title: Comparative efficacies of antibiotics in a rat model of meningoencephalitis due to Listeria monocytogenes.
abstract: The antibacterial activities of amoxicillin-gentamicin, trovafloxacin, trimethoprim-sulfamethoxazole (TMP-SMX) and the combination of trovafloxacin with TMP-SMX were compared in a model of meningoencephalitis due to Listeria monocytogenes in infant rats. At 22 h after intracisternal infection, the cerebrospinal fluid was cultured to document meningitis, and the treatment was started. Treatment was instituted for 48 h, and efficacy was evaluated 24 h after administration of the last dose. All tested treatment regimens exhibited significant activities in brain, liver, and blood compared to infected rats receiving saline (P < 0.001). In the brain, amoxicillin plus gentamicin was more active than all of the other regimens, and trovafloxacin was more active than TMP-SMX (bacterial titers of 4.1 +/- 0.5 log10 CFU/ml for amoxicillin-gentamicin, 5.0 +/- 0.4 log10 CFU/ml for trovafloxacin, and 5.8 +/- 0.5 log10 CFU/ml for TMP-SMX; P < 0.05). In liver, amoxicillin-gentamicin and trovafloxacin were similarly active (2.8 +/- 0.8 and 2.7 +/- 0.8 log10 CFU/ml, respectively) but more active than TMP-SMX (4.4 +/- 0. 6 log10 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 active therapy in this study, but the activity of trovafloxacin suggests that further studies with this drug for the treatment of Listeria infections may be warranted.
authors.affiliation: Institute for Medical Microbiology, CH-3010 Bern, Switzerland. christian.michelet@univ-rennes1.fr
authors.forename: C
authors.initials: C
authors.lastname: Michelet
authors.forename: S L
authors.initials: SL
authors.lastname: Leib
authors.forename: D
authors.initials: D
authors.lastname: Bentue-Ferrer
authors.forename: M G
authors.initials: MG
authors.lastname: Täuber
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D008089:Listeria monocytogenes / Q000187:drug effects; D008088:Listeriosis / Q000188:drug therapy* / Q000473:pathology; D008590:Meningoencephalitis / Q000188:drug therapy* / Q000473:pathology; D008826:Microbial Sensitivity Tests; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000900:Anti-Bacterial Agents