Management of Indeterminate Resistance on Sputum CBNAAT for Tuberculosis

Diagnostic Approach

When sputum CBNAAT shows indeterminate resistance to rifampicin, the next step is to collect additional sputum specimens for culture and comprehensive drug susceptibility testing (DST) while initiating empirical treatment based on clinical judgment, as recommended by the Centers for Disease Control and Prevention 1, 2
Testing for inhibitors in the specimen is crucial, as 3-7% of sputum specimens might contain substances that prevent or reduce amplification and cause false-negative or indeterminate NAA results, according to the Morbidity and Mortality Weekly Report 3

Culture remains the gold standard for laboratory confirmation of TB and is required for isolating bacteria for comprehensive drug susceptibility testing, as stated by the Morbidity and Mortality Weekly Report 5
Liquid culture methods have higher sensitivity (88-90%) and shorter detection time (10-14 days) compared to solid culture methods, as reported in Clinical Infectious Diseases 2

The Centers for Disease Control and Prevention recommends never adding a single drug to a potentially failing regimen, as this leads to acquired resistance to the added drug, and instead suggests considering initiating an empirical retreatment regimen that includes at least three effective drugs 4
Adjusting the treatment regimen based on DST results when they become available is crucial, as emphasized by the World Health Organization 4

For patients with HIV co-infection or paucibacillary disease, sensitivity of all TB diagnostic tests may be reduced, requiring stronger reliance on clinical judgment, as noted by the Centers for Disease Control and Prevention 6

Failing to collect specimens for culture and DST before changing therapy is a common pitfall, as warned by the American Thoracic Society 4
Relying solely on CBNAAT results without considering culture, which remains essential for comprehensive drug susceptibility testing, is another pitfall to avoid, as cautioned by the Morbidity and Mortality Weekly Report 5