Pyrosequencing, a new tool in management of tuberculosis. In the traditional management of tuberculosis, the gold standard test for detecting antibiotic resistance is the bactec mgit system. However it takes 3 to 6 weeks for the results to come and this delays proper att regimen for each patient. To overcome this drawback there is a new genetic technology called as pyrosequencing assay. This can be performed on sputum, CSF and other body fluids. Principle is that it detects resistance to 6 att drugs which is INH, RCIN, ETB, Aminoglycosides, quinolones. The turn around time is fast and it gives results in 2 days time. Principle: During synthesis of complimentary DNA strand by the DNA polymerase, when nucleotides are added to the chain pyrophosphate is released. This emits light which is picked up by a sensor and a peak is generated. The height of the peak is proportional to dNTP. Pyogram then reveals the mutated sequence. Pyrosequencing detects the following mutations suggesting drug resistance: katG--INH rpoB--- RCIN embB---ETB rrs--- aminoglycosides gyrA---quinolones Presence of these mutations implies that particular drug cannot be used. Pyrosequencing results are 95% concordant with results from traditional bactec mgit system as per clinical studies and trials. Clinical applications: now if we have a critical case of meningitis in icu or a suspected MDR TB of lungs its easy to perform this test and start appropriate regimen within 2 days time. No more delay. Drawbacks: Expensive, not available at all labs, can detect resistance to only 6 drugs. What if there is a new mutation affecting a particular group of drugs. It may get missed out since the system detects small regions of dna. If used correctly pyrosequencing can be a game changer in management of tuberculosis. Dr Hardik Thakker, MD MED, ECFMG (USA).