From the Guidelines
The treatment of multidrug-resistant tuberculosis (MDR-TB) should follow the World Health Organization's latest guidelines, which recommend a 6-month treatment regimen composed of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) for most patients, including those with extensive pulmonary TB and extrapulmonary TB, except for TB involving the central nervous system, miliary TB, and osteoarticular TB 1.
Step-by-Step Treatment Approach
The treatment of MDR-TB requires a comprehensive approach, starting with:
- Diagnosis confirmation through drug susceptibility testing
- Designing an individualized regimen containing at least four effective drugs
- The standard MDR-TB regimen typically includes a later-generation fluoroquinolone (levofloxacin or moxifloxacin), bedaquiline, linezolid, and cycloserine, with additional drugs like clofazimine or pyrazinamide based on susceptibility
Medication Dosage and Duration
- Bedaquiline is typically given at 400mg daily for 2 weeks, then 200mg three times weekly
- Linezolid starts at 600mg daily but may require dose reduction to 300mg daily due to toxicity
- Levofloxacin is dosed at 750-1000mg daily, while cycloserine is given at 500-750mg daily in divided doses
- Treatment duration is usually 6 months for the BPaLM regimen, with the possibility of longer treatments (9-month or 18-month regimens) in certain cases, such as intolerance, drug-drug interactions, extensively drug-resistant tuberculosis, or previous failure
Monitoring and Support
- Patients need monthly sputum cultures to monitor response
- Regular audiometry, vision testing, ECG monitoring for QT prolongation, and blood tests to detect adverse effects
- Directly observed therapy ensures adherence
- Nutritional support, management of comorbidities like HIV, and psychosocial support are essential components of care
Treatment Success
Treatment success depends on addressing drug resistance patterns, managing side effects promptly, and maintaining patient adherence through the treatment course, as recommended by the World Health Organization's latest guidelines 1.
From the FDA Drug Label
Trecator is primarily indicated for the treatment of active tuberculosis in patients with M. tuberculosis resistant to isoniazid or rifampin, or when there is intolerance on the part of the patient to other drugs. If the susceptibility tests indicate that the patient's organism is resistant to one of the first-line anti-tuberculosis drugs (i.e., isoniazid or rifampin) yet susceptible to ethionamide, ethionamide should be accompanied by at least one drug to which the M. tuberculosis isolate is known to be susceptible. If the tuberculosis is resistant to both isoniazid and rifampin, yet susceptible to ethionamide, ethionamide should be accompanied by at least two other drugs to which the M. tuberculosis isolate is known to be susceptible. Pyrazinamide is indicated for the initial treatment of active tuberculosis in adults and children when combined with other antituberculous agents Patients with drug-resistant disease should be treated with regimens individualized to their situation.
The step-by-step treatment of MDR TB involves:
- Identifying susceptibility: Conducting susceptibility tests to determine which drugs the M. tuberculosis isolate is susceptible to 2.
- Selecting companion drugs: Choosing companion drugs based on susceptibility test results, with at least one drug for patients resistant to one first-line drug and at least two drugs for patients resistant to both isoniazid and rifampin 2.
- Using pyrazinamide: Considering pyrazinamide as an important component of therapy for patients with drug-resistant disease 3.
- Individualizing treatment: Treating patients with drug-resistant disease with regimens individualized to their situation 3.
- Directly observed therapy: Recommending directly observed therapy for all patients receiving treatment for tuberculosis to ensure adherence to the drug regimen 2.
From the Research
Step-by-Step Treatment of MDR TB
The treatment of multidrug-resistant tuberculosis (MDR TB) involves a combination of drugs and a personalized approach to improve outcomes. The following steps are based on the available evidence:
- Diagnosis and Drug Susceptibility Testing: Accurate diagnosis and drug susceptibility testing are crucial to determine the appropriate treatment regimen 4.
- Treatment Regimen: The treatment regimen for MDR TB typically includes a combination of first-line and second-line drugs. Newer drugs such as bedaquiline and delamanid have shown promising results in treating MDR TB 5, 6.
- Oral Regimens: All-oral regimens, including bedaquiline, delamanid, linezolid, and clofazimine, have been shown to be effective in treating MDR TB with minimal cardiotoxicity 5.
- Individualized Treatment: Individualized treatment regimens based on drug susceptibility testing have been shown to improve treatment outcomes compared to standardized regimens 7.
- Treatment Duration: The treatment duration for MDR TB is typically 24-36 weeks, with a minimum of two years in some cases 8, 5.
- Monitoring and Adverse Event Management: Regular monitoring and management of adverse events, such as myelosuppression and peripheral neuropathy, are essential to ensure treatment success and minimize toxicity 5.
Treatment Options
The following treatment options are available for MDR TB:
- Bedaquiline, Delamanid, Linezolid, and Clofazimine: This all-oral regimen has been shown to be effective in treating MDR TB with minimal cardiotoxicity 5.
- Kanamycin, Ethionamide, PAS, and Cycloserine: This regimen has been shown to be effective and safe in treating MDR TB, with a cure rate of 74.3% 8.
- New and Repurposed Drugs: New and repurposed drugs, such as bedaquiline and delamanid, have shown excellent bactericidal and sterilizing activity against Mycobacterium tuberculosis and are being used to treat MDR TB 6.