What to do for a patient with persistent AFB (Acid-Fast Bacilli) positive TB (tuberculosis) on rifampicin-based therapy?

Management of Persistent AFB Positive TB on Rifampicin-Based Therapy

For patients with persistent AFB positive tuberculosis despite rifampicin-based therapy, treatment failure should be presumed, and a new regimen with at least three effective drugs should be initiated after collecting specimens for culture and drug susceptibility testing. 1

Evaluation of Treatment Failure

• Treatment failure is defined as continued or recurrently positive cultures after 3 months of appropriate multidrug therapy, with patients who remain culture-positive after 4 months definitively considered treatment failures 1
• Possible causes of persistent AFB positivity include:
  • Nonadherence to the prescribed regimen (most common cause) 1
  • Unrecognized drug resistance 1
  • Malabsorption of medications 1
  • Laboratory error (cross-contamination or mislabeling) 1

Immediate Management Steps

• Collect sputum specimens for AFB smear, culture, and drug susceptibility testing (DST) for both first-line and second-line drugs before changing therapy 1
• If the patient is seriously ill or has positive sputum AFB smears, start an empirical retreatment regimen immediately without waiting for DST results 1
• Never add a single drug to a failing regimen as this leads to acquired resistance to the added drug 1
• Add at least three new drugs to which susceptibility can be logically inferred 1

Empirical Retreatment Regimen

For patients with treatment failure on rifampicin-based therapy, an empirical regimen might include:

• A fluoroquinolone (e.g., levofloxacin or moxifloxacin) 1
• An injectable agent (e.g., amikacin, kanamycin, or capreomycin - not streptomycin if previously used) 1
• Additional oral agents such as p-aminosalicylic acid (PAS), cycloserine, or ethionamide 1

Follow-up and Monitoring

• Adjust the regimen based on drug susceptibility test results when available 1
• Monitor sputum cultures monthly until two consecutive specimens are AFB smear- and culture-negative 1
• Perform drug susceptibility testing if cultures remain positive after 2 months of the new regimen 1
• Monitor for adverse effects of second-line drugs, which are more frequent and severe than first-line drugs 1

Special Considerations

• For multidrug-resistant TB (MDR-TB, resistant to at least isoniazid and rifampicin), consult with or refer to a specialized TB treatment center 1
• For patients with rifampicin-resistant TB, newer evidence supports the use of a 24-week all-oral regimen containing bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM), which has shown superior outcomes compared to standard care regimens 2, 3
• If rifampicin intolerance rather than resistance is the issue, alternative regimens using isoniazid, ethambutol, pyrazinamide, and a fluoroquinolone may be effective 4

Common Pitfalls to Avoid

• Failing to collect specimens for culture and DST before changing therapy 1
• Adding only one new drug to a failing regimen 1
• Delaying treatment modification in seriously ill patients while waiting for DST results 1
• Not considering the possibility of nonadherence, malabsorption, or laboratory error 1
• Failing to consult with TB experts for complex drug-resistant cases 1

Early recognition of treatment failure and prompt initiation of an appropriate retreatment regimen with multiple effective drugs is essential to prevent further drug resistance and improve patient outcomes.