title: Enrofloxacin against Escherichia coli in turkeys: which treatment scheme is effective?
abstract: The efficacy of enrofloxacin (ENRO) was evaluated against multidrug-resistant avian pathogenic Escherichia coli correlating the minimum inhibitory concentrations (MIC) of 235 E. coli field strains with its pharmacokinetics (PK) in 50 healthy turkeys (5 groups) with a PK/pharmacodynamic approach. The treatments were as follows: a) single oral gavage and b) single subcutaneous (SC) treatment at the recommended dose of 10 mg/kg; c) single oral gavage, d) 5 d of 10-h pulsed water medication, and e) 5 d of 24-h continuous water medication at the doubled dose of 20 mg/kg. Blood samples were collected at established times over 24 h. Plasma was analyzed using a liquid chromatography tandem mass spectrometry method that was validated in house. A monocompartmental and a noncompartmental model were applied to the data to obtain the PK results. After gavage administration, the mean maximum concentration Cmax/MIC50 and area under the curve AUC0-24/MIC50 ratios were, respectively, 3.07 ± 0.62 and 7.01 ± 1.03 and 25.48 ± 3.04 and 57.2 ± 3.73 for the 10 and 20 mg/kg doses, respectively. After SC administration of 10 mg/kg, Cmax/MIC50 and AUC0-24/MIC50 ratios were 3.45 ± 0.75 and 33.96 ± 7.46, respectively. After the administration of 10-h pulsed or 24-h continuous medicated water at 20 mg/kg, lower values of Cmax/MIC50 (10-h pulsed: 3.45 ± 0.7; 24-h continuous: 3.05 ± 0.48) and AUC0-24/MIC50 (10-h pulsed: 42.42 ± 6.17; 24-h continuous: 53.32 ± 5.55) were obtained. Based on these results, the European Union-recommended dosage of 10 mg/kg seems ineffective to achieve adequate drug plasma concentrations and even the 20 mg/kg by 10 h pulsed or continuous medicated water administration did not reach completely efficacious concentrations in plasma against colibacillosis. Although the results obtained were not completely encouraging, the medicated water should preferably be provided continuously. To conclude about the efficacy of ENRO treatment against colibacillosis, target tissue concentration should be extensively considered.
authors.affiliation: Università degli Studi di Milano, Dip. Scienze Veterinarie per la Salute, la Produzione Animale e la Sicurezza Alimentare, Via Celoria, 10, 20133 Milano, Italy petra.cagnardi@unimi.it.
authors.forename: P
authors.initials: P
authors.lastname: Cagnardi
authors.affiliation: Università degli Studi di Milano, Dip. Scienze Veterinarie per la Salute, la Produzione Animale e la Sicurezza Alimentare, Via Celoria, 10, 20133 Milano, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Ferraresi
authors.affiliation: Università degli Studi di Padova, Dip. Biomedicina Comparata e Alimentazione, Via dell'Università 16, 35020 Legnaro, Padova, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Lucatello
authors.affiliation: Università di Pisa, Dip. Scienze Veterinarie, Via Livornese (Lato monte), 56122 San Piero a Grado, Pisa, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Meucci
authors.affiliation: Università di Pisa, Dip. Scienze Veterinarie, Via Livornese (Lato monte), 56122 San Piero a Grado, Pisa, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Intorre
authors.affiliation: Università degli Studi di Milano, Dip. Scienze Veterinarie e Sanità Pubblica, Via Celoria, 10, 20133 Milano, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Grilli
authors.affiliation: Università degli Studi di Padova, Dip. Biomedicina Comparata e Alimentazione, Via dell'Università 16, 35020 Legnaro, Padova, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Piccirillo
authors.affiliation: Università degli Studi di Padova, Dip. Biomedicina Comparata e Alimentazione, Via dell'Università 16, 35020 Legnaro, Padova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Giacomelli
authors.affiliation: Università degli Studi di Padova, Dip. Biomedicina Comparata e Alimentazione, Via dell'Università 16, 35020 Legnaro, Padova, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Montesissa
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D002853:Chromatography, Liquid / Q000662:veterinary; D004305:Dose-Response Relationship, Drug; D000077422:Enrofloxacin; D004926:Escherichia coli / Q000187:drug effects; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology / Q000662:veterinary*; D005260:Female; D024841:Fluoroquinolones / Q000493:pharmacokinetics / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests / Q000662:veterinary; D011201:Poultry Diseases / Q000188:drug therapy* / Q000382:microbiology; D053719:Tandem Mass Spectrometry / Q000662:veterinary; D014422:Turkeys
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D000077422:Enrofloxacin
keywords: colibacillosis; enrofloxacin; pharmacokinetics/pharmacodynamics; turkey