Gentamicin plasma concentrations in hospitalized horses and retrospective minimal inhibitory concentrations of gram-negative equine pathogens.

Abstract

The optimal dosage regimen of gentamicin in horses is still under investigation. The objectives of this study were to determine gentamicin plasma concentrations in hospitalized horses treated with 10mg/kg gentamicin (IV, q 24 h) and to determine whether a plasma concentration to minimum inhibitory concentration (MIC) ratio of 10:1 is reached for equine pathogens using this dose. Prospective clinical observational study; retrospective study on MICs of 131 gram-negative bacteria isolated from horses (2012-2015). University teaching hospital. Ninety-eight horses>6 months old, treated with gentamicin for their primary disease, consecutive samples. Plasma concentrations were measured 1hour (C1h ) and 20hours (C20h ) after gentamicin administration using fluorescence polarization. Presence of systemic inflammatory response syndrome (SIRS) and azotemia was recorded, as well as the reason for antimicrobial administration (primary disease) and whether administration was prophylactic or therapeutic. The target C1h of ≥20µg/mL gentamicin was reached in 90% of horses and was sufficient to reach a plasma concentration:MIC of 10:1 in 32 of 131 (24%) of gram-negative aerobic bacteria. A C20h ≤2µg/mL was reached in 97% horses. Therapeutic versus prophylactic administration, primary disease, azotemia, and systemic inflammatory response syndrome were not associated with a failure to reach a desired peak or trough. The gentamicin dose of 10mg/kg every 24hours should be further investigated and safety assessed because a target gentamicin plasma concentration of ≥20µg/mL was achieved in the majority of cases. Nephrotoxic side effects were not assessed. Individual drug monitoring should be performed because clinical factors are unreliable predictors of plasma concentrations. A gentamicin target concentration of ≥40µg/mL does not offer additional benefits compared to ≥20µg/mL, due to the bimodal distribution of resistance in bacterial isolates.