Performance of an Xpert-based diagnostic algorithm for the rapid detection of drug-resistant tuberculosis among high-risk populations in a low-incidence setting.

Timely diagnosis of drug-resistant tuberculosis (DR-TB) is beneficial for case treatment and management. We implemented an algorithm to improve molecular diagnostic utilization to intensify DR-TB case findings. The GeneXpert MTB/RIF (Xpert) test was used for initial diagnosis. Samples with Mycobacterium tuberculosis complex (MTBC)-positive and rifampicin resistance (RR) results were subsequently and simultaneously tested using the GenoType MTBDRplus (DRplus) and MTBDRsl (DRsl) tests. This prospective cohort study enrolled 2957 high-risk DR-TB cases. We tested sputum specimens using conventional mycobacteriological and molecular tests. Gene sequencing was performed to resolve discordant results. According to the Xpert test, 33.6% of specimens were MTBC-positive and 5.1% were RR. RR specimens were further analyzed in the DRplus and DRsl tests. We identified 1 extensively drug-resistant (XDR), 8 pre-XDR, 18 simple multidrug-resistant (MDR), 22 mono-RR, and 2 RR cases with concurrent second-line injection DR-TB. Of these, 25 (49%) were relapses, 13 (25.5%) were treatment failures, 10 (19.6%) were from MDR-TB high-incidence areas/countries, 1 was from MDR-TB contact and 2 were unknown. Among culture-positive TB cases, the sensitivities, specificities, and positive predictive values (PPVs) of the Xpert test and RR cases were 73.6% and 100.0%, 85.7% and 98.6%, and 73.5% and 80.0%, respectively. Gene sequencing of discordant results revealed 7 disputed rpoB mutations and 2 silent mutations for RIF, 1 ahpC mutation for isoniazid and 1 gyrA mutation for fluoroquinolone. The algorithm effectively identified approximately 23% of annual MDR-/XDR-TB and 37.5% of RR-TB cases that were enrolled in our DR-TB treatment and management program within 3 days.

Population-Based Drug Resistance Surveillance of Multidrug-Resistant Tuberculosis in Taiwan, 2007-2014.

OBJECTIVE: To determine the extent of drug resistance in multidrug-resistant tuberculosis (MDR-TB) cases, we conducted a retrospective, population-based analysis using drug susceptibility testing (DST) results of MDR Mycobacterium tuberculosis complex isolates obtained from 2007-2014 in Taiwan. METHODS: M. tuberculosis isolates collected from 1,331 MDR-TB cases were included in this survey. Treatment histories, age, sex, chest radiograph and bacteriological results of patients were analyzed. Standard DST was performed to assess resistance to the following drugs: isoniazid (INH), rifampicin (RIF), streptomycin (SM), ethambutol (EMB), amikacin (AM), kanamycin (KM), capreomycin (CAP), ofloxacin (OFX), moxifloxacin (MOX), levofloxacin (LVX), gatifloxacin (GAT), para-aminosalicylate (PAS), ethionamide (EA), and pyrazinamide (PZA). The Cochran-Armitage trend test was used for statistical analysis. RESULTS: We observed a significant increasing trend in portion of new MDR-TB cases, from 59.5% to 80.2% (p < 0.0001), and significant decreasing trend of portion in the 15-44-year-old age group (p < 0.05). Of the MDR M. tuberculosis isolates tested, 6.2% were resistant to AM, 8.6% were resistant to KM, 4.6% were resistant to CAP, 19.5% were resistant to OFX, 17.1% were resistant to MOX, 16.0% were resistant to LVX, 5.8% were resistant to GAT, 9.5% were resistant to PAS, 28.5% were resistant to EA and 33.3% were resistant to PZA. Fifty (3.8%) extensively drug-resistant TB cases were identified. No significant differences were found in drug resistance frequencies between new and previously treated MDR cases. However, we observed significant decreases in the rates of AM resistance (p < 0.05), OFX resistance (p < 0.00001), PAS resistance (p < 0.00001), EA resistance (p < 0.05) and PZA resistance (p < 0.05). Moreover, younger age groups had higher rates of resistance to fluoroquinolones. CONCLUSION: A policy implemented in 2007 to restrict the prescription of fluoroquinolones was shown to be effective. Our survey revealed a decreasing trend of resistance to PZA, OFX and AM, which suggests the feasibility of adopting a short-course regimen and demonstrates the effectiveness of our management program for MDR-TB.