title: Impact of Timing and Dosage of a Fluoroquinolone Treatment on the Microbiological, Pathological, and Clinical Outcomes of Calves Challenged with Mannheimia haemolytica.
abstract: The efficacy of an early and low inoculum-adjusted marbofloxacin treatment was evaluated on microbiological and clinical outcomes in calves infected with 4.10(7) CFU of Mannheimia haemolytica A1. Twenty-two calves were included based on their rectal temperature rise in the 10 h after challenge and allocated in four groups, receiving a single intramuscular injection of saline (CON), 2 mg/kg marbofloxacin 2-4 h after inclusion (early treatment, E2), 2 or 10 mg/kg marbofloxacin 35-39 h after inclusion (late treatments, L2, L10). In CON calves, M. haemolytica DNA loads in bronchoalveolar lavages continuously increased from inclusion to day 4, and were associated with persistent respiratory clinical signs and lung lesions. At times of early and late treatments, M. haemolytica loads ranged within 3.5-4 and 5.5-6 log10 DNA copies/mL, respectively. Early 2 mg/kg marbofloxacin treatment led to rapid and total elimination of bacteria in all calves. The late treatments induced a reduction of bacterial loads, but 3 of 6 L2 and 1 of 6 L10 calves were still positive for M. haemolytica at day 4. Except for CON calves, all animals exhibited clinical improvement within 24 h after treatment. However, early 2 mg/kg treatment was more efficacious to prevent pulmonary lesions, as indicated by the reduction of the extension and severity of gross lesions and by the histopathological scores. These results demonstrated for the first time that a reduced antibiotic regimen given at an early stage of the disease and targeting a low bacterial load could be efficacious in a natural bovine model of pneumonia.
authors.affiliation: Vetoquinol Global Drug DevelopmentLure, France; Ecole Nationale Vétérinaire de Toulouse, Institut National Polytechnique de Toulouse, Université de ToulouseToulouse, France; LUNAM Université, Oniris, UMR BioEpARNantes, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Lhermie
authors.affiliation: Ecole Nationale Vétérinaire de Toulouse, Institut National Polytechnique de Toulouse, Université de ToulouseToulouse, France; Institut National de la Recherche Agronomique, UMR1331 ToxAlimToulouse, France.
authors.forename: Aude A
authors.initials: AA
authors.lastname: Ferran
authors.affiliation: LUNAM Université, Oniris, UMR BioEpARNantes, France; Institut National de la Recherche Agronomique, UMR1300 BioEpARNantes, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Assié
authors.affiliation: Ecole Nationale Vétérinaire de Toulouse, Institut National Polytechnique de Toulouse, Université de Toulouse Toulouse, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Cassard
authors.affiliation: Vetoquinol Global Drug Development Lure, France.
authors.forename: Farid
authors.initials: F
authors.lastname: El Garch
authors.affiliation: Vetoquinol Global Drug Development Lure, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Schneider
authors.affiliation: Vetoquinol Global Drug Development Lure, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Woerhlé
authors.affiliation: Ecole Nationale Vétérinaire de Toulouse, Institut National Polytechnique de Toulouse, Université de Toulouse Toulouse, France.
authors.forename: Diane
authors.initials: D
authors.lastname: Pacalin
authors.affiliation: Ecole Nationale Vétérinaire de Toulouse, Institut National Polytechnique de Toulouse, Université de ToulouseToulouse, France; Institut National de la Recherche Agronomique, UMR1225 IHAPToulouse, France.
authors.forename: Maxence
authors.initials: M
authors.lastname: Delverdier
authors.affiliation: Ecole Nationale Vétérinaire de Toulouse, Institut National Polytechnique de Toulouse, Université de ToulouseToulouse, France; Institut National de la Recherche Agronomique, UMR1331 ToxAlimToulouse, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Bousquet-Mélou
authors.affiliation: Ecole Nationale Vétérinaire de Toulouse, Institut National Polytechnique de Toulouse, Université de ToulouseToulouse, France; Institut National de la Recherche Agronomique, UMR1225 IHAPToulouse, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Meyer
keywords: Pasteurellaceae; bovine model; decreased regimen; early treatment; fluoroquinolone