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

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.

Drug Resistance and Molecular Characteristics of Mycobacterium tuberculosis: A Single Center Experience

“…Globally, there were an estimated 9.9 million new cases of MTB in 2020 [1], and about half a million of these cases were multidrug-resistant TB (MDR-TB) [2]. The emergency of drug-resistant TB (DR-TB) has threatened global public health efforts to control TB [3,4]. China has the third-highest burden of MTB in the world [5], in particular a significant increase in DR-TB, which severely impacts treatment outcomes [6].…”

QMAC-DST for Rapid Detection of Drug Resistance in Pulmonary Tuberculosis Patients: A Multicenter Pre–Post Comparative Study

“…They also depend on the skill of laboratory personnel for result interpretation and are not efficient for processing large sample volumes [22][23][24][25]. QMAC-DST addresses several limitations of traditional pDST by offering rapid TAT, the ability to test various first-and second-line drugs, high throughput, reduced labor intensity, effectiveness regardless of inoculum size, enhanced safety with sealing film and a locking lid, along with an agarose matrix embedding the MTB and elimination of errors due to the MTB tracking failure [12][13][14][15]. However, because QMAC-DST uses colonies derived from the LJ medium, the timing for the confirmation of QMAC-DST results after the start of treatment can be delayed, depending on the time required for the MTB culture.…”

“…By using a microfluidic chip and imaging technologies, QMAC-DST is capable of determining resistance to >15 anti-TB drugs within a week using a culture specimen [12]. Its high concordance with the conventional LJ-DST has been validated in previous studies [13][14][15]. This multicenter study seeks to investigate the impact of QMAC-DST on the treatment of pulmonary TB patients, with a particular focus on comparing QMAC-DST and LJ-DST.…”