What is the treatment protocol for drug-resistant tuberculosis (TB), including extensively drug-resistant tuberculosis (XDR-TB) and totally drug-resistant tuberculosis (TDR-TB)?

Treatment of Tuberculosis Preventive Therapy (TPT) in Drug-Resistant TB

For contacts exposed to patients with MDR-TB, offer 6-12 months of treatment with a later-generation fluoroquinolone (levofloxacin or moxifloxacin) alone or combined with a second drug based on the source patient's drug susceptibility pattern, rather than observation alone. 1

Core Principles for TPT in Drug-Resistant TB Contacts

When to Offer TPT

• TPT should be offered to all contacts of patients with MDR-TB rather than observation alone (conditional recommendation based on very low certainty evidence). 1
• The decision to treat is based on exposure to an infectious MDR-TB source case, not on the contact's own infection status. 1

Recommended Regimen Components

Fluoroquinolone-Based Therapy:

• Use a later-generation fluoroquinolone (levofloxacin or moxifloxacin) as the backbone of the preventive regimen. 1
• The fluoroquinolone can be used alone or with a second drug, selected based on the drug susceptibility testing (DST) results from the source patient's M. tuberculosis isolate. 1

Duration:

• Treat for 6-12 months total duration. 1

Critical Drug Selection Guidance

What NOT to Use:

• Do NOT routinely include pyrazinamide as the second drug due to significantly increased toxicity, adverse events, and treatment discontinuations. 1
• Avoid drugs to which the source case has documented resistance. 1

What TO Consider as Second Drug:

• Select the second drug based on the source patient's DST results to ensure susceptibility. 1
• Options may include ethambutol or other agents depending on the resistance pattern, though specific second-line agents are not explicitly detailed in guidelines beyond avoiding pyrazinamide. 1

Common Pitfalls and How to Avoid Them

Pitfall #1: Using Pyrazinamide Routinely

• Evidence shows increased toxicity and discontinuation rates when pyrazinamide is added to fluoroquinolone-based preventive therapy. 1
• Only consider pyrazinamide if no other options exist and benefits clearly outweigh risks. 1

Pitfall #2: Ignoring Source Case DST

• Always obtain and review the source patient's drug susceptibility results before selecting the preventive regimen. 1
• Using drugs to which the source case is resistant renders the preventive therapy ineffective. 1

Pitfall #3: Inadequate Treatment Duration

• Treating for less than 6 months may be insufficient for preventing progression to active disease. 1
• The 6-12 month range allows flexibility based on tolerability and adherence, but shorter durations are not recommended. 1

Monitoring During TPT

Adherence Support:

• Directly observed therapy (DOT) principles should be applied when feasible to ensure completion of the preventive regimen. 2

Adverse Event Monitoring:

• Monitor for fluoroquinolone-related adverse effects including tendinopathy, QTc prolongation, and neuropsychiatric effects. 1
• Regular clinical assessment for symptom development suggesting progression to active TB disease. 2

Special Considerations

XDR-TB Contacts

• For contacts of XDR-TB patients (resistant to fluoroquinolones), preventive therapy options are extremely limited and no proven effective regimen exists. 3
• In such cases, close clinical monitoring without preventive therapy may be the only option, with low threshold for evaluation if symptoms develop. 3

HIV-Positive Contacts

• The same fluoroquinolone-based approach applies to HIV-positive contacts, though outcomes may be less favorable. 3
• Ensure no drug-drug interactions with antiretroviral therapy when selecting the fluoroquinolone. 3