Department of Pharmacology & Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
BMC Pharmacol Toxicol. 2019 May 23;20(1):31. doi: 10.1186/s40360-019-0313-y.
Nephrotoxicity and ototoxicity are clinically significant dose-related adverse effects associated with second-line anti-tubercular injectables drugs (aminoglycosides and capreomycin) used during intensive phase of treatment of multi-drug resistant tuberculosis (MDR-TB) patients. Data are scarce on injectable-induced nephrotoxicity and ototoxicity in Ethiopian MDR-TB patients. The aim of this study was to assess the prevalence, management of nephrotoxicity and ototoxic symptoms and treatment outcomes of patients treated for MDR-TB with injectable-based regimens.
This was retrospective cohort study based on review of medical records of about 900 patients on MDR-TB treatment from January 2010 to December 2015 at two large TB referral hospitals in Addis Ababa, Ethiopia. Nephrotoxicity in study participants was screened using baseline and monthly measurement of serum creatinine and clinical diagnosis and patient reports.
Overall, 473 (54.2%) of participants were male. Children accounted for 47 (5.5%) of cases and the mean age of participants was 32 ± 12.6 years with range of 2-75 years. The majority (n = 788, 84.6%) of participants had past history of TB. The most commonly used injectable anti-TB drug was capreomycin (n = 789, 84.7%), while kanamycin and amikacin were also used. There was a statistically significant increment (p<0.05) in the mean serum creatinine values from baseline throughout intensive phase of treatment with a 10-18% prevalence of nephrotoxicity. Based on clinical criteria, nephrotoxicity was detected in 62 (6.7%) and ototoxic symptoms were detected in 42 (4.8%) participants. Nephrotoxicity and ototoxic symptoms were clinically managed by modification of treatment regimens including dose and frequency of drug administration.
Nephrotoxicity and ototoxic symptoms were significant problems among patients on follow-up for MDR-TB treatment. Based on laboratory criteria (serum creatinine), nephrotoxicity remained significant adverse events throughout intensive phase of treatment, indicating close monitoring of patients for successful outcome is mandatory until countries adopt the recent injectable-free WHO guideline and under specific conditions.
肾毒性和耳毒性是与二线抗结核注射药物（氨基糖苷类和卷曲霉素）相关的临床显著的剂量相关不良反应，这些药物在治疗耐多药结核病（MDR-TB）患者的强化期使用。关于埃塞俄比亚 MDR-TB 患者注射引起的肾毒性和耳毒性的数据很少。本研究的目的是评估接受基于注射的方案治疗的 MDR-TB 患者的肾毒性和耳毒性症状的发生率、管理和治疗结果。
这是一项回顾性队列研究，基于对 2010 年 1 月至 2015 年 12 月在埃塞俄比亚亚的斯亚贝巴的两家大型结核病转诊医院接受 MDR-TB 治疗的约 900 名患者的病历回顾。通过基线和每月测量血清肌酐以及临床诊断和患者报告来筛查研究参与者的肾毒性。
总体而言，473 名（54.2%）参与者为男性。儿童占 47 例（5.5%），参与者的平均年龄为 32±12.6 岁，范围为 2-75 岁。大多数（n=788，84.6%）参与者有既往结核病病史。最常用的注射用抗结核药物是卷曲霉素（n=789，84.7%），同时也使用卡那霉素和阿米卡星。从基线到强化期治疗期间，血清肌酐值呈显著递增（p<0.05），肾毒性的发生率为 10-18%。根据临床标准，62 名（6.7%）参与者检测到肾毒性，42 名（4.8%）参与者检测到耳毒性症状。通过修改治疗方案，包括药物剂量和给药频率，对肾毒性和耳毒性症状进行了临床管理。
在接受耐多药结核病治疗的患者中，肾毒性和耳毒性症状是一个重大问题。根据实验室标准（血清肌酐），肾毒性在强化期治疗期间仍然是一个显著的不良事件，这表明在各国采用新的无注射物的世卫组织指南和在特定条件下，有必要密切监测患者以取得成功的治疗结果。
