scholarly journals Multicenter Noninferiority Evaluation of Hain GenoType MTBDRplusVersion 2 and Nipro NTM+MDRTB Line Probe Assays for Detection of Rifampin and Isoniazid Resistance

2016 ◽  
Vol 54 (6) ◽  
pp. 1624-1630 ◽  
Author(s):  
Ruvandhi R. Nathavitharana ◽  
Doris Hillemann ◽  
Samuel G. Schumacher ◽  
Birte Schlueter ◽  
Nazir Ismail ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Phase 1 ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Phase 2 ◽  
Reference Standard ◽  
Two Phase ◽  
Mdr Tb ◽  
Resistance Detection

Less than 30% of multidrug-resistant tuberculosis (MDR-TB) patients are currently diagnosed, due to laboratory constraints. Molecular diagnostics enable rapid and simplified diagnosis. Newer-version line probe assays have not been evaluated against the WHO-endorsed Hain GenoType MTBDRplus(referred to as Hain version 1 [V1]) for the rapid detection of rifampin (RIF) and isoniazid (INH) resistance. A two-phase noninferiority study was conducted in two supranational reference laboratories to allow head-to-head comparisons of two new tests, Hain Genotype MTBDRplusversion 2 (referred to as Hain version 2 [V2]) and Nipro NTM+MDRTB detection kit 2 (referred to as Nipro), to Hain V1. In phase 1, the results for 379 test strains were compared to a composite reference standard that used phenotypic drug susceptibility testing (DST) and targeted sequencing. In phase 2, the results for 644 sputum samples were compared to a phenotypic DST reference standard alone. Using a challenging set of strains in phase 1, the values for sensitivity and specificity for Hain V1, Hain V2, and Nipro, respectively, were 90.3%/98.5%, 90.3%/98.5%, and 92.0%/98.5% for RIF resistance detection and 89.1%/99.4%, 89.1%/99.4%, and 89.6%/100.0% for INH resistance detection. Testing of sputa in phase 2 yielded values for sensitivity and specificity of 97.1%/97.1%, 98.2%/97.8%, and 96.5%/97.5% for RIF and 94.4%/96.4%, 95.4%/98.8%, and 94.9%/97.6% for INH. Overall, the rates of indeterminate results were low, but there was a higher rate of indeterminate results with Nipro than with Hain V1 and V2 in samples with low smear grades. Noninferiority of Hain V2 and Nipro to Hain V1 was demonstrated for RIF and INH resistance detection in isolates and sputum specimens. These results serve as evidence for WHO policy recommendations on the use of line probe assays, including the Hain V2 and Nipro assays, for MDR-TB detection.

scholarly journals Multicenter Study of the Accuracy of the BD MAX Multidrug-resistant Tuberculosis Assay for Detection of Mycobacterium tuberculosis Complex and Mutations Associated With Resistance to Rifampin and Isoniazid

2019 ◽  
Vol 71 (5) ◽  
pp. 1161-1167 ◽  
Author(s):  
Maunank Shah ◽  
Sonia Paradis ◽  
Joshua Betz ◽  
Natalie Beylis ◽  
Renu Bharadwaj ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Sensitivity And Specificity ◽  
High Sensitivity ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Sputum Smear ◽  
Smear Microscopy ◽  
Resistant Tuberculosis ◽  
Mdr Tb

Abstract Background Tuberculosis (TB) control is hindered by absence of rapid tests to identify Mycobacterium tuberculosis (MTB) and detect isoniazid (INH) and rifampin (RIF) resistance. We evaluated the accuracy of the BD MAX multidrug-resistant (MDR)-TB assay (BD MAX) in South Africa, Uganda, India, and Peru. Methods Outpatient adults with signs/symptoms of pulmonary TB were prospectively enrolled. Sputum smear microscopy and BD MAX were performed on a single raw sputum, which was then processed for culture and phenotypic drug susceptibility testing (DST), BD MAX, and Xpert MTB/RIF (Xpert). Results 1053 participants with presumptive TB were enrolled (47% female; 32% with human immunodeficiency virus). In patients with confirmed TB, BD MAX sensitivity was 93% (262/282 [95% CI, 89–95%]); specificity was 97% (593/610 [96–98%]) among participants with negative cultures on raw sputa. BD MAX sensitivity was 100% (175/175 [98–100%]) for smear-positive samples (fluorescence microscopy), and 81% (87/107 [73–88%]) in smear-negative samples. Among participants with both BD MAX and Xpert, sensitivity was 91% (249/274 [87–94%]) for BD MAX and 90% (246/274 [86–93%]) for Xpert on processed sputa. Sensitivity and specificity for RIF resistance compared with phenotypic DST were 90% (9/10 [60–98%]) and 95% (211/222 [91–97%]), respectively. Sensitivity and specificity for detection of INH resistance were 82% (22/27 [63–92%]) and 100% (205/205 [98–100%]), respectively. Conclusions The BD MAX MDR-TB assay had high sensitivity and specificity for detection of MTB and RIF and INH drug resistance and may be an important tool for rapid detection of TB and MDR-TB globally.

scholarly journals Rapid Molecular Diagnosis of Tuberculosis and Its Resistance to Rifampicin and Isoniazid with Automated MDR/MTB ELITe MGB® Assay

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 797
Author(s):  
Vichita Ok ◽  
Alexandra Aubry ◽  
Florence Morel ◽  
Isabelle Bonnet ◽  
Jérôme Robert ◽  
...  
Keyword(s):  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Clinical Samples ◽  
Great Promise ◽  
Routine Practice ◽  
Pcr Assay ◽  
Perfect Agreement ◽  
Mdr Tb ◽  
Good Agreement

The MDR/MTB ELITe MGB® kit (ELITech) carried on the ELITe InGenius® platform is a new real-time PCR assay allowing automated extraction and detection of DNA of the Mycobacterium tuberculosis complex (MTB) and mutations in the rpoB and katG genes and inhA promoter region (pro-inhA) associated to resistance to rifampicin and isoniazid, the two markers of multidrug-resistant TB (MDR). We assessed the performances of the test on a collection of strains (n = 54) and a set of clinical samples (n = 242) from routine practice, comparatively to TB diagnosis and genotypic drug susceptibility testing (gDST) as references. Regarding the 242 clinical samples, the sensitivity and specificity of MTB detection by ELITe were 90.9% and 97.5%, respectively. For the detection of resistance-conferring mutations on positive clinical samples, we observed perfect agreement with gDST for katG and pro-inhA (κ = 1.0) and two discordant results for rpoB (κ = 0.82). Considering the 54 cultured strains, very good agreement with gDST was observed for the detection of the 25 distinct mutations in rpoB, katG, and pro-inhA, (κ = 0.95, 0.88, and 0.95, respectively). In conclusion, the automated MDR/MTB ELITe MGB® assay shows great promise and appears to be a valuable tool for rapid detection of pre-MDR- and MDR-TB directly from clinical specimens.

scholarly journals Cost of illness of non-multidrug-resistant tuberculosis in Germany: an update

2020 ◽  
Vol 6 (4) ◽  
pp. 00329-2020
Author(s):  
Roland Diel ◽  
Albert Nienhaus
Keyword(s):  
Central Committee ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Current Therapy ◽  
Productivity Losses ◽  
Public Health Screening ◽  
Mdr Tb ◽  
The Mean ◽  
Mean Cost

BackgroundA total of 5429 new cases of tuberculosis (TB) were reported in Germany in 2018; out of the 3780 TB cases for whom drug susceptibility testing was available, the proportion of multidrug-resistant TB (MDR-TB) cases was only 3.1% (118 cases).MethodsOn the basis of the current therapy guidelines of the German Central Committee against Tuberculosis, this study estimates the mean direct outpatient and combined in- and outpatient costs per non-MDR-TB patient from the perspective of the German statutory health insurance (SHI) system, together with costs arising from productivity losses and costs due to public health screening for TB in close contacts.ResultsFrom the insurance perspective, the mean outpatient costs (rounded) per case were €1628 for adults and €1179 for children for standard therapy; the mean cost of inpatient treatment amounted to €8626. The mean combined inpatient/outpatient cost was €8756 for adults and €8512 for children. As 95% of all TB patients were adults, the weighted treatment cost per patient in Germany in 2018 was €8746. These are in addition to the mean cost arising from productivity losses (€1839) and, weighted by pulmonary infectivity, cost of contact investigations (€368), coming to a total of €10 953.ConclusionGiven the clear increase in the number of non-MDR-TB cases since 2015, TB is still a disease of significant economic impact in Germany.

scholarly journals Molecular characterisation of multidrug-resistantMycobacterium tuberculosisisolates from a high-burden tuberculosis state in Brazil

2019 ◽  
Vol 147 ◽  
Author(s):  
R. S. Salvato ◽  
S. Schiefelbein ◽  
R. B. Barcellos ◽  
B. M. Praetzel ◽  
I. S. Anusca ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Molecular Characterisation ◽  
Drug Resistant ◽  
Isoniazid Resistance ◽  
High Burden ◽  
Brics Countries ◽  
Mdr Tb

AbstractTuberculosis (TB) is the leading cause of death among infectious diseases worldwide. Among the estimated cases of drug-resistant TB, approximately 60% occur in the BRICS countries (Brazil, Russia, India, China and South Africa). Among Brazilian states, primary and acquired multidrug-resistant TB (MDR-TB) rates were the highest in Rio Grande do Sul (RS). This study aimed to perform molecular characterisation of MDR-TB in the State of RS, a high-burden Brazilian state. We performed molecular characterisation of MDR-TB cases in RS, defined by drug susceptibility testing, using 131Mycobacterium tuberculosis (M.tb)DNA samples from the Central Laboratory. We carried out MIRU-VNTR 24loci, spoligotyping, sequencing of thekatG,inhA andrpoB genes and RDRiosublineage identification. The most frequent families found were LAM (65.6%) and Haarlem (22.1%). RDRiodeletion was observed in 42 (32%) of theM.tbisolates. Among MDR-TB cases, eight (6.1%) did not present mutations in the studied genes. In 116 (88.5%)M.tbisolates, we found mutations associated with rifampicin (RIF) resistance inrpoB gene, and in 112 isolates (85.5%), we observed mutations related to isoniazid resistance inkatG andinhA genes. An insertion of 12 nucleotides (CCAGAACAACCC) at the 516 codon in therpoB gene, possibly responsible for a decreased interaction of RIF and RNA polymerase, was found in 19/131 of the isolates, belonging mostly to LAM and Haarlem families. These results enable a better understanding of the dynamics of transmission and evolution of MDR-TB in the region.

A Rapid and Accurate Detection Approach for Multidrug-Resistant Tuberculosis Based on PCR-ELISA Microplate Hybridization Assay

2020 ◽  
Vol 51 (6) ◽  
pp. 606-613
Author(s):  
Ye-Cheng Zhou ◽  
Shu-Mei He ◽  
Zi-Lu Wen ◽  
Jun-Wei Zhao ◽  
Yan-Zheng Song ◽  
...  
Keyword(s):  
Clinical Care ◽  
Pcr Amplification ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Hybridization Assay ◽  
Enzyme Linked Immunosorbent Assay ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

Abstract Rapid and accurate diagnosis of multidrug-resistant tuberculosis (MDR-TB) is important for timely and appropriate therapy. In this study, a rapid and easy-to-perform molecular test that integrated polymerase chain reaction (PCR) amplification and a specific 96-well microplate hybridization assay, called PCR-ELISA (enzyme-linked immunosorbent assay), were developed for detection of mutations in rpoB, katG, and inhA genes responsible for rifampin (RIF) and isoniazid (INH) resistance and prediction of drug susceptibility in Mycobacterium tuberculosis clinical isolates. We evaluated the utility of this method by using 32 multidrug-resistent (MDR) isolates and 22 susceptible isolates; subsequently, we compared the results with data obtained by conventional drug susceptibility testing and DNA sequencing. The sensitivity and specificity of the PCR-ELISA test were 93.7% and 100% for detecting RIF resistance, and 87.5% and 100% for detecting INH resistance, respectively. These results were comparable to those yielded by commercially available molecular tests such as the GenoType MTBDRplus assay. Based on the aforementioned results, we conclude that the PCR-ELISA microplate hybridization assay is a rapid, inexpensive, convenient, and reliable test that will be useful for rapid diagnosis of MDR-TB, for improved clinical care.

Multidrug-resistant tuberculosis in the Kharkiv Region, Ukraine

2020 ◽  
Vol 24 (5) ◽  
pp. 485-491
Author(s):  
D. Butov ◽  
C. Lange ◽  
J. Heyckendorf ◽  
I. Kalmykova ◽  
T. Butova ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Poor Treatment ◽  
Mdr Tb ◽  
Observational Cohort

OBJECTIVE: To document the level of drug resistance in MDR-TB patients and to characterize management capacities for their medical care and MDR-TB treatment outcomes in the Kharkiv region of Ukraine. This area has one of the highest frequencies of MDR-TB worldwide.METHODS: A retrospective observational cohort study was performed on registry data from the regional anti-TB dispensary in Kharkiv. All microbiologically confirmed MDR-TB patients registered in 2014 were included. Diagnostic, treatment and post-treatment follow-up data were analysed.RESULTS: Of 169 patients with MDR-TB, 55.0% had pre-extensively drug-resistant (pre-XDR) or XDR resistant patterns. Rapid molecular diagnosis by GeneXpert and liquid M. tuberculosis cultures were only available for 66.9% and 56.8% of patients, respectively. Phenotypic drug-susceptibility testing (DST) for high priority TB drugs (bedaquiline, linezolid, clofazimine) were not available. DST for later generation fluroquinolones was available only in 53.2% of patients. 50.9% of patients had less than 4 drugs in the treatment regimen proven to be effective by DST. More than 23.1% of patients with MDR-TB failed their treatment and only 45.0% achieved a cure.CONCLUSION: The high prevalence of MDR-TB and poor MDR-TB treatment outcomes in the Kharkiv region, is associated with substantial shortages in rapid molecular and phenotypic DST, a lack of high priority MDR-TB drugs, poor treatment monitoring and follow-up capacities.

scholarly journals Assessing spatiotemporal patterns of multidrug-resistant and drug-sensitive tuberculosis in a South American setting

2010 ◽  
Vol 139 (11) ◽  
pp. 1784-1793 ◽  
Author(s):  
H. LIN ◽  
S. SHIN ◽  
J. A. BLAYA ◽  
Z. ZHANG ◽  
P. CEGIELSKI ◽  
...  
Keyword(s):  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Urban Setting ◽  
South American ◽  
Resistant Disease ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Incident Cases

SUMMARYWe examined the spatiotemporal distribution of laboratory-confirmed multidrug-resistant tuberculosis (MDR TB) cases and that of other TB cases in Lima, Peru with the aim of identifying mechanisms responsible for the rise of MDR TB in an urban setting. All incident cases of TB in two districts of Lima, Peru during 2005–2007 were included. The spatiotemporal distributions of MDR cases and other TB cases were compared with Ripley's K statistic. Of 11 711 notified cases, 1187 received drug susceptibility testing and 376 were found to be MDR. Spatial aggregation of patients with confirmed MDR disease appeared similar to that of other patients in 2005 and 2006; however, in 2007, cases with confirmed MDR disease were found to be more tightly grouped. Subgroup analysis suggests the appearance of resistance may be driven by increased transmission. Interventions should aim to reduce the infectious duration for those with drug-resistant disease and improve infection control.

scholarly journals Mycobacterium Tuberculosis Strain Lineage in Mixed Tribal Population Across India and Andaman Nicobar Island

2021 ◽  
Author(s):  
Azger Dusthackeer V. N. ◽  
Azger Dusthackeer V. N. ◽  
Ashok Kumar ◽  
Kannappan Kannappan Sucharitha ◽  
S. Shivakumar ◽  
...  
Keyword(s):  
Small Sample Size ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Small Sample ◽  
Clinical Isolates ◽  
Nicobar Island ◽  
Tribal Population ◽  
Indian States ◽  
Mdr Tb

Abstract In India, the tribal population constitutes almost 8.6% of the nation’s total population. This study attempts to provide information pertaining to the TB strain diversity, its public health implications, and distribution among the tribal population in 10 Indian states and Andaman & Nicobar (A&N) Island. Clinical isolates were received from 66 villages (10 states and island). A total of 78 M. tuberculosis clinical isolates were received from 10 different states and A&N Island. Among these, 16 different strains were observed. The major M. tuberculosis strains spoligotype belong to the Beijing, CAS1_DELHI, and EAI5 family followed by EAI1_SOM, EAI6_BGD1, LAM3, LAM6, LAM9, T1, T2, U strains. Drug-susceptibility testing (DST) results showed almost 15.4% of clinical isolates found to be resistant to isoniazid (INH) or rifampicin (RMP) + INH. Predominant multidrug-resistant tuberculosis (MDR-TB) isolates seem to be Beijing strain. Beijing, CAS1_DELHI, EAI3_IND, and EAI5 were the principal strains infecting mixed tribal populations across India. Despite the small sample size, this study has demonstrated higher diversity among the TB strains with significant MDR-TB findings. Prevalence of Beijing MDR-TB strains in Central, Southern, Eastern India and A&N Island indicates the transmission of the TB strains.

scholarly journals Clinical evaluation of the Xpert MTB/XDR assay for rapid detection of isoniazid, fluoroquinolone, ethionamide and second-line drug resistance: A cross-sectional multicentre diagnostic accuracy study

2021 ◽  
Author(s):  
Adam Penn-Nicholson ◽  
Sophia B Georghiou ◽  
Nelly Ciobanu ◽  
Mubin Kazi ◽  
Manpreet Bhalla ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Diagnostic Accuracy ◽  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Foreign Affairs ◽  
Second Line ◽  
Reference Standard ◽  
Composite Reference Standard ◽  
Resistance Detection

Background The WHO End TB Strategy requires universal drug susceptibility testing and treatment of all people with tuberculosis. However, available second-line diagnostic tools are cumbersome and require sophisticated laboratory infrastructure, and ultimately less than half of those with drug-resistant tuberculosis receive appropriate treatment. Xpert MTB/XDR was developed to help overcome these limitations. Methods We assessed the diagnostic accuracy of sputum-based Xpert MTB/XDR for isoniazid, fluoroquinolone, ethionamide and second-line injectable resistance detection in adults with an Xpert MTB/RIF or Ultra Mycobacterium tuberculosis-positive result against a composite reference standard of phenotypic drug-susceptibility testing and whole genome sequencing (NCT03728725). Participants with pulmonary tuberculosis symptoms and ≥1 risk factor for drug resistance were consecutively enrolled between four clinical sites in India, Moldova and South Africa. Findings Between 31 July 2019 and 21 March 2020, we enrolled 710 patients, of which 611 (86.1%) had results from index and composite reference standard tests and were included in analysis. The sensitivity of Xpert MTB/XDR was 94% for isoniazid, 95% for fluoroquinolones, 54% for ethionamide, 73% for amikacin, 86% for kanamycin, and 61% for capreomycin resistance detection. Specificity was 98-100% for all drugs. Performance was equivalent to line-probe assays. The non-determinate rate of Xpert MTB/XDR was 2.96%. Interpretation This first prospective, multicentre clinical study of the Xpert MTB/XDR assay demonstrated high diagnostic test accuracy, meeting target product profile criteria for a next-generation drug susceptibility test. Funding German Federal Ministry of Education and Research through KfW, Dutch Ministry of Foreign Affairs, and Australian Department of Foreign Affairs and Trade.

scholarly journals MIC of Delamanid (OPC-67683) against Mycobacterium tuberculosis Clinical Isolates and a Proposed Critical Concentration

2016 ◽  
Vol 60 (6) ◽  
pp. 3316-3322 ◽  
Author(s):  
Kelly Stinson ◽  
Natalia Kurepina ◽  
Amour Venter ◽  
Mamoru Fujiwara ◽  
Masanori Kawasaki ◽  
...  
Keyword(s):  
South Africa ◽  
Pathogenic Bacteria ◽  
Critical Concentration ◽  
Drug Susceptibility Testing ◽  
Clinical Isolates ◽  
Pharmacokinetic Data ◽  
Phase 2 ◽  
The European Union ◽  
Two Phase ◽  
Mdr Tb

The increasing global burden of multidrug-resistant tuberculosis (MDR-TB) requires reliable drug susceptibility testing that accurately characterizes susceptibility and resistance of pathogenic bacteria to effectively treat patients with this deadly disease. Delamanid is an anti-TB agent first approved in the European Union in 2014 for the treatment of pulmonary MDR-TB in adults. Using the agar proportion method, delamanid MIC was determined for 460 isolates: 316 from patients enrolled in a phase 2 global clinical trial, 76 from two phase 2 early bactericidal activity trials conducted in South Africa, and 68 isolates obtained outside clinical trials (45 from Japanese patients and 23 from South African patients). With the exception of two isolates, MICs ranged from 0.001 to 0.05 μg/ml, resulting in an MIC50of 0.004 μg/ml and an MIC90of 0.012 μg/ml. Various degrees of resistance to other anti-TB drugs did not affect the distribution of MICs, nor did origin of isolates from regions/countries other than South Africa. A critical concentration/breakpoint of 0.2 μg/ml can be used to define susceptible and resistant isolates based on the distribution of MICs and available pharmacokinetic data. Thus, clinical isolates from delamanid-naive patients with tuberculosis have a very low MIC for delamanid and baseline resistance is rare, demonstrating the potential potency of delamanid and supporting its use in an optimized background treatment regimen for MDR-TB.

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