scholarly journals Research article Evaluation of Genotype MTBDRplus Assay for identifying Multidrug Resistant Mycobacterium tuberculosis isolates in Nepal

2013 ◽  
Vol 1 (1) ◽  
pp. 30-37 ◽  
Author(s):  
B Dahal ◽  
N Adhikari ◽  
Y Shah ◽  
RC Simkhada ◽  
B Maharjan ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Hot Spot ◽  
Regulatory Region ◽  
Rpob Gene ◽  
Multidrug Resistant ◽  
New Genotype ◽  
Mdr Tb ◽  
Proportion Method ◽  
Resistant Strains ◽  
Genotype Mtbdrplus

Background and Objectives: Multidrug-resistant (MDR) Mycobacterium tuberculosis strains are serious threats to the control of tuberculosis and comprise an increasing public health problem. Rapid detection of such strains is quite critical in timely management of such issues. The study was performed with an objective to compare Genotype MTBDRplus reverse hybridization probe assay (Hain Lifescince, GmBH, Nehern, Germany) with culture based proportion method for rapidly identifying MDR-TB strains from suspected multi drug resistant cases, referred to GENETUP Kathmandu, Nepal. Methodology: A commercially available new Genotype MTBDRplus assay was evaluated for its ability to detect mutations in Mycobacterial isolates conferring resistance to rifampicin (RMP) and isoniazid (INH). A total of 64 MDR isolates (i.e., at least resistant to RMP and INH), 5 fully susceptible strains and 1 RMP sensitive strains by conventional proportion method were analyzed using Genotype MTBDRplus assay. MTBDRplus assay is designed to detect the mutations in the hot spot region of rpoB gene, katG and regulatory region of inhA gene. Results: The MTBDRplus assay detected 59 of 61 RMP resistant strains (96.72%) with mutations on 81-bp hot spot region of rpoB gene and 60 of 63 INH resistant strains (95.23%) with mutation in codon 315 katG and regulatory region of inhA. The sensitivity and specificity for the detection of RMP resistance were 96.72% and 100% respectively. While, value of the same two variables for INH resistance were 95.23% and 100%, respectively. Conclusions: The new Genotype MTBDRplus assay represents a rapid, reliable, upgraded tool with high sensitivity and specificity for the detection of INH and RMP resistance strains that can readily be included in a routine laboratory work for the early diagnosis and control of MDR-TB. DOI: http://dx.doi.org/10.3126/jmcjms.v1i1.7884 Janaki Medical College Journal of Medical Sciences (2013) Vol. 1 (1):30-37

scholarly journals Constraints of Drug Resistance in Mycobacterium tuberculosis - Prospects for Pharmacological Reversion of Susceptibility to Antibiotics

2017 ◽  
Vol 8 (1) ◽  
pp. 33-43 ◽  
Author(s):  
Aleksandr I. Ilin ◽  
Murat E. Kulmanov ◽  
Ilya S. Korotetskiy ◽  
Marina V. Lankina ◽  
Gulshara K. Akhmetova ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Genetic Heterogeneity ◽  
Multidrug Resistant ◽  
Resistance Mutations ◽  
General Increase ◽  
Drug Induced ◽  
Mdr Tb ◽  
Resistant Strains

Emergence of multidrug resistant strains ofMycobacterium tuberculosis(MDR-TB) threatens humanity. This problem was complicated by the crisis in development of new anti-tuberculosis antibiotics. Induced reversion of drug resistance seems promising to overcome the problem. Successful clinical trial of a new anti-tuberculosis nanomolecular complex FS-1 has demonstrated prospectively of this approach in combating MDR-TB. Several clinical MDR-TB cultures were isolated from sputum samples prior and in the process of the clinical trial. Every isolate was tested for susceptibility to antibiotics and then they were sequenced for comparative genomics. It was found that the treatment with FS-1 caused an increase in the number of antibiotic susceptible strains among Mtb isolates that was associated with a general increase of genetic heterogeneity of the isolates. Observed impairing of phthiocerol dimycocerosate biosynthesis by disruptive mutations inppsACDsubunits indicated a possible virulence remission for the sake of persistence. It was hypothesized that the FS-1 treatment eradicated the most drug resistant Mtb variants from the population by aggravating the fitness cost of drug resistance mutations. Analysis of distribution of these mutations in the global Mtb population revealed that many of them were incompatible with each other and dependent on allelic states of many other polymorphic loci. The latter discovery may explain the negative correlation between the genetic heterogeneity of the population and the level of drug tolerance. To the best of our knowledge, this work was the first experimental confirmation of the drug induced antibiotic resistance reversion by the induced synergy mechanism that previously was predicted theoretically.

