Assessment of Amikacin- and Capreomycin-Related Adverse Drug Reactions in Patients with Multidrug-Resistant Tuberculosis and Exploring the Role of Genetic Factors

• Published in: Journal of personalized medicine Vol. 13; no. 4; p. 599
• Main Authors: Freimane, Lauma, Barkāne, Linda, Kivrane, Agnija, Sadovska, Darja, Ulanova, Viktorija, Ranka, Renāte
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29.03.2023; MDPI
• Subjects: Adverse events; Amikacin; Analysis; Body mass index; Capreomycin; Collaboration; Diabetes; DNA sequencing; Drug dosages; Drug resistance; Drug resistance in microorganisms; Drug therapy; Genetic factors; Genetic testing; Genomes; Genomics; Health risk assessment; Hearing loss; Lung diseases; MDR-TB; Medical research; Medicine, Experimental; Mitochondrial DNA; Multidrug resistance; Multidrug resistant organisms; Mutation; nephrotoxicity; Nucleotide sequencing; Ototoxicity; Patients; Precision medicine; Public health; Risk factors; Tinnitus; Tuberculosis; Vertigo; Latvia; United States > US; capreomycin; MDR-TB; amikacin; nephrotoxicity; ototoxicity
• ISSN: 2075-4426; 2075-4426
• DOI: 10.3390/jpm13040599

Following the introduction of all-oral treatment regimens for patients with drug-resistant tuberculosis (TB), second-line injectable drug applications have been reduced in the last few years. However, they are still important for anti-TB therapy. This study aims to analyze the occurrence of amikacin- and capreomycin-related adverse drug reactions (ADR) in patients with multidrug-resistant tuberculosis (MDR-TB) and evaluate the role of multiple patient-, disease-, and therapy-related factors on the frequency of the observed adverse events. In addition, the possible role of genetic risk factors was studied by full-length mitochondrial DNA sequencing. Toward this aim, we retrospectively evaluated 47 patients with MDR-TB who received amikacin and/or capreomycin. In total, 16 (34.0%) patients developed ototoxicity and 13 (27.7%) developed nephrotoxicity, including 3 (6.4%) patients who experienced both adverse events. Ototoxicity development was more common in patients who received amikacin. No other factors showed a significant impact. Nephrotoxicity was likely associated with previous renal health impairment. Full mitochondrial genome sequencing did not reveal any specific ADR-associated variants, and results showed no differences in adverse event occurrence for any specific variants, mutation count, or mitochondrial haplogroup. The absence of the previously reported ototoxicity-related mtDNA variants in our patients with ototoxicity and nephrotoxicity highlighted the complex nature of the ADR occurrence.