Innowave MTB/RIF/INH facilitates timely and accurate diagnosis of multiple-drug resistant tuberculosis as a near POCT technique: a multicenter prospective on-site performance evaluation study.

Abstract

Background: Many rifampicin (RIF)-resistant (RR) tuberculosis (TB) patients remain sensitive to isoniazid (INH), which challenges the strategy of using RR as an instant indicator of multiple-drug resistance tuberculosis (MDR-TB). A molecular test capable of concurrently detecting RIF and INH resistance is urgently needed.

Methods: The performance of a novel rapid molecular test, Innowave MTB/RIF/INH (InnowaveDX) was evaluated prospectively in three tertiary hospitals. Its capability of detecting resistance to RIF and INH was assessed.

Results: In 767 pulmonary tuberculosis (PTB) patients, InnowaveDX showed significantly higher sensitivity than the Xpert MTB/RIF assay (Cepheid, USA) (74.97% versus 68.18%; p = 0.003, χ² = 8.664). This difference was particularly notable in culture-negative PTB cases (52.73% versus 41.29%; p = 0.001, χ² = 10.565). Both tests demonstrated high specificity in 286 non-TB patients. The overall consistency in RIF susceptibility prediction between InnowaveDX and the Xpert assay was 97.3% (505/519). InnowaveDX identified 83.05% (98/118) of INH-resistant cases as predicted by phenotypic drug susceptibility testing (pDST) and 95.45% (105/110) by another molecular method (MeltPro, Zeesan, China) for INH resistance detection on isolates. In addition, InnowaveDX showed a 99.35% consistency (154/155) with katG, inhA, and ahpC sequencing on sputum samples. The consistency rate for MDR-TB prediction between InnowaveDX and pDST was 93.25% (332/356). The accuracy of using RR to predict MDR-TB varied between 64.1 and 80.5%, depending on the reference method.

Conclusion: InnowaveDX is an easy, rapid, and sensitive molecular test for PTB diagnosis that can detect INH and RIF resistance within 3 h, facilitating MDR-TB diagnosis on the first day of hospital admission.