scholarly journals Performance of GenoType MTBDRsl assay for detection of second-line drugs and ethambutol resistance directly from sputum specimens of MDR-TB patients in Bangladesh

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261329
Author(s):  
S. M. Mazidur Rahman ◽  
Rumana Nasrin ◽  
Arfatur Rahman ◽  
Shahriar Ahmed ◽  
Razia Khatun ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Rapid Test ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Timely Initiation ◽  
Resistant Tuberculosis ◽  
Mdr Tb ◽  
Lowenstein Jensen ◽  
Sensitivity Specificity

Background Rapid and early detection of drug susceptibility among multidrug-resistant tuberculosis (MDR-TB) patients could guide the timely initiation of effective treatment and reduce transmission of drug-resistant TB. In the current study, we evaluated the diagnostic performance of GenoType MTBDRsl (MTBDRsl) ver1.0 assay for detection of resistance to ofloxacin (OFL), kanamycin (KAN) and ethambutol (EMB), and additionally the XDR-TB among MDR-TB patients in Bangladesh. Methods The MTBDRsl assay was performed directly on 218 smear-positive sputum specimens collected from MDR-TB patients and the results were compared with the phenotypic drug susceptibility testing (DST) performed on solid Lowenstein-Jensen (L-J) media. We also analyzed the mutation patterns of gyrA, rrs, and embB genes for detection of resistance to OFL, KAN and EMB, respectively. Results The sensitivity and specificity of the MTBDRsl compared to phenotypic L-J DST were 81.8% (95% CI, 69.1–90.9) and 98.8% (95% CI, 95.6–99.8), respectively for OFL (PPV: 95.7% & NPV: 94.1%); 65.1% (95% CI, 57.5–72.2) and 86.7% (95% CI, 73.2–94.9), respectively for EMB (PPV: 94.9% & NPV: 39.4%); and 100% for KAN. The diagnostic accuracy of KAN, OFL and EMB were 100, 94.5 and 69.6%, respectively. Moreover, the sensitivity, specificity and diagnostic accuracy of MtBDRsl for detection of XDR-TB was 100%. The most frequently observed mutations were at codon D94G (46.8%) of gyrA gene, A1401G (83.3%) of rrs gene, and M306V (41.5%) of the embB gene. Conclusion Considering the excellent performance in this study we suggest that MTBDRsl assay can be used as an initial rapid test for detection of KAN and OFL susceptibility, as well as XDR-TB directly from smear-positive sputum specimens of MDR-TB patients in Bangladesh.

Evaluation of MTBDRsl for detecting resistance in Mycobacterium tuberculosis to second-line drugs

2019 ◽  
Vol 23 (12) ◽  
pp. 1257-1262 ◽  
Author(s):  
R. J. Chandak ◽  
B. Malhotra ◽  
S. Bhargava ◽  
S. K. Goel ◽  
D. Verma ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Rapid Test ◽  
Drug Susceptibility ◽  
Turnaround Time ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

SETTING: Patients with presumed multidrug-resistant tuberculosis (MDR-TB) and undergoing MDR-TB treatment from Rajasthan, India.OBJECTIVE: To compare the GenoType® MTBDRsl v.1.0 (MTBDRsl) assay capacity to detect resistance to ofloxacin, amikacin, capreomycin, kanamycin and ethambutol in Mycobacterium tuberculosis with phenotypic drug susceptibility testing (DST) using MGIT™960™ in sputum samples and isolates.DESIGN: Fifty-three smear-positive sputum samples were tested directly by MTBDRsl and 205 MDR-TB isolates were processed using MTBDRsl and DST for five drugs on MGIT960. DNA sequencing was performed in isolates with discordance in the results between the two methods for the gyrA, gyrB and rrs genes.RESULT: Sensitivity and specificity of MTBDRsl was found to be respectively 93.1% and 100% for fluoroquinoline, respectively 75–78% and 100% for aminoglycosides/cyclopeptides, respectively 70% and 92% for ethambutol and respectively 92.3% and 100% for extensively drug-resistant (XDR) TB detection. On sequencing eight discordant isolates for quinolones, mutations were seen in 12.5% of the gyrB gene and among 20 discordant isolates for aminoglycosides/cyclopeptides in the rrs gene in 15% isolates. The turnaround time was 2 days for MTBDRsl vs. 10 days for MGIT960.CONCLUSIONS: MTBDRsl can be used as an initial rapid test for detecting XDR-TB, resistance to quinolones and aminogycosides/cyclopeptides in smear-positive sputum samples.

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 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 Drug susceptibility patterns of Mycobacterium tuberculosis from adults with multidrug-resistant tuberculosis and implications for a household contact preventive therapy trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Anne-Marie Demers ◽  
◽  
Soyeon Kim ◽  
Sara McCallum ◽  
Kathleen Eisenach ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Sputum Sample ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Preventive Therapy ◽  
Drug Susceptibility Testing ◽  
Study Entry ◽  
Resistant Tuberculosis ◽  
Mdr Tb ◽  
Therapy Trial

Abstract Background Drug susceptibility testing (DST) patterns of Mycobacterium tuberculosis (MTB) from patients with rifampicin-resistant tuberculosis (RR-TB) or multidrug-resistant TB (MDR-TB; or resistant to rifampicin and isoniazid (INH)), are important to guide preventive therapy for their household contacts (HHCs). Methods As part of a feasibility study done in preparation for an MDR-TB preventive therapy trial in HHCs, smear, Xpert MTB/RIF, Hain MTBDRplus, culture and DST results of index MDR-TB patients were obtained from routine TB programs. A sputum sample was collected at study entry and evaluated by the same tests. Not all tests were performed on all specimens due to variations in test availability. Results Three hundred eight adults with reported RR/MDR-TB were enrolled from 16 participating sites in 8 countries. Their median age was 36 years, and 36% were HIV-infected. Routine testing on all 308 were confirmed as having RR-TB, but only 75% were documented as having MDR-TB. The majority of those not classified as having MDR-TB were because only rifampicin resistance was tested. At study entry (median 59 days after MDR-TB treatment initiation), 280 participants (91%) were able to produce sputum for the study, of whom 147 (53%) still had detectable MTB. All but 2 of these 147 had rifampicin DST done, with resistance detected in 89%. Almost half (47%) of the 147 specimens had INH DST done, with 83% resistance. Therefore, 20% of the 280 study specimens had MDR-TB confirmed. Overall, DST for second-line drugs were available in only 35% of the 308 routine specimens and 15% of 280 study specimens. Conclusions RR-TB was detected in all routine specimens but only 75% had documented MDR-TB, illustrating the need for expanded DST beyond Xpert MTB/RIF to target preventive therapy for HHC.

scholarly journals The epidemiological characteristics and profile of drug-resistant tuberculosis among children with tuberculosis in Sichuan, China, 2015-2018: A retrospective study

2020 ◽  
Author(s):  
Yuanhong Xu ◽  
Qingfeng Li ◽  
Ma Zhu ◽  
Xueqi Wu ◽  
Dongmei Wang ◽  
...  
Keyword(s):  
Clinical Information ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Mdr Tb ◽  
History Of ◽  
Epidemiological Characteristics

Abstract Background: The aim of this study was to investigate the epidemiological characteristics and profile of drug-resistant tuberculosis (DR-TB) among children with TB in Sichuan province of China.Methods: From January 2015 to December 2018, microbiological culture-confirmed child TB cases (aged<15 years old) were enrolled retrospectively. Epidemiological and clinical information from these cases, and the drug susceptibility testing (DST) results of the isolates were collected and analyzed.Results: Of 317 culture-confirmed child TB cases, 16.7% (53/317) were aged under 5 years old. 54.9% were Tibetans, and 31.9% had clear history of contact with TB patients. More than half (53.9%) weren’t vaccinated by Calmette–Guérin bacillus (BCG). 30% (n=95) were diagnosed as severe TB, and 92.4% (n=293) were new cases. The ratio of severe TB in BCG vaccinated group was significant lower than that observed in unvaccinated group (p<0.01). Significantly higher proportion of severe TB among Tibetans than Han child TB cases was observed in BCG unvaccinated group (p<0.01). The overall rate of DR-TB in this study was 24.3% (77/317) and 17 multidrug-resistant tuberculosis (MDR-TB) cases were identified with rate of MDR-TB at 5.4% (17/317). No XDR case was found. 13 out of 17 MDR-TB cases (76.4%) were Tibetan children. The ratio of any resistance to four first-line drugs identified were: INH, 15.5%; RIF, 9.1%; EMB, 0.6% and SM, 6.0%, respectively. More than half of MDR patterns were resistant to INH+RIF (9/17), followed by at least resistance to INH+RIF+SM (n=7). Conclusions: This was the first investigation on the epidemiological characteristics and profiles of DR-TB among child TB cases in Southwest of China. Our findings indicated a potentially high risk of TB infection to Tibetan children in the concentrated Tibetan communities of Sichuan.

scholarly journals EXTENSIVELY DRUG RESISTANT TUBERCULOSIS (XDR TB)

