Nephrotoxicity Associated with Intravenous Polymyxin B Once versus Twice Daily Dosing Regimen [PublishAheadOfPrint]

Nephrotoxicity is a known adverse effect of polymyxin B (PMB). Animal data suggests that once daily dosing may reduce the rate and delay the onset of acute kidney injury (AKI).

In a multicenter, retrospective study, we evaluated adult patients with a creatinine clearance (CrCl) ≥30 mL/min who received ≥48h of PMB therapy. The primary endpoint was the difference in rate of AKI comparing once and twice daily PMB dosing. Secondary endpoints included time to AKI and recovery of renal function.

Of 273 eligible patients, 100 from each group were matched based on propensity scores. In the matched groups, nephrotoxicity, defined according to RIFLE criteria, was more frequent with once versus twice daily dosing (47% vs. 17% P=0.0005). After adjusting for residual differences by multivariate conditional logistic regression, once daily dosing was more likely to result in nephrotoxicity (adjusted odds ratio 2.5, 95% CI 1.413-4.541, P=0.002). Among 64 patients who developed AKI, the median onset was similar between groups (7 days with once vs. 6 days with twice daily dosing, P=0.095). Of 37 patients who had their serum creatinine evaluated subsequently, 29/37 (78%) had recovery of renal function. No patient required renal replacement therapy.

Our findings suggest that AKI is significantly more common with PMB once daily as compared to twice daily dosing with no difference in time to AKI. Prospective randomized study is warranted to validate these results.

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