scholarly journals Genotypic Analysis of Genes Associated with Independent Resistance and Cross-Resistance to Isoniazid and Ethionamide in Mycobacterium tuberculosis Clinical Isolates

2015 ◽  
Vol 59 (12) ◽  
pp. 7805-7810 ◽  
Author(s):  
Johana Rueda ◽  
Teresa Realpe ◽  
Gloria Isabel Mejia ◽  
Elsa Zapata ◽  
Juan Carlos Rozo ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Multidrug Resistant ◽  
Cross Resistance ◽  
Resistance Mutations ◽  
Content Type ◽  
Genotypic Analysis ◽  
Mdr Tb ◽  
Proportion Method ◽  
Emergence Of Resistance ◽  
Phenotypic Susceptibility

ABSTRACTEthionamide (ETH) is an antibiotic used for the treatment of multidrug-resistant (MDR) tuberculosis (TB) (MDR-TB), and its use may be limited with the emergence of resistance in theMycobacterium tuberculosispopulation. ETH resistance inM. tuberculosisis phenomenon independent or cross related when accompanied with isoniazid (INH) resistance. In most cases, resistance to INH and ETH is explained by mutations in theinhApromoter and in the following genes:katG,ethA,ethR,mshA,ndh, andinhA. We sequenced the above genes in 64M. tuberculosisisolates (n= 57 ETH-resistant MDR-TB isolates;n= 3 ETH-susceptible MDR-TB isolates; andn= 4 fully susceptible isolates). Each isolate was tested for susceptibility to first- and second-line drugs using the agar proportion method. Mutations were observed in ETH-resistant MDR-TB isolates at the following rates: 100% inkatG, 72% inethA, 45.6% inmshA, 8.7% inndh, and 33.3% ininhAor its promoter. Of the three ETH-susceptible MDR-TB isolates, all showed mutations inkatG; one had a mutation inethA, and another, inmshAandinhA. Finally, of the four fully susceptible isolates, two showed no detectable mutation in the studied genes, and two had mutations inmshAgene unrelated to the resistance. Mutations not previously reported were found in theethA,mshA,katG, andndhgenes. The concordance between the phenotypic susceptibility testing to INH and ETH and the sequencing was 1 and 0.45, respectively. Among isolates exhibiting INH resistance, the high frequency of independent resistance and cross-resistance with ETH in theM. tuberculosisisolates suggests the need to confirm the susceptibility to ETH before considering it in the treatment of patients with MDR-TB.

scholarly journals Direct Detection of Pyrazinamide Resistance in Mycobacterium tuberculosis by Use of pncA PCR Sequencing

2019 ◽  
Vol 57 (8) ◽  
Author(s):  
Kingsley King-Gee Tam ◽  
Kenneth Siu-Sing Leung ◽  
Gilman Kit-Hang Siu ◽  
Kwok-Chiu Chang ◽  
Samson Sai-Yin Wong ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Direct Detection ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Activity Data ◽  
Content Type ◽  
Treatment Regimens ◽  
Mdr Tb ◽  
Resistant Strains ◽  
Respiratory Specimens

