What is the recommended treatment regimen for a patient with rifampin (Rifampicin)-resistant tuberculosis (TB)?

Treatment of Rifampin-Resistant Tuberculosis

For rifampin-resistant tuberculosis, the 6-month BPaLM regimen (bedaquiline, pretomanid, linezolid, and moxifloxacin) is the preferred treatment for patients without documented resistance to fluoroquinolones or bedaquiline. 1

First-Line Approach: Shorter BPaLM Regimen

The BPaLM regimen represents a major advancement, reducing treatment duration from 15-24 months (conventional longer regimens) or 9-12 months (older standardized regimens) to just 6 months. 1 This regimen is indicated for:

• Confirmed MDR/RR-TB patients with no documented resistance to fluoroquinolones or bedaquiline 1
• Extrapulmonary disease, including intestinal TB 1
• Both HIV-infected and uninfected patients, though HIV-positive patients require extended treatment (at least 9 months and for at least 6 months beyond culture conversion) 1

When to Use Longer Oral Regimens Instead

Individualized longer oral regimens (18-20 months) are necessary when:

• Resistance to fluoroquinolones exists 1
• Resistance to bedaquiline is documented 1
• Drug susceptibility testing shows the patient is ineligible for the shorter regimen 1

Composition of Longer Regimens

Core drugs (Group A - all three should be included): 2

• Levofloxacin or moxifloxacin (strong recommendation) 2
• Bedaquiline for patients ≥18 years (strong recommendation) 2
• Linezolid (strong recommendation) 2

Additional agents (Group B - at least one required): 2

• Clofazimine 2
• Cycloserine or terizidone 2

Supplementary agents (Group C - if needed): 2

• Ethambutol 2
• Delamanid (for patients ≥3 years) 2
• Pyrazinamide 1

The regimen must include at least 5 effective drugs total. 1 If only one or two Group A agents can be used, both Group B agents must be included. 2

Critical Pitfalls to Avoid

Do NOT use kanamycin or capreomycin in MDR/RR-TB treatment on longer regimens. 2 These injectable agents are explicitly not recommended in current guidelines.

Do NOT use streptomycin or other injectable agents even in isoniazid-resistant TB when rifampin is susceptible. 2

Avoid the combination of bedaquiline, moxifloxacin, and clofazimine without careful QT interval monitoring, as this may excessively prolong the QT interval. 3

Drug Susceptibility Testing Requirements

Perform drug susceptibility testing on all initial isolates before starting treatment. 4 Ideally, test for fluoroquinolones, bedaquiline, and linezolid susceptibility as a minimum. 3 The risk of acquired bedaquiline resistance is significant, especially in patients with undetected fluoroquinolone resistance. 3

Repeat cultures throughout therapy to monitor treatment response, as resistance can emerge rapidly. 4 Monthly sputum cultures are recommended. 1

Treatment Monitoring and Support

Directly observed therapy (DOT) is strongly recommended for all TB patients to ensure adherence and prevent drug resistance. 1, 5

Implement treatment adherence interventions including digital monitoring, material support, and psychological support. 1

Monitor for adverse effects carefully, particularly:

• Linezolid and cycloserine have high frequencies of serious adverse events 3
• QT prolongation with bedaquiline-containing regimens 3
• Hepatotoxicity (the leading cause of rifampin discontinuation) 6

Special Consideration: Rifampin-Susceptible, Isoniazid-Resistant TB

For patients with isoniazid resistance but rifampin susceptibility, use a 6-month regimen of rifampin, ethambutol, pyrazinamide, and levofloxacin (a later-generation fluoroquinolone). 2, 1 Do not add streptomycin or other injectable agents. 2