Reply to Dookie et al., "Whole-Genome Sequencing To Guide the Selection of Treatment for Drug-Resistant Tuberculosis".

Abstract

We would like to thank Dr. Navisha Dookie and colleagues for their comment and for sharing their view on genotypic drug-susceptibility testing (DST) to predict phenotypic drug-susceptibility for the management of patients with drug-resistant tuberculosis (1, 2). We agree that DST should ideally be conducted for all drugs in a regimen, particularly given the severe adverse effects of second-line anti-tuberculosis drugs. Yet, even whole-genome sequencing in not a one-size-fits-all solution. Instead, the goal has to be to optimally combine genotypic and phenotypic assays in a diagnostic algorithm that capitalises on the strengths of both approaches whilst including appropriate reflex and confirmatory testing to minimize the impact of their respective limitations, including systematic errors (3).