BACKGROUND 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. METHOD 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. RESULTS 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. CONCLUSION 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.

中文翻译：

---

在埃塞俄比亚接受耐多药结核病治疗的患者中可注射的二线抗结核药物的肾毒性和耳毒性症状：一项回顾性队列研究。

背景技术肾毒性和耳毒性是与在多药耐药性肺结核（MDR-TB）患者的强化治疗期间使用的二线抗结核注射药物（氨基糖苷和毛霉素）相关的临床上显着的剂量相关的不良反应。在埃塞俄比亚耐多药结核病患者中，有关注射剂引起的肾毒性和耳毒性的数据很少。这项研究的目的是评估以可注射方式治疗耐多药结核病的患者的患病率，肾毒性和耳毒性症状的管理以及治疗结果。方法这项回顾性队列研究基于对埃塞俄比亚亚的斯亚贝巴的两家大型结核病转诊医院从2010年1月至2015年12月约900名接受耐多药结核病治疗的患者的医疗记录的回顾。使用基线和每月血肌酐的测定以及临床诊断和患者报告筛选研究参与者的肾毒性。结果总体上，有473位参与者（54.2％）是男性。儿童占病例的47％（5.5％），参与者的平均年龄为32±12.6岁，范围为2-75岁。大多数参与者（n = 788，84.6％）具有结核病的既往史。最常用的可注射抗结核药物是红霉素（n = 789，84.7％），同时也使用卡那霉素和丁胺卡那霉素。在整个强化治疗阶段，平均血清肌酐值相对于基线水平有统计学上的显着增加（p <0.05），其肾毒性患病率为10-18％。根据临床标准，在62名（6.7％）患者中检测到肾毒性，在42名（4.8％）患者中检测到耳毒性症状。通过修改治疗方案（包括给药的剂量和频率）在临床上管理肾毒性和耳毒性症状。结论在MDR-TB治疗的随访患者中，肾毒性和耳毒性症状是严重的问题。根据实验室标准（血清肌酐），在整个强化治疗阶段，肾毒性仍然是重大不良事件，这表明必须严格监控患者的成功结局，直到各国采用最新的无注射WHO指南并在特定条件下。