2019 ◽  
Vol 5 (2) ◽  
pp. 26
Author(s):  
Sarah Rahmayani Siregar
Keyword(s):  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Tuberculosis Programme ◽  
Mdr Tb ◽  
Directly Observed Treatment

Tuberkulosis adalah penyakit infeksi kronis menular yang masih merupakan masalah kesehatan masyarakat di dunia termasuk Indonesia. Tuberkulosis (TB) sebagian besar akan mengalami penyembuhan dengan pengobatan. Namun tidak semua penyakit TB sembuh dengan pengobatan. Hal ini disebabkan pengobatan dari TB yang belum terlaksana dengan baik sehingga dapat pula menyebabkan terjadinya resistensi terhadap Obat Anti Tuberkulosis (OAT), berupa Multidrug Resistant Tuberkulosis (MDR TB) dan Extensively Drug Resistant Tuberculosis (XDR TB). XDR TB adalah TB yang disebabkan oleh strain yang resistensi terhadap isoniazid dan rifampisin, disertai resisten terhadap salah satu fluorokuinolon dan salah satu dari tiga obat injeksi lini kedua (amikasin, kapreomisin atau kanamisin). XDR TB diperkenalkan tahun 2006 ketika terjadi epidemi yang sangat fatal di Afrika Selatan. XDR-TB dapat ditularkan melalui bakteri yang disebarkan oleh orang yang sudah terkena resistensi obat. Diagnosis XDR-TB ditegakkan dengan uji sensitiviti obat atau Drug Susceptibility Testing (DST), bukan sekedar berdasarkan gambaran foto toraks dan adanya faktor resiko yang ada pada seseorang. WHO telah merancang strategi Directly Observed Treatment Short Course (DOTS-Plus) untuk mengelola TB M/XDR di negara-negara miskin sumber daya. Revisi National Tuberculosis Programme (RNTCP) di bawah DOTS-Plus akan menggunakan rejimen pengobatan standar (STR) kategori IV, yang terdiri dari 6 obat (kanamisin, levofloxacin, etionamid, sikloserin, pirazinamid, dan etambutol) selama 6-9 bulan fase intensif dan 4 obat (levofloxacin, ethionamide, cycloserine, dan ethambutol) selama 18 bulan dari fase lanjutan. Penyembuhan tergantung pada tingkat resistensi obat, tingkat keparahan penyakit dan apakah sistem kekebalan pasien terganggu.

scholarly journals Drug Susceptibility Profile of Mycobacterium tuberculosis Isolated from Patients Visiting National Tuberculosis Centre, Nepal

2018 ◽  
Vol 5 ◽  
pp. 63-68
Author(s):  
S. Dahal ◽  
M.R. Banjara ◽  
D. Khadka ◽  
G. Ghimire ◽  
S. Sharma
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Drug Susceptibility ◽  
Cross Sectional Study ◽  
Drug Susceptibility Testing ◽  
Biochemical Tests ◽  
Cross Sectional ◽  
Resistant Tuberculosis ◽  
National Tuberculosis ◽  
Mdr Tb ◽  
Lowenstein Jensen

Objectives: The objective of this study was to assess drug susceptibility pattern of Mycobacterium tuberculosis (MTB). Methods: This cross-sectional study was carried out among 145 clinically suspected and previously treated pulmonary tuberculosis patients visiting National Tuberculosis Centre, Bhaktapur, Nepal. After obtaining written informed consent, questionnaire was administered and sputum samples were collected from each patient. Each sample was subjected to Ziehl-Neelsen (ZN) staining and cultured on Lowenstein Jensen (LJ) medium at 37ºC for 8 weeks. MTB isolates were identified by growth rate and colony morphology, confirmed by biochemical tests and drug susceptibility testing (DST) of identified isolates was performed by proportion method. Results: A total of 49.7% (n=72) sputum samples were positive for MTB by culture and 46.9% (n=68) were positive by ZN staining. Among culture positive isolates of MTB (n= 72), 25% (n=18) were resistant to at least one drug. The prevalence of multi drug resistant tuberculosis (MDR-TB) was 15.3% (n=11) of which 5.56% (n=4) were resistant to rifampicin (RIF) only, 1.39% (n= 1) were resistant to isoniazid (INH) only. Out of 18 resistant isolates, 61.1% (n=11) were resistant to both RIF and INH, 21.43% (n=3) resistant to INH were susceptible to RIF and 26.67% (n=4) resistant to RIF were susceptible to INH. Smoking (P=0.001) and coughing (P=0.009) were statistically significant with isolation of MTB. Conclusion: Since the prevalence of MDR-TB was high, MDR-TB strains should be identified in order to initiate second line treatment.

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