What are the current treatment guidelines for Mycobacterium tuberculosis (MTB)?

Current Treatment Guidelines for Mycobacterium Tuberculosis (MTB)

Drug-Susceptible Pulmonary Tuberculosis

The standard treatment for drug-susceptible pulmonary TB is a 4-drug regimen of isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months (intensive phase), followed by isoniazid and rifampin for 4 months (continuation phase). 1, 2, 3

Initial Phase (2 months)

• All four drugs should be given together daily to prevent resistance development 4
• Dosing for adults: isoniazid 5 mg/kg (max 300 mg), rifampin 10 mg/kg (max 600 mg), pyrazinamide 15-30 mg/kg, and ethambutol 15-25 mg/kg 2, 3
• Dosing for children: isoniazid 10-15 mg/kg (max 300 mg), rifampin 10-20 mg/kg (max 600 mg), with similar weight-based dosing for pyrazinamide and ethambutol 2, 3
• Treatment should be initiated promptly even before diagnostic test results are known in patients with high likelihood of TB 1

Continuation Phase (4 months)

• Isoniazid and rifampin daily or 2-3 times weekly 2
• Treatment duration may be extended if the patient remains sputum or culture positive, or if resistant organisms are present 3

Administration Considerations

• Oral rifampin should be administered 1 hour before or 2 hours after a meal with a full glass of water 3
• Directly observed therapy (DOT) remains the standard of care, though virtual treatment monitoring using digital technologies is becoming more common 5
• Fixed-dose combinations minimize the opportunity for selective medication adherence 1

Isoniazid-Resistant Tuberculosis

For isoniazid-resistant TB, add a later-generation fluoroquinolone to a 6-month regimen of daily rifampin, ethambutol, and pyrazinamide. 6

• This is a conditional recommendation based on very low certainty evidence 6
• Pyrazinamide duration can be shortened to 2 months in selected situations (noncavitary, lower burden disease, or pyrazinamide toxicity) 6
• The 6-month regimen of isoniazid, rifampin, pyrazinamide, and ethambutol has shown successful outcomes in clinical practice, with low relapse rates 7

Multidrug-Resistant Tuberculosis (MDR-TB)

For MDR-TB (resistance to at least isoniazid and rifampin), use at least 5 effective drugs in the intensive phase and 4 drugs in the continuation phase, with bedaquiline, a later-generation fluoroquinolone, linezolid, and clofazimine as core components. 1, 4

Treatment Duration

• Intensive phase: 5-7 months after culture conversion 1
• Total treatment duration: 15-21 months after culture conversion 1
• For XDR-TB: 15-24 months after culture conversion 1

Drug Selection Algorithm

• Only include drugs to which the patient's M. tuberculosis isolate has documented or high likelihood of susceptibility 6
• Drugs known to be ineffective based on in vitro or molecular drug susceptibility testing should not be used 6
• Core MDR-TB drugs include bedaquiline, later-generation fluoroquinolones (levofloxacin or moxifloxacin), linezolid, and clofazimine 1, 4
• Additional drugs may include cycloserine, ethambutol, pyrazinamide, ethionamide, p-aminosalicylic acid, and carbapenems with clavulanic acid 6

Critical Pitfall

• Using fewer than 5 effective drugs in MDR-TB treatment leads to poorer outcomes 1
• Never add a single drug to a failing regimen, as this promotes resistance development 4
• Consultation with a TB expert is strongly recommended for MDR-TB cases 6

Special Populations

Pregnancy

• All first-line drugs (rifampin, isoniazid, ethambutol, pyrazinamide) can be used during pregnancy 2
• Streptomycin should be avoided due to fetal ototoxicity 2
• Prophylactic pyridoxine 10 mg/day is recommended 2

HIV Co-infection

• The same 4-drug regimen is used for HIV-positive patients 1
• Antiretroviral therapy should be delayed 4-8 weeks after starting antitubercular therapy to minimize drug interactions and paradoxical reactions 4
• Rifampin induces metabolism of protease inhibitors and reduces their efficacy, requiring careful ART selection 4
• These patients may require longer treatment courses and have higher relapse rates 1

Extrapulmonary Tuberculosis

• The same 6-month regimen is effective for most extrapulmonary TB 1
• TB meningitis with basal exudate requires 9-12 months of therapy 8
• Adjuvant corticosteroid therapy (dexamethasone or prednisone) for 6-8 weeks is strongly recommended for TB meningitis to decrease neurologic sequelae 8
• Miliary TB, bone/joint TB, and tuberculous meningitis in infants and children should receive 12 months of therapy 2

CNS Tuberculosis (Intramedullary and Intracranial Tuberculoma)

• Standard 4-drug regimen with extended duration (9-12 months) 8
• For MDR-TB with CNS involvement: 18-20 months or 15-21 months after culture conversion, whichever is longer 4

Contacts to MDR-TB Patients

Offer treatment for latent TB infection to contacts of MDR-TB patients rather than observation alone. 6

• Treat with a later-generation fluoroquinolone alone or with a second drug for 6-12 months, based on source-case drug susceptibility 6
• Pyrazinamide should not be routinely used as the second drug due to increased toxicity, adverse events, and discontinuations 6

Role of Surgery in MDR-TB

Elective partial lung resection (lobectomy or wedge resection) should be considered for adults with MDR-TB receiving antimicrobial therapy when clinical judgment, bacteriological, and radiographic data suggest strong risk of treatment failure or relapse with medical therapy alone. 6