Response to Therapy in an Experimental Rabbit Model of Meningitis Due to Listeria monocytogenes

Abstract

A uniformly fatal, reproducible model of experimental meningitis due to Listeria monocytogenes was developed in rabbits for study of the natural progression of the disease and was used to evaluate treatment regimens. Bacterial titers in cerebrospinal fluid and pleocytosis approximated those found in humans. Therapeutic studies in vivo revealed that rifampin was less rapidly bactericidal than ampicillin or penicillin, the agents usually recommended for treatment of meningitis; that penicillin plus rifampin was no more efficacious than penicillin alone; that ampicillin demonstrated greater bactericidal activity in vivo than did penicillin; and that addition of an aminoglycoside (gentamicin) to either penicillin or ampicillin significantly enhanced their bactericidal activity in vivo. Ampicillin plus gentamicin was the most effective combination in vivo and may represent the preferred mode of therapy for listeria meningitis.