What does NTEP recommend for managing TB cases with indeterminate resistance results from CBNAAT?

Management of TB Cases with Indeterminate Resistance Results from CBNAAT

When CBNAAT shows indeterminate resistance to rifampicin, the National Tuberculosis Elimination Programme (NTEP) recommends collecting additional sputum specimens for culture and comprehensive drug susceptibility testing while initiating empirical treatment based on clinical judgment. 1

Initial Management Steps

• When CBNAAT results show indeterminate resistance, collect additional sputum specimens for culture and comprehensive drug susceptibility testing (DST) immediately 1
• Culture remains the gold standard for laboratory confirmation of TB and is required for isolating bacteria for comprehensive drug susceptibility testing 1
• Test for inhibitors in the specimen as 3-7% of sputum specimens might contain substances that prevent or reduce amplification, causing indeterminate results 1
• Initiate empirical treatment based on clinical judgment while awaiting culture and DST results 1

Treatment Considerations

• Never add a single drug to a potentially failing regimen, as this leads to acquired resistance to the added drug 2, 1
• For patients with suspected treatment failure, start an empirical retreatment regimen with at least three effective drugs 2
• The empirical regimen might include:
  • A fluoroquinolone 2
  • An injectable agent (if not used previously) 2
  • Additional oral agents such as p-aminosalicylic acid (PAS), cycloserine, or ethionamide 2
• Adjust the treatment regimen based on DST results when they become available 1

Monitoring and Follow-up

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

Special Considerations

• For patients with HIV co-infection or paucibacillary disease, sensitivity of all TB diagnostic tests may be reduced, requiring stronger reliance on clinical judgment 1
• For multidrug-resistant TB (MDR-TB, resistant to at least isoniazid and rifampicin), consult with or refer to a specialized TB treatment center 2
• Liquid culture methods have higher sensitivity (88-90%) and shorter detection time (10-14 days) compared to solid culture methods 1

Common Pitfalls to Avoid

• Failing to collect specimens for culture and DST before changing therapy 2, 1
• Relying solely on CBNAAT results without considering culture, which remains essential for comprehensive drug susceptibility testing 1
• Delaying treatment modification in seriously ill patients while waiting for DST results 2
• Not considering the possibility of nonadherence, malabsorption, or laboratory error when evaluating treatment failure 2
• Adding only one new drug to a failing regimen, which leads to acquired resistance to the added drug 2, 3

Importance of Culture and DST

• CBNAAT should be accompanied with liquid culture wherever possible, irrespective of the CBNAAT result 4
• Studies show that some drug-resistant isolates may be missed or mislabeled by CBNAAT alone 4
• The positive and negative agreements between liquid culture and CBNAAT for detection of M. tuberculosis were 67.1% and 92.7% respectively 4
• Between line probe assay and CBNAAT for rifampicin resistance detection, agreements were 98.9% and 92.9% respectively 4

By following these recommendations for managing TB cases with indeterminate resistance results from CBNAAT, clinicians can ensure appropriate diagnosis and treatment while preventing the development of drug resistance.