scholarly journals Inquiry into GeneXpert as a complementary MDR-TB diagnostic tool in North Korea: A follow-up study of North Korean TB drug resistance patterns

2021 ◽  
Author(s):  
Noori Lee ◽  
Hojeong Kwon ◽  
Yoohyun Hwang ◽  
Sungweon Ryoo
Keyword(s):  
Drug Resistance ◽  
Diagnostic Tool ◽  
North Korea ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Diagnostic Tools ◽  
The North ◽  
Resistance Patterns ◽  
Mdr Tb

Abstract Background: This study aims to investigate the usefulness of GeneXpert MTB/RIF (Xpert) in diagnosing rifampicin (RIF) resistance among the patients in the secluded sanatoria of North Korea. This article is a follow up of a report that explored the characteristics of drug resistance in North Korean Sanatoria, published in 2017. Xpert is used as a diagnostic tool to check for multidrug-resistant tuberculosis (MDR-TB) in specific areas of North Korea by the Eugene Bell Foundation (EBF). While there are other diagnostic tools are used to test for RIF resistance, there is no other feasible method to consistently test for MDR-TB in North Korea. Currently, EBF exclusively uses Xpert in tuberculosis and RIF resistance diagnosis when providing medical support for tuberculosis patients in North Korea, where there is limited international access. Methods: We performed Xpert using cultured tuberculous bacilli of North Koreans and compared the result to the corresponding phenotypic drug susceptibility tests (pDST) and rifampicin resistant-determining region sequencing (RRDR). All samples were target-sequenced at the rpoB region, where unique RIF resistance related mutations, potentially specific to North Korea, were discovered.Results: Using the RRDR sequencing as the gold standard, Xpert’s sensitivity and specificity was 94.9% and 88.0%, respectively. In addition, we discovered several rare or novel mutations among the North Korean Mycobacterium tuberculosis isolates.Conclusions: RIF detection in North Korea is possible using Xpert as an alternative to pDST, as this research has shown. This research is not only imperative to North Korea, but also in locations where there is limited access to conventional pDST.

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 Prevalence of Extensively Drug Resistant Tuberculosis among Archived Multidrug Resistant Tuberculosis Isolates in Zimbabwe

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Tichaona Sagonda ◽  
Lucy Mupfumi ◽  
Rumbidzai Manzou ◽  
Beauty Makamure ◽  
Mqondisi Tshabalala ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Drug Resistance ◽  
Multidrug Resistant ◽  
Cross Sectional Study ◽  
Second Line ◽  
Cross Sectional ◽  
Resistant Tuberculosis ◽  
Resistance Patterns ◽  
Mdr Tb ◽  
Definition Of

We conducted a cross-sectional study of second line drug resistance patterns and genetic diversity of MDR-TB isolates archived at the BRTI-TB Laboratory, Harare, between January 2007 and December 2011. DSTs were performed for second line antituberculosis drugs. XDR-TB strains were defined as MDR-TB strains with resistance to either kanamycin and ofloxacin or capreomycin and ofloxacin. Strain types were identified by spoligotyping. No resistance to any second line drugs was shown in 73% of the isolates, with 23% resistant to one or two drugs but not meeting the definition of XDR-TB. A total of 26 shared types were identified, and 18 (69%) matched preexisting shared types in the current published spoligotype databases. Of the 11 out of 18 clustered SITs, 4 predominant (>6 isolates per shared type) were identified. The most and least abundant types were SIT 1468 (LAM 11-ZWE) with 12 (18%) isolates and SIT 53 (T1) with 6 (9%) isolates, respectively. XDR-TB strains are rare in Zimbabwe, but the high proportion of “pre-XDR-TB” strains and treatment failure cases is of concern. The genetic diversity of the MDR-TB strains showed no significant association between SITs and drug resistance.

Molecular Characterization of Levofloxacin, Moxifloxacin, Bedaquiline, Linezolid, Clofazimine, and Delamanid against Multidrug-resistant Tuberculosis in Southwest of China

2021 ◽  
Author(s):  
Huiwen Zheng ◽  
Wencong He ◽  
Weiwei Jiao ◽  
Hui Xia ◽  
Lin Sun ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Southwest China ◽  
Resistance Mutation ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Resistance Rate ◽  
Genetic Characteristics ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

Abstract Objectives: To explore the drug susceptibility of levofloxacin (LFX), moxifloxacin (MFX), bedaquiline (BDQ), linezolid (LZD), clofazimine (CFZ) and delamanid (DLM) against multidrug resistant tuberculosis (MDR-TB) isolates from drug resistance survey of southwest China, and to illustrate the genetic characteristics of MDR-TB isolates with acquired drug resistance. Methods: A total of 339 strains were collected from smear-positive TB patients in the drug resistance survey of southwest China between January 2014 and December 2016. The MICs were determined for MDR-TB identified by conventional drug susceptibility testing. Genes related to drug resistance were amplified with their corresponding pairs of primers. Results: MDR was observed in 88 (26.0%; 88/339) isolates. LFX had the highest resistance rate (50.0%; 44/88), followed by MFX (38.6%; 34/88). The resistance rate to LZD, CFZ, and DLM was 4.5% (4/88), 3.4% (3/88), and 4.5% (4/88), respectively, and the lowest resistance rate was observed in BDQ (2.3%; 2/88). Of the 45 isolates resistant to LFX and MFX, the most prevalent resistance mutation was found in gyrA with the substitution of codon 94 (34/45, 75.6%). All two CFZ - BDQ cross resistant strains had a mutation in the Rv0678 gene. Two of four LZD resistant isolates carried mutations in rplC gene. Of the four isolates resistant to DLM, one isolate with the mutations in codon 318 of fbiC gene and two isolates in codon 81 of ddn gene. Conclusion: This study provided evidence for further application of new anti-TB drugs in the treatment of MDR-TB in China.

scholarly journals Diagnostic Value of GeneChip for Detection of Resistant Mycobacterium tuberculosis in Patients with Differing Treatment Histories

2014 ◽  
Vol 53 (1) ◽  
pp. 131-135 ◽  
Author(s):  
Limei Zhu ◽  
Qiao Liu ◽  
Leonardo Martinez ◽  
Jinyan Shi ◽  
Cheng Chen ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Diagnostic Value ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Standard Drug ◽  
Related Data ◽  
Resistant Tuberculosis ◽  
Mdr Tb ◽  
Previously Treated

The increasing burden of drug-resistant tuberculosis (TB) poses an escalating threat to national TB control programs. To assist appropriate treatment for TB patients, accurate and rapid detection of drug resistance is critical. The GeneChip test is a novel molecular tool for the diagnosis of TB drug resistance. Performance-related data on GeneChip are limited, and evaluation in new and previously treated TB cases has never been performed. We evaluated the diagnostic performance of GeneChip in detecting resistance to rifampin (RMP) and isoniazid (INH) and in detecting multidrug-resistant tuberculosis (MDR-TB) in comparison with standard drug susceptibility testing (DST) and compared the results in a group of previously treated and newly detected TB patients in an urban area in southeastern China. One thousand one hundred seventy-three (83.8%) new cases and 227 (16.2%) previously treated cases were collected between January 2011 and September 2013. The GeneChip showed a specificity of 97.8% and a sensitivity of 94.8% for detection of RMP resistance and 97.3% and 70.9%, respectively, for INH resistance in new cases. For previously treated cases, the overall sensitivity, specificity, and agreement rate are 94.6%, 91.3%, and 92.1%, respectively, for detection of RMP resistance and 69.7%, 95.4%, and 86.8%, respectively, for INH resistance. The sensitivity and specificity of MDR-TB were 81.8% and 99.0% in new cases and 77.8% and 93.4% in previously treated cases, respectively. The GeneChip system provides a simple, rapid, reliable, and accurate clinical assay for the detection of TB drug resistance, and it is a potentially important diagnostic tool in a high-prevalence area.

scholarly journals Transmission patterns of rifampicin resistant Mycobacterium tuberculosis complex strains in Cameroon: a genomic epidemiological study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Matthias Merker ◽  
Nkongho F. Egbe ◽  
Yannick R. Ngangue ◽  
Comfort Vuchas ◽  
Thomas A. Kohl ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Prolonged Exposure ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
High Dose ◽  
Factors Affecting ◽  
Recent Transmission ◽  
Mdr Tb

Abstract Background Determining factors affecting the transmission of rifampicin (RR) and multidrug-resistant (MDR) Mycobacterium tuberculosis complex strains under standardized tuberculosis (TB) treatment is key to control TB and prevent the evolution of drug resistance. Methods We combined bacterial whole genome sequencing (WGS) and epidemiological investigations for 37% (n = 195) of all RR/MDR-TB patients in Cameroon (2012–2015) to identify factors associated with recent transmission. Results Patients infected with a strain resistant to high-dose isoniazid, and ethambutol had 7.4 (95% CI 2.6–21.4), and 2.4 (95% CI 1.2–4.8) times increased odds of being in a WGS-cluster, a surrogate for recent transmission. Furthermore, age between 30 and 50 was positively correlated with recent transmission (adjusted OR 3.8, 95% CI 1.3–11.4). We found high drug-resistance proportions against three drugs used in the short standardized MDR-TB regimen in Cameroon, i.e. high-dose isoniazid (77.4%), ethambutol (56.9%), and pyrazinamide (43.1%). Virtually all strains were susceptible to fluoroquinolones, kanamycin, and clofazimine, and treatment outcomes were mostly favourable (87.5%). Conclusion Pre-existing resistance to high-dose isoniazid, and ethambutol is associated with recent transmission of RR/MDR strains in our study. A possible contributing factor for this observation is the absence of universal drug susceptibility testing in Cameroon, likely resulting in prolonged exposure of new RR/MDR-TB patients to sub-optimal or failing first-line drug regimens.

scholarly journals Comparative Utility of Genetic Determinants of Drug Resistance and Phenotypic Drug Susceptibility Profiling in Predicting Clinical Outcomes in Patients With Multidrug-Resistant Mycobacterium tuberculosis

2021 ◽  
Vol 9 ◽  
Author(s):  
Yang Che ◽  
Tianchi Yang ◽  
Lv Lin ◽  
Yue Xiao ◽  
Feng Jiang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Latent Class ◽  
Treatment Success ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Sputum Smear ◽  
Genetic Determinants ◽  
Resistant Tuberculosis ◽  
Mdr Tb

Setting: Programmatic management of drug-resistant tuberculosis in Ningbo, China.Objective: To assess whether data-driven genetic determinants of drug resistance patterns could outperform phenotypic drug susceptibility testing in predicting clinical meaningful outcomes among patients with multidrug-resistant tuberculosis (MDR-TB).Design: We conducted a prospective cohort study of 104 MDR-TB patients. All MDR-TB isolates underwent drug susceptibility testing and genotyping for mutations that could cause drug resistance. Study outcomes were time to sputum smear conversion and probability of treatment success, as well as time to culture conversion within 6 months. Data were analyzed using latent class analysis, Kaplan–Meier curves, and Cox regression models.Results: We report that latent class analysis of data identified two latent classes that predicted sputum smear conversion with P = 0.001 and area under receiver-operating characteristic curve of 0.73. The predicted latent class memberships were associated with superior capability in predicting sputum culture conversion at 6 months and overall treatment success compared to phenotypic drug susceptibility profiling using boosted logistic regression models.Conclusion: These results suggest that genetic determinants of drug resistance in combination with phenotypic drug-resistant tests could serve as useful biomarkers in predicting treatment prognosis in MDR-TB.

scholarly journals A Systematic Follow-Up ofMycobacterium tuberculosisDrug-Resistance and Associated Genotypic Lineages in the French Departments of the Americas over a Seventeen-Year Period

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Julie Millet ◽  
Elisabeth Streit ◽  
Mylène Berchel ◽  
Anne-Gaël Bomer ◽  
Franziska Schuster ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Latin American ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
Incidence Rates ◽  
Drug Resistant ◽  
East African ◽  
Mdr Tb

The population of the French Departments of the Americas (FDA) is highly influenced by the intense migratory flows with mainland France and surrounding countries of the Caribbean and Latin America, some of which have high incidence rates of tuberculosis (Haiti: 230/100,000; Guyana: 111/100,000; and Suriname: 145/100,000) and drug resistance. Since the development of drug resistance to conventional antituberculous drugs has a major impact on the treatment success of tuberculosis, we therefore decided to review carefullyMycobacterium tuberculosisdrug resistance and associated genotypic lineages in the FDA over a seventeen-year period (January 1995–December 2011). A total of 1239 cases were studied, including 153 drug-resistant and 26 multidrug-resistant- (MDR-) TB cases, representing 12.3% and 2.1% of the TB cases in our study setting. A significantly higher proportion ofM. tuberculosisisolates among relapse cases showed drug resistance to isoniazid (22.5%,P=0.002), rifampicin (20.0%,P<0.001), or both (MDR-TB, 17.5%;P<0.001). Determination of spoligotyping based phylogenetic clades showed that among the five major lineages observed—T family (30.1%); Latin-American and Mediterranean (LAM, 23.7%); Haarlem (H, 22.2%); East-African Indian (EAI, 7.2%); and X family (6.5%)—two lineages, X and LAM, were overrepresented in drug-resistant and MDR-TB cases, respectively. Finally, 19 predominant spoligotypes were identified for the 1239 isolates ofM. tuberculosisin our study among which 4 were significantly associated with drug resistance corresponding to SIT20/LAM1, SIT64/LAM6, SIT45/H1, and SIT46/undefined lineage.

scholarly journals Epidemiology of Antituberculosis Drug Resistance in Saudi Arabia: Findings of the First National Survey

2013 ◽  
Vol 57 (5) ◽  
pp. 2161-2166 ◽  
Author(s):  
Sahal Al-Hajoj ◽  
Bright Varghese ◽  
Mohammed M. Shoukri ◽  
Ruba Al-Omari ◽  
Mais Al-Herbwai ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Saudi Arabia ◽  
National Survey ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Control Measures ◽  
Foreign Born ◽  
Primary Drug Resistance ◽  
Mdr Tb

ABSTRACTThe real magnitude of antituberculosis (anti-TB) drug resistance in Saudi Arabia is still unknown because the available data are based on retrospective laboratory studies that were limited to hospitals or cities. A representative national survey was therefore conducted to investigate the levels and patterns of anti-TB drug resistance and explore risk factors. Between August 2009 and July 2010, all culture-positive TB patients diagnosed in any of the tuberculosis reference laboratories of the country were enrolled. Isolates obtained from each patient were tested for susceptibility to first-line anti-TB drugs by the automated Bactec MGIT 960 method. Of the 2,235 patients enrolled, 75 cases (3.4%) were lost due to culture contamination and 256 (11.5%) yielded nontuberculous mycobacteria (NTM). Finally, 1,904 patients (85.2% of those enrolled) had available drug susceptibility testing results. Monoresistance to streptomycin (8.1%; 95% confidence interval [CI], 7.2 to 9.1), isoniazid (5.4%; 95% CI, 4.7 to 6.2), rifampin (1%; 95% CI, 0.7 to 1.3) and ethambutol (0.8%; 95% CI, 0.5 to 1.2) were observed. Multidrug-resistant TB (MDR-TB) was found in 1.8% (95% CI, 1.4 to 2.4) and 15.9% (95% CI, 15.4 to 16.5) of new and previously treated TB cases, respectively. A treatment history of active TB, being foreign-born, having pulmonary TB, and living in the Western part of the country were the strongest independent predictors of MDR-TB. Results from the first representative national anti-TB drug resistance survey in Saudi Arabia suggest that the proportion of MDR-TB is relatively low, though there is a higher primary drug resistance. A strengthened continuous surveillance system to monitor trends over time and second-line anti-TB drug resistance as well as implementation of innovative control measures, particularly among immigrants, is warranted.

scholarly journals Age-stratified anti-tuberculosis drug resistance profiles in South Korea: a multicenter retrospective study

2020 ◽  
Author(s):  
Eung Gu Lee ◽  
Jinsoo Min ◽  
Ji Young Kang ◽  
Sung Kyoung Kim ◽  
Jin Woo Kim ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Young Patients ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Fluoroquinolone Resistance ◽  
Second Line ◽  
Injectable Drugs ◽  
Resistant Tuberculosis ◽  
Age Related ◽  
Mdr Tb

Abstract Background: The emergence of drug-resistant tuberculosis (DR-TB) is a major healthcare concern worldwide. Here, we analyzed age-related trends in DR-TB rates in South Korea.Methods: Drug susceptibility test results were collected from patients with culture-confirmed TB between 2015 and 2018 from eight university-affiliated hospitals. Patients were divided into three subgroups: younger (15–34 years), middle (35–59 years), and older (≥60 years) to compare drug-resistance patterns.Results: Among the 4,417 cases investigated, 179 (4.1%), 53 (1.2%), and 316 (7.2%) were multidrug-resistant TB (MDR-TB), rifampicin-mono-resistant TB (RR-TB), and isoniazid-mono-resistant TB (Hr-TB), respectively. Proportions of Hr-TB cases were similar among the three groups (11.2%, 12.2%, and 10.4% in the younger, middle, and older groups, respectively). MDR/RR-TB case numbers decreased significantly as age increased (8.6%, 6.3%, 3.3%, respectively). Proportions of MDR/RR-TB among retreated patients in the younger generation decreased from 50.0% to 18.2%, but remained higher than that in the older generation. Fluoroquinolone resistance was highest among second-line drugs, and there were no differences in resistance to fluoroquinolones and second-line injectable drugs among the three age groups.Conclusions: The number of MDR/RR-TB cases was highest in young patients. Effective public health interventions should include increased focus on rifampicin resistance in young patients.

scholarly journals Diagnosis of Multidrug-Resistant Tuberculosis and Extensively Drug-Resistant Tuberculosis: Current Standards and Challenges

2008 ◽  
Vol 19 (2) ◽  
pp. 169-172 ◽  
Author(s):  
Giovanni Battista Migliori ◽  
Alberto Matteelli ◽  
Daniela Cirillo ◽  
Madhukar Pai
Keyword(s):  
Drug Resistance ◽  
Rapid Determination ◽  
Scale Up ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Mdr Tb

INTRODUCTION: The emergence of multidrug-resistant tuberculosis (MDR-TB) and, more recently, extensively drug-resistant TB (XDR-TB) is widely considered a serious threat to global TB control. Over 400,000 new cases of MDR-TB occur each year and, although their rates are currently unknown, XDR-TB cases have been detected in every country where there is capacity to detect them (including Canada).METHODS: The present article provides a narrative overview of the various diagnostic options available for XDR-TB, including conventional tools and newer rapid tests for drug resistance. Available data suggest that automated liquid cultures are highly accurate and their use is rapidly expanding. Newly developed phenotypic tests include TK Medium (Salubris Inc, USA), microscopic-observation drug-susceptibility assay, FASTPlaque-Response bacteriophage assay (Biotec Laboratories Ltd, UK), colorimetric redox indicator methods and the microcolony method. These tests are usually cheaper but not always simple to perform, with some requiring high standards of biosafety and quality control. Among the newly developed phenotypic methods, reverse hybridization-based assays, referred to as line probe assays, represent a useful tool because of their superior accuracy and cost-effectiveness.CONCLUSIONS: To effectively address the threats of MDR-TB and XDR-TB, global initiatives are required to scale-up culture and drug susceptibility testing capacities, especially in high-burden countries where such capacity is scarce. In parallel, efforts are needed to expand the use of novel and emerging technologies (ie, molecular diagnostics) for the rapid determination of drug resistance.

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