Pharmacodynamics and bactericidal activity of moxifloxacin in experimental Escherichia coli meningitis

• Published in: Antimicrobial agents and chemotherapy Vol. 45; no. 11; pp. 3092 - 3097
• Main Authors: RODRIGUEZ-CERRATO, Violeta, MCCOIG, Cynthia C, MICHELOW, Ian C, GHAFFAR, Faryal, JAFRI, Hasan S, HARDY, Robert D, PATEL, Chetan, OLSEN, Kurt, MCCRACKEN, George H
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for Microbiology 01.11.2001
• Subjects: Animals; Anti-Infective Agents - cerebrospinal fluid; Anti-Infective Agents - pharmacokinetics; Anti-Infective Agents - therapeutic use; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Area Under Curve; Aza Compounds; Biological and medical sciences; Ceftriaxone - therapeutic use; Cephalosporins - therapeutic use; Escherichia coli - drug effects; Experimental Therapeutics; Fluoroquinolones; Male; Medical sciences; Meningitis, Escherichia coli - cerebrospinal fluid; Meningitis, Escherichia coli - drug therapy; Meningitis, Escherichia coli - microbiology; Microbial Sensitivity Tests; Pharmacology. Drug treatments; Quinolines; Rabbits; Thienamycins - therapeutic use; Intravenous administration; Escherichia coli; Rabbit; Ceftriaxone; Cerebrospinal fluid; Moxifloxacin; Carbapenem derivatives; Fluoroquinolone derivatives; Bacteria; Meningitis; Meropenem; Quinolone derivatives; Enterobacteriaceae; Nervous system diseases; β-Lactams; Single dose; Lagomorpha; Biological activity; Vertebrata; Antibiotic; Chemotherapy; Cephalosporin derivatives; Mammalia; Treatment; Animal; Central nervous system disease; Antibacterial agent; Pharmacokinetics
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.45.11.3092-3097.2001

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.