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

Abstract

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 newgeneration 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 g/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.

The antifungal caspofungin increases fluoroquinolone activity against Staphylococcus aureus biofilms by inhibiting N-acetylglucosamine transferase

“…Biofilms were then allowed to develop in vivo for 24 h, after which animals were treated twice daily with either 40 mg kg −1 of fluoroquinolone alone or once daily with 4 mg kg −1 of caspofungin alone or with their combination for 7 days. These doses and schedules were selected as mimicking human exposure in clinical practice taking into consideration the shorter half-life of moxifloxacin in mice compared with humans34353637. For delafloxacin, in the absence of published humanized pharmacokinetic data, we selected as a starting point a dose equivalent to that of moxifloxacin, taking also into account its short half-live and high protein binding in mice38.…”

Fragmentation of Moxifloxacin and Its Analogs by Electrospray Ionization Time-of-Flight Mass Spectrometry

“…As previously reviewed (Doerge and Bajic 1995;Volmer, Mansoori, and Locke 1997;Golet et al 2001;Schilling et al 1996), quinolones have been extensively studied by high-performance liquid chromatography (HPLC), mass spectrometry, and HPLC-tandem mass spectrometry (HPLC-MS-MS). Fourth-generation quinolones are more effective against both Gram-positive and Gram-negative bacteria in vitro and in vivo (Jacobsen et al 2011;Ardila, Fernández, and Guzmán 2009;Galania et al 2008;Sakka et al 2005;Grayo et al 2008).…”

Early Infection Termination Affects Number of CD8+ Memory T Cells and Protective Capacities in Listeria monocytogenes-Infected Mice upon Rechallenge

“…This was probably due to their failure to penetrate into cells or to their accumulation in the compartment other than cytosol. Finally, we turned to the antibiotics Moxi, which has been shown to effectively kill intracellular LM both in cell and animal models (25,26). At first, we used the same treatment protocol as Amp to see whether Moxi could clear LM rapidly in vivo under our experimental conditions.…”