Nephrotoxicity Associated with Intravenous Polymyxin B Once- versus Twice-Daily Dosing Regimen

Abstract

Nephrotoxicity is a known adverse effect of polymyxin B (PMB). Animal data suggest 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) of ≥30 ml/min who received ≥48 h of PMB therapy. The primary endpoint was the difference in rate of AKI comparing once- and twice-daily PMB dosing. The secondary endpoints included the time to AKI and the recovery of renal function. Of 273 eligible patients, 100 from each group were matched on the basis of propensity scores. In the matched groups, nephrotoxicity, defined according to risk, injury, failure, loss, and end-stage renal disease (RIFLE) criteria, was more frequent with once- than with twice-daily dosing (47% versus 17%, respectively; 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% confidence interval [CI], 1.413 to 4.541; P = 0.002). Among 64 patients who developed AKI, the median onsets were similar between the groups (7 days with once versus 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 than with twice-daily dosing with no difference in time to AKI. A prospective randomized study is warranted to validate these results.

Keywords: clinical practice; nephrotoxicity; polymyxin B.

FIG 1

Kaplan-Meier survival analysis for acute kidney injury as a function of treatment group. Green line, polymyxin B twice-daily dosing; blue line, polymyxin B once-daily dosing.