Acquired Drug Resistance During the Turnaround Time for Drug Susceptibility Testing Impacts Outcome of Tuberculosis

Background: The impacts of acquired resistance to first-line drugs (FLDs) during turnaround time (TAT) for drug susceptibility testing (DST) are still unclear. Thus, we aimed to investigate the impacts of acquired resistance to FLDs during TAT for DST on tuberculosis (TB) standard treatment.MethodWe performed a prospective cohort study between 2013 and 2018 in China, including sputum culture-positive TB patients with a baseline DST result for a Mycobacterium tuberculosis (Mtb) isolate collected at TB diagnosis and a follow-up DST result for a Mtb isolate collected when baseline DST result became available. Mtb isolates with acquired drug resistance were identified by the comparison between baseline and follow-up DST. Treatment outcome were evaluated by sputum culture conversion and World Health Organization (WHO) treatment outcome definitions. ResultsIn total, 65 patients with Mtb isolates with acquired resistance to any FLDs and 130 patients with consistent drug susceptibility profile were included in the analysis. In a Cox proportional hazard regression analysis, acquired pyrazinamide-resistance (aHR 0.54, 95%CI: 0.36-0.81) and acquired isoniazid-resistance (aHR 0.50, 95%CI: 0.29-0.85) were associated with prolonged time to sputum culture conversion. Furthermore, independent risk factors of treatment failure included acquired INH-resistance (aOR 7.64, 95%CI: 2.39-16.08) and acquired PZA-resistance (aOR 5.71, 95%CI: 2.31-14.12).ConclusionThe association between acquisition of drug resistance and treatment outcome highlights the importance of shortening the turnaround time of DST.