Rates and risk factors for nephrotoxicity and ototoxicity among tuberculosis patients in Tbilisi, Georgia

• Authors: M. Buziashvili, National Center for Tuberculosis and Lung Diseases, Tbilisi; V. Mirtskhulava, David Tvildiani Medical University; M. Kipiani, National Center for Tuberculosis and Lung Diseases, Tbilisi; Henry Blumberg, Emory University; D. Baliashvili, Emory University; Matthew Magee, Emory University; J. J. Furin, Case Western Reserve University; N. Tukvadze, National Center for Tuberculosis and Lung Diseases, Tbilisi; Russell Kempker, Emory University
• Journal Title: International Journal of Tuberculosis and Lung Disease
• Volume: Volume 23, Number 9
• Publisher: International Union Against Tuberculosis and Lung Disease | 2019-09-01, Pages 1005-+
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.5588/ijtld.18.0626
• Subjects: Health Sciences, Epidemiology; Biology, Biostatistics; Health Sciences, Public Health; Health Sciences, Immunology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Infectious Diseases; Respiratory System; drug resistance; second-line drugs; kanamycin; capreomycin; ADRs; Multidrug resistant tuberculosis; Acute kidney injury; Adverse events; Hearing loss; MDR-TB; Toxicity; Rifle; Akin

Abstract

SETTING: Treatment of multidrug-resistant tuberculosis (MDR-TB) is lengthy and utilizes second-line anti-TB drugs associated with frequent adverse drug reactions (ADRs). OBJECTIVE: To evaluate the prevalence of and risk factors for ADRs among patients with MDR- and extensively drug-resistant TB (XDR-TB). DESIGN: A retrospective chart review of patients initiating treatment for M/XDR-TB in 2010–2012 in Tbilisi, Georgia. RESULTS: Eighty (54%) and 38 (26%) of 147 patients developed nephrotoxicity per RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) classification and ototoxicity, respectively. Twenty-five (17%) patients required permanent interruption of injectables due to an ADR. Median hospital stay, total treatment duration and number of regimen changes were higher among those with nephrotoxicity and/or ototoxicity, compared to those without (P < 0.01). Multinomial logistic regression analysis identified increasing age (per year) as a risk factor for nephrotoxicity (aOR 1.08,95%CI 1.03–1.12) and for both, nephro- and ototoxicity (aOR 1.11, 95%CI 1.05–1.17). Low baseline creatinine clearance (CrCl) was a significant risk factor for developing nephrotoxicity (aOR 1.05, 95%CI 1.02–1.07). CONCLUSION: Second-line injectable drug-related ADRs are common among M/XDR-TB patients. Patients with increasing age and low baseline CrCl should be monitored closely for injectable-related ADRs. Notably, our findings support WHO’s latest recommendations on introduction of injectable free anti-TB treatment regimens.