From the Guidelines
To start antituberculous treatment in a patient with extensively drug-resistant pulmonary tuberculosis (XDR-PTB), an individualized regimen of at least five effective drugs should be initiated based on drug susceptibility testing results, with a minimum treatment duration of 18 months, as recommended by the latest WHO guidelines 1.
Key Considerations
- The regimen should include at least three Group A agents (bedaquiline, levofloxacin/moxifloxacin, and linezolid) and at least one Group B agent (cycloserine/terizidone and/or clofazimine) 1.
- The treatment should be initiated in a specialized center with experience managing drug-resistant TB, with directly observed therapy when possible 1.
- Close monitoring for adverse effects is essential, including ECG monitoring for QT prolongation with bedaquiline and clofazimine, peripheral neuropathy with linezolid, and psychiatric symptoms with cycloserine 1.
Treatment Regimen
- A typical XDR-TB regimen includes bedaquiline (400mg daily for 2 weeks, then 200mg three times weekly), linezolid (600mg daily), clofazimine (100mg daily), cycloserine (250-500mg twice daily), and possibly high-dose moxifloxacin (600-800mg daily) if there's partial fluoroquinolone susceptibility 1.
- Additional agents may include delamanid (100mg twice daily), pretomanid (as part of specific regimens), imipenem-cilastatin with clavulanate, or high-dose isoniazid if low-level resistance is present 1.
Patient-Centered Care
- Patients should receive comprehensive health education, counseling, and shared decision-making regarding their health, as well as support for adherence and completion of treatment 1.
- Social issues should be addressed, and patients should receive support for these, including nutritional and psychological support, and drug and alcohol services if needed 1.
- Active TB drug safety monitoring and management, and regular assessments for treatment effectiveness, are crucial components of care 1.
From the Research
Starting Antituberculous Treatment in Patients with XDR PTB
To initiate antituberculous treatment in patients with extensively drug-resistant pulmonary tuberculosis (XDR PTB), the following steps and considerations are crucial:
- Drug Selection: The treatment regimen should include a combination of at least four drugs to which the Mycobacterium tuberculosis isolate is likely to be susceptible 2.
- Stepwise Selection Process: Drugs are chosen based on efficacy, safety, and cost, categorized into five groups:
- First group: Oral first-line drugs (high-dose isoniazid, pyrazinamide, and ethambutol) 2.
- Second group: Fluoroquinolones, with high-dose levofloxacin as the first choice 2.
- Third group: Injectable drugs (capreomycin, kanamycin, then amikacin) 2.
- Fourth group: Second-line drugs (thioamides, cycloserine, then aminosalicylic acid) 2.
- Fifth group: Less effective drugs or those with sparse clinical data (clofazimine, amoxicillin with clavulanate, linezolid, carbapenems, thioacetazone, then clarithromycin) 2.
- Newer Regimens: Consideration of newer, entirely oral regimens that include bedaquiline, delamanid, linezolid, and clofazimine for 24-36 weeks may offer favorable outcomes for patients with MDR-TB, including those with additional resistance to fluoroquinolones or second-line injectables 3, 4.
- Treatment Monitoring and Adjustment: Regular monitoring for adverse effects, such as myelosuppression and peripheral neuropathy, is essential, as well as adjusting the regimen based on drug susceptibility testing results and patient response 4, 5.
- Challenges and Considerations: The treatment of XDR TB poses challenges, including the potential for acquired resistance, particularly to bedaquiline, and the management of adverse effects in resource-limited settings 6.
Key Considerations for Treatment Regimens
- Bedaquiline, Delamanid, Linezolid, and Clofazimine Regimen: This regimen has shown promise in treating MDR-TB with additional resistance, offering a favorable outcome in a significant proportion of patients 4.
- All-Oral Regimens: The use of all-oral regimens, including bedaquiline, levofloxacin (or moxifloxacin), and linezolid, supplemented by cycloserine and/or clofazimine, is recommended by the WHO for MDR/RR-TB treatment, despite uncertainties regarding their effectiveness and potential risks 6.
- Drug Susceptibility Testing: Ideally, all MDR-TB patients should have their isolate tested for susceptibility to key drugs before starting treatment, but capacity limitations in resource-limited settings pose a challenge 6.