Comparison of the In Vitro Efficacies of Moxifloxacin and Amoxicillin against Listeria monocytogenes

Abstract

Listeria monocytogenes is a facultative intracellular bacterium that causes severe infections associated with a high mortality rate. Moxifloxacin presents extended activity against gram-positive bacteria and has recently been suggested to be a potential alternative in the treatment of listeriosis. We evaluated the in vitro efficacy of moxifloxacin against L. monocytogenes using a combination of epidemiological and experimental approaches. The median MIC of moxifloxacin for a large collection of L. monocytogenes strains of various origins (human, food, and environment) was 0.5 g/ml (MIC range, 0.064 to 1 g/ml). No differences were observed, irrespective of the origin of the strains. Moreover, no cross-resistance with fluoroquinolones was detected in strains that have been reported to be resistant to ciprofloxacin. The in vitro activities of moxifloxacin and amoxicillin were compared by time-kill curve and inhibition of intracellular growth experiments by using a model of bone marrow-derived mouse macrophages infected by L. monocytogenes EGDe. Both moxifloxacin and amoxicillin were bactericidal in broth against extracellular forms of L. monocytogenes. However, moxifloxacin acted much more rapidly, beginning to exert its effects in the first 3 h and achieving complete broth sterilization within 24 h of incubation. Moxifloxacin has a rapid bactericidal effect against intracellular reservoirs of bacteria, whereas amoxicillin is only bacteriostatic and appears to prevent cellular lysis and the subsequent bacterial spreading to adjacent cells. No resistant bacteria were selected during the in vitro experiments. Taken together, our results suggest that moxifloxacin is an interesting alternative to the reference treatment, combining rapid and bactericidal activity, even against intracellular bacteria.

Impact of a Low-Oxygen Environment on the Efficacy of Antimicrobials against Intracellular Chlamydia trachomatis

“…TKC therefore evolved as a suitable tool to evaluate antimicrobial growth inhibition of bacteria at different intracellular developmental stages (15,31). In this study, we investigated the impact of low oxygen, which can be observed in the female urogenital tract under physiological conditions, on the antichlamydial activities of doxycycline, azithromycin, rifampin, and moxifloxacin.…”

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

“…However, moxifloxacin is the only one of these antibiotics released on the market and still commercially available that combines useful pharmacokinetic and pharmacodynamic properties with rapid bactericidal activity in vitro against both extracellular forms of L. monocytogenes and intracellular reservoirs of bacteria (6,14,28,36). Determination of MICs for a large collection of strains did not detect any resistant strains, whatever their origins (14). Moreover, no cross-resistance was observed with ciprofloxacin resistance expressed by clinical isolates due to an efflux mechanism (12,14).…”

“…Moxifloxacin, clinafloxacin, and gemifloxacin are the most effective against intracellular L. monocytogenes (28,36). However, moxifloxacin is the only one of these antibiotics released on the market and still commercially available that combines useful pharmacokinetic and pharmacodynamic properties with rapid bactericidal activity in vitro against both extracellular forms of L. monocytogenes and intracellular reservoirs of bacteria (6,14,28,36). Determination of MICs for a large collection of strains did not detect any resistant strains, whatever their origins (14).…”

The use ofListeria monocytogenesas a DNA delivery vector for cancer gene therapy

“…It is significant that Maciag and co-workers recently performed Phase I trials in human subjects with can improve efficacy, being commercially available and highly effective against intracellular and extracellular listeria. 8 We are currently investigating whether more effective elimination of the vector occurs when similar experiments are conducted in immunocompetent mice.…”