Plasma Peak and Trough Gentamicin Concentrations in Hospitalized Horses Receiving Intravenously Administered Gentamicin

Abstract

BackgroundGentamicin is an aminoglycoside antimicrobial commonly used in horses at 6.6 mg/kg IV once daily. Therapeutic drug monitoring (TDM) can confirm desired peak concentration is reached for common bacterial isolates, and detect toxicosis associated with high trough values.ObjectivesDetermine the relationship between gentamicin dose and plasma concentration in hospitalized horses, and identify a starting dose range to achieve peaks > 32 μg/mL.AnimalsSixty‐five horses (2002–2010) receiving once‐daily gentamicin with TDM performed (N = 99 sets).MethodsRetrospective study. Data from hospitalized horses including weight, dose, plasma peak, and trough gentamicin concentration, creatinine concentrations and presence of focal or systemic disease were collected from medical records. Peak concentrations measured 25–35 minutes after administration were included (N = 77). Data were divided into low (<7.7 mg/kg), medium (7.7–9.7 mg/kg) and high (>9.7 mg/kg) dose groups, and were grouped by the horse having focal or systemic disease.ResultsPeak concentrations resulting from doses ≥7.7 mg/kg were 5.74 μg/mL (SE 2.1 μg/mL) greater than peaks from doses <7.7 mg/kg (P = .007). Peak concentrations was 3.6 times more likely to be >32 μg/mL if dose was ≥7.7 mg/kg (P = .04). There were no significant effects of dose on trough or creatinine concentration. At a given dose, horses with focal disease had higher peaks than those with systemic disease (P = .039).Conclusions and Clinical ImportanceThese data suggest gentamicin dosage should be individually determined in horses using TDM, but support an initial once‐daily dose of 7.7–9.7 mg/kg IV to achieve peaks >32 μg/mL and trough concentrations <2 μg/mL. Further studies evaluating the safety of doses >6.6 mg/kg are required.

An evaluation of serum gentamicin concentrations and bacterial susceptibility to gentamicin in equine practice

“…Thus, the present study found that very few horses receiving 6.6 mg/kg IV q24h attained C 60min results considered adequate to kill bacteria with MIC ≥ 4 μg/mL as has been found previously 8. Bacterial MIC ≤2 μg/mL are very common in infections of horses sampled in ambulatory practice and would be expected to respond well to standard gentamicin dosages.…”

“…Recommended target trough concentrations are variable although generally considered to be no higher than 1–2 μg/mL, although little evidence supports this concentration range 9. In the present study, and in another recent report,8 C 24h concentrations were rarely of concern, being >2 μg/mL in only 2.6% of cases, although more work needs to be done.…”

“…Therefore, using peak plasma concentration at a given time point is always a compromise and most likely often inaccurately reflects actual peak concentration at the infection site. Thus, given these variables for measuring a clinically meaningful peak plasma concentration, the current study and a previous study8 probably offer the most useful approximations and had similar findings, given the earlier sampling time of 30 minutes in the previous study 8. Neither study supported the use of gentamicin at a dosage of 6.6 mg/kg IV for the treatment of infections caused by bacteria with MIC ≥4 μg/mL, and it seems inconceivable that success could be obtained against bacteria with MIC ≥8 μg/mL.…”

“…CLSI, Clinical Laboratory Standards Institute; EUCAST, European Committee on Antimicrobial Susceptibility Testing.a6.6 mg/kg IM 8, 9…”

Pharmacokinetics of intravenous gentamicin in healthy young‐adult compared to aged alpacas

“…These high gentamicin C peak :MIC concentrations potentiate the aminoglycoside postantibiotic effect (PAE), which is characterized by persistent suppression of bacterial growth at sub‐MIC or even undetectable gentamicin concentrations (Mueller & Boucher, ). Considering a reported gentamicin break point MIC of 2 μg/ml, for bacteria isolated from animals (Papich, ), the C peak values observed in this study result in estimated C peak :MIC ratios of 11.9 ± 1 in young adults and 13 ± 1 in aged alpacas, both well above the recommended target range of eight to 10 times MIC (Bauquier et al., ; Fraisse et al., ; Tudor, Papich, & Redding, ). For infectious organisms with intermediate susceptibility (MIC ≤4 μg/ml), the extrapolated C peak :MIC ratio of 6.0 ± 0.5 in young adults and 6.5 ± 0.5 in aged alpacas would not reach a target of 8–10 × MIC in either group.…”