What is the recommended treatment for a patient suspected of having a tuberculosis (TB) brain infection, presenting with symptoms such as headache, nausea, vomiting, seizures, or focal neurological deficits?

Treatment of Tuberculous Meningitis (TB Brain Infection)

Initiate immediate empiric four-drug anti-tuberculosis therapy with isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months, followed by isoniazid and rifampin for an additional 7-10 months (total 9-12 months), plus adjunctive dexamethasone for all patients regardless of disease severity. 1, 2

Immediate Treatment Initiation

• Do not wait for microbiological confirmation—tuberculous meningitis is a medical emergency where treatment delay is strongly associated with death and permanent neurological disability 2
• Begin treatment as soon as clinical suspicion is supported by initial CSF findings (lymphocytic pleocytosis, elevated protein, low glucose with CSF:plasma glucose <50%) 2, 3
• For patients with altered mental status who cannot take oral medications, use parenteral formulations: isoniazid, rifampin, aminoglycosides, capreomycin, and fluoroquinolones are all available intravenously 1

Standard Four-Drug Regimen

Initial Intensive Phase (2 months):

• Isoniazid (INH): 5 mg/kg up to 300 mg daily (adults); 10-15 mg/kg up to 300 mg daily (children) 4
• Rifampin (RIF): 10 mg/kg up to 600 mg daily (adults and children) 5
• Pyrazinamide (PZA): standard dosing per weight 1
• Ethambutol (EMB): 15 mg/kg daily 6

Continuation Phase (7-10 months):

• Continue isoniazid and rifampin only after completing the 2-month intensive phase 1
• Total treatment duration should be 9-12 months minimum for CNS tuberculosis 1, 2

Adjunctive Corticosteroid Therapy

Dexamethasone dosing (strongly recommended for all patients):

• Adults and children ≥25 kg: 12 mg/day for 3 weeks, then taper gradually over the following 3 weeks 1
• Children <25 kg: 8 mg/day for 3 weeks, then taper gradually over the following 3 weeks 1
• Corticosteroids improve survival and reduce neurological sequelae, with greatest benefit in patients with altered consciousness (Stage II disease: lethargic patients showed mortality reduction from 40% to 15%) 1
• Even patients presenting in coma (Stage III) should receive corticosteroids, though benefit is less pronounced 1

Monitoring and Follow-Up

• Perform repeated lumbar punctures to monitor CSF cell count, glucose, and protein changes, especially during early treatment 1
• Monitor for hepatotoxicity, particularly during the first 2 months of treatment 7
• Watch for paradoxical tuberculoma development during therapy—this does not necessarily indicate treatment failure 1
• Consider CT or MRI imaging to assess for hydrocephalus, basilar meningeal enhancement, and tuberculomas 8, 2

Special Populations

HIV-Infected Patients:

• Use the same standard four-drug regimen for 9-12 months 1, 2
• Avoid highly intermittent (once- or twice-weekly) regimens in patients with CD4+ counts <100 cells/mm³ due to risk of rifampin resistance 1
• Coordinate antiretroviral therapy carefully due to drug interactions; consult experts in both TB and HIV management 1, 2
• The benefit of adjunctive corticosteroids in HIV-positive patients remains unclear 3

Pregnant Women:

• Use isoniazid, rifampin, ethambutol, and pyrazinamide—all can be used during pregnancy 7
• Avoid streptomycin as it causes congenital deafness 4

Children:

• Manage with the same principles as adults using appropriately adjusted doses 9
• Children with tuberculous meningitis should receive 12 months of treatment 1
• Ethambutol should not be used in children whose visual acuity cannot be monitored 4

Drug-Resistant TB Meningitis

• If multidrug-resistant TB (resistant to at least isoniazid and rifampin) is suspected or confirmed, treatment must include at least 3 drugs to which the organism is susceptible 1
• Never add a single drug to a failing regimen—this creates de facto monotherapy and promotes further resistance 1
• Consider second-line agents: fluoroquinolones (moxifloxacin, levofloxacin), linezolid, bedaquiline, or aminoglycosides based on susceptibility testing 7, 3, 10
• Consult an expert in tuberculosis management for all drug-resistant cases 1

Critical Pitfalls to Avoid

• Do not delay treatment waiting for culture confirmation—cultures may take weeks and early treatment is critical for preventing death and disability 2, 3
• Do not use intermittent (twice-weekly) dosing for tuberculous meningitis—daily therapy is essential 1
• Do not stop corticosteroids abruptly—taper gradually over 3 weeks after the initial 3-week course 1
• Do not treat for only 6 months—CNS tuberculosis requires extended therapy of 9-12 months minimum 1, 2