scholarly journals Drug resistance gene mutations and treatment outcomes in MDR-TB: A prospective study in Eastern China

2021 ◽  
Vol 15 (1) ◽  
pp. e0009068
Author(s):  
Qiao Liu ◽  
Dandan Yang ◽  
Beibei Qiu ◽  
Leonardo Martinez ◽  
Ye Ji ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Treatment Outcomes ◽  
Eastern China ◽  
Multivariable Analysis ◽  
Resistance Mutation ◽  
Gene Mutations ◽  
Drug Resistance Mutation ◽  
Drug Susceptibility ◽  
Phenotypic Resistance ◽  
Mdr Tb

Background Multidrug-resistant tuberculosis (MDR-TB) poses a serious challenge to TB control. It is of great value to search for drug resistance mutation sites and explore the roles that they play in the diagnosis and prognosis of MDR-TB. Methods We consecutively enrolled MDR-TB patients from five cities in Jiangsu Province, China, between January 2013 and December 2014. Drug susceptibility tests of rifampin, isoniazid, ofloxacin, and kanamycin were routinely performed by proportion methods on Lowenstein–Jensen (LJ) medium. Drug resistance-related genes were sequenced, and the consistency of genetic mutations and phenotypic resistance was compared. The association between mutations and treatment outcomes was expressed as odds ratios (ORs) and 95% confidence intervals (CIs). Results Among 87 MDR-TB patients, 71 with treatment outcomes were involved in the analysis. The proportion of successful treatment was 50.7% (36/71). The rpoB gene exhibited the highest mutation rate (93.0%) followed by katG (70.4%), pncA (33.8%), gyrA (29.6%), eis (15.5%), rrs (12.7%), gyrB (9.9%) and rpsA (4.2%). Multivariable analysis demonstrated that patients with pncA gene mutations (adjusted OR: 19.69; 95% CI: 2.43–159.33), advanced age (adjusted OR: 13.53; 95% CI: 1.46–124.95), and nonstandard treatment (adjusted OR: 7.72; 95% CI: 1.35–44.35) had a significantly higher risk of poor treatment outcomes. Conclusions These results suggest that Mycobacterium tuberculosis gene mutations may be related to phenotypic drug susceptibility. The pncA gene mutation along with treatment regimen and age are associated with the treatment outcomes of MDR-TB.

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 Relapse or Re-Infection, the Situation of Recurrent Tuberculosis in Eastern China

2021 ◽  
Vol 11 ◽  
Author(s):  
Yan Shao ◽  
Honghuan Song ◽  
Guoli Li ◽  
Yan Li ◽  
Yishu Li ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Eastern China ◽  
Drug Susceptibility ◽  
Population Based ◽  
Variable Number ◽  
Efficient Treatment ◽  
Significant Difference ◽  
Mdr Tb ◽  
Culture Positive ◽  
Recurrent Tuberculosis

PurposeRecurrent tuberculosis (TB) is defined by more than one TB episode per patient and is caused by re-infection with a new Mycobacterium tuberculosis (Mtb) strain or relapse with the previous strain. Recurrence of TB is one important obstacle for End TB strategy in the world and elucidating the triggers of recurrence is important for the current TB control strategy in China. This study aimed to analyze the sources of recurrent TB by the molecular genotyping method.MethodA population-based surveillance was undertaking on all culture-positive TB cases in Jiangsu province, China from 2013 to 2019. Phenotypic drug susceptibility test (DST) by proportion method and mycobacterial interspersed repetitive units-variable number of tandem repeat (MIRU-VNTR) were adopted for drug resistance and genotype detection.ResultsA total of 1451 culture-positive TB patients were collected and 30 (2.06%, 30/1451) TB cases had recurrent TB episodes. Except 7 isolates were failed during subculture, 23 paired isolates were assessed. After genotyping by MIRU-VNTR, 12 (52.17%, 12/23) paired recurrence TB were demonstrated as relapse and 11 (47.83%,11/23) paired cases were identified as re-infection. The average interval time for recurrence was 24.04 (95%CI: 19.37-28.71) months, and there was no significant difference between relapse and re-infection. For the relapsed cases, two paired isolates exhibited drug resistance shifting, while four paired isolates revealed inconsistent drug resistance among the re-infection group including two multidrug-resistant tuberculosis (MDR-TB) at the second episode.ConclusionRelapse and re-infection contributed equally to the current situation of recurrence TB in Jiangsu, China. Besides, more efficient treatment assessment, specific and vigorous interventions are urgently needed for MDR-TB patients, considering obvious performance among re-infection cases.

scholarly journals Dual targeting of EGFR can overcome a major drug resistance mutation in mouse models of EGFR mutant lung cancer

2009 ◽  
Author(s):  
Lucia Regales ◽  
Yixuan Gong ◽  
Ronglai Shen ◽  
Elisa de Stanchina ◽  
Igor Vivanco ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Mouse Models ◽  
Resistance Mutation ◽  
Drug Resistance Mutation ◽  
Dual Targeting ◽  
Egfr Mutant ◽  
Major Drug

scholarly journals Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap–Core Interface of HIV-1 Protease

ACS Omega ◽  
2018 ◽  
Vol 3 (9) ◽  
pp. 12132-12140 ◽  
Author(s):  
Andres Wong-Sam ◽  
Yuan-Fang Wang ◽  
Ying Zhang ◽  
Arun K. Ghosh ◽  
Robert W. Harrison ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Resistance Mutation ◽  
Drug Resistance Mutation ◽  
Hiv 1

scholarly journals Shall I trust the report? Variable performance of Sanger sequencing revealed by deep sequencing on HIV drug resistance mutation detection

2020 ◽  
Vol 93 ◽  
pp. 182-191 ◽  
Author(s):  
Nan-Yu Chen ◽  
Shu-Wei Kao ◽  
Zhuo-Hao Liu ◽  
Ting-Shu Wu ◽  
Chia-Lung Tsai ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Deep Sequencing ◽  
Sanger Sequencing ◽  
Mutation Detection ◽  
Resistance Mutation ◽  
Drug Resistance Mutation ◽  
Hiv Drug Resistance ◽  
Variable Performance

scholarly journals Monitoring of HIV Drug Resistance Mutations in Newly Diagnosed Patients in Cyprus (2010–2012)

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S424-S424
Author(s):  
Ioannis Demetriades
Keyword(s):  
Drug Resistance ◽  
Phylogenetic Trees ◽  
Resistance Mutation ◽  
Drug Resistance Mutation ◽  
High Rate ◽  
Resistance Testing ◽  
Newly Diagnosed ◽  
Resistance Mutations ◽  
Subtype B ◽  
Hiv 1

Abstract Background A molecular epidemiology study of HIV-1 infection was conducted in 100 HIV-1 diagnosed and untreated patients in Cyprus representing 65.4 percent of all the reported HIV-1 infections in Cyprus between 2010 and 2012. Methods Eighty-two patients were newly diagnosed (genotypic drug resistance testing within six months from diagnosis), and 18 patients were HIV-1 diagnosed for a longer period or the diagnosis date was unknown. Results Phylogenetic trees of the pol sequences obtained in this study with reference sequences indicated that subtypes B and A1 were the most common subtypes present and accounted for 41.0 and 19.0% respectively, followed by subtype C (7.0%), F1 (8.0%), CRF02_AG (4.0%), A2 (2.0%), other CRFs (7.0%) and unknown recombinant forms, URFs (12%). Most of newly-diagnosed study subjects were Cypriots (63%), males (78%) with median age 39 (Interquartