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Nephrotoxicity Associated with Intravenous Polymyxin B Once- versus Twice-Daily Dosing Regimen
Adeola Okoduwa1, Nabeela Ahmed2, Yi Guo1
1Department of Pharmacy, Montefiore Medical Center, Bronx, New York, New York, USA.
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.
Insights
Once-daily polymyxin B (PMB) dosing is associated with a higher rate of acute kidney injury (AKI) compared to twice-daily dosing. This study found increased nephrotoxicity with once-daily PMB, suggesting twice-daily dosing may be safer.
Area of Science:
- Nephrology
- Pharmacology
- Critical Care Medicine
Background:
- Polymyxin B (PMB) is crucial for treating multidrug-resistant Gram-negative infections.
- Nephrotoxicity is a significant adverse effect of PMB therapy.
- Previous animal studies suggested once-daily dosing might mitigate kidney injury.
Purpose of the Study:
- To compare the incidence of acute kidney injury (AKI) in adult patients receiving once-daily versus twice-daily polymyxin B (PMB).
- To evaluate the time to AKI and renal function recovery based on PMB dosing frequency.
Main Methods:
- Multicenter retrospective study of adult patients with creatinine clearance (CrCl) ≥30 ml/min receiving ≥48 hours of PMB.
- Propensity score matching was used to create comparable groups for once-daily and twice-daily PMB dosing.
- Nephrotoxicity was assessed using Risk, Injury, Failure, Loss, and End-stage renal disease (RIFLE) criteria.
Main Results:
- Nephrotoxicity occurred more frequently in the once-daily PMB group (47%) compared to the twice-daily group (17%) (P = 0.0005).
- Once-daily dosing remained significantly associated with increased nephrotoxicity after adjusting for confounders (aOR, 2.5; P = 0.002).
- Time to AKI onset was similar between groups, and most patients who developed AKI showed renal function recovery without requiring renal replacement therapy.
Conclusions:
- In this retrospective analysis, once-daily polymyxin B dosing was associated with a significantly higher rate of acute kidney injury compared to twice-daily dosing.
- The findings contradict animal data and suggest that twice-daily PMB dosing may be preferable for reducing nephrotoxicity in adult patients.
- A prospective randomized trial is recommended to confirm these clinical observations.
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