ABSTRACT An in-house-developed pncA sequencing assay for analysis of pyrazinamide (PZA) resistance was evaluated using 162 archived Mycobacterium tuberculosis complex (MTBC) isolates with phenotypic PZA susceptibility profiles that were well defined by analysis of Bactec MGIT 960 PZA kit and PZase activity data. Preliminary results showed 100% concordance between pncA sequencing and phenotypic PZA drug susceptibility test (DST) results among archived isolates. Also, 637 respiratory specimens were prospectively collected, and 158 were reported as MTBC positive by the Abbott Realtime MTB assay (96.3% sensitivity [95% confidence interval {CI}: 92.2% to 98.7%]; 100% specificity [95% CI: 99.2% to 100.0%]). Genotypic and phenotypic PZA resistance profiles of these 158 MTBC-positive specimens were analyzed by pncA sequencing and Bactec MGIT 960 PZA kit, respectively. For analysis of PZA resistance, pncA sequencing detected pncA mutations in 5/5 (100%) phenotypic PZA-resistant respiratory specimens within 4 working days. No pncA mutations were detected among PZA-susceptible specimens. Combining archived isolates with prospective specimens, 27 were identified as phenotypic PZA resistant with pncA mutation. Among these 27 samples, 6/27 (22.2%) phenotypic PZA-resistant strains carried novel pncA mutations without rpsA and panD mutations. These included 5 with mutations (a deletion [Del] at 383T [Del383T], Del 380 to 390, insertion of A [A Ins] at position 127, A Ins at position 407, and G Ins at position 508) in pncA structural genes and 1 with a mutation (T-12C) at the pncA promoter region. All six of these strains had no or reduced PZase activities, indicating that the novel mutations might confer PZA resistance. Additionally, 25/27 phenotypic PZA-resistant strains were confirmed multidrug-resistant tuberculosis (MDR-TB) strains. As PZA is commonly used in MDR-TB treatment regimens, direct pncA sequencing will rapidly detect PZA resistance and facilitate judicious use of PZA in treating PZA-susceptible MDR-TB.

scholarly journals Epidemiology of Rifampicin Resistant Tuberculosis and Common Mutations in rpoB Gene of Mycobacterium tuberculosis: A Retrospective Study from Six Districts of Punjab (India) Using Xpert MTB/RIF Assay

2016 ◽  
Vol 8 (02) ◽  
pp. 096-100 ◽  
Author(s):  
Ramandeep Kaur ◽  
Neerja Jindal ◽  
Shilpa Arora ◽  
Shajla Kataria
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Surrogate Marker ◽  
Rpob Gene ◽  
Multidrug Resistant ◽  
Resistance Pattern ◽  
Resistance Mutations ◽  
Resistant Tuberculosis ◽  
Mdr Tb ◽  
Previously Treated Patients ◽  
User Friendly

ABSTRACT Background: Xpert MTB/RIF assay has revolutionized the diagnosis of tuberculosis (TB) by simultaneously detecting the bacteria and resistance to rifampicin (RIF), a surrogate marker for multidrug-resistant TB (MDR-TB) in <2 h. The RIF resistance pattern in Malwa region of Punjab, India, is not documented. Here, we report the epidemiology of RIF-resistant TB and mutations in rpoB gene of Mycobacterium tuberculosis (MTB). Materials and Methods: A total of 1612 specimens received between October 2013 and February 2015 were tested by Xpert MTB/RIF assay following manufacturer’s instructions. The results thus obtained were analyzed using SPSS version 20.0.0 (SPSS Inc., Chicago, IL, USA) statistical software. Result: RIF resistance was statistically higher in previously treated patients in comparison to the new patients (P = 0.006) and in patients with acid fast-Bacilli (AFB) positive smears to AFB-negative smears (P = 0.048). RIF resistance mutations in 130 specimens revealed frequency of E 73/130 (56%), B 28/130 (21.5%), D 18/130 (13.8%), A 11/130 (8.4%), and C 1/130 (0.7%) while in one specimen, mutation combination, i.e., mutations associated with more than one probe (A and B both) was present. Conclusion: Xpert MTB/RIF assay is a user-friendly screening tool for detection of MTB and RIF resistance from suspected TB/MDR cases in a shorter period of time. It could also serve as a useful technique to have simultaneous preliminary information regarding the mutation pattern of RIF resistance in MTB isolates.

scholarly journals Effect of Mutation and Genetic Background on Drug Resistance in Mycobacterium tuberculosis

2012 ◽  
Vol 56 (6) ◽  
pp. 3047-3053 ◽  
Author(s):  
Lukas Fenner ◽  
Matthias Egger ◽  
Thomas Bodmer ◽  
Ekkehardt Altpeter ◽  
Marcel Zwahlen ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Hot Spot ◽  
Multidrug Resistant ◽  
Beijing Genotype ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
Content Type ◽  
Drug Resistance Mutations ◽  
Resistant Strains

