Adverse effects of polymyxin B administration to healthy horses.
Abstract: Polymyxin B (PolyB) is used to treat endotoxemia in horses; neurologic and nephrogenic adverse effects occur in humans. Objective: To describe PolyB adverse effects in horses. Methods: Five healthy horses (ataxia 0/5), 1 horse with cervical osteoarthritis (ataxia 1/5). Methods: Prospective blinded randomized cross-over trial; 3-weeks wash out. Horses received PolyB (PolyB 6000 IU/kg IV, 7 doses q12h, n = 6) and PolyB/gentamicin (PolyB 6000 IU/kg IV, q12h 7 doses; gentamicin 10 mg/kg IV q24h 4 doses n = 4, or q12-24 h 5 doses because of an additional erroneous dose, n = 2). Daily neurological examinations were video recorded, and ataxia graded by 3 observers. Urine status, urinary GGT/creatinine ratio, plasma creatinine, and urea were assessed every other day, EMG daily. Mixed model analysis was used to evaluate factors associated with ataxia grade and [PolyB]. Results: Median ataxia score increased from 0/5 (range 0-2/5) to 2/5 (range 1-3/5) during administration and declined to 0.5/5 (range 0-2/5) after cessation. Gentamicin co-administration (P < .01, effect size: .8), number of PolyB doses (P < .001, effect size: .6), and time since last PolyB dose (P < .001, effect size: .5) had a significant effect on ataxia grades, while horse, day, [Genta], [PolyB], and [PolyB] did not. Gentamicin co-administration and [Genta] C had no effect on median [PolyB] C (4.67 and 4.89 μg/ml for PolyB and PolyB/gentamicin, respectively). Urinary GGT/creatinine ratio was elevated in 3/6 horses receiving PolyB/gentamicin. The EMG remained unchanged. Conclusions: PolyB caused transient ataxia, worsening with cumulative PolyB doses and gentamicin co-administration. Nephrotoxicity of PolyB was only evident when gentamicin was co-administered.
© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.
Publication Date: 2022-07-07 PubMed ID: 35801274PubMed Central: PMC9308405DOI: 10.1111/jvim.16470Google Scholar: Lookup
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- Journal Article
- Randomized Controlled Trial
- Veterinary
Summary
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The research article presents the adverse effects of administering polymyxin B, a drug used to treat endotoxemia in horses. The study indicates that the drug causes transient ataxia in horses, which aggravates when the dose is increased or combined with gentamicin. Additionally, the researchers found a possible risk of kidney damage when polymyxin B is co-administered with gentamicin.
Objective & Methods
- This research aimed to report the adverse effects of polymyxin B (PolyB) in horses. It focuses particularly on the neurologic and nephrogenic effects, previously observed in humans and suspected to occur in horses too.
- The study was conducted as a prospective blinded randomized cross-over trial with a 3-week washout period. The subjects were five healthy horses and one horse with cervical osteoarthritis.
- The horses were administered with PolyB alone and a combination of PolyB/gentamicin in varying doses. The researchers conducted daily neurological examinations, assessments of urine status, urinary GGT/creatinine ratio, plasma creatinine, and urea, and EMG.
- The data were analyzed using mixed model analysis to identify factors associated with ataxia grade (a measure of incoordination and imbalance in horses) and blood concentration of PolyB.
Results
- The study found that the median ataxia score of the horses increased during PolyB administration and reduced after its cessation. The increase was significantly affected by the co-administration of gentamicin, the number of PolyB doses, and the time since the last PolyB dose.
- The co-administration of gentamicin, however, did not affect the median blood concentration of PolyB.
- Three out of six horses treated with PolyB/gentamicin showed an elevated urinary GGT/creatinine ratio, potentially signaling kidney damage. However, the EMG remained unchanged throughout the study in all horses.
Conclusions
- The research concluded that administering PolyB to horses caused transient ataxia, a condition that worsened with the increase in PolyB doses and when co-administered with gentamicin.
- The potential kidney damage (nephrotoxicity) associated with PolyB, indicated by an elevated urinary GGT/creatinine ratio, was evident only when gentamicin was co-administered.
Cite This Article
APA
van Spijk JN, Beckmann K, Wehrli Eser M, Boxler M, Stirn M, Rhyner T, Kaelin D, Saleh L, Schoster A.
(2022).
Adverse effects of polymyxin B administration to healthy horses.
J Vet Intern Med, 36(4), 1525-1534.
https://doi.org/10.1111/jvim.16470 Publication
Researcher Affiliations
- Equine Department, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
- Department of Veterinary Medicine, Equine Clinic, Freie Universität Berlin, Berlin, Germany.
- Department of Small Animals, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
- Equine Department, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
- Institute of Forensic Medicine, University of Zurich, Zurich, Switzerland.
- Department of Clinical Services, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
- Equine National Center Berne, Berne, Switzerland.
- Equine Department, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
- Institute of Clinical Chemistry, University Hospital Zurich, Zurich, Switzerland.
- Equine Department, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
MeSH Terms
- Animals
- Ataxia / veterinary
- Creatinine
- Gentamicins
- Horse Diseases / chemically induced
- Horse Diseases / drug therapy
- Horses
- Humans
- Polymyxin B / adverse effects
- Prospective Studies
Grant Funding
- 569545 / American College of Veterinary Internal Medicine
- 2018-02 / Stiftung Pro Pferd, Switzerland
Conflict of Interest Statement
Authors declare no conflict of interest.
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Citations
This article has been cited 3 times.- van Spijk JN, Beckmann K, Wehrli Eser M, Stirn M, Steuer AE, Saleh L, Schoster A. Preliminary Investigation of Side Effects of Polymyxin B Administration in Hospitalized Horses. Antibiotics (Basel) 2023 May 5;12(5).
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