Comparison of plasma and intra-articular gentamicin levels after intravenous administration in healthy horses

Septic arthritis is considered one of the most severe disorders that affect horses’ joints. Therapy is intended to eliminate the microorganisms that cause this infection. The intravenous administration of antibiotics is an easily performed technique, but there is no guarantee that the antibiotics will reach the joint milieu at high concentrations and remain elevated for a certain period of time. This study aimed to determine and compare the levels of gentamicin in the plasma and synovial fluid of healthy horses after intravenous administration for seven days. Five horses received 6.6 mg/kg intravenous gentamicin every 24 h for seven consecutive days. Blood and synovial fluid samples were collected from the right metacarpal-phalangeal joint before the start of the treatment (T0) and after 6 h (T6), 12 h (T12), and every 24 h during antibiotic therapy for seven days (D1 to D7). The levels of gentamicin in serum and synovial fluid were quantified by Enzyme-Linked Immunosorbent Assay (ELISA). The intravenous administration of 6.6 mg/kg of gentamicin, in horses, after a period of 24 h, promotes synovial fluid concentrations below the MIC of the drug, in spite of reaching high plasma concentrations of gentamicin, daily mean serum concentration which was 29-fold higher than the minimum inhibitory concentration (MIC) of the drug. The intravenous administration every 24 h during seven consecutive days did not cause systemic side effects, such as hepatic or renal injury. Septic arthritis, ELISA, minimal inhibitory concentration The joints and their adjacent tissues, like cartilage and synovial membrane, are predisposed sites for bacterial infection, due to reduced vascularization and reduced oxygen, leading to septic arthritis (Meijer et al. 2000; Taylor et al. 2010). In horses, appropriate treatment should be initiated as soon as possible, to avoid the degeneration of the articulation and synovial structures (Nix et al. 1991; Morton 2005). Traditionally, systemic antibiotic therapy, joint lavage, and intra-articular administration of antibiotics are used for the treatment of septic arthritis, given that appropriate concentrations of antibiotics in the infected joint are important, so that the infection can be eliminated (Doria et al. 2010; Motta et al. 2017). The aminoglycosides amikacin and gentamicin are effective antibiotics against Gram negative bacteria, used to treat severe conditions (Firth 1983; Nix et al. 1991; Durham 2018). In horses, the administration of gentamicin is recommended at a dose of 6.6 mg/kg intravenously with a volume of distribution of 0.18–0.3 l/kg; clearance of 1.1–2.2 ml/min/kg; and half-life of 1.5–4 h, as pharmacokinetic characteristics (Spinosa 2006). Gentamicin is effective against more than 80% of bacteria isolated from musculoskeletal diseases of horses, and is active in the synovial fluid (Snyder et al. 1987). The minimum inhibitory concentration (MIC) of gentamicin in horses is 2 μg/ml (Moore et al. 1987; Lloyd et al.1988; Skopnik et al. 1992). The therapeutic success of aminoglycoside antibiotics is associated with the maximum concentration of the drug (Cmax) that is 8–10 fold higher than the MIC (Moore et al. 1987; ACTA VET. BRNO 2020, 89: 225–230; https://doi.org/10.2754/avb202089030225 Address for correspondence: Marília Alves Ferreira Campus Fernando Costa – USP Avenue Duque de Caxias Norte, 225 13635-900, Pirassununga, São Paulo, Brazil Phone: +55 (19) 3565-4200 E-mail: marilia.alves. ferreira@usp.br http://actavet.vfu. cz/