scholarly journals Analysis of drug resistance and mutation profiles in Mycobacterium tuberculosis isolates in a surveillance site in Beijing, China

2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098493
Author(s):  
Jie Zhang ◽  
Yixuan Ren ◽  
Liping Pan ◽  
Junli Yi ◽  
Tong Guan ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Drug Testing ◽  
Multidrug Resistant ◽  
High Rate ◽  
Drug Resistant ◽  
Surveillance Site ◽  
Mdr Tb ◽  
Previously Treated Patients ◽  
Beijing China

Objective This study analyzed drug resistance and mutations profiles in Mycobacterium tuberculosis isolates in a surveillance site in Huairou District, Beijing, China. Methods The proportion method was used to assess drug resistance profiles for four first-line and seven second-line anti-tuberculosis (TB) drugs. Molecular line probe assays were used for the rapid detection of resistance to rifampicin (RIF) and isoniazid (INH). Results Among 235 strains of M. tuberculosis, 79 (33.6%) isolates were resistant to one or more drugs. The isolates included 18 monoresistant (7.7%), 19 polyresistant (8.1%), 28 RIF-resistant (11.9%), 24 multidrug-resistant (MDR) (10.2%), 7 pre-extensively drug-resistant (XDR, 3.0%), and 2 XDR strains (0.9%). A higher rate of MDR-TB was detected among previously treated patients than among patients with newly diagnosed TB (34.5% vs. 6.8%). The majority (62.5%) of RIF-resistant isolates exhibited a mutation at S531L in the DNA-dependent RNA polymerase gene. Meanwhile, 62.9% of INH-resistant isolates carried a mutation at S315T1 in the katG gene. Conclusion Our results confirmed the high rate of drug-resistant TB, especially MDR-TB, in Huairou District, Beijing, China. Therefore, detailed drug testing is crucial in the evaluation of MDR-TB treatment.

scholarly journals Prevalence of Multi-Drug Resistant Mycobacterium Tuberculosis in Khyber Pakhtunkhwa – A High Tuberculosis Endemic Area of Pakistan

2020 ◽  
Vol 69 (2) ◽  
pp. 133-137 ◽  
Author(s):  
SAJID ALI ◽  
MUHAMMAD TAHIR KHAN ◽  
ANWAR SHEED KHAN ◽  
NOOR MOHAMMAD ◽  
MUHAMMAD MUMTAZ KHAN ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Large Scale ◽  
Simple Random Sampling ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Drug Resistant ◽  
Khyber Pakhtunkhwa ◽  
Mdr Tb

Anti-tuberculosis therapy involves the combination of drugs to hamper the growth of Mycobacterium tuberculosis (MTB). The emergence of multidrug-resistant tuberculosis (MDR-TB) is a global concern. Pakistan has been ranked 5th position in terms of a high burden of MDR-TB in the world. The aim of the current study was to investigate the prevalence of drug resistance in MTB in Khyber Pakhtunkhwa. Random samples were collected from 25 districts using the simple random sampling formula. All samples were processed in a biosafety level 3 laboratory for culture and drug susceptibility testing. Among 5759 presumptive tuberculosis (TB) cases, 1969 (34%) were positive. The proportion of TB was higher in females (39%) than males (29%), thus it represents a significant association between gender and tuberculosis (p < 0.05). People ages between 25 to 34 years were more likely to be infected with MTB (40%). Drug-resistant profile showed 97 (4.9%) patients were infected with MDR-TB. Streptomycin resistance was the highest and was observed in 173 (9%) isolates followed by isoniazid in 119 (6%) isolates. The lowest resistance was observed to pyrazinamide (3%). The prevalence of MDR-TB (10.4%) among patients that previously received anti-tuberculosis treatment is seemingly high. A large-scale drug resistance survey is required to evaluate the drug resistance for better management of tuberculosis.

scholarly journals Comparison of In Vitro Activity and MIC Distributions between the Novel Oxazolidinone Delpazolid and Linezolid against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis in China

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Zhaojing Zong ◽  
Wei Jing ◽  
Jin Shi ◽  
Shu'an Wen ◽  
Tingting Zhang ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Novel Mutation ◽  
Multidrug Resistant ◽  
23S Rrna ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Significant Difference ◽  
Mdr Tb

