Most nucleic acid amplification methods to detect M. tuberculosis are complex, labour-intensive, and have variable sensitivity and specificity. Currently there are no data derived from children or using non-respiratory specimens in HIV-infected persons.

All specimens, even those negative for M. tuberculosis on polymerase chain reaction (PCR), still require culture because a negative PCR does not exclude TB and a positive PCR does not indicate the drug susceptibility profile . 

The Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) identifies >97% of all patients with culture-confirmed TB, including >90% of patients with smear-negative disease. The result can be available in hours. The assay has also been developed as a laboratory-based and point-of-care test for developing countries.

Molecular tests for rifampicin resistance are useful especially when MDR-TB is suspected, as about 95% of isolates that are rifampicin resistant will also be isoniazid resistant. Patients with positive molecular-based rifampicin resistance should be treated as having MDR-TB until the full resistance profile from cultures is available.