What are the treatment guidelines for a patient with pulmonary tuberculosis (TB), including those with drug-resistant TB and underlying conditions such as human immunodeficiency virus (HIV) infection?

Pulmonary Tuberculosis Treatment Guidelines

Drug-Susceptible Pulmonary TB

For drug-susceptible pulmonary TB, use a 6-month regimen consisting of isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months (intensive phase), followed by isoniazid and rifampin for 4 months (continuation phase). 1, 2, 3, 4

Initial Phase (2 months)

• Four-drug regimen is mandatory unless community isoniazid resistance is documented to be <4% AND the patient has no prior TB treatment, no exposure to drug-resistant cases, and is not from a high-prevalence resistance country 1, 4
• Include ethambutol (or streptomycin in young children who cannot be monitored for visual acuity) until drug susceptibility results confirm no isoniazid resistance 1, 3, 4
• Ethambutol can be omitted only if the above low-resistance criteria are met 5

Continuation Phase (4 months)

• Continue isoniazid and rifampin daily or 2-3 times weekly 1, 4
• If isoniazid resistance is confirmed, continue rifampin and ethambutol for a minimum of 12 months total 4

Alternative 9-Month Regimen

• Use isoniazid and rifampin for 9 months when pyrazinamide cannot be used (contraindicated or not tolerated) 4
• Add ethambutol until susceptibility results are available 4

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Drug-Resistant Pulmonary TB

Isoniazid-Resistant, Rifampin-Susceptible TB

Treat with a 6-month regimen of rifampin, ethambutol, pyrazinamide, and a later-generation fluoroquinolone (levofloxacin preferred over moxifloxacin). 6, 5

Multidrug-Resistant TB (MDR-TB) and Rifampin-Resistant TB (RR-TB)

For MDR/RR-TB without documented fluoroquinolone or bedaquiline resistance, use the 6-month BPaLM regimen (bedaquiline, pretomanid, linezolid, moxifloxacin). 6, 5

When BPaLM Cannot Be Used (fluoroquinolone or bedaquiline resistance present):

Construct an individualized longer oral regimen using at least 5 drugs in the intensive phase and 4 drugs in the continuation phase. 7

Core drugs to ALWAYS include (strong recommendations):

• Later-generation fluoroquinolone (levofloxacin or moxifloxacin) 7
• Bedaquiline 7

Additional drugs to include (conditional recommendations, in order of preference):

• Linezolid 7
• Clofazimine 7
• Cycloserine 7
• Pyrazinamide (if susceptibility confirmed) 7
• Ethambutol (only when other more effective drugs cannot assemble 5 total drugs) 7
• Delamanid (may be included per WHO recommendations for patients >3 years) 7

Injectable agents (use only when necessary to reach 5 drugs):

• Amikacin or streptomycin (when susceptibility confirmed) 7
• Carbapenem (always with amoxicillin-clavulanic acid) 7

Drugs to AVOID:

• Do NOT use amoxicillin-clavulanate (except with carbapenems) 7
• Do NOT use macrolides (azithromycin, clarithromycin) 7
• Do NOT use kanamycin or capreomycin 7
• Avoid ethionamide/prothionamide if more effective drugs available 7
• Avoid p-aminosalicylic acid if more effective drugs available 7

Treatment Duration for MDR/RR-TB:

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

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Special Populations

HIV-Infected Patients

• Use the same 6-month regimen for drug-susceptible TB, but critically assess clinical and bacteriologic response 4
• If slow or suboptimal response, prolong therapy on a case-by-case basis 4
• For drug-resistant TB with HIV, extend treatment to at least 9 months and for at least 6 months beyond culture conversion 6
• Screen for drug malabsorption in advanced HIV disease to prevent emergence of resistance 1

Pregnant Women

• Do NOT use streptomycin (causes congenital deafness) 1
• Avoid pyrazinamide due to inadequate teratogenicity data 1
• Use isoniazid, rifampin, and ethambutol as initial regimen (unless isoniazid resistance <4%) 1

Extrapulmonary TB

• Use the same 6-month regimen as pulmonary TB for most extrapulmonary sites 5, 4
• Extend to 9-12 months for TB meningitis, miliary TB, or bone/joint involvement 5, 4
• Extend to 9-18 months for osteoarticular TB depending on severity 5
• 12 months minimum for miliary TB, bone/joint TB, and tuberculous meningitis in infants and children 1, 4
• Consider adjunctive corticosteroids for TB meningitis (decreases neurologic sequelae) and tuberculous pericarditis (prevents cardiac constriction) 1

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Critical Management Principles

Directly Observed Therapy (DOT)

All TB patients should receive directly observed therapy to ensure adherence and prevent resistance development. 6, 5, 1, 4

• Patient noncompliance is a major cause of drug-resistant TB 1
• Implement treatment adherence interventions including digital monitoring, material support, and psychological support 6

Monitoring

• Obtain bacteriologic cultures before starting therapy to confirm susceptibility 1, 3
• Monitor monthly sputum cultures until negative to assess treatment response 6, 5
• Repeat susceptibility testing if cultures remain positive during treatment 1, 3
• Instruct patients to report symptoms of hepatotoxicity 5

Key Pitfalls to Avoid

• Never add a single drug to a failing regimen - this rapidly leads to acquired resistance 5
• Only use drugs to which the organism has documented or high likelihood of susceptibility 7
• Do not use drugs with documented resistance based on in vitro or molecular testing 7
• Consult a TB expert for all MDR-TB cases 1, 4, 8