Quinolines; D013296:Streptococcus pneumoniae / Q000187:drug effects*
chemical_list: D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin