Clinical Impact on Tuberculosis Treatment Outcomes of Discordance Between Molecular and Growth-Based Assays for Rifampin Resistance, California 2003–2013

Shah, Neha; Lin, S-Y Grace; Barry, Pennan M.; Cheng, Yi-Ning; Schecter, Gisela; Desmond, Ed

doi:10.1093/ofid/ofw150

Cited by 27 publications

(27 citation statements)

References 35 publications

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“…In contrast, a portion of the isolates with intermediate resistance and substitutions in codons 516 and 526 were identified as susceptible by Bactec MGIT 960, which was in line with previous reports [12]. Previous reports noted the clinical importance of “disputed” mutations in the rpoB gene [34, 35, 36]. Because the standard treatment of these patients might result in a poor clinical outcome [37, 38], the use of higher doses of RMP [25] or substitution with RFB [39] is proposed.…”

Section: Discussionsupporting

confidence: 87%

A Comparison of the Sensititre MycoTB Plate, the Bactec MGIT 960, and a Microarray-Based Molecular Assay for the Detection of Drug Resistance in Clinical Mycobacterium tuberculosis Isolates in Moscow, Russia

Nosova¹,

Zimenkov

Khakhalina³

et al. 2016

PLoS ONE

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BackgroundThe goal of this study was to compare the consistency of three assays for the determination of the drug resistance of Mycobacterium tuberculosis (MTB) strains with various resistance profiles isolated from the Moscow region.MethodsA total of 144 MTB clinical isolates with a strong bias toward drug resistance were examined using Bactec MGIT 960, Sensititre MycoTB, and a microarray-based molecular assay TB-TEST to detect substitutions in the rpoB, katG, inhA, ahpC, gyrA, gyrB, rrs, eis, and embB genes that are associated with resistance to rifampin, isoniazid, fluoroquinolones, second-line injectable drugs and ethambutol.ResultsThe average correlation for the identification of resistant and susceptible isolates using the three methods was approximately 94%. An association of mutations detected with variable resistance levels was shown. We propose a change in the breakpoint minimal inhibitory concentration for kanamycin to less than 5 μg/ml in the Sensititre MycoTB system. A pairwise comparison of the minimal inhibitory concentrations (MICs) of two different drugs revealed an increased correlation in the first-line drug group and a partial correlation in the second-line drug group, reflecting the history of the preferential simultaneous use of drugs from these groups. An increased correlation with the MICs was also observed for drugs sharing common resistance mechanisms.ConclusionsThe quantitative measures of phenotypic drug resistance produced by the Sensititre MycoTB and the timely detection of mutations using the TB-TEST assay provide guidance for clinicians for the choice of the appropriate drug regimen.

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Section: Discussionsupporting

confidence: 87%

A Comparison of the Sensititre MycoTB Plate, the Bactec MGIT 960, and a Microarray-Based Molecular Assay for the Detection of Drug Resistance in Clinical Mycobacterium tuberculosis Isolates in Moscow, Russia

Nosova¹,

Zimenkov

Khakhalina³

et al. 2016

PLoS ONE

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“…In the current study, the most common pattern of discrepancy was genotypic susceptibility and phenotypic resistance to INH, which is a similar to findings reported from the USA (14,26). This phenomenon is reasonable because whereas MTBDRplus test can detect specific mutations at katG and inhA genes, 20% of INH resistance is known to be developed by mutations at regions other the above two genes, such as ahpC gene (27).…”

Section: Clinical Profiles and Treatment Outcome In The 63 Tb Patientsupporting

confidence: 89%

“…Clinicians usually treated these patients by replacing RIF with other drugs including an MDR regimen with a longer duration. Other reports have also shown that, in the case of RIF discordance with genotypic resistance, treatment failure develops more frequently, and an extended-duration or second-line anti-TB regimen might be more successful (14)(15)(16).…”

Section: Clinical Profiles and Treatment Outcome In The 63 Tb Patientmentioning

confidence: 97%

Clinical implications of discrepant results between genotypic MTBDRplus and phenotypic Löwenstein-Jensen method for isoniazid or rifampicin drug susceptibility tests in tuberculosis patients

