Adverse effects of polymyxin B administration to healthy horses

Polymyxin B (PolyB) is used to treat endotoxemia in horses; neurologic and nephrogenic adverse effects occur in humans.To describe PolyB adverse effects in horses.Five healthy horses (ataxia 0/5), 1 horse with cervical osteoarthritis (ataxia 1/5).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].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]PolyB caused transient ataxia, worsening with cumulative PolyB doses and gentamicin co-administration. Nephrotoxicity of PolyB was only evident when gentamicin was co-administered.