What is the recommended treatment regimen, including drug doses and adjunctive corticosteroids, for tuberculous meningitis in adults?

Treatment of Tuberculous Meningitis

Initiate immediate four-drug therapy with isoniazid, rifampicin, pyrazinamide, and ethambutol for 2 months, followed by isoniazid plus rifampicin for an additional 7–10 months (total 9–12 months, preferably 12 months), and start adjunctive dexamethasone 12 mg IV daily (or prednisolone 60 mg oral daily) tapered over 6–8 weeks concurrently with the first anti-TB dose. 1

Anti-Tuberculosis Drug Regimen

Intensive Phase (First 2 Months)

• Administer daily isoniazid, rifampicin, pyrazinamide, and ethambutol for the first 2 months; daily dosing is strongly preferred over intermittent regimens. 1, 2
• Ethambutol is the preferred fourth drug for adults over streptomycin or other aminoglycosides based on expert consensus. 1, 2
• In children, replace ethambutol with ethionamide or an aminoglycoside because visual-acuity monitoring is unreliable in young patients. 1, 3

Continuation Phase (Months 3–12)

• After confirming susceptibility to isoniazid and rifampicin, discontinue pyrazinamide and ethambutol and continue daily isoniazid plus rifampicin for an additional 7–10 months. 1, 2
• Total treatment duration must be 9–12 months (preferably 12 months)—this is the single most critical point. 1, 3, 2

Critical Treatment Error to Avoid

• Never use a 6-month regimen—this is adequate for pulmonary TB but insufficient for CNS disease and represents the most common critical error in TB meningitis management, leading to higher failure and relapse rates. 1, 2
• Do not stop therapy early even if CSF parameters normalize; complete the full 9–12 month course regardless of clinical improvement. 1

Adjunctive Corticosteroid Therapy

Mortality Benefit and Universal Indication

• Corticosteroids reduce mortality by approximately 25% (relative risk 0.75) and are strongly recommended for all patients with tuberculous meningitis, regardless of disease severity, HIV status, or age. 1, 3, 2
• The greatest absolute benefit occurs in Stage II (lethargic) patients, where dexamethasone lowers mortality from approximately 40% to 15%. 1, 2
• Even in comatose (Stage III) patients, complete the full corticosteroid course. 1

Dexamethasone Regimen (Preferred)

Adult Dosing (≥25 kg)

• Initial dose: 12 mg IV daily (or 0.4 mg/kg/day, maximum 12 mg) for the first 3 weeks. 1, 3, 2
• Administer intravenously for the initial 3 weeks. 1, 3
• Taper gradually over the next 3 weeks for a total 6-week course. 1, 3, 2

Pediatric Dosing

• Children <25 kg: 8 mg IV daily. 1, 3
• Children ≥25 kg: 12 mg IV daily (same as adult dose). 1, 3
• Use the same 3-week full-dose followed by 3-week taper schedule. 1, 3

Prednisolone Alternative (When IV Access Unavailable)

• Initial dose: 60 mg oral daily, tapered over 6–8 weeks. 1, 3, 2
• Specific tapering schedule: 60 mg daily × 4 weeks → 30 mg daily × 4 weeks → 15 mg daily × 2 weeks → 5 mg daily × 1 week. 1, 3

Critical Timing and Safety Points

• Corticosteroids must be started immediately before or concurrently with the first anti-TB dose—any delay is prohibited. 1, 2
• Never discontinue steroids abruptly—complete the full 6–8 week tapered course regardless of clinical improvement to prevent life-threatening adrenal crisis from HPA axis suppression. 1, 3, 2
• Development of tuberculomas or paradoxical radiologic worsening during therapy does not indicate treatment failure and is not a reason to stop steroids; this represents a paradoxical inflammatory response. 1, 2

Monitoring During Treatment

Cerebrospinal Fluid Surveillance

• Perform repeat lumbar punctures early in therapy to monitor CSF cell count, glucose, and protein trends; serial CSF parameters help assess biological response but do not dictate treatment duration. 1, 2

Clinical and Laboratory Monitoring

• Conduct regular neurological examinations to detect improvement or deterioration. 1, 2
• Monitor liver function tests for hepatotoxicity from isoniazid, rifampicin, and pyrazinamide. 1, 2
• Watch for steroid-related complications including hyperglycemia, gastrointestinal bleeding, and secondary bacterial infections. 1, 2

Special Populations

HIV-Positive Patients

• Delay antiretroviral therapy (ART) for 8 weeks after starting anti-TB treatment, even when CD4 count is <50 cells/µL, to minimize the risk of severe or fatal neurological immune reconstitution inflammatory syndrome (IRIS). 1, 2
• For moderate-to-severe paradoxical TB-IRIS after ART initiation, prednisone 1.25 mg/kg/day significantly lowers the need for hospitalization and surgical intervention. 1, 2
• Avoid cobicistat-containing ART regimens when co-administered with rifampicin because rifampicin markedly lowers cobicistat levels, leading to sub-therapeutic antiretroviral concentrations. 1
• Dolutegravir-based regimens are preferred for patients receiving rifampicin, though rifampicin reduces dolutegravir plasma exposure by approximately 26%, which may require dose adjustment. 1

Drug-Resistant TB Meningitis

• Manage suspected or confirmed drug-resistant TB meningitis in specialized centers using ≥5 effective drugs, including a fluoroquinolone and an injectable agent. 2

Neurosurgical Referral Indications

Immediate neurosurgical consultation is indicated for: 1, 2

• Hydrocephalus requiring ventriculoperitoneal shunt placement
• Tuberculous cerebral abscesses needing drainage
• Paraparesis or spinal cord compression caused by tuberculous lesions
• Progressive neurological deficits despite optimal medical therapy