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<h3>Background</h3> The Xpert MTB/RIF is a point of care, fully-automated diagnostic molecular test that simultaneously detects tuberculosis and rifampicin drug resistance which is used as a surrogate for multidrug resistant tuberculosis (MDR-TB). However, not much is known about susceptibility to other anti-TB drugs in patients having Rifampicin susceptibility on the Xpert. The Indian National Tuberculosis Programme recommends isoniazid and rifampicin in the continuation phase as part of category I first line therapy. However, in cases with isoniazid monoresistance, which may be missed by the Xpert MTB/Rif, this would lead to rifampicin monotherapy and possible amplification of resistance. Hence it is essential to know the background rates for isoniazid resistance, before deciding on the drugs to be used in the continuation phase. <h3>Aim</h3> To analyse drug susceptibility patterns (DST) in patients with rifampicin susceptibility. <h3>Methods</h3> This study was carried out at the microbiology laboratory of PD Hinduja National Hospital, Mumbai, India. All Mycobacterium tuberculosis (MTB) isolates who underwent 14 drug susceptibility testing (DST) between December 2015- November 2016 were analysed retrospectively. All drugs were tested at WHO defined critical concentrations (CC). <h3>Results</h3> Of a total of 2750 samples undergoing 14 drug DST, 1383 (50.29%) were rifampicin susceptible. Among the rifampicin susceptible isolates, the most common resistance was observed to Isoniazid (INH) in 182 (13.1%) samples of which 127 (9.18%) were isoniazid monoresistant. Ofloxacin resistance was seen in 55 (3.97%) samples; of these 33 (2.38%) were also moxifloxacin resistant at CC of 0.5 mcg/ml. Polydrug resistance was seen in 71 (5.1%) isolates; of these the most common cross resistance involved INH and Ethionamide seen in 55 (3.97%) isolates. Concomitant INH and fluoroqiunolone resistance was seen in 11 (0.8%) isolates. Concomitant resistance to INH, Pyrazinamide and Ethambutol was seen in 2 isolates. <h3>Conclusion</h3> Complete DST, when available, can identify polydrug resistance and help design a more effective regimen. Increased access to Line probe assays would identify isoniazid resistance even in patients showing rifampicin susceptibility on the Xpert MTB/Rif. With high rates of INH resistance observed (13.1%) in our setting, it may be prudent to include Ethambutol in the continuation phase to avoid rifampicin monotherapy.