Rapid eradication of Listeria monocytogenes by moxifloxacin in a murine model of central nervous system listeriosis.
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 microg/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.
Grayo
Solène
S
Laboratoire de Listeria, Centre National de Référence des Listeria, World Health Organization Collaborating Centre for Foodborne Listeriosis, Institut Pasteur, Paris, France.
Lott-Desroches
Marie-Catherine
MC
Dussurget
Olivier
O
Respaud
Renaud
R
Fontanet
Arnaud
A
Join-Lambert
Olivier
O
Singlas
Eric
E
Le Monnier
Alban
A
D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001372:Aza Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000382:microbiology; D001927:Brain Diseases / Q000188:drug therapy / Q000382:microbiology; D020806:Central Nervous System Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D004195:Disease Models, Animal; D024841:Fluoroquinolones; D008089:Listeria monocytogenes / Q000187:drug effects*; D008088:Listeriosis / Q000188:drug therapy / Q000382:microbiology; D051379:Mice; D000077266:Moxifloxacin; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin