scholarly journals Drug resistance mechanisms and drug susceptibility testing for tuberculosis

Respirology ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 1098-1113 ◽  
Author(s):  
Paolo Miotto ◽  
Ying Zhang ◽  
Daniela Maria Cirillo ◽  
Wing Cheong Yam
Keyword(s):  
Drug Resistance ◽  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Resistance Mechanisms ◽  
Drug Susceptibility Testing

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 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.

Resistance mechanisms and drug susceptibility testing of nontuberculous mycobacteria

2012 ◽  
Vol 15 (3) ◽  
pp. 149-161 ◽  
Author(s):  
Jakko van Ingen ◽  
Martin J. Boeree ◽  
Dick van Soolingen ◽  
Johan W. Mouton
Keyword(s):  
Susceptibility Testing ◽  
Nontuberculous Mycobacteria ◽  
Drug Susceptibility ◽  
Resistance Mechanisms ◽  
Drug Susceptibility Testing

scholarly journals Anti-tuberculosis Drug Resistance Pattern among Different Category of Tuberculosis Patients

1970 ◽  
Vol 10 (2) ◽  
pp. 45-47 ◽  
Author(s):  
Mostafizur Rahman ◽  
SM Mostafa Kamal ◽  
Fazle Rabbi Mohammed ◽  
Md Billal Alam ◽  
HAM Nazmul Ahasan
Keyword(s):  
Drug Resistance ◽  
Susceptibility Testing ◽  
Absolute Number ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Therapeutic Interventions ◽  
Multi Drug Resistance ◽  
Resistance Pattern ◽  
Drug Resistance Pattern ◽  
Mdr Tb

Background: Anti-Tuberculosis (TB) drug resistance is emerging as a new global health problem. No national data on drug resistance is available in Bangladesh. The absolute number of multidrug resistant TB (MDR-TB) is expected to be high considering high TB burden. This study was aimed to determine the resistance pattern of mycobacterium tuberculosis (MTB) isolates among different category of patient. Method: A total 1123 randomly selected patients having clinical and or radiological features of tuberculosis attending out patients department of NIDCH were enrolled in this study during January to December, 2008. Sputum were collected and processed for culture by digestion, decontamination and concentration following modified Petroff's method and were inoculated on to two slopes of Lowenstein- Jensen (L-J) media for six weeks. The identity of the isolates was made by growth rate, colony morphology, P-nitrobenzoic acid (PNB) susceptibility, catalase and nitrate reduction tests. Ultimately drug susceptibility testing (DST) were performed. Result: Drug susceptibility testing for Isoniazid (INH), Rifampicin (RIF), Ethambutol (EMB) and Streptomycin (SM) was done among 363 cases. Resistance rates for INH, RIF, EMB and SM were 76.03%, 71.63%, 27.55% and 55.65% respectively. According to DST report, total 221 cases were detected as multi drug resistant TB (MDR-TB). Among them, 87% cases were MDR-TB in category II (CAT - II) failure and 13% were MDR-TB in category I (CAT - I) failure and it was 0% in new cases. Conclusion: Pattern of anti TB drug resistance was identified in this study. More surveillance and immediate therapeutic interventions should be performed in order to combat the threat of MDR-TB to the general population. Keywords: Tuberculosis, Multi drug resistance, Drug susceptibility testing.   doi: 10.3329/jom.v10i2.2812 J MEDICINE 2009; 10 : 45-47

scholarly journals Mortality of Drug-resistant Tuberculosis in High-burden Countries: Comparison of Routine Drug Susceptibility Testing with Whole-genome Sequencing

2020 ◽  
Author(s):  
Martina L. Reichmuth ◽  
Kathrin Zürcher ◽  
Marie Ballif ◽  
Chloé Loiseau ◽  
Sonia Borrell ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Whole Genome ◽  
Drug Resistant ◽  
Hiv Status ◽  
High Burden

AbstractBackgroundDrug-resistant Mycobacterium tuberculosis (Mtb) strains threaten tuberculosis (TB) control. We compared data on drug resistance obtained at clinics in seven high TB burden countries during routine care with whole-genome sequencing (WGS) carried out centrally.MethodsWe collected pulmonary Mtb isolates and clinical data from adult TB patients in Africa, Latin America, and Asia, stratified by HIV status and drug resistance, from 2013 to 2016. Participating sites performed drug susceptibility testing (DST) locally, using routinely available methods. WGS was done using Illumina HiSeq 2500 at laboratories in the USA and Switzerland. We used TBprofiler to analyse the genomes. We used multivariable logistic regression adjusted for sex, age, HIV-status, history of TB, sputum positivity, and Mtb-lineage to analyse mortality.FindingsWe included 582 TB patients. The median age was 32 years (interquartile range: 27-43 years), 225 (39%) were female, and 247 (42%) were HIV-positive. Based on WGS, 339 (58%) isolates were pan-susceptible, 35 (6%) monoresistant, 146 (25%) multidrug-resistant, and 24 (4%) pre-/ extensively drug-resistant (pre-XDR/XDR-TB). The local DST results were discordant compared to WGS results in 130/582 (22%) of patients. All testing methods identified isoniazid and rifampicin resistance with relatively high agreement (kappa 0.69 for isoniazid and 0.88 rifampicin). Resistance to ethambutol, pyrazinamide, and second-line drugs was rarely tested locally. Of 576 patients with known treatment, 86 (15%) patients received inadequate treatment according to WGS results and the World Health Organization treatment guidelines. The analysis of mortality was based on 530 patients; 63 patients (12%) died and 77 patients (15%) received inadequate treatment. Mortality ranged from 6% in patients with pan-susceptible Mtb (18/310) to 39% in patients with pre-XDR/XDR-TB (9/23). The adjusted odds ratio for mortality was 4.82 (95% CI 2.43-9.44) for under-treatment and 0.52 (95% CI 0.03-2.73) for over-treatment.InterpretationIn seven high-burden TB countries, we observed discrepancies between drug resistance patterns from local DST and WGS, which resulted in inadequate treatment and higher mortality. WGS can provide accurate and detailed drug resistance information, which is required to improve the outcomes of drug-resistant TB in high burden settings. Our results support the WHO’s call for point-of-care tests based on WGS.

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 Impact of Drug Susceptibility Testing on Drug Choice in a Tuberculosis Cohort With High Rates of Drug Resistance From the Private Sector in Mumbai

2016 ◽  
Vol 3 (suppl_1) ◽  
Author(s):  
Zarir F Udwadia ◽  
Jeffrey A. Tornheim ◽  
Shashank Ganatra ◽  
Andrea Deluca ◽  
Radhika Banka ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Private Sector ◽  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Drug Choice
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