ABSTRACTBacterial factors may contribute to the global emergence and spread of drug-resistant tuberculosis (TB). Only a few studies have reported on the interactions between different bacterial factors. We studied drug-resistantMycobacterium tuberculosisisolates from a nationwide study conducted from 2000 to 2008 in Switzerland. We determined quantitative drug resistance levels of first-line drugs by using Bactec MGIT-960 and drug resistance genotypes by sequencing the hot-spot regions of the relevant genes. We determined recent transmission by molecular methods and collected clinical data. Overall, we analyzed 158 isolates that were resistant to isoniazid, rifampin, or ethambutol, 48 (30.4%) of which were multidrug resistant. Among 154 isoniazid-resistant strains,katGmutations were associated with high-level andinhApromoter mutations with low-level drug resistance. OnlykatG(S315T) (65.6% of all isoniazid-resistant strains) andinhApromoter −15C/T (22.7%) were found in molecular clusters.M. tuberculosislineage 2 (includes Beijing genotype) was associated with any drug resistance (adjusted odds ratio [OR], 3.0; 95% confidence interval [CI], 1.7 to 5.6;P< 0.0001). Lineage 1 was associated withinhApromoter −15C/T mutations (OR, 6.4; 95% CI, 2.0 to 20.7;P= 0.002). We found that the genetic strain background influences the level of isoniazid resistance conveyed by particular mutations (interaction tests of drug resistance mutations across all lineages;P< 0.0001). In conclusion,M. tuberculosisdrug resistance mutations were associated with various levels of drug resistance and transmission, andM. tuberculosislineages were associated with particular drug resistance-conferring mutations and phenotypic drug resistance. Our study also supports a role for epistatic interactions between different drug resistance mutations and strain genetic backgrounds inM. tuberculosisdrug resistance.

scholarly journals Evolutionary trajectories and transmission dynamics of multidrug-resistant Mycobacterium tuberculosis in Tibet, China

2021 ◽  
Author(s):  
Qi Jiang ◽  
Hai-can Liu ◽  
Qing-yun Liu ◽  
Jody E. Phelan ◽  
Li Shi ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Phylogenetic Trees ◽  
Multidrug Resistant ◽  
Rifampicin Resistance ◽  
Whole Genome Sequencing Data ◽  
High Burden ◽  
Increased Risk ◽  
Mdr Tb ◽  
Resistant Strains ◽  
The Impact

ABSTRACTObjectiveTibet has the highest prevalence of both tuberculosis disease and multidrug-resistant tuberculosis (MDR-TB) in China. The circulated Mycobacterium tuberculosis strains from Tibet were sequenced to investigate the underlying drivers for the high burden of MDR-TB.MethodsUsing whole-genome sequencing data of 576 M. tuberculosis strains isolated from consecutive patients in Tibet, we mapped resistance-conferring mutations onto phylogenetic trees to determine their evolution and spread. The impact of drug resistance on bacterial population growth was assessed with a Bayesian (Skyline Plot) analysis. Multivariable logistic regression was used to identify risk factors for the development of rifampicin resistance.ResultsOf the 576 isolates, 284 (49.3%), 280 (48.6%), and 236 (41.0%) were, respectively, genetically resistant to isoniazid, rifampicin, or both (MDR-TB). Among the isoniazid- and rifampicin-resistant strains, the proportions in phylogenetically-inferred clusters were 77.8% (221/284) and 62.1% (174/280), respectively. Nearly half (47.2%, 134/284) of the isoniazid-resistant strains were in six major clades, which contained between 8 and 58 strains with katG S315T, katG S315N, or fabG1 promoter −15 C>T resistance mutations. These major clades exponentially expanded after emerging with isoniazid resistance and stabilized before evolving into MDR-TB twenty years later. Isoniazid-resistant isolates showed an increased risk of accumulating rifampicin resistance compared to isoniazid-susceptible strains, with an adjusted odds ratio of 3.81 (95% confidence interval 2.47-5.95).ConclusionHistorical expansion of isoniazid-resistant strains and their increased likelihood of acquiring rifampicin resistance both contributed to the high burden of MDR-TB in Tibet, highlighting the need to detect INH-resistant strains promptly and to control their transmission.

scholarly journals Use of Genotype MTBDRplus Assay for Diagnosis of Multidrug-Resistant Tuberculosis in Nepal

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Elina Maharjan ◽  
Narayan Dutt Pant ◽  
Sanjeev Neupane ◽  
Jyoti Amatya ◽  
Bhawana Shrestha
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Conventional Drug ◽  
Mdr Tb ◽  
Genotype Mtbdrplus

