Patients with pulmonary tuberculosis who had linezolid added to their treatment regimen for either 2 or 4 weeks did not have higher culture conversion rates compared with individuals who received standard treatment, according to study results published in the Lancet Infectious Disease.
In this phase 2 multicenter randomized open-label clinical trial (ClinicalTrials.gov Identifier: NCT01994460), negative culture conversion rates from patients aged 20 to 80 years with positive sputum for pulmonary tuberculosis but without resistance to rifampicin were compared among 3 randomized treatment groups following 8 weeks of treatment. The control group received ethambutol for 2 months with isoniazid, rifampicin, and pyrazinamide. The other treatment groups substituted linezolid for ethambutol at a duration of either 2 weeks or 4 weeks.
Of the 429 patients enrolled, 428 were randomly assigned into 1 of 3 treatment groups. Of these patients, 143 were assigned to the control group, 142 were assigned to the 2-week linezolid group, and 143 were assigned to the 4-week linezolid group. Negative cultures in liquid media at 8 weeks of treatment were observed in 76.9% of control patients, 82.2% of the linezolid 2-week group, and 75.8% of the linezolid 4-week group. The difference was 5.4% for the 2-week linezolid group from the control group (95% CI, –4.3% to 15.0%; P =.28) and –1.1% (95% CI, –11.3% to 9.1%; P =.83) for the 4-week linezolid group.
Furthermore, adverse event rates were similar across the groups, ranging from 57.2% to 62.8%. Resistance to linezolid was not identified in any patient during this short treatment window.
Although the researchers noted they did not observe higher culture conversion rates using linezolid vs ethambutol, they added that “[l]onger use of linezolid (eg, for 8 weeks) might provide different results.”
Lee J-K, Lee JY, Kim DK, et al. Substitution of ethambutol with linezolid during the intensive phase of treatment of pulmonary tuberculosis: a prospective, multicentre, randomised, open-label, phase 2 trial. Lancet Infect Dis. 2019;19(1):46-55.