Nephrotoxicity and ototoxic symptoms of injectable second-line anti-tubercular drugs among patients treated for MDR-TB in Ethiopia: a retrospective cohort study

Abstract

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.

Keywords: Injectables; MDR-TB; Nephrotoxicity; Ototoxicity.