The main aims of this study were to study the patterns of mutations in rpoB, katG, and inhA genes in Mycobacterium tuberculosis strains isolated from patients from Nepal and to evaluate the performance of genotype MTBDRplus assay, taking conventional drug susceptibility testing as gold standard for diagnosis of MDR-TB. A total of 69 Mycobacterium tuberculosis strains isolated from 73 smear positive sputum samples from patients suspected of suffering from multidrug-resistant tuberculosis were used in our study. The drug susceptibility pattern of Mycobacterium tuberculosis isolated from these sputum specimens was determined by using genotype MTBDRplus assay taking conventional drug susceptibility testing as reference. The sensitivity and specificity of the genotype MTBDRplus assay for the detection of MDR-TB were found to be 88.7% and 100%, respectively. 88.7% of the rifampicin resistant isolates had mutations in rpoB gene. Similarly, 79.7% and 9.4% of isoniazid resistant isolates had mutations in katG and inhA genes, respectively. Genotype MTBDRplus assay was found to be very rapid and highly sensitive and specific method for diagnosis of MDR-TB and will be very helpful for early diagnosis of MDR-TB in high tuberculosis burden countries.

scholarly journals Molecular characterization of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates identifies local transmission of infection in Kuwait, a country with a low incidence of TB and MDR-TB

2019 ◽  
Vol 24 (1) ◽  
Author(s):  
Noura M. Al-Mutairi ◽  
Suhail Ahmad ◽  
Eiman M. Mokaddas
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Phylogenetic Tree ◽  
Sequence Data ◽  
Regulatory Region ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Beijing Genotype ◽  
Mdr Tb ◽  
Low Incidence ◽  
Local Transmission

Abstract Background Increasing incidence of multidrug-resistant Mycobacterium tuberculosis infections is hampering global tuberculosis control efforts. Kuwait is a low-tuberculosis-incidence country, and ~ 1% of M. tuberculosis strains are resistant to rifampicin and isoniazid (MDR-TB). This study detected mutations in seven genes predicting resistance to rifampicin, isoniazid, pyrazinamide, ethambutol and streptomycin in MDR-TB strains. Sequence data were combined with spoligotypes for detecting local transmission of MDR-TB in Kuwait. Methods Ninety-three MDR-TB strains isolated from 12 Kuwaiti and 81 expatriate patients and 50 pansusceptible strains were used. Phenotypic drug susceptibility was determined by MGIT 460 TB/960 system. Mutations conferring resistance to rifampicin, isoniazid, pyrazinamide, ethambutol and streptomycin were detected by genotype MTBDRplus assay and/or PCR sequencing of three rpoB regions, katG codon 315 (katG315) + inhA regulatory region, pncA, three embB regions and rpsL + rrs-500–900 regions. Spoligotyping kit was used, spoligotypes were identified by SITVIT2, and phylogenetic tree was constructed by using MIRU-VNTRplus software. Phylogenetic tree was also constructed from concatenated sequences by MEGA7 software. Additional PCR sequencing of gidB and rpsA was performed for cluster isolates. Results Pansusceptible isolates contained wild-type sequences. Mutations in rpoB and katG and/or inhA were detected in 93/93 and 92/93 MDR-TB strains, respectively. Mutations were also detected for pyrazinamide resistance, ethambutol resistance and streptomycin resistance in MDR-TB isolates in pncA, embB and rpsL + rrs, respectively. Spoligotyping identified 35 patterns with 18 isolates exhibiting unique patterns while 75 isolates grouped in 17 patterns. Beijing genotype was most common (32/93), and 11 isolates showed nine orphan patterns. Phylogenetic analysis of concatenated sequences showed unique patterns for 51 isolates while 42 isolates grouped in 16 clusters. Interestingly, 22 isolates in eight clusters by both methods were isolated from TB patients typically within a span of 2 years. Five of eight clusters were confirmed by additional gidB and rpsA sequence data. Conclusions Our study provides the first insight into molecular epidemiology of MDR-TB in Kuwait and identified several potential clusters of local transmission of MDR-TB involving 2–6 subjects which had escaped detection by routine surveillance studies. Prospective detection of resistance-conferring mutations can identify possible cases of local transmission of MDR-TB in low MDR-TB settings.

