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Antimicrobial Agents and Chemotherapy, September 2008, p. 3210-3215, Vol. 52, No. 9
0066-4804/08/$08.00+0     doi:10.1128/AAC.00177-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Rapid Eradication of Listeria monocytogenes by Moxifloxacin in a Murine Model of Central Nervous System Listeriosis{triangledown}

Solène Grayo,1 Marie-Catherine Lott-Desroches,2 Olivier Dussurget,3,4,5 Renaud Respaud,2 Arnaud Fontanet,6 Olivier Join-Lambert,7 Eric Singlas,2 and Alban Le Monnier1*

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,1 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,2 Unité des Interactions Bactéries-Cellules, Institut Pasteur, 25 rue du Dr Roux, 75015 Paris, France,3 INSERM U604, 25 rue du Dr Roux, 75015 Paris, France,4 INRA USC2020, 25 rue du Dr Roux, 75015 Paris, France,5 Unité d'Epidémiologie des Maladies Emergentes, 25 rue du Dr Roux, Institut Pasteur, 75015 Paris, France,6 Unité INSERM U570, Université Paris Descartes, Faculté de Médecine, Site Necker, 156 rue de Vaugirard, 75015 Paris, France7

Received 7 February 2008/ Returned for modification 13 April 2008/ Accepted 16 June 2008

Listeriosis is a rare but life-threatening infection. A favorable outcome is greatly aided by early administration of antibiotics with rapid bactericidal activity against Listeria monocytogenes. Moxifloxacin, a new-generation fluoroquinolone with 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 by studying the kinetics of bacterial growth in blood and organs in a murine model of central nervous system (CNS) listeriosis. We combined pharmacokinetic and pharmacodynamic approaches to correlate the observed efficacy in vivo with plasma and tissue moxifloxacin concentrations. Death was significantly delayed for animals treated with a single dose of moxifloxacin compared to a single dose of amoxicillin. We observed 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 the brain at 1.92 ± 0.32 µg/g 1 hour after intraperitoneal injection. This suggests that moxifloxacin rapidly crosses the blood-brain barrier and diffuses into the 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 that it may be a valuable alternative for the treatment of CNS listeriosis.

* Corresponding author. Mailing address: Laboratoire des Listeria, 25 rue du Dr Roux, 75724 Paris Cedex 15, France. Phone: 33 1 40 61 39 62. Fax: 33 1 40 61 35 67. E-mail: alm{at}pasteur.fr

{triangledown} Published ahead of print on 23 June 2008.

Antimicrobial Agents and Chemotherapy, September 2008, p. 3210-3215, Vol. 52, No. 9
0066-4804/08/$08.00+0     doi:10.1128/AAC.00177-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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