Comparative efficacies of antibiotics in a rat model of meningoencephalitis due to Listeria monocytogenes

The antibacterial activities of amoxicillin-gentamicin, trovafloxacin, trim elhoprim-sulfamethoxazole (TMP SMX) and the combination of trovafloxacin wi th TMP-SMX were compared in a model of meningoencephalitis due to Listeria monocytogenes in infant rats. At 22 h after intracisternal infection, the c erebrospinal fluid was cultured to document meningitis, and the treatment w as started. Treatment was instituted for 48 h, and efficacy was evaluated 2 4 h after administration of the last dose. All tested treatment regimens ex hibited significant activities in brain, liver, and blood compared to infec ted rats receiving saline (P < 0.001). In the brain, amoxicillin plus genta micin was more active than all of the other regimens, and trovafloxacin was more active than TMP-SMX (bacterial titers of 4.1 +/- 0.5 log(10) CFU/ml f or amoxicillin-gentamicin, 5.0 +/- 0.4 log(10) CFU/ml for trovafloxacin, an d 5.8 +/- 0.5 log(10) CFU/ml for TMP-SMX; P < 0.05), Tn liver, amoxicillin- gentamicin and trovafloxacin were similarly active (2.8 +/- 0.8 and 2.7 +/- 0.8 log(10) CFU/ml, respectively) but more active than TMP-SMX (4.4 +/- 0. 6 log(10) CFU/ml; P < 0.05), The combination of trovafloxacin with TMP-SMX did not alter the antibacterial effect in the brain, but it did reduce the effect of trovafloxacin in the liver. Amoxicillin-gentamicin was the most a ctive therapy in this study, but the activity of trovafloxacin suggests tha t further studies with this drug for the treatment of Listeria infections m ay be warranted.