Department of Pharmacy, Montefiore Medical Center, Bronx, New York, New York, USA.
Department of Pharmacy, NYU Langone Health, New York, New York, USA.
Antimicrob Agents Chemother. 2018 Jul 27;62(8). doi: 10.1128/AAC.00025-18. Print 2018 Aug.
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; = 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; = 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, = 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.
肾毒性是多粘菌素 B（PMB）已知的不良反应。动物数据表明，每日一次给药可能会降低急性肾损伤（AKI）的发生率并延迟其发病时间。在一项多中心回顾性研究中，我们评估了肌酐清除率（CrCl）≥30 ml/min 且接受≥48 小时 PMB 治疗的成年患者。主要终点是比较每日一次和两次 PMB 给药的 AKI 发生率差异。次要终点包括 AKI 的发生时间和肾功能恢复情况。在 273 名符合条件的患者中，根据倾向评分，对每组各 100 名患者进行了匹配。在匹配组中，根据风险、损伤、衰竭、丧失和终末期肾病（RIFLE）标准定义的肾毒性，每日一次给药组比每日两次给药组更常见（分别为 47%和 17%；=0.0005）。在通过多变量条件逻辑回归调整了残余差异后，每日一次给药更有可能导致肾毒性（调整后的优势比，2.5；95%置信区间[CI]，1.413 至 4.541；=0.002）。在 64 名发生 AKI 的患者中，两组的中位发病时间相似（每日一次为 7 天，每日两次为 6 天，=0.095）。在随后评估血清肌酐的 37 名患者中，29/37（78%）患者的肾功能恢复。没有患者需要肾脏替代治疗。我们的研究结果表明，与每日两次给药相比，PMB 每日一次给药导致 AKI 的发生率显著更高，而 AKI 的发生时间没有差异。需要进行前瞻性随机研究来验证这些结果。
