Diagnostic performance of DNA microarray for detecting rifampicin and isoniazid resistance in Mycobacterium tuberculosis

Abstract

Background: While rifampicin (RFP) and isoniazid (INH) are the most commonly used first-line antituberculosis drugs, multidrug resistance in Mycobacterium tuberculosis poses a threat to the success of tuberculosis (TB) control programs. Clinical practice guidelines and expert consensuses recommend drug susceptibility testing (DST) before the initiation of antituberculosis treatment. However, traditional DST is time-consuming and has high requirements for laboratory conditions. The recently developed molecular diagnostic techniques, such as DNA microarray, offer new options. We thus investigated the diagnostic value of DNA microarray in detecting RFP + INH-resistant TB, with an attempt to identify simple, efficient, and accurate drug-resistant TB testing methods. Methods: The clinical features and DST results of patients diagnosed with pulmonary tuberculosis by Bactec MGIT 960 liquid culture system (Becton, Dickinson and Company, Franklin Lakes, NJ, USA) who received DNA microarray analysis in our center from July 2019 to July 2020 were retrospectively analyzed.Level of agreement between liquid culture and DNA microarray technology was assessed by using the Cohen kappa coefficient. With the results of liquid culture as the gold standard, the sensitivity and specificity of the DNA microarray were calculated, and the receiver operating characteristic (ROC) curves were used to assess the diagnostic values of the DNA microarray in detecting RFP + INH-resistant TB. Results: A total of 825 patients were enrolled. The sensitivity and specificity of DNA microarray were 0.84 and 0.94, respectively, in the detection of RFP resistance, with an area under the curve (AUC) of 0.89 [95% confidence interval (CI): 0.87-0.91)] and a Cohen kappa coefficient of 0.78 (95% CI: 0.72-0.83). For INH resistance, the sensitivity and specificity of the DNA microarray were 0.73 and 0.97, respectively, with an AUC of 0.85 (95% CI: 0.82-0.87) and a Cohen kappa coefficient of 0.75 (95% CI: 0.70-0.80). Conclusions:The DNA microarray had high specificity and sensitivity in detecting RFP + INH-resistant TB. As a rapid, accurate, and practical technique, it can be routinely performed in clinical laboratories.

Exploring Diagnostic Methods for Drug-Resistant Tuberculosis: A Comprehensive Overview

“…In those conditions, it is recommended to repeat the Xpert testing in case of a first positive result. Other in-house molecular methods are also available, and they might be useful especially at the local level or in low-resource settings since they are relatively inexpensive, see for example [52,53]. However, standardization and cross-laboratory reproducibility are difficult to obtain with these methods.…”

“…Compared to the MGIT, the assay reported a sensitivity and a specificity of 84.0% and 94.0% for RIF-resistance detection and 73.0% and 97.0% for INH-resistance detection. However, it was not possible to determine which mutations in the rpoB, inhA and katG genes were targeted by the microarray system, making it difficult to compare it with other DST methods [52].…”

New insight in molecular detection of Mycobacterium tuberculosis

“…Although microarray can detect many genes at the same time, for simplicity of procedure it can be used in identifying mutations in the rpoB , gyrA, and pncA genes, predicting resistance to RIF, fluoroquinolones, and PZA, respectively (Havlicek et al 2019 ; Wade et al 2004 ). For this purpose, samples should be placed into a microarray platform and recorded the results with a microarray scanner such as LuxScan™ from CapitalBio Co. (Sun and Sun 2021 ).…”

Advances in the application of molecular diagnostic techniques for the detection of infectious disease pathogens (Review)

“…Ma et al (82) developed and evaluated a solid-phase chip for the simultaneous detection of 15 types of bacteria directly from respiratory tract specimens of patients with pneumonia, thus reducing detection time, facilitating the early administration of antimicrobial drugs and preventing bacterial resistance caused by empirical antibiotic treatment. Recent studies have shown that the CapitalBio DNA chip (CapitalBio Corporation) can detect the resistance of MTB to rifampicin and isoniazid, and the corresponding gene mutations within 6 h, which is quicker and more accurate than traditional bacterial culture and drug susceptibility tests (83)(84)(85). Currently, a number of automatic detection platforms based on solid-phase chips are entering the market.…”