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 Molecular Detection of Mutations Associated with First- and Second-Line Drug Resistance Compared with Conventional Drug Susceptibility Testing of Mycobacterium tuberculosis

2011 ◽  
Vol 55 (5) ◽  
pp. 2032-2041 ◽  
Author(s):  
Patricia J. Campbell ◽  
Glenn P. Morlock ◽  
R. David Sikes ◽  
Tracy L. Dalton ◽  
Beverly Metchock ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Dna Sequencing ◽  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Second Line ◽  
First Line ◽  
Content Type ◽  
Line Drug

ABSTRACTThe emergence of multi- and extensively drug-resistant tuberculosis is a significant impediment to the control of this disease because treatment becomes more complex and costly. Reliable and timely drug susceptibility testing is critical to ensure that patients receive effective treatment and become noninfectious. Molecular methods can provide accurate and rapid drug susceptibility results. We used DNA sequencing to detect resistance to the first-line antituberculosis drugs isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB) and the second-line drugs amikacin (AMK), capreomycin (CAP), kanamycin (KAN), ciprofloxacin (CIP), and ofloxacin (OFX). Nine loci were sequenced:rpoB(for resistance to RIF),katGandinhA(INH),pncA(PZA),embB(EMB),gyrA(CIP and OFX), andrrs,eis, andtlyA(KAN, AMK, and CAP). A total of 314 clinicalMycobacterium tuberculosiscomplex isolates representing a variety of antibiotic resistance patterns, genotypes, and geographical origins were analyzed. The molecular data were compared to the phenotypic data and the accuracy values were calculated. Sensitivity and specificity values for the first-line drug loci were 97.1% and 93.6% forrpoB, 85.4% and 100% forkatG, 16.5% and 100% forinhA, 90.6% and 100% forkatGandinhAtogether, 84.6% and 85.8% forpncA, and 78.6% and 93.1% forembB. The values for the second-line drugs were also calculated. The size and scope of this study, in numbers of loci and isolates examined, and the phenotypic diversity of those isolates support the use of DNA sequencing to detect drug resistance in theM. tuberculosiscomplex. Further, the results can be used to design diagnostic tests utilizing other mutation detection technologies.

scholarly journals A Multimethod, Multicountry Evaluation of Breakpoints for Bedaquiline Resistance Determination

2020 ◽  
Vol 64 (9) ◽  
Author(s):  
Nazir Ahmed Ismail ◽  
Akio Aono ◽  
Emanuele Borroni ◽  
Daniela Maria Cirillo ◽  
Christel Desmaretz ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Drug Resistant ◽  
Reference Standard ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Cutoff Value ◽  
Resistant Tuberculosis ◽  
Composite Reference Standard

ABSTRACT Criteria defining bedaquiline resistance for tuberculosis have been proposed addressing an emerging concern. We evaluated bedaquiline phenotypic drug susceptibility testing (pDST) criteria using drug-resistant tuberculosis clinical isolates tested at five reference laboratories. Isolates were tested at the proposed bedaquiline MGIT960 and 7H11 agar proportion (AP) critical concentrations and also at higher dilutions. The epidemiological cutoff value for the broth microdilution (BMD) plates (frozen and dry) was investigated. Sanger sequencing was performed (atpE and Rv0678 genes) for any isolate testing resistant. The composite reference standard (CRS) defined susceptibility or resistance as is if all pDST methods agreed. If the pDST result was discordant, sequencing results were used for final classification. Geographically diverse and bedaquiline-unexposed isolates were tested (n = 495). The epidemiological cutoff value for BMD was confirmed to be 0.12 μg/ml. The majority of isolates were determined to be susceptible by all methods (467/495; 94.3%), and 28 were determined to be resistant by at least one method; 4 of these were determined to be resistant by all methods. Of the 28 resistant isolates, 12 harbored Rv0678 mutations exclusively. Isolates with insertions/deletions were more likely to be determined to be resistant by more than one method (5/7) compared to isolates with a single nucleotide polymorphism (1/5). Applying the CRS to 24 discordant pDST, BMD dry correctly detected most (15/24; 63%), followed by MGIT960 and BMD frozen (13/24; 61%) and lastly AP (12/24; 50%). Applying the CRS, the prevalence of bedaquiline resistance was 2.2% and ranged from 1.4 to 3.4%, depending on the method used. All methods performed well for bedaquiline susceptibility determination; however, resistance detected should be investigated by a second, alternative method.

