Predictable repeatability issues with GeneXpert-Xpert MTB/RIF (version 4) derived rifampicin resistant tuberculosis results from South India: Appreciating the limits of a technological marvel!

Sanker, Praveen; Kottuthodi, Ramya Puthukkudi; Ambika, Anusree P; Santhosh, Vishnu T; Balakrishnan, Ravikrishnan; Mrithunjayan, Sunil Kumar; Moosan, Hisham

doi:10.4103/bbrj.bbrj_6_17

Cited by 7 publications

(4 citation statements)

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“…The current study findings revealed 6.9% false positive rifampicin resistance cases, among low and very low mycobacterial levels, this is supported by previous studies in other settings. The current study findings were markedly low compared with those recorded in previous studies conducted in Haiti (62.8%) [8], India (66%) [15], Korea (20%) [16], Australia (31%) [17], but they were low compared to previous findings in Kenya (12%) [18] and Turkey (11.7%) [19]. On the other hand the findings were higher than those documented previously in Egypt (2.0%) [20], Pakistan (0.8%) [21], China (0.41%) [22], South Africa (0.9%) [13], but comparable with previous findings in studies conducted in Vietnam (6%) [23] and India (6%) [24].…”

Section: Discussioncontrasting

confidence: 99%

False Positive Rifampicin Resistance among HIV Patients attending Bahati Comprehensive Care Centre, Nairobi, Kenya

Nyang’au¹,

Amukoye²,

Kangethe³

et al. 2020

J Tuberc

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Introduction: Tuberculosis is a chronic airborne and infectious disease which remains a leading cause of death in people living with Human Immunodeficiency Virus (HIV). Globally in 2018, there were 251,000 documented cases of death in HIV positive people. Timely diagnosis of tuberculosis and detection of drug resistance to TB drugs in such patients remains a challenge because of non specific presentation and disseminated nature of the disease. GeneXpert MTB/RIF assay is a molecular technique capable of simultaneously diagnosing tuberculosis and providing susceptibility status of rifampicin which is a surrogate marker of multidrug resistant tuberculosis. Despite the improved detection capacity in both tuberculosis and rifampicin susceptibility status previous studies have reported on false positive rifampicin resistance associated with Xpert MTB/RIF assay.Objective: This study sought to determine the prevalence of false positive rifampicin resistance among HIV patients attending Bahati comprehensive care centre. Materials and Methods:In a seven month period a retrospective cohort study was conducted among consented 346 people living with human immunodeficiency virus (HIV) attending a comprehensive care centre in Nairobi, Kenya. Detection and isolation of Mycobacterium tuberculosis from patient sputa was done using Xpert MTB/RIF assay and BACTEC MGIT 960 machine, on the other hand first line drug susceptibility testing was done by use of BACTEC MGIT 960 machine. All collected data was analyzed using Statistical Package for the Social Sciences (SPSS) version 20.0.Results: Of the 72(93.5%) Xpert MTB/RIF assay culture positive isolates subjected to drug susceptibility, results revealed 4(6.5%) and 1(10%) false rifampicin resistant cases in the non isoniazid preventive therapy and isoniazid preventive therapy (non-IPT and IPT) arms respectively; OR=1.583[95% C.I= 0.159-15.813]; P=0.538. There were no significant differences regarding false rifampicin resistant

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Section: Discussioncontrasting

confidence: 99%

False Positive Rifampicin Resistance among HIV Patients attending Bahati Comprehensive Care Centre, Nairobi, Kenya

Nyang’au¹,

Amukoye²,

Kangethe³

et al. 2020

J Tuberc

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“…On the one hand, the universal >4-cycle difference in Ct values between probes for interpreting RIF resistance should be redefined by classifying results for clinical samples according to initial bacterial load, especially for samples with a very low bacterial load. On the other hand, the Xpert MTB/RIF has been recommended to diagnose TB in children, HIV-infected individuals, and extrapulmonary TB patients, samples of which have extremely low bacterial loads that often fall below detection limits of conventional methods [ 17 , 21 ]. Due to the fact that a high proportion of very low bacterial load results can be expected, increased rates of false RIF resistance results would also be expected that would lead to inappropriate treatment of these populations with toxic and unnecessary second-line drugs.…”

