Adverse effects of polymyxin B administration to healthy horses.
Authors: van Spijk Julia N, Beckmann Katrin, Wehrli Eser Meret, Boxler Martina, Stirn Martina, Rhyner Thea, Kaelin Dana, Saleh Lanja, Schoster Angelika
Journal: Journal of veterinary internal medicine
Summary
# Editorial Summary: Polymyxin B Neurotoxicity in Horses Polymyxin B remains a valuable tool for managing endotoxaemia in equine practice, yet its safety profile in horses has received limited scrutiny despite well-documented neurological and renal complications in human patients. This prospective, blinded cross-over trial evaluated six horses (five healthy, one with cervical osteoarthritis) receiving either polymyxin B monotherapy (6000 IU/kg intravenously, seven doses every 12 hours) or combination therapy with gentamicin, measuring neurological status via daily video-recorded examinations and renal function markers every 48 hours. Median ataxia scores increased significantly from baseline (0/5) to 2/5 during treatment, with deterioration correlating strongly to cumulative dosing (P<0.001) and gentamicin co-administration (P<0.01); importantly, ataxia resolved within days of cessation, confirming the effect was polymyxin B-related rather than permanent. Nephrotoxicity—evidenced by elevated urinary GGT/creatinine ratios—emerged only when gentamicin was administered concurrently, whereas monotherapy showed no renal compromise. These findings suggest that whilst transient ataxia is an expected dose-dependent consequence of polymyxin B therapy in horses, clinicians should exercise particular caution with combination antibiotic protocols and consider renal monitoring when gentamicin co-administration is unavoidable, especially in extended treatment courses.
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Practical Takeaways
- •When using polymyxin B for endotoxemia treatment in horses, expect transient ataxia that worsens with each dose and improves after stopping—monitor neurological status daily and plan treatment duration accordingly
- •Avoid combining polymyxin B with gentamicin if possible, as co-administration significantly increases ataxia severity and causes kidney injury markers in urine
- •Ataxia from polymyxin B appears neurological rather than related to drug levels in blood or cerebrospinal fluid, so dose adjustment based on plasma concentration monitoring may not prevent adverse effects
Key Findings
- •Polymyxin B caused transient ataxia that increased from median 0/5 to 2/5 during administration and declined to 0.5/5 after cessation
- •Gentamicin co-administration significantly worsened ataxia (P<0.01, effect size 0.8) and cumulative PolyB doses increased ataxia grade (P<0.001, effect size 0.6)
- •Nephrotoxicity (elevated urinary GGT/creatinine ratio) occurred in 3/6 horses only when gentamicin was co-administered with PolyB
- •EMG remained unchanged throughout study, and PolyB plasma concentration and CSF concentration did not correlate with ataxia severity