scholarly journals Prevalence of Pre - Extensively Drug Resistance Tuberculosis (Pre XDR-TB) & Extensively Drug Resistance Tuberculosis (XDR-TB) among Pulmonary Multidrug Resistance Tuberculosis at a Tertiary Care Hospital, Jamnagar

2019 ◽  
pp. 1-9
Author(s):  
Dipali Gavali ◽  
Binita Aring ◽  
Hiral Gadhavi ◽  
Akhlakahemad Nathamehta ◽  
Abhishek Dave ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Care Hospital ◽  
Second Line ◽  
Testing Laboratory ◽  
High Prevalence ◽  
Mdr Tb ◽  
Extensively Drug Resistance

Aims and Objective: Many diseases have a high prevalence in India, accounting for one-fourth of the Tuberculosis (TB) cases in the world. In our study, we aimed to find the prevalence of Pre XDR-TB and XDR-TB amongst newly diagnosed cases of pulmonary MDR-TB who had never been previously treated with second-line drugs. A prospective study was conducted in Culture and Drug susceptibility testing laboratory, Jamnagar and its associated Drug-Resistant Tuberculosis (DR-TB) centre. Materials and Methods: Baseline second-line liquid culture DST has been recently integrated with the Revised National Tuberculosis Control Programme (RNTCP) diagnostic algorithm. We included 500 patients who were diagnosed in cases of pulmonary MDR-TB never exposed to second-line TB-Drugs. Mycobacterial Growth Indicator Tube method conducted in an RNTCP accredited Culture and Drug susceptibility testing laboratory, Jamnagar, as part of the evaluation in the public healthcare system from where patients were referred for diagnosis to us. Results: 585 MDR suspected sputum samples were received, 466 sputum samples were showing culture positive for acid-fast bacilli which were screened against second-line drug susceptibility testing by using of BACTEC MGIT 960 (MGIT 960) instrument. About 293 Mycobacterium samples were MDR-TB, 151 were Pre- XDR TB and 22 were XDR-TB. Conclusion: The prevalence of Pre XDR-TB and XDR-TB among MDR-TB patients were 32.4% and 4.7% respectively. The high prevalence of Pre XDR-TB (FQ) is alarming and of concern in the management of MDR-TB control in Jamnagar area.

scholarly journals Comparison of the Performances of Two In-House Rapid Methods for Antitubercular Drug Susceptibility Testing

2008 ◽  
Vol 53 (2) ◽  
pp. 808-810 ◽  
Author(s):  
Agustina I. de la Iglesia ◽  
Emma J. Stella ◽  
Héctor R. Morbidoni
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Sensitivity And Specificity ◽  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Antitubercular Drug ◽  
Rapid Methods ◽  
Resistance Assessment

ABSTRACT Resistance to rifampin (rifampicin), isoniazid, and streptomycin of 69 Mycobacterium tuberculosis isolates was analyzed by an in-house method based on mycobacteriophage D29 and a colorimetric micromethod. Both methods showed sensitivity and specificity values ranging from 93% to 100%. These simple methods offer an option for drug resistance assessment of M. tuberculosis.

scholarly journals Low Occurrence of Tuberculosis Drug Resistance among Pulmonary Tuberculosis Patients from an Urban Setting, with a Long-Running DOTS Program in Zambia

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Chanda Mulenga ◽  
Allan Chonde ◽  
Innocent C. Bwalya ◽  
Nathan Kapata ◽  
Mathilda Kakungu-Simpungwe ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Urban Setting ◽  
Second Line ◽  
Community Based ◽  
Proportion Method ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Low Levels

We set out to determine the levels ofMycobacterium tuberculosisresistance to first- and second-line TB drugs in an urban population in Zambia. Sputum samples were collected consecutively from all smear-positive, new and previously treated patients, from four diagnostic centres in Ndola between January and July 2006. Drug susceptibility testing was performed using the proportion method against four first- and two second-line TB drugs.Results. Among 156 new cases, any resistance was observed to be 7.7%, monoresistance to isoniazid and rifampicin was 4.5% and 1.3%, respectively. Of 31 retreatment cases, any resistance was observed to be 16.1%, monoresistance to isoniazid and rifampicin was 3.3% for each drug, and one case of resistance to both isoniazid and rifampicin (multidrug resistance) was detected. No resistance to kanamycin or ofloxacin was detected.Conclusion. Although not representative of the country, these results show low levels of drug resistance in a community with a long-standing DOTS experience. Resource constrained countries may reduce TB drug resistance by implementing community-based strategies that enhance treatment completion.

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