Tuberculosis with discordant drug resistance patterns- A diagnostic dilemma

Programmatic management of drug-resistant tuberculosis (PMDT) guidelines in India specify the use of cartridge based nucleic acid amplification test (CBNAAT) and Line probe assay (LPA) for early diagnosis of drug-resistant Tuberculosis. However, discrepancy among these genotypic tests (CBNAAT and LPA) or with the phenotypic DST in real practice poses a clinical dilemma. The usual solutions are to rely on methods with short turnaround times like CBNAAT and LPA to start an initial regimen. The culture and DST results, that are typically available after at least a few weeks, are used to modify the regimen if required. This practice is based on the fact that culture and DST based sensitivity patterns are considered the gold standard for diagnosing and drug resistance. DNA sequencing by pyrosequencing, Sanger sequencing and next generation sequencing (NGS) are being evaluated; their future availability may help in early clarifications in discordant drug resistance patterns. Such tests are costly and have limited availability, however, in view of immense benefit to detect TB Drug-resistant phenotypes, national guidelines plan to scale up their use in national and well-performing intermediate TB reference laboratories.