Use of Longer Oral M/XDR-TB Regimen in Severe Forms of Extrapulmonary TB and TB Meningitis

Longer oral Multi (M)/ Extensively Drug-resistant TB (XDR-TB) regimen can be given to patients with Extrapulmonary (EP) disease. Drug adjustments may be required, depending on the specific location of the disease.

Treatment of Multidrug-resistant (MDR)/ Rifampicin-resistant TB (RR-TB) meningitis is best guided by Drug Susceptibility Testing (DST) of the infecting strain and by the ability of TB medicines to cross the blood-brain barrier. 

• Group A Fluoroquinolones (FQs) - Levofloxacin (Lfx), Moxifloxacin (Mfx) and Linezolid (Lzd) have good penetration across the blood-brain barrier (i.e., the Central Nervous System (CNS)), as do Ethionamide (Eto), Cycloserine (Cs) and Imipenem-Cilastatin (Imp-Cls).
• High dose Isoniazid (H^h) and Pyrazinamide (Z) can also reach therapeutic levels in the Cerebrospinal Fluid (CSF) and may be useful if the strains are susceptible.
• Amikacin (Am) and Streptomycin (Sm) only penetrate the CNS in the presence of meningeal inflammation.
• There is limited information available on the CNS penetration of Clofazimine, Bedaquiline (Bdq) or Delamanid (Dlm). 
• P-aminosalicylic acid (PAS) and Ethambutol (E) do not penetrate the CNS well and should not be counted on as effective agents for MDR-TB meningitis. Hence, the longer oral M/XDR-TB regimen must be modified as per the replacement table considering this important factor and also other sites of the diseases.
• Seizures may be more common in children with meningitis treated with Imipenem, and hence Meropenem (Mpm) is preferred for patients of TB meningitis and in children.

Resources

• Guidelines for Programmatic Management of Drug-resistant Tuberculosis in India, March 2021.
• WHO Consolidated Guidelines on Tuberculosis: Module 4 - Treatment: Drug-resistant TB Treatment, 2020.

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