Comorbid diabetes, hepatitis worsen toxicity in pre-XDR tuberculosis care

Treating drug-resistant tuberculosis is already difficult, and researchers led by Alexey M. Tikhonov set out to understand how common additional health problems change that picture. They looked at people with pre-extensively drug-resistant (Pre-XDR) pulmonary tuberculosis who did not have HIV, because many patients carry other long-term conditions such as diabetes mellitus and viral hepatitis B/C. These comorbidities can tax the body in different ways, and the investigators were particularly interested in a concept they describe as a combined “mitochondrial hit” — a situation where both the disease and the medicines used to treat it strain the energy-producing parts of cells. Using a retrospective cohort of 247 patients, the team examined how often adverse drug reactions (ADRs) occurred during standard regimens used before the 2021 WHO update. Their goal was to see whether diabetes mellitus or viral hepatitis affected the frequency and type of side effects, especially those that damage nerves (neurotoxicity) or hearing (ototoxicity). The study links clinical outcomes with patterns of toxicity, offering a clearer view of where extra caution and monitoring may be needed.

To reach these findings the researchers reviewed treatment records from 247 HIV-negative patients with Pre-XDR tuberculosis. Patients received chemotherapy regimens containing linezolid, fluoroquinolones, and injectable agents consistent with guidelines prior to the 2021 WHO update. Toxicity was graded according to CTCAE standards, and the team used multivariate regression analysis to test links between comorbidities and adverse events. They found a high prevalence of viral hepatitis B/C (up to 12.2%) and diabetes mellitus (up to 10.2%). The most frequent ADRs observed were eosinophilia (33.6%), ototoxicity (26.3%), and polyneuropathy (up to 15.2% in previously treated patients). A higher overall comorbidity burden independently predicted treatment failure (OR=3.45; p=0.007). Age < 40 years was unexpectedly associated with poor outcomes (OR=4.15; p=0.013), a finding the authors suggest may reflect lower adherence. Severe ADRs also raised the risk of treatment failure (OR=4.17; p=0.037). The analysis highlights a specific increase in neurotoxicity attributed to linezolid alongside ototoxicity.

The study’s conclusions point to practical implications for clinicians and patients. By describing a synergistic “mitochondrial hit” when Pre-XDR tuberculosis coincides with metabolic conditions like diabetes mellitus and viral hepatitis, Alexey M. Tikhonov and colleagues emphasize that toxicity is not only a drug problem but a broader clinical interaction. The observed rise in neurotoxicity, particularly linked to linezolid, and the substantial rates of ototoxicity suggest that monitoring should be intensified where these comorbidities are present. Even as tuberculosis treatment moves toward all-oral regimens in many settings, the authors caution that linezolid-based therapy combined with diabetes requires enhanced neuroprotective monitoring. The findings also underscore the need to address adherence, especially among younger patients, and to consider the full comorbidity profile when tailoring treatment plans. In short, better surveillance for nerve and hearing damage, and attention to metabolic health, could reduce treatment failures and improve outcomes for people with Pre-XDR tuberculosis.