Escalate: Linezolid as an add on treatment in the intensive phase of tubercular meningitis. A randomized controlled pilot trial

Abstract

Most drugs used in the treatment of Tuberculous Meningitis have limited CNS penetration thereby limiting efficacy. CSF penetration of linezolid is 80–100%.The study was a prospective, randomized, open label with blinded outcome assessment pilot trial carried out in patients with TBM. Patients were randomized in a 1:1 ratio into two treatment groups either to receive standard ATT alone or add on oral 600 mg BD Linezolid for 4 weeks along with standard four drug ATT [HRZE/S]. Primary outcome was safety and mortality at the end of one and three months measured by intention to treat analysis. 29 patients were recruited and 27 completed three months of follow up. There was no significant difference in terms of mortality with Odds ratio (95% CI) of 2 (0.161–24.87; p = 1) at one month and 0.385 (0.058–2.538; p = 0.39) at three months. There was a significant improvement in GCS in Linezolid group at one month and mRS within the Linezolid group at one and three months. No major safety concerns were observed. The sample size is underpowered to draw any definitive conclusions but improvement in mRS and GCS as well as mortality change make a case for a large sample size trial.