Xpert<SUP>®</SUP> MTB/RIF detection of rifampin resistance and time to treatment initiation in Harare, Zimbabwe

Abstract

Background Patients at elevated risk of drug-resistant tuberculosis are prioritized for testing with Xpert MTB/RIF® (“Xpert”), though clinical utility in this population is understudied. Design From November 2011 to June 2014, consecutive outpatients with history of prior tuberculosis in high-density suburbs of Harare, Zimbabwe were tested with Xpert, solid and liquid culture, and the microscopically-observed drug susceptibility assay. Diagnostic accuracy for rifampin-resistance and time to second-line regimens were ascertained. The rpoB gene was sequenced in cases of culture-confirmed rifampin resistance and genotypic sensitivity. Results Among 352 retreatment patients, 71 (20%) had rifampin-resistant, 98 (28%) rifampin-susceptible, 64 (18%) culture-negative/Xpert-positive, and 119 (34%) culture-negative/Xpert-negative TB. Xpert was 86% (95% CI 75-93%) sensitive and 98% (95% CI 92-100%) specific for rifampin-resistant TB. The positive predictive value of Xpert-determined rifampin resistance for MDR-TB was 82% (95% CI 70-91%). Fifty-nine of 71 (83%) participants initiated SLDs, with a median time to regimen initiation of 18 days (IQR, 10-44 days). Conclusion The diagnostic accuracy of Xpert for rifampin-resistance is high, though predictive value for MDR-TB is lower than anticipated. Xpert allows for faster SLD initiation under programmatic conditions, relative to culture-based drug susceptibility testing.

Molecular Epidemiology of Rifampicin Resistance in Mycobacterium tuberculosis Using the GeneXpert MTB/RIF Assay from a Rural Setting in India

“…Our results and the review of six studies performed in other developing countries from Africa and Asia indicate that the most common mutations conferring RR are located in the region of Probe E, followed by Probe B and Probe D, while mutations in the region of Probe A and Probe C were less common [ 8 – 13 ]. The predominance of Probe E and the fact that the Xpert assay does not provide information of specific mutations in the rpoB gene limit its value as an epidemiological tool to study RR-TB.…”

“…The PubMed search strategy showed 47 studies, and 41 were excluded because they did not provide information about the probes that conferred RR. Finally, six studies were included in the analysis [ 8 – 13 ]. The results of these studies and our study are compared in Figure 2 .…”

“…Probe E was the most common in all studies, followed by Probe B, although Probe D was more frequent than Probe B in our study and in the one by Ochang et al [ 10 ]. Probe C was seen rarely, except in the study by Metcalfe et al in Zimbabwe [ 13 ]. The pooled prevalence of probe mutations across studies was 4.73% (95% CI, 1.92–7.54) for Probe A, 15.02% (95% CI, 11.94–18.1) for Probe B, 1.61% (95% CI, 0.67–2.54) for Probe C, 13.35% (95% CI, 10.01–16.69) for Probe D, 63.6% (95% CI, 56.26–70.94) for Probe E, and 1.69% (95% CI, 0.73–2.66) for probe combinations.…”

Mycobacterial genomic DNA from used Xpert MTB/RIF cartridges can be utilised for accurate second-line genotypic drug susceptibility testing and spoligotyping

“…Xpert is one of the most widely used tests for TB and drug-resistance 9 , 34 and although it is a significant advancement, time-to-treatment – especially for MDR- and XDR-TB - is still very long 35 – 38 . Our results show that accurate second-line drug testing using MTBDR sl is possible on CE from Xpert cartridges that would otherwise be discarded.…”

Diagnosing Drug-Resistant Tuberculosis with the Xpert&lt;sup&gt;&#174;&lt;/sup&gt;MTB/RIF. The Risk for Rifampin Susceptible Cases

“…For example, in a report from Haiti, 86.9% of patients with rifampin resistance detected by the Xpert®MTB/RIF were later proved to have MDR-TB due to simultaneous resistance to isoniazid (INH) [8], while a report from Zimbabwe found that 85.2% of patients detected with the Xpert®MTB/RIF as resistant to rifampin were actually MDR [9].…”