title: Pharmacodynamics and bactericidal activity of moxifloxacin in experimental Escherichia coli meningitis.
abstract: Moxifloxacin, an 8-methoxyquinolone with broad-spectrum activity in vitro, was studied in the rabbit model of Escherichia coli meningitis. The purposes of this study were to evaluate the bactericidal effectiveness and the pharmacodynamic profile of moxifloxacin in cerebrospinal fluid (CSF) and to compare the bactericidal activity with that of ceftriaxone and meropenem therapy. After induction of meningitis, animals were given single doses of 10, 20, and 40 mg/kg or divided-dose regimens of 5, 10, and 20 mg/kg twice, separated by 6 h. After single doses, the penetration of moxifloxacin into purulent CSF, measured as percentage of the area under the concentration-time curve (AUC) in CSF relative to the AUC in plasma, was approximately 50%. After single doses of 10, 20, and 40 mg/kg, the maximum CSF concentration (C(max)) values were 1.8, 4.2, and 4.9 microg/ml, respectively; the AUC values (total drug) were 13.4, 25.4, and 27.1 microg/ml x h, respectively, and the half-life values (t(1/2)) were 6.7, 6.6, and 4.7 h, respectively. The bacterial killing in CSF for moxifloxacin, calculated as the Deltalog(10) CFU per milliliter per hour, at 3, 6, and 12 h after single doses of 10, 20, and 40 mg/kg were -5.70, -6.62, and -7.02; -7.37, -7.37, and -6.87; and -6.62, -6.62, and -6.62, respectively, whereas those of ceftriaxone and meropenem were -4.18, -5.24, and -4.43, and -3.64, -3.59, and -4.12, respectively. The CSF pharmacodynamic indices of AUC/MBC and C(max)/MBC were interrelated (r = 0.81); there was less correlation with T > MBC (r = 0.74). In this model, therapy with moxifloxacin appears to be at least as effective as ceftriaxone and more effective than meropenem therapy in eradicating E. coli from CSF.
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9063, USA. rodriguez_cerrato@yahoo.com
authors.forename: V
authors.initials: V
authors.lastname: Rodriguez-Cerrato
authors.forename: C C
authors.initials: CC
authors.lastname: McCoig
authors.forename: I C
authors.initials: IC
authors.lastname: Michelow
authors.forename: F
authors.initials: F
authors.lastname: Ghaffar
authors.forename: H S
authors.initials: HS
authors.lastname: Jafri
authors.forename: R D
authors.initials: RD
authors.lastname: Hardy
authors.forename: C
authors.initials: C
authors.lastname: Patel
authors.forename: K
authors.initials: K
authors.lastname: Olsen
authors.forename: G H
authors.initials: GH
authors.lastname: McCracken
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019540:Area Under Curve; D001372:Aza Compounds; D002443:Ceftriaxone / Q000627:therapeutic use; D002511:Cephalosporins / Q000627:therapeutic use; D004926:Escherichia coli / Q000187:drug effects; D024841:Fluoroquinolones; D008297:Male; D020814:Meningitis, Escherichia coli / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000382:microbiology; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D000077266:Moxifloxacin; D011804:Quinolines; D011817:Rabbits; D013845:Thienamycins / Q000627:therapeutic use
chemical_list: D000890:Anti-Infective Agents; D001372:Aza Compounds; D002511:Cephalosporins; D024841:Fluoroquinolones; D011804:Quinolines; D013845:Thienamycins; D002443:Ceftriaxone; D000077731:Meropenem; D000077266:Moxifloxacin