Section: Discussionmentioning

confidence: 99%

“…Due to the fact that a high proportion of very low bacterial load results can be expected, increased rates of false RIF resistance results would also be expected that would lead to inappropriate treatment of these populations with toxic and unnecessary second-line drugs. Considering that Xpert is endorsed over other tests due to its superior performance in detecting drug-resistant MTB in samples with low bacterial load, such as samples from pediatric, extrapulmonary, and HIV-coinfected pulmonary TB patients, more attention should be paid to understand the increased risk for false-positive RIF resistance results when evaluating these cases [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Interpretation of Discordant Rifampicin Susceptibility Test Results Obtained Using GeneXpert vs Phenotypic Drug Susceptibility Testing

Huo

Liu

et al. 2020

Open Forum Infectious Diseases

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Abstract Background The three-month difference in turnaround time between Xpert and conventional phenotypic drug susceptibility testing (pDST) causes patient treatment challenges when pDST rifampin (RIF) susceptibility results and earlier Xpert results disagree, resulting in unnecessary tuberculosis (TB) patient exposure to toxic second-line drugs. Here, the prevalence of discordant RIF susceptibility test results, specifically Xpert (resistant) versus pDST (susceptible) results, was determined. Methods Tuberculosis patients enrolled between January 2015 and June 2018 at Beijing Chest Hospital who consecutively tested positive for RIF resistance using Xpert then negative using pDST were studied. DNA sequences and minimal inhibitory concentration (MIC) results provided insights for understanding discordant results. Results Of 26,826 patients with suggestive TB symptoms undergoing Xpert MTB/RIF testing, 728 diagnosed as RIF-resistant were evaluated. Of these, 118 (16.2%) exhibiting Xpert RIF resistance and phenotypic RIF susceptibility yielded 104 successfully subcultured isolates; of these, 86 (82.7%) harbored rpoB gene RRDR mutations and 18 (17.3%) did not. Leu511Pro (25.0%) and Leu533Pro (17.3%) mutants were most frequently associated with discordant RIF susceptibility test results. Of the 86 isolates with rpoB mutations, 42 (48.8%) with MICs ≤1.0 mg/L were assigned to the RIF-susceptible group, with Leu511Pro the most common mutation observed. Isolates with very low bacterial load were most frequently misdiagnosed as RIF-resistant by Xpert. Conclusion Approximately one-sixth of RIF-resistant TB isolates identified via Xpert yielded discordant pDST results due to questionable interpretation of specific “disputed” mutations. Thus, a diagnostic flow chart should be used to correctly interpret Xpert RIF-resistance results to best guide patient treatment.

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“…This is in concordance with previous studies in the literature. [67] Single sample with delayed Ct for all probes showed a mutation in PSQ and subsequent resistance to RIF in MGIT DST.…”

Section: Discussionmentioning

confidence: 99%

Interpreting very low Mycobacterium tuberculosis detected on Xpert Mycobacterium tuberculosis/rifampicin

et al. 2019

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Predictable repeatability issues with GeneXpert-Xpert MTB/RIF (version 4) derived rifampicin resistant tuberculosis results from South India: Appreciating the limits of a technological marvel!

Cited by 7 publications

References 1 publication

False Positive Rifampicin Resistance among HIV Patients attending Bahati Comprehensive Care Centre, Nairobi, Kenya

False Positive Rifampicin Resistance among HIV Patients attending Bahati Comprehensive Care Centre, Nairobi, Kenya

Interpretation of Discordant Rifampicin Susceptibility Test Results Obtained Using GeneXpert vs Phenotypic Drug Susceptibility Testing

Interpreting very low Mycobacterium tuberculosis detected on Xpert Mycobacterium tuberculosis/rifampicin

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