title: Evaluation of moxifloxacin, a new 8-methoxyquinolone, for treatment of meningitis caused by a penicillin-resistant pneumococcus in rabbits.
abstract: Moxifloxacin is a new 8-methoxyquinolone with high activity against gram-positive bacteria, including penicillin-resistant pneumococci. In an experimental meningitis model, we studied the pharmacokinetics of moxifloxacin in infected and uninfected rabbits and evaluated the antibiotic efficacies of moxifloxacin, ceftriaxone, and vancomycin against a penicillin-resistant Streptococcus pneumoniae strain (penicillin, ceftriaxone, vancomycin, and moxifloxacin MICs were 1, 0.5, 0.5, and 0.125 microgram/ml, respectively). Moxifloxacin entered cerebrospinal fluid (CSF) readily, with peak values within 15 to 30 min after bolus intravenous infusion and with a mean percent penetration into normal and purulent CSF of approximately 50 and 80%, respectively. The bactericidal effect of moxifloxacin was concentration dependent, and regrowth was seen only when the concentration of moxifloxacin in CSF was below the minimal bactericidal concentration. All antibiotic-treated groups (moxifloxacin given in two doses of 40 mg/kg of body weight, moxifloxacin in two 20-mg/kg doses, ceftriaxone in one 125-mg/kg dose, and vancomycin in two 20-mg/kg doses) had significantly higher reductions in CSF bacterial concentration than the untreated group (P < 0.05). Moxifloxacin was as effective as vancomycin and ceftriaxone in reducing bacterial counts at all time points tested (3, 5, 10, and 24 h). Moreover, moxifloxacin given in two 40-mg/kg doses resulted in a significantly higher reduction in CSF bacterial concentration (in log10 CFU per milliliter) than vancomycin within 3 h after the start of antibiotic treatment (3.49 [2.94 to 4.78] versus 2.50 [0.30 to 3.05]; P < 0.05). These results indicate that moxifloxacin could be useful in the treatment of meningitis, including penicillin-resistant pneumococcal meningitis.
authors.affiliation: Department of Clinical Microbiology, Statens Serum Institut, Copenhagen, Denmark. coa@ssi.dk
authors.forename: C
authors.initials: C
authors.lastname: Ostergaard
authors.forename: T K
authors.initials: TK
authors.lastname: Sørensen
authors.forename: J D
authors.initials: JD
authors.lastname: Knudsen
authors.forename: N
authors.initials: N
authors.lastname: Frimodt-Møller
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics; D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001372:Aza Compounds; D002443:Ceftriaxone / Q000493:pharmacokinetics; D002511:Cephalosporins / Q000493:pharmacokinetics; D004341:Drug Evaluation; D024841:Fluoroquinolones; D008586:Meningitis, Pneumococcal / Q000188:drug therapy*; D008826:Microbial Sensitivity Tests; D000077266:Moxifloxacin; D010403:Penicillin Resistance; D011485:Protein Binding; D011804:Quinolines; D015363:Quinolones / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011817:Rabbits; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013997:Time Factors; D014640:Vancomycin / Q000493:pharmacokinetics
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D001372:Aza Compounds; D002511:Cephalosporins; D024841:Fluoroquinolones; D011804:Quinolines; D015363:Quinolones; D014640:Vancomycin; D002443:Ceftriaxone; D000077266:Moxifloxacin