Kang¹,

Jung²,

Kim³

et al. 2019

J. Thorac. Dis.

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Background: The widespread use of molecular, genotypic drug susceptibility tests (DSTs) for antituberculosis (anti-TB) drugs has led to the dilemma of interpreting discordant results between genotypic and conventional, phenotypic DSTs. We investigated the clinical characteristics, including treatment patterns and outcomes, of TB patients with a genotype-phenotype discrepancy in susceptibility to isoniazid (INH) or rifampicin (RIF). Methods: We retrospectively reviewed the medical records of TB patients who had results for 2 DSTs (genotypic method, MTBDRplus test for INH and RIF, and phenotypic method) treated between August 2010 and October 2016 in a tertiary university hospital. Results: Among 1,069 TB patients, 63 (5.9%) had discrepant results for the 2 DSTs. Of the 57 multidrugresistant (MDR) TB cases diagnosed by either DST, 18 (31.6%) showed discordant results for INH or RIF. The most frequent pattern of discordance was genotypic susceptibility with phenotypic resistance to INH. RIF-discordant subjects with genotypic resistance were more likely to have been exposed previously to anti-TB drugs and to have an MDR TB diagnosis and concurrent INH resistance. Forty-five of the 54 patients managed in our hospital (83.3%) had a favorable outcome with a mean treatment duration of 14.0 months. Ten of the 16 INH-discrepant patients with a genotypic mutation continued taking INH, but more than half patients in the RIF-discrepant group (8/14) with a genotypic mutation discontinued taking RIF. Conclusions: Despite the low frequency, discordant results were obtained between the genotypic and phenotypic DSTs for INH or RIF, especially for patients with MDR TB or INH resistance. Furthermore, it seemed that RIF discrepancy with a genotypic mutation might have a greater impact on the clinical outcome than INH discrepancy.

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“…Although, the association of D516F substitution with discordant susceptibility tests was reported in previous studies [32,33], our data was not in agreement with the results of Tan et al, Berrada et al,. The occurrence of mutation D516F has been proposed to cause low-level rifampicin resistance [32,37]. Low level rifampicin resistance may influence the treatment; particularly phenotypic DST outcomes may vary from the actual effectiveness of anti-TB drugs in patients [38].…”

Section: Discussionmentioning

confidence: 99%

Molecular diagnosis, genetic diversity and drug sensitivity patterns of Mycobacterium tuberculosis strains isolated from tuberculous meningitis patients at a tertiary care hospital in South India

Krishnakumariamma

Kalaiarasan

Muthuraj³

et al. 2020

PLoS ONE

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Tuberculous meningitis (TBM) is the most severe form of Mycobacterium tuberculosis (Mtb) infection in humans and is a public health concern worldwide. We evaluated the performance of GeneXpert MTB/RIF (GeneXpert) for the diagnosis of TBM. In addition, genetic diversity and drug susceptibility profiling of Mtb strains isolated from TBM patients were also investigated. A total of 293 TBM suspected cerebrospinal fluid (CSF) samples were collected and subjected to GeneXpert and Mycobacterial Growth Indicator Tube (MGIT 960) culture, respectively. Sensitivity and specificity of GeneXpert was 72.7% and 98.5%, respectively by using MGIT 960 as a gold standard (GeneXpert (n = 20, 6.8%) vs MGIT 960 (n = 22, 7.5%)). All Mtb positive cultures were subjected to 24-locus Mycobacterial Interspersed Repetitive Unit Variable Number Tandem Repeat (MIRU-VNTR) typing, Line probe assay (LPA) and MGIT 960-Drug Susceptibility Testing (DST). The rpoB gene was amplified and sequenced for selected isolates. Among our TBM patients, East African Indian (EAI) lineage (n = 16, 72.7%) was most predominant followed by Beijing (n = 3, 13.6%), Sfamily (n = 2, 9.1%) and Delhi/CAS (n = 1, 4.5%). Three Mtb strains were found to be Isoniazid (INH) resistant by MGIT 960; however LPA revealed that two strains were INH resistant and one strain was multi drug resistant (MDR) (Resistant to Isoniazid and Rifampicin (RIF)). We identified rifampicin resistant isolate with the mutation D516F in rifampicin resistancedetermining region (RRDR) and observed discordant results between LPA, GeneXpert and MGIT 960. In addition, GeneXpert showing false RIF resistance was identified (no mutation in RRDR). We conclude that GeneXpert is useful for the diagnostic confirmation of TBM; however a GeneXpert negative sample should be subjected to MGIT 960 culture or LPA to rule out TBM. EAI lineage was the most predominant among TBM patients in South India and associated with drug resistance. The discordance between GeneXpert, MGIT 960 and

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Clinical Impact on Tuberculosis Treatment Outcomes of Discordance Between Molecular and Growth-Based Assays for Rifampin Resistance, California 2003–2013

Cited by 27 publications

References 35 publications

A Comparison of the Sensititre MycoTB Plate, the Bactec MGIT 960, and a Microarray-Based Molecular Assay for the Detection of Drug Resistance in Clinical Mycobacterium tuberculosis Isolates in Moscow, Russia

A Comparison of the Sensititre MycoTB Plate, the Bactec MGIT 960, and a Microarray-Based Molecular Assay for the Detection of Drug Resistance in Clinical Mycobacterium tuberculosis Isolates in Moscow, Russia

Clinical implications of discrepant results between genotypic MTBDRplus and phenotypic Löwenstein-Jensen method for isoniazid or rifampicin drug susceptibility tests in tuberculosis patients

Molecular diagnosis, genetic diversity and drug sensitivity patterns of Mycobacterium tuberculosis strains isolated from tuberculous meningitis patients at a tertiary care hospital in South India

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