ABSTRACT Oxazolidinones are efficacious in treating mycobacterial infections, including tuberculosis (TB) caused by drug-resistant Mycobacterium tuberculosis. In this study, we compared the in vitro activities and MIC distributions of delpazolid, a novel oxazolidinone, and linezolid against multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) in China. Additionally, genetic mutations in 23S rRNA, rplC, and rplD genes were analyzed to reveal potential mechanisms underlying the observed oxazolidinone resistance. A total of 240 M. tuberculosis isolates were included in this study, including 120 MDR-TB isolates and 120 XDR-TB isolates. Overall, linezolid and delpazolid MIC90 values for M. tuberculosis isolates were 0.25 mg/liter and 0.5 mg/liter, respectively. Based on visual inspection, we tentatively set epidemiological cutoff (ECOFF) values for MIC determinations for linezolid and delpazolid at 1.0 mg/liter and 2.0 mg/liter, respectively. Although no significant difference in resistance rates was observed between linezolid and delpazolid among XDR-TB isolates (P > 0.05), statistical analysis revealed a significantly greater proportion of linezolid-resistant isolates than delpazolid-resistant isolates within the MDR-TB group (P = 0.036). Seven (53.85%) of 13 linezolid-resistant isolates were found to harbor mutations within the three target genes. Additionally, 1 isolate exhibited an amino acid substitution (Arg126His) within the protein encoded by rplD that contributed to high-level resistance to linezolid (MIC of >16 mg/liter), compared to a delpazolid MIC of 0.25. In conclusion, in vitro susceptibility testing revealed that delpazolid antibacterial activity was comparable to that of linezolid. A novel mutation within rplD that endowed M. tuberculosis with linezolid, but not delpazolid, resistance was identified.

scholarly journals Increasing prevalence of resistance to second-line drugs among multidrug-resistant Mycobacterium tuberculosis isolates in Kuwait

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Noura M. Al-Mutairi ◽  
Suhail Ahmad ◽  
Eiman Mokaddas
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Mutation Detection ◽  
Susceptibility Testing ◽  
Multidrug Resistant ◽  
Genetic Mutations ◽  
Second Line ◽  
Injectable Drugs ◽  
Mdr Tb ◽  
Phenotypic Susceptibility

AbstractMolecular methods detect genetic mutations associated with drug resistance. This study detected resistance-conferring mutations in gyrA/gyrB for fluoroquinolones and rrs/eis genes for second-line injectable drugs (SLIDs) among multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates in Kuwait. Fifty pansusceptible M. tuberculosis and 102 MDR-TB strains were tested. Phenotypic susceptibility testing was performed by MGIT 960 system using SIRE drug kit. GenoType MTBDRsl version 1 (gMTBDRslv1) and GenoType MTBDRsl version 2 (gMTBDRslv2) tests were used for mutation detection. Results were validated by PCR-sequencing of respective genes. Fingerprinting was performed by spoligotyping. No mutations were detected in pansusceptible isolates. gMTBDRslv1 detected gyrA mutations in 12 and rrs mutations in 8 MDR-TB isolates. gMTBDRsl2 additionally detected gyrB mutations in 2 and eis mutation in 1 isolate. Mutations in both gyrA/gyrB and rrs/eis were not detected. gMTBDRslv1 also detected ethambutol resistance-conferring embB mutations in 59 isolates. Although XDR-TB was not detected, frequency of resistance-conferring mutations for fluoroquinolones or SLIDs was significantly higher among isolates collected during 2013–2019 versus 2006–2012. Application of both tests is warranted for proper management of MDR-TB patients in Kuwait as gMTBDRslv2 detected resistance to fluoroquinolones and/or SLIDs in 3 additional isolates while gMTBDRslv1 additionally detected resistance to ethambutol in 58% of MDR-TB isolates.

scholarly journals Genotypes of Mycobacterium tuberculosis isolates circulating in Shaanxi Province, China

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0242971
Author(s):  
Yan Li ◽  
Yu Pang ◽  
Tianhua Zhang ◽  
Xiaoping Xian ◽  
Jian Yang ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Multidrug Resistant ◽  
Shaanxi Province ◽  
Drug Resistant ◽  
Beijing Family ◽  
Tuberculosis Patients ◽  
Smear Positive Pulmonary Tuberculosis ◽  
Discriminatory Index

Objectives The prevalence of drug-resistant TB in Shaanxi Province is higher than other areas. This study was aimed to investigate the genetic diversity and epidemiology of Mycobacterium tuberculosis clinical strains in Shaanxi Province, China. Methods From January to December 2016, a total of 298 Mycobacterium tuberculosis clinical isolates from smear-positive pulmonary tuberculosis patients were genotyped by Mcspoligotyping and 15-locus VNTR. Results We found that the Beijing family strains was the most prominent family(81.54%, 243/298). Other family strains included T family(9.06%, 27/298), U family(0.67%, 2/298), LAM9 family(0.34%, 1/298) and Manu family(0.34%, 1/298). The rates of multidrug-resistant (MDR) M.Tuberculosis, age, type of case and education between Beijing and non-Beijing family strains were not statistically different, while the distribution in the three different regions among these was statistically significant. VNTR results showed that strains were classified into 280 genotypes, and 33 (11.07%) strains could be grouped into 14 clusters. 11 of the 15-VNTR loci were highly or moderately discriminative according to the Hunter-Gaston discriminatory index. Conclusions We concluded that the Beijing family genotype was the most prevalent genotype and 15-locus VNTR typing might be suitable for genotyping of M. tuberculosis in Shaanxi Province. There was less association between Beijing family genotypes and drug resistance in our study area.

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 Drug-resistant Mycobacterium tuberculosis and its genotypes isolated from an outbreak in western Thailand

2020 ◽  
Author(s):  
Janisara Rudeeaneksin ◽  
Benjawan Phetsuksiri ◽  
Chie Nakajima ◽  
Supranee Bunchoo ◽  
Krairerk Suthum ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Variable Number Tandem Repeat ◽  
Multidrug Resistant ◽  
Variable Number ◽  
Drug Resistant ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Extensively Drug Resistant ◽  
Mdr Tb ◽  
Vntr Analysis

Abstract Background Multidrug-resistant TB (MDR-TB) outbreaks have occurred in the Thamaka district, Kanchanaburi province in Thailand. Methods Seventy-two isolates, which included 7% mono-, 30.6% MDR and extensively drug-resistant TB (XDR-TB), were genotyped by spoligotyping, mycobacterial interspersed repetitive unit-variable-number tandem repeat (MIRU-VNTR) and single nucleotide polymorphism genotyping, and their drug resistance was analysed. Results The spoligotyping results showed that Beijing spoligo-international type (SIT)1 was predominant (n=38; 52.8%) while the remaining were non-Beijing sublineages (n=34). The MIRU-VNTR analysis showed that Beijing isolates, most of which belonged to the modern type (n=37), formed 5 clusters and 13 individual patterns. In katG, only mutation Ser315Thr was identified. In rpoB, Ser531Leu was predominant, except for His526Arg and Leu533Pro, which were found in two isolates. A cluster of 14 Beijing strains contained these common mutations and shared the MIRU-VNTR genotype with isolates in the Thamaka district that had spread previously. Two U SIT523 isolates contained the mutations A1400G in rrs and Asp94Gly in gyrA genes, indicating a spread of XDR-TB. Conclusions Most mutations were associated with drug resistance and the specific MDR Beijing and XDR-TB in U SIT523 isolates remain. This genotyping is a key tool for tracking TB transmission in the Thamaka district of Thailand.

scholarly journals Association between embB Codon 306 Mutations and Drug Resistance in Mycobacterium tuberculosis

2007 ◽  
Vol 51 (7) ◽  
pp. 2618-2620 ◽  
Author(s):  
Xin Shen ◽  
Guo-miao Shen ◽  
Jie Wu ◽  
Xiao-hong Gui ◽  
Xia Li ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Odds Ratio ◽  
Rapid Detection ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Candidate Marker ◽  
Resistant Tuberculosis

ABSTRACT embB306 mutants were detected in both ethambutol (EMB)-resistant and EMB-susceptible strains of Mycobacterium tuberculosis. Multidrug-resistant (MDR) strains had a higher proportion of embB306 mutants than non-MDR strains (odds ratio, 6.78; P < 0.001). The embB306 locus is a candidate marker for rapid detection of MDR and extremely drug resistant tuberculosis.

scholarly journals CBNAAT Based Identification and Demographic Pattern of Drug Resistant Mycobacterium Tuberculosis in South Kashmir, India- a One Year Retrospective Study

2021 ◽  
pp. 1-5
Author(s):  
Rubeena Hakkak ◽  
Saqib Rishi ◽  
Javid Ahmed Bhat
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Retrospective Study ◽  
State Level ◽  
Prolonged Treatment ◽  
Drug Resistant ◽  
Average Percentage ◽  
The World ◽  
Mdr Tb ◽  
Extra Pulmonary

India is the highest TB burden country in the world having an estimated incidence of 26.9 lakh cases in 2019. With a population of 1.32 billion, India has the highest burden of drug resistant TB (DR-TB) in the world. North zone of India is the second highest MDR-TB prevalent zone after the West zone of India. MDR TB treatment involves prolonged treatment with injectable second-line drugs, associated with more adverse effects, suboptimal treatment outcomes and higher risks of mortality compared to patients with drug-sensitive TB and those with lesser resistant forms of TB. Materials methods: This retrospective study was conducted in the department of Microbiology Government Medical College Anantnag, data was analyzed from March 2017 to February 2018. Non-sterile specimens were processed by Modified Petroff Method. Sterile specimens were concentrated by centrifugation and smear and cultures was inoculated from the sediment. CBNAAT assay was performed by Gene Xpert (Cepheid) 4 system according to the manufacturers’ recommendations. Results: Of the total 1497 clinically suspected tuberculosis specimens collected, 1370 (91.5%) were pulmonary and 127 (8.5%) were presumptive extra pulmonary tuberculosis received from different anatomical sites. Maximum clustering of cases was seen in 10-20 years age group. Out of the total 1497 samples 200 were CBNAAT confirmed Mycobacterium Tuberculosis positive samples. In which 155 were pulmonary and 45 were extra pulmonary. The average percentage positivity rate (i.e. percentage of MTB positive samples out of total samples tested) was 13.3% (200/1497).  Rifampicin resistance (RR-TB) was seen in 5.5% (11/200) samples. Out of the samples detected positive (200): 155 were pulmonary samples and out of these 155 pulmonary samples 8 were found to be RR MTB 5.1% (8/155).  Also out of the 200 positive samples 45 were extra pulmonary and out of these 45 extra pulmonary samples 3 were found to be RR MTB 6.6% (3/45). Conclusion: In this study we found that in our region 5.5%  cases of TB were RR-TB, 3.2% were new cases and 13% RR-TB was seen in  previously treated cases of MTB. The screening of drug resistance has to be expanded to offer universal DST including expanded DST .The second and most important activity is to strengthen drug resistance surveillance under the various national programs with inclusion of laboratories in the private sector as well. The state level regional studies also give us the opportunity to plan and execute intervention prioritization, based on the drug resistance trends observed.

scholarly journals Genotypic diversity of multi- and pre-extremely drug-resistant Mycobacterium tuberculosis isolates from Morocco

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0253826
Author(s):  
Amal Oudghiri ◽  
Ghizlane Momen ◽  
Achraf Aainouss ◽  
Amin Laglaoui ◽  
My Driss El Messaoudi ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Mycobacterium Tuberculosis ◽  
Genotypic Diversity ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Control Programs ◽  
Resistant Tuberculosis ◽  
Mdr Tb ◽  
Database Clustering ◽  
High Level

In Morocco, the prevalence of multidrug resistant tuberculosis (MDR-TB) continues to increase especially within previously treated cases; these MDR cases may evolve to extensively drug resistant tuberculosis (XDR-TB) raising major concern to TB control programs. From an epidemiological window, scarce informations are available about the genetic diversity of Mycobacterium tuberculosis (MTB) strains fueling these forms of resistance. The aim of this study was to assess to genetic diversity of MDR-MTB strains. Hence, this prospective study was conducted on patients diagnosed with MDR-TB at Pasteur Institute of Casablanca from 2010 to 2013. A total of 70 MDR-MTB isolates were genotyped by spoligotyping and 15-loci MIRU-VNTR methods. Spoligotyping generated four orphan patterns, five unique profiles whereas 61 strains were grouped in nine clusters (2 to 25 strains per cluster), the clustering rates being 87.1%. Subtyping by 15 loci MIRU-VNTR splitted all clusters already established by spoligotyping and generated 70 unique profiles not recognized in SITVIT2 database; clustering rate was equal to zero. HGDI analysis of 15 loci MIRU demonstrated that eight out of 15 loci were highly discriminant. Of note, all pre-XDR strains belongs to many clades, meaning that there no association between gyrA mutants and particular clade. Overall, the data generated by this study (i) describe the population structure of MDR MTBC in Morocco which is highly homogenous, (ii) confirm that TB in Morocco is almost exclusively transmitted by modern and evolutionary lineages with high level of biodiversity seen by MIRU, and (iii) validate the use of optimized 15-loci MIRU-VNTR format for future investigations in Morocco.

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.

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