Linezolid As An Add On Treatment In The Intensive Phase Of Tubercular Meningitis. A Randomized Controlled Pilot Trial. (S25.004)

Abstract

<h3>Objective:</h3> To study whether administration of linezolid given for 4 weeks along with four drug standard weight-based Anti-Tubercular (ATT) regimen in intensive phase of tubercular meningitis (TBM) will help reduce mortality and morbidity. <h3>Background:</h3> Most agents used in the treatment of TBM have limited CNS penetration thereby limiting its efficacy. CSF penetration of linezolid is about 80–100 % and has been repurposed as a class C, core MDR-TB drug. <h3>Design/Methods:</h3> The study was a prospective, single center, randomized, open label with blinded outcome assessment pilot trial carried out in patients with TBM. Patients fulfilling the eligibility criteria were randomized using computer generated numbers and permuted randomization block design in a 1:1 ratio into two treatment groups either to receive standard ATT alone or add on oral 600 mg BD linezolid daily for 4 weeks along with standard ATT[rifampicin (10 mg/kg), isoniazid (5mg/kg), pyrazinamide (15–30 mg/kg, ethambutol (15 mg/kg) or streptomycin (0.75–1gm/day)]. Primary outcome was safety and mortality at the end of one and three months measured by intention to treat analysis. <h3>Results:</h3> A total of 29 patients (15 in intervention and 14 in the control arm) were recruited and 27 completed three months of follow up. There was no significant difference between two groups in mortality at one and three months with Odds ratio (95% CI) of 2[0.161 to 24.87] and p=1 at one month and 0.385[0.058 to 2.538] with p=value 0.39 at three months respectively. No major safety concerns were observed with the use of Linezolid. Favorable shift of mRS(modified Rankin Scale) at three months was observed in the Linezolid arm only (intra group p= 0.031with effect size (95% CI )1.667[0.353 to 7.875]. <h3>Conclusions:</h3> Linezolid was not effective in improving the mortality in TBM patients. Study with a larger sample size is desirable to demonstrate the benefits of Linezolid in TBM. <b>Disclosure:</b> Dr. Sahib has nothing to disclose. Dr. Bhatia has nothing to disclose. M.V. Padma Srivastava has nothing to disclose. Mamta Singh Bhushan has nothing to disclose. Vishnu VY has nothing to disclose. Roopa Rajan has received research support from DBT. Roopa Rajan has received research support from DST-SERB. The institution of Roopa Rajan has received research support from Michael J Fox Foundaton. The institution of Anu Gupta has received research support from ICMR. Dr. Srivastava has nothing to disclose.