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Antimicrob. Agents Chemother. doi:10.1128/AAC.00177-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Rapid eradication of Listeria monocytogenes by moxifloxacin in a murine model of central nervous system listeriosis

Laboratoire de Listeria, Centre National de Référence des Listeria and World Health Organization Collaborating Centre for Foodborne Listeriosis, Institut Pasteur, 25 rue du Dr Roux, 75015 Paris, France; Laboratoire de suivi thérapeutique et de contrôle des médicaments, service de Pharmacie, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), 149 rue de Sèvres, 75015 Paris, France; Unité des Interactions Bactéries-Cellules, Institut Pasteur, 25 rue du Dr Roux, 75015 Paris, France; INSERM U604, 25 rue du Dr Roux, 75015 Paris, France; INRA USC2020, 25 rue du Dr Roux, 75015 Paris, France; Unité d'Epidémiologie des Maladies Emergentes, 25 rue du Dr Roux, Institut Pasteur, 75015 Paris, France; Unité INSERM U570, Université Paris Descartes, Faculté de médecine, site Necker, 156 rue de Vaugirard, 75015 Paris, France

^* To whom correspondence should be addressed. Email: alm{at}pasteur.fr.

	Abstract

Listeriosis is a rare but life-threatening infection. Outcome is greatly favored by early administration of antibiotics with a rapid bactericidal activity against Listeria monocytogenes. Moxifloxacin, a new generation fluoroquinolone with an extended activity against gram-positive bacteria, has proved its effectiveness in vitro against intracellular reservoirs of bacteria. The efficacies of moxifloxacin and amoxicillin were compared in vivo by survival curve assays and studying the kinetics of bacterial growth in blood and organs in a murine model of CNS-listeriosis. We combined pharmacokinetic and pharmacodynamic approaches to correlate observed efficacy in vivo to plasma and tissue concentrations of moxifloxacin. Death was significantly later for animals treated with a single dose of moxifloxacin than of amoxicillin. We observed a rapid bacterial clearance from blood and organs of animals treated with moxifloxacin. The decrease in the bacterial counts in blood and brain correlated with plasma and cerebral concentrations of antibiotic. Moxifloxacin peaked in brain at 1.92±0.32 µg/g one hour after intraperitoneal injection. This suggests that moxifloxacin rapidly crosses the blood-brain-barrier and diffuses into cerebral parenchyma. Moreover, no resistant strains were selected during in vivo experiments. Our results indicate that moxifloxacin combines useful pharmacokinetic properties and rapid bactericidal activity, and may be a valuable alternative for the treatment of CNS-listeriosis.