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

Abstract

BackgroundTherapeutic drug monitoring and minimum inhibitory concentration (MIC) data allow more informed use of gentamicin.Hypothesis/ObjectivesTo measure peak and trough serum gentamicin concentrations in horses after a 6.6 mg/kg dose of gentamicin given IV and the MIC of gentamicin of bacteria for which gentamicin might be selected.MethodsRetrospective analysis of hospital records. Peak and trough plasma gentamicin concentrations were measured after 6.6 mg/kg gentamicin IV in 339 hospitalized horses. The MIC of gentamicin was measured for 503 isolates from ambulatory practice and 33 from hospital practice. The distribution of gentamicin concentrations and MIC results were compared to current recommendations for MIC breakpoints.ResultsThe median serum gentamicin concentration at 60 minutes after administration (C 60min) was 21.4 μg/mL with a distribution indicating that bacteria with MIC ≥2 μg/mL were unlikely to be exposed to sufficient gentamicin for effective killing. Approximately 90% of isolates from ambulatory practice and 36% of hospital isolates had MICs at or below breakpoints for susceptibility with most of the remainder unlikely to be responsive, even to higher IV doses.Conclusions and Clinical ImportanceGentamicin at a dosage of 6.6 mg/kg IV is likely to be effective against the majority of infections encountered in ambulatory practice, but less effective in an equine hospital. Because there was a dichotomy of most bacteria as being clearly susceptible or clearly resistant to gentamicin, it appears unlikely that higher doses would have been more efficacious, especially in the hospitalized population in our study.

Antimicrobial susceptibility of bacterial isolates from ambulatory practice and from a referral hospital

“…The finding of higher resistance rates in isolates from a referral hospital compared to those obtained from ambulatory practices (Tables ) also has been found in previous studies . This observation probably can be explained because of higher antimicrobial exposure among a hospital bacterial population because resistance genes are put under more environmental pressure as well as other factors such as greater potential for transmission of resistant strains or resistance determinants among hospitalized horses and for stress to precipitate increased shedding of resistant strains .…”

“…Responsible use of antimicrobials is facilitated by in vitro antimicrobial susceptibility testing to inform antimicrobial choice. Breakpoints are determined based on the minimum inhibitory concentration (MIC) of an antimicrobial to separate isolates for which there is a high likelihood of treatment success (sensitive) versus those for which treatment is more likely to be ineffective (intermediate or resistant) . International groups including the Clinical and Laboratory Standards Institute (CLSI) and the European Union Committee on Antimicrobial Susceptibility Testing (EUCAST) have published suggested breakpoints for clinical application based on pharmacokinetics and pharmacodynamics to predict clinical efficacy .…”

“…The prevalence of sensitivity to first‐line antimicrobials (parenteral P‐G and PO TMPS) was determined and subsequently the sensitivity to alternative antimicrobials was examined for the isolates found to be resistant to first‐line choices. The hypotheses were that bacteria cultured from a hospital population would have lower prevalence of in vitro sensitivity compared to ambulatory isolates as previously described and that organisms resistant to P‐G or TMPS still could be treated successfully with noncritically important antimicrobials such as tetracyclines.…”

Retrospective assessment of perioperative antimicrobial use for elective arthroscopy in horses

“…A dose of 6.6 mg/kg has traditionally been used; however, higher doses (eg, 7.7-9.7 mg/kg) have been recommended, particularly for equine hospitals in which the minimum inhibitory concentrations of targeted organisms could be higher. 15,20 The gentamicin dose used for most treated horses was below even the lower (6.6 mg/kg) limit, presumably from combination of targeting the lower 6.6 mg/kg dose and imprecision in dosing or weighing. The impact of mostly minor underdosing is not clear, but this is a situation easily avoided through weighing and properly calculating doses.…”

Antimicrobial dosing for common equine drugs: a content review and practical advice for veterinarians in Australia

“…Most susceptible pathogens, and those of intermediate susceptibility, have a MIC < 4 μg/mL, so the C max should reach 32–48 μg/mL . There is no consensus on the minimum effective concentration, but the medical and veterinary literature suggests a range of < 0.5–2 μg/mL . Peak and trough concentrations of gentamicin can be measured, but cost and the time taken to obtain these results limit this to referral hospitals that have in‐house laboratories.…”