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: Objectives This study aimed to compare the antibacterial activity of moxifloxacin and ampicillin + gentamicin in the treatment of Listeria monocytogenes meningitis in a rabbit meningitis model. : Methods Meningitis was induced by direct inoculation of a clinical strain isolated from an immunocompromised patient (107cfu/mL) into the cisterna magna of New Zealand rabbits. After 16 h of incubation, rabbits were separated into four groups: moxifloxacin (M), ampicillin + gentamicin (A), ampicillin + gentamicin 2 (A2) and control (C). Group M received 20 mg/kg moxifloxacin at the end of the incubation time and 5 h later by intravenous (iv) route. Group A received ampicillin (30 mg/kg/h) and gentamicin (2.5 mg/kg/h) by iv route with continuous infusion for 8 h in 36 mL of 0.9% NaCl, group A2 received the same dosage of gentamicin and ampicillin in two different 36 mL 0.9% NaCl solutions and group C did not receive any treatment. Cerebrospinal fluid (CSF) samples (0.1–0.25 mL) were obtained 16 and 24 h after induction of meningitis. : Results At the end of the 16 h of incubation, CSF bacterial counts were similar in all groups (P > 0.05). At the final stage of the study (24 h after induction of meningitis), bacterial counts in all treatment groups were significantly lower than the control group (P < 0.05). When the three treatment groups were compared, bacterial counts were found to be similar (P > 0.05). : Conclusions These data suggest that antibacterial activity of moxifloxacin is similar to ampicillin + gentamicin in the treatment of experimental L. monocytogenes meningitis of rabbits. [ABSTRACT FROM AUTHOR]