scholarly journals 759. Molecular Characterization and Epidemiology of Multidrug-Resistant Mycobacterium tuberculosis (MDR-TB) and Identification of Possible Cases of Local Transmission of MDR-TB in Kuwait

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S272-S272
Author(s):  
Eiman Mokaddas ◽  
Suhail Ahmad ◽  
Noura Al-Mutairi
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Phylogenetic Tree ◽  
Regulatory Region ◽  
Multidrug Resistant ◽  
Sequencing Data ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Routine Surveillance ◽  
Mdr Tb ◽  
Local Transmission

Abstract Background Increasing incidence of multidrug-resistant tuberculosis (MDR-TB) is hampering efforts to control TB. Kuwait is a low (25/100,000) TB incidence country and ~1% of Mycobacterium tuberculosis strains are resistant to rifampin, RIF and isoniazid, INH (MDR-TB). Analysis of resistance conferring mutations in seven genes was combined with spoligotyping for detecting local transmission of MDR-TB in Kuwait. Methods MDR-TB strains (n = 131) from 88 TB patients and 50 susceptible strains were used. Susceptibility testing was done by MGIT 960 system, gMTBDRplus assay and PCR-sequencing of three regions of rpoB, katG codon 315 (katG315) + inhA regulatory region, embB (embB306/embB406/embB497 regions), rpsL + rrs-500–900 regions and pncA for RIF, INH, ethambutol (EMB), streptomycin (SM) and pyrazinamide (PZA), respectively. Sequencing data were used to construct phylogenetic tree by MEGA7 software. Spoligotypes were identified by SITVIT2 and phylogenetic tree was made by MIRU-VNTRplus software. Results Mutations were detected in most isolates in rpoB, katG+inhA, embB, rpsL+rrs and pncA which confer resistance to RIF, INH, EMB, SM and PZA, respectively. Phylogenetic analysis of multi-locus concatenated sequences showed unique patterns for 51 patient’s isolates while 37 patient’s isolates grouped in 14 clusters. Spoligotyping identified 35 patterns (19 unique patterns and 69 patients’s isolates in 16 patterns) including 11 orphan patterns. Sixteen isolates yielded six clusters (each containing two to five isolates) by both fingerprinting methods. Conclusion Our study provides the first insight into molecular epidemiology of MDR-TB in Kuwait and identified six potential cases of local transmission of MDR-TB involving two to five subjects (including five Kuwaiti patients) which had escaped detection by routine surveillance studies. Prospective detection of resistance conferring mutations thus identifies possible cases of local transmission of MDR-TB in low TB incidence countries. Disclosures All authors: No reported disclosures.

scholarly journals Evaluating the Frequency of Resistance to Pyrazinamide Among Drug-resistant Strains of Mycobacterium tuberculosis in Isfahan, Iran

2021 ◽  
Vol 16 (2) ◽  
Author(s):  
Bahram Nasr-Esfahani ◽  
Sharareh Moghim ◽  
Mahshid Salehi ◽  
Masoud Keikha
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Drug Susceptibility ◽  
Drug Susceptibility Test ◽  
Sequencing Method ◽  
Mdr Tb ◽  
Proportion Method ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
The City ◽  
New Mutations

Background: Pyrazinamide is one of the most important first-line medications for the treatment of tuberculosis and an alternative intake for MDR-TB and XDR-TB patients. Objectives: The purpose of this study was to evaluate resistance to pyrazinamide in the isolates resistant to the Mycobacterium tuberculosis drug in patients in the city of Isfahan. Methods: In this study, the drug susceptibility test was performed with pyrazinamide using the proportion method and PZA assay on 47 isolates resistant to Mycobacterium tuberculosis. Then, the mutations of the pncA and rpsA genes of the isolates resistant to pyrazinamide were evaluated by the sequencing method. Results: According to the proportion method, 19 cases were resistant to pyrazinamide, 16 of which had mutations in their pncA and rpsA genes. Besides, five new mutations were recorded, and three isolates lacked mutations in the mentioned genes. Conclusions: Pyrazinamide resistance is high in MDR-TB and INH mono-resistant isolates. Therefore, evaluating the susceptibility to pyrazinamide in patients with MDR-TB before the initiation of treatment with pyrazinamide is considered essential.

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