Omrani Ali S, Alfahad Wafa A, Shoukri Mohamed M, Baadani Abeer M, Aldalbahi Sultan, Almitwazi Ali A, Albarrak Ali M
Section of Infectious Diseases, Department of Medicine, King Faisal Specialist Hospital and Research Centre, PO Box 3354, MBC 46, Riyadh, 11211, Saudi Arabia.
Department of Pharmacy, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
Ann Clin Microbiol Antimicrob. 2015 Jan 16;14:3. doi: 10.1186/s12941-015-0062-8.
Nephrotoxicity is an important adverse effect of colistin methanesulfonate (CMS) therapy. No data exist on rates and risk factors for colistin-related nephrotoxicity in Saudi Arabia (SA). We conducted a prospective cohort study to identify rates and risk factors for CMS nephrotoxicity in our patient population.
We prospectively included adult patients who received ≥48 hours of intravenous CMS therapy. Pregnant patients and those on renal replacement were excluded. Patients received 9 million units (mU) loading dose followed by 3 mU 8 hourly. In renal impairment, CMS dosing was adjusted according to calculated creatinine clearance (CrCl). Nephrotoxicity was defined as per RIFLE criteria (Risk, Injury, Failure, Loss and End-stage renal disease). Statistical analysis was performed using SPSS version 20.0 (IBM, Armonk, New York, USA). The study was approved by the institution's Research Ethics Committee.
A total of 67 patients were included in the study. Mean (±standard deviation) age was 57.5 (±24.0) years, Charlson Co-morbidity Score 2.88 (±2.39), CrCl 133.60 (±92.54) mL/min and serum albumin 28.65 (±4.45) g/L. Mean CMS dose was 0.11 (±0.04) mU/kg/day and mean total CMS dose received was 101.21 (±47.37) mU. Fifty-one (76.1%) patients developed RIFLE-defined nephrotoxicity. Mean total CMS dose and duration of therapy before onset of nephrotoxicity were 66.71 (±43.45) mU and 8.70 (±6.70) days, respectively. In bivariate analysis, patients with nephrotoxicity were significantly older (P 0.013) and had lower baseline serum albumin (P 0.008). Multivariate logistic regression identified serum albumin [odds ratio (OR) 0.72; 95% confidence interval (CI) 0.57-0.93; P 0.010] and intensive care admission (OR 16.38; 95% CI 1.37-195.55; P 0.027) as independent risk factors for CMS nephrotoxicity.
High dose intravenous CMS therapy is associated with high rates of nephrotoxicity in SA. Independent risk factors for colistin nephrotoxicity were baseline hypoalbuminemia and intensive care admission.
肾毒性是甲磺酸多粘菌素（CMS）治疗的重要不良反应。沙特阿拉伯（SA）尚无关于多粘菌素相关肾毒性发生率及危险因素的数据。我们开展了一项前瞻性队列研究，以确定我们患者群体中CMS肾毒性的发生率及危险因素。
我们前瞻性纳入接受静脉CMS治疗≥48小时的成年患者。排除孕妇及接受肾脏替代治疗的患者。患者接受900万单位（mU）负荷剂量，随后每8小时300万单位。在肾功能损害患者中，根据计算的肌酐清除率（CrCl）调整CMS剂量。肾毒性根据RIFLE标准（风险、损伤、衰竭、丧失和终末期肾病）定义。使用SPSS 20.0版（IBM，美国纽约州阿蒙克）进行统计分析。本研究经机构研究伦理委员会批准。
共67例患者纳入研究。平均（±标准差）年龄为57.5（±24.0）岁，Charlson合并症评分2.88（±2.39），CrCl为133.60（±92.54）mL/分钟，血清白蛋白为28.65（±4.45）g/L。平均CMS剂量为0.11（±0.04）mU/（kg·天），平均接受的总CMS剂量为101.21（±47.37）mU。51例（76.1%）患者发生了RIFLE定义的肾毒性。肾毒性发生前的平均总CMS剂量和治疗持续时间分别为66.71（±43.45）mU和8.70（±6.70）天。在双变量分析中，发生肾毒性的患者年龄显著更大（P=0.013），基线血清白蛋白更低（P=0.008）。多变量逻辑回归确定血清白蛋白[比值比（OR）0.72；95%置信区间（CI）0.57 - 0.93；P=0.010]和入住重症监护病房（OR 16.38；95%CI 1.37 - 195.55；P=0.027）为CMS肾毒性的独立危险因素。
在沙特阿拉伯，高剂量静脉CMS治疗与高肾毒性发生率相关。多粘菌素肾毒性的独立危险因素为基线低白蛋白血症和入住重症监护病房。
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