What is the treatment approach for patients with Mycobacterium tuberculosis (MTB) multiresistance or extensive resistance?

Treatment Approach for Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis

For patients with multidrug-resistant tuberculosis (MDR-TB) or extensively drug-resistant tuberculosis (XDR-TB), an individualized all-oral regimen with at least five effective drugs during the intensive phase and four drugs during the continuation phase is strongly recommended, with treatment duration of 15-24 months after culture conversion. 1

Diagnosis and Drug Susceptibility Testing

• Drug susceptibility testing (DST) should be performed on the first isolate from all patients with TB to guide appropriate treatment selection 1
• Molecular diagnostic methods (like Xpert MTB/XDR) can provide rapid results to detect resistance patterns and optimize early treatment decisions 2
• Only drugs to which the patient's M. tuberculosis isolate has documented or high likelihood of susceptibility should be included in the treatment regimen 1

Recommended Treatment Regimen Components

Core Drugs for MDR-TB Regimen:

• Include a later-generation fluoroquinolone (levofloxacin or moxifloxacin) as a cornerstone of the regimen (strong recommendation) 1
• Include bedaquiline in the regimen (strong recommendation) 1
• Include linezolid in the regimen (conditional recommendation) 1
• Include clofazimine in the regimen (conditional recommendation) 1
• Include cycloserine in the regimen (conditional recommendation) 1

Additional Considerations:

• Pyrazinamide should be included only when the M. tuberculosis isolate has not been found resistant to it (conditional recommendation) 1
• Ethambutol should be included only when other more effective drugs cannot be assembled to achieve a total of five drugs in the regimen (conditional recommendation) 1
• Injectable agents: If needed, amikacin or streptomycin may be included when susceptibility is confirmed, but kanamycin and capreomycin should NOT be used (conditional recommendation) 1
• Carbapenems (always used with amoxicillin-clavulanic acid) may be included if needed to compose an effective regimen (conditional recommendation) 1

Drugs NOT Recommended:

• Do NOT include amoxicillin-clavulanate except when the patient is receiving a carbapenem (strong recommendation) 1
• Do NOT include macrolides (azithromycin and clarithromycin) (strong recommendation) 1
• Do NOT include ethionamide/prothionamide if more effective drugs are available (conditional recommendation) 1
• Do NOT include p-aminosalicylic acid if more effective drugs are available (conditional recommendation) 1

Treatment Duration

• Intensive phase: 5-7 months after culture conversion (conditional recommendation) 1
• Total treatment duration: 15-21 months after culture conversion for MDR-TB (conditional recommendation) 1
• For XDR-TB: 15-24 months after culture conversion (conditional recommendation) 1

Special Considerations

Pretomanid-Based Regimen for XDR-TB

• For adults with pulmonary XDR-TB or treatment-intolerant/nonresponsive MDR-TB, a regimen of pretomanid, bedaquiline, and linezolid (BPaL) has shown high success rates (89%) 3
• When using linezolid in this regimen, 600 mg once daily is preferred over 1,200 mg once daily due to better safety profile 3

Surgical Management

• Elective partial lung resection (lobectomy or wedge resection) may be considered for adults with MDR-TB receiving antimicrobial therapy (conditional recommendation) 1
• Surgery should be performed by experienced surgeons only after the patient has received several months of intensive chemotherapy 1

Common Pitfalls and Caveats

• Never add a single drug to a failing regimen as this leads to acquired resistance to the new drug 1
• When initiating therapy for suspected drug-resistant TB, add at least two, preferably three, new drugs to which susceptibility can be inferred 1
• Molecular tests may occasionally yield false-resistance or false-susceptibility results, so both phenotypic and genotypic approaches are complementary for accurate detection 4, 5
• Treatment adherence is critical for successful outcomes; directly observed therapy (DOT) is strongly recommended 1, 6

Treatment of Contacts to MDR-TB Patients

• Treatment for latent TB infection is recommended for contacts to patients with MDR-TB (conditional recommendation) 1
• A 6-12 month regimen with a later-generation fluoroquinolone alone or with a second drug is suggested, based on drug susceptibility of the source case 1
• Pyrazinamide should not be routinely used as the second drug due to increased toxicity and adverse events 1

The management of MDR/XDR-TB requires considerable expertise and should be done by or in close consultation with specialists experienced in treating these complex cases 1.