What is the recommended treatment approach for drug-resistant tuberculosis (TB) in India?

Treatment Approach for Drug-Resistant Tuberculosis in India

For drug-resistant tuberculosis in India, an all-oral regimen including bedaquiline, a later-generation fluoroquinolone (levofloxacin or moxifloxacin), linezolid, clofazimine, and cycloserine is strongly recommended as the core treatment approach. 1, 2

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 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
• Local drug resistance patterns in high MDR regions such as Mumbai should be considered, as they may not be adequately reflected in standardized regimens 3

Recommended MDR-TB Treatment Regimen Components

• Include a later-generation fluoroquinolone (levofloxacin or moxifloxacin) as a cornerstone of the regimen (strong recommendation) 1, 2
• Include bedaquiline in the regimen (strong recommendation) 1, 2
• Include linezolid in the regimen (conditional recommendation) 1, 2
• Include clofazimine in the regimen (conditional recommendation) 1, 2
• Include cycloserine in the regimen (conditional recommendation) 1, 2
• Pyrazinamide should be included only when the M. tuberculosis isolate has not been found resistant to it 1
• Ethambutol should be included only when other more effective drugs cannot be assembled to achieve a total of five drugs in the regimen 1

Number of Drugs and Treatment Duration

• Use at least five drugs in the intensive phase of treatment 1
• Use at least four drugs in the continuation phase of treatment 1
• Intensive phase duration should be 5-7 months after culture conversion 1, 2
• Total treatment duration should be 15-21 months after culture conversion for MDR-TB 1, 2
• For XDR-TB, total treatment duration should be 15-24 months after culture conversion 1, 2

Injectable Agents and Other Second-Line Drugs

• Injectable agents should no longer be considered mandatory components of MDR-TB regimens 1
• If needed, amikacin or streptomycin may be included when susceptibility is confirmed 1
• Kanamycin and capreomycin should NOT be used due to poor outcomes 1
• Carbapenems (always used with amoxicillin-clavulanic acid) may be included if needed to compose an effective regimen 1
• Ethionamide should be administered with at least one, sometimes two, other drugs to which the organism is known to be susceptible 4

Special Considerations for India

• In Mumbai and other high MDR-TB regions, high rates of fluoroquinolone resistance (up to 40%) have been reported, necessitating careful drug selection 3, 5
• Local DST patterns suggest that only 33.5% of patients would receive 4 or more effective drugs from standardized regimens, highlighting the need for individualized approaches based on DST 3
• HIV co-infection is common in India and requires concurrent antiretroviral therapy, ideally within two months of initiating MDR-TB treatment 5

Treatment Monitoring and Adherence

• Directly observed therapy (DOT) is strongly recommended to ensure adherence 6, 2
• Regular clinical assessment for symptom improvement is essential 6
• Monitor for adverse events, as up to 45% of patients may experience moderate to severe side effects requiring regimen modification 5

Surgical Considerations

• Elective partial lung resection (lobectomy or wedge resection) may be considered for adults with MDR-TB receiving antimicrobial therapy when clinical judgment suggests a high risk of treatment failure or relapse with medical therapy alone 1, 2

Common Pitfalls and Caveats

• Never add a single drug to a failing regimen as this leads to acquired resistance 2
• When initiating therapy for suspected drug-resistant TB, add at least two, preferably three, new drugs to which susceptibility can be inferred 2
• Drug malabsorption should be suspected in patients who adhere to therapy but fail to respond appropriately, particularly in those with HIV co-infection 4
• In India, high rates of resistance to both first-line and second-line drugs necessitate careful drug selection based on DST rather than empiric standardized regimens 3