P59 Linezolid in short- term regimens for drug-resistant TB: balancing efficacy and toxicity

Abstract Background Short-term regimens with linezolid are an effective treatment for patients with MDR and pre-XDR TB (MDR/pre-XDR TB). However, their use is limited by the risk of adverse drug reactions (ADRs) associated with this drug. Objective To analyse the efficacy and risk of ADRs in patients with MDR/pre-XDR TB undergoing short-term regimens that include linezolid. Patients and methods The study included 61 patients with MDR/pre-XDR TB who received 9 month treatment regimens between 2023 and 2024 from five regions of the Russian Federation. The five-drug combination included bedaquiline, linezolid, delamanid, cycloserine/terizidone and clofazimine/levofloxacin/moxifloxacin/pyrazinamide. Among them, 34 (55.7%) were male and 27 (44.3%) were female. The median age was 40.0 [32.0–46.5] years. The study included 54 (88.5%) patients with newly diagnosed TB and 7 (11.5%) with disease relapse. Laboratory confirmation of the diagnosis by rapid TB tests was registered in 58 patients (95.1%), and drug resistance was confirmed in all by culture-based testing. MDR-TB was registered in 45 (73.8%) and pre-XDR TB in 16 (26.2%) patients. Patients had no concomitant pathologies in the decompensation stage. Diabetes was present in 3 (4.9%) patients and hepatitis C in 4 (6.6%). The severity of ADRs was assessed using the CTCAE scale. Results Cessation of bacterial excretion was observed in all patients by the 4th month of treatment; however, the treatment course was successfully completed by 58 patients (95.1%). A total of 52 ADRs were registered in 28 (45.9%) patients. The most common were polyneuropathy (13 cases; 25.0%), diarrhoea (7 cases; 13.5%), nausea and myelosuppression (6 cases each; 11.5% each). Grade 1–2 ADRs occurred in 46 cases (88.5%). Grade 3 and higher ADRs occurred in 6 cases (11.5%) (leukopenia, neutropenia and erythrocytopenia (one case each) and polyneuropathy (3 cases; 50.0%)). Linezolid was the causative drug in 36.5% of all ADRs (in 22 patients). Due to the development of ADRs, therapy was modified for eight patients: complete discontinuation of linezolid was required for four patients, and a dose reduction from 600 mg to 300 mg was required for another four. Conclusions Short-term regimens including linezolid are characterized by high treatment efficacy (95.1%) but a high frequency of associated ADRs (36.5% of patients). This underscores the need for careful monitoring of ADRs for timely treatment adjustment.