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


Schoster, Angelika; Amsler Medvet, Morena; Kirchgaessner, Constanze; Saleh, Lanja; Schwarzwald, Colin C; Schmitt, Sarah (2020). Gentamicin plasma concentrations in hospitalized horses and retrospective minimal inhibitory concentrations of gram‐negative equine pathogens. Journal of Veterinary Emergency and Critical Care:Epub ahead of print.

Abstract

Objectives: 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 10 mg/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.
Design: Prospective clinical observational study; retrospective study on MICs of 131 gram-negative bacteria isolated from horses (2012-2015).
Setting: University teaching hospital.
Animals: Ninety-eight horses >6 months old, treated with gentamicin for their primary disease, consecutive samples.
Measurements and main results: Plasma concentrations were measured 1 hour (C1h ) and 20 hours (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 ≥20 µg/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 ≤ 2 µg/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.
Conclusions: The gentamicin dose of 10 mg/kg every 24 hours should be further investigated and safety assessed because a target gentamicin plasma concentration of ≥20 µg/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 ≥40 µg/mL does not offer additional benefits compared to ≥20 µg/mL, due to the bimodal distribution of resistance in bacterial isolates.

Abstract

Objectives: 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 10 mg/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.
Design: Prospective clinical observational study; retrospective study on MICs of 131 gram-negative bacteria isolated from horses (2012-2015).
Setting: University teaching hospital.
Animals: Ninety-eight horses >6 months old, treated with gentamicin for their primary disease, consecutive samples.
Measurements and main results: Plasma concentrations were measured 1 hour (C1h ) and 20 hours (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 ≥20 µg/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 ≤ 2 µg/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.
Conclusions: The gentamicin dose of 10 mg/kg every 24 hours should be further investigated and safety assessed because a target gentamicin plasma concentration of ≥20 µg/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 ≥40 µg/mL does not offer additional benefits compared to ≥20 µg/mL, due to the bimodal distribution of resistance in bacterial isolates.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Clinical Chemistry
05 Vetsuisse Faculty > Institute of Food Safety and Hygiene
05 Vetsuisse Faculty > Veterinary Clinic > Equine Department
Dewey Decimal Classification:570 Life sciences; biology
630 Agriculture
Scopus Subject Areas:Health Sciences > General Veterinary
Uncontrolled Keywords:General Veterinary
Language:English
Date:4 December 2020
Deposited On:11 Jan 2021 16:16
Last Modified:23 Feb 2021 12:25
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:1476-4431
OA Status:Closed
Publisher DOI:https://doi.org/10.1111/vec.13035
PubMed ID:33274835

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