title: Ex vivo antibacterial activity of levofloxacin against Escherichia coli and its pharmacokinetic profile following intravenous and oral administrations in broilers.
abstract: The use of antibiotics is necessary to treat bacterial diseases. Determination of optimal dosage in the target animals is increasingly being recognized as vital for maximizing efficacy and minimizing the risk of resistance, so this study aimed to evaluate the pharmacokinetics/pharmacodynamics (PK/PD) of levofloxacin in broilers. Using a parallel study design, each group of animals (n=20) received 5mg/kg of levofloxacin intravenously (IV) and orally (PO). Plasma, serum and tissues were collected for PK and PD studies. Plasma concentrations of levofloxacin were determined by HPLC. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were determined against E. coli, isolated in clinical broilers. Ex vivo antibacterial activity was evaluated using the time killing method. Mean values of terminal half-life for IV and PO groups were 6.93 and 8.09h, respectively. Following oral administration, the peak plasma concentration was achieved at 0.88h (Tmax). Mean value of oral bioavailability was 123.25%. Levofloxacin residues were found in all the tissues tested (muscle, liver, kidney and lung). Plasma concentration above 8× MIC lead to eradication of E. coli (incubation period of 24h). The results of ex vivo growth inhibition curves were consistent with the in vitro time-kill study. Levofloxacin showed dependent plasma concentration antibacterial activity against a clinical isolate of E. coli. According to the assessment of PK/PD relationship, administration of 5mg/kg of levofloxacin seems to be effective in killing E. coli. Also, simulated optimal dose based on the ex vivo PK/PD approach was 2.9mg/kg/day (bactericidal) to 4.3mg/kg/day (eradication) PO against E. coli (MIC=0.125μg/ml).
authors.affiliation: Department of Veterinary Sciences, University of Pisa, Via Livornese (lato monte) 1, San Piero a Grado, Pisa, Italy.
authors.forename: Hong Ki
authors.initials: HK
authors.lastname: Lee
authors.affiliation: Department of Veterinary Medicine, University of Sassari, Via Vienna 2, 07100 Sassari, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: DeVito
authors.affiliation: Department of Veterinary Sciences, University of Turin, Largo Paolo Braccini 2, 10095 Grugliasco, Turin, Italy. Electronic address: cristina.vercelli@unito.it.
authors.forename: Cristina
authors.initials: C
authors.lastname: Vercelli
authors.affiliation: Department of Veterinary Sciences, University of Turin, Largo Paolo Braccini 2, 10095 Grugliasco, Turin, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Tramuta
authors.affiliation: Department of Veterinary Sciences, University of Turin, Largo Paolo Braccini 2, 10095 Grugliasco, Turin, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Nebbia
authors.affiliation: Department of Veterinary Sciences, University of Turin, Largo Paolo Braccini 2, 10095 Grugliasco, Turin, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Re
authors.affiliation: Faculty of Veterinary Medicine, University of Agriculture, Jelgava LV-3004, Latvia.
authors.forename: Kaspars
authors.initials: K
authors.lastname: Kovalenko
authors.affiliation: Department of Veterinary Sciences, University of Pisa, Via Livornese (lato monte) 1, San Piero a Grado, Pisa, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Giorgi
mesh_terms: D061605:Administration, Intravenous / Q000662:veterinary; D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D001682:Biological Availability; D002645:Chickens / Q000097:blood / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects*; D006207:Half-Life; D064704:Levofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D014018:Tissue Distribution
chemical_list: D000900:Anti-Bacterial Agents; D064704:Levofloxacin
keywords: Broilers; Escherichia coli; Levofloxacin; Pharmacodynamics; Pharmacokinetics