Clinical Validation of the QMAC-DST System for Testing the Drug Susceptibility of Mycobacterium tuberculosis to First- and Second-Line Drugs.

Sangyeop Lee,Suyeoun Kim,Sunghoon Kwon,Eunji Jo,Daehyun Chu,Haeun Kim,Mi-Na Kim,Heungsup Sung,Youn Mi Choi,Bonghwan Jin,Eun-Geun Kim,Hyun Jung Kim,Jeonghyun Chang,Geumrae Kang

doi:10.3389/fmicb.2019.00706

Abstract

There is a high demand for novel approaches to counter the various challenges of conventional drug susceptibility testing (DST) for tuberculosis, the most prevalent infectious disease with significant global mortality. The QMAC-DST system was recently developed for rapid DST using image technology to track the growth of single cells of Mycobacterium tuberculosis (MTB). The purpose of this study was to clinically validate the QMAC-DST system compared to conventional DST. In total, 178 MTB isolates recovered from clinical specimens in Asan Medical Center in 2016 were tested by both QMAC-DST and absolute concentration methods using Lowenstein-Jensen media (LJ-DST). Among the isolates, 156 were subjected to DST using BACTEC MGIT 960 SIRE kits (BD, Sparks, MD, United States) (MGIT-DST). The susceptibility/resistance results obtained by QMAC-DST were read against 13 drugs after 7 days of incubation and compared with those of LJ-DST. Based on the gold standard LJ-DST, the agreement rates of QMAC-DST for all drugs were 97.8%, 97.9%, and 97.8% among susceptible, resistant, and total isolates, respectively, while the overall agreement of MGIT-DST tested for 156 isolates against first-line drugs was 95.5%. QMAC-DST showed the highest major error of 6.4% for rifampin, however, it could be corrected by a revised threshold of growth since false-resistant isolates showed grew only half than the true-resistant isolates. The rapid and accurate performance of QMAC-DST warrants ideal phenotypic DST for a wide range of first-line and second-line drugs.

Highlights

Tuberculosis is a major global health problem, and emergence of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) and extensively drug-resistant M. tuberculosis TB (XDR-TB) is a threat to public health efforts to control tuberculosis
The overall agreement rate of QMAC-drug susceptibility testing (DST) to LJ-DST for the 13 drugs was 97.8% and that of Mycobacteria Growth Indicator Tube (MGIT)-DST for first-line drugs was 95.5%
A very major error (vME) of QMAC-DST was 25% among the paraaminosalicylic acid (PAS)-resistant isolates because there was one mismatch found among four resistant isolates

Summary

Introduction

Tuberculosis is a major global health problem, and emergence of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) and extensively drug-resistant M. tuberculosis TB (XDR-TB) is a threat to public health efforts to control tuberculosis. Molecular methods to detect drug-resistant MTB are widely available in clinical laboratories due to rapid and robust performance They are only complementary to phenotypic DST, because it is limited to detecting resistance of a few primary drugs whose molecular mechanisms have been well established (Boehme et al, 2010, 2011; Hanrahan et al, 2012). QMAC-DST (QuantaMatrix, Seoul, Korea) was developed based on microfluidic chip technology to monitor the microscopic growth of MTB colonies (Choi et al, 2016) It has high flexibility in the types and concentrations of drugs tested, no inoculum effects within the wide range of 103–108 cells/mL, excellent reproducibility when using lyophilized drugs, and a rapid turnaround time within 7 days (Jung et al, 2018). The purpose of this study was to compare performance of the QMAC-DST system against the two WHO-endorsed DST methods, LJ-DST and MGIT-DST

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