Adjunctive Linezolid for the Treatment of Tuberculous Meningitis

Inclusion Criteria 1. Age \> 18 years 2. Written informed consent from participant or proxy 3. Definite, probable, possible, or suspected TBM diagnosis wherein the patient is being committed to a full course of anti-TB treatment for TBM in the setting of routine care. All participants must have at least one of the following signs/symptoms: headache, irritability, vomiting, fever, neck stiffness, convulsions, focal neurological deficits, altered consciousness, or lethargy. In addition, participants must have CSF glucose to plasma ratio \< 0.5 OR positive CSF acid-fast bacilli (AFB) smear OR positive CSF GeneXpert or Xpert Ultra OR clinician intent to initiate TB treatment for suspected TB meningitis. Definite, probable and possible TBM will be defined as: Definite TBM is defined by the presence of one or more of the following: * Acid- fast bacilli (AFB) seen in the CSF, M tuberculosis cultured from CSF, or a CSF M tuberculosis-positive nucleic acid amplification test (e.g., Gene Xpert Ultra) performed within 14 days of entry * AFB seen in the context of histological changes consistent with tuberculosis in the brain with suggestive symptoms or signs and CSF changes. Probable and possible TBM are defined using previously published consensus criteria as shown in Appendix A45. * Probable TBM is defined as a total score of ≥12 when neuroimaging is available or total score of ≥10 when neuroimaging is unavailable. At least two points should either come from CSF or cerebral imaging criteria. * Possible TBM is defined as a total score of 6-11 when neuroimaging is available, or total score of 6-9 when neuroimaging is unavailable. Exclusion of the most likely alternative diagnoses is also required (e.g., negative cryptococcal antigen). Because culture confirmation is rarely available or often delayed in TBM, patients with probable or possible TBM will be recruited based on these predefined criteria, and CSF will be collected for mycobacterial culture and molecular testing. Classification of participants as definite, probable, or possible TBM will be made retrospectively once all necessary data are available. Exclusion criteria 1. \>5 doses of TB treatment received within previous 5 days 2. Discontinued TB treatment in prior 14 days 3. Known current/previous drug resistant TB infection 4. Known allergy to RIF, INH, PZA, EMB, LZD 5. Previous treatment of TB or TBM with LZD 6. Concomitant or planned use of monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, HIV protease inhibitors, or any other drug with significant interaction with RIF, LZD, or any TB drugs (see Appendices C and D) 7. Women who are pregnant or breastfeeding, or women or men of reproductive potential who are unwilling to use at least one reliable form of barrier contraception or to abstain from sexual activity while receiving study drug treatment and for 30 days after stopping study treatment. Acceptable forms of contraception include: condoms (male or female) with or without a spermicidal agent, or diaphragm or cervical cap with spermicide. Hormonal contraception is not recommended as it may be ineffective due to induction of metabolism when receiving rifampicin. 8. Unwillingness to be an inpatient for 2 weeks for initial treatment or to attend follow up clinic visits 9. Lack of informed consent from participant or next of kin/caregiver 10. Serum creatinine \>1.8 times upper limit of normal, hemoglobin \<7.0 g/dL for men, \<6.5 g/dL for women, platelet count \<50,000/mm3, absolute neutrophil count \<600/mm3, alanine aminotransferase (ALT) \>3 times the upper limit of normal, total bilirubin \>2 times the upper limit of normal. 11. Severe peripheral neuropathy defined by Grade 3 symptoms AND vibratory loss OR absent ankle jerks for participants able to undergo the Brief Peripheral Neuropathy Screen (see Appendix B). 12. Contraindication to LP, including PLT \<50 cells/mm3 or unequal pressures between intracranial compartments (e.g., due to mass lesion, non-communicating hydrocephalus), or unwillingness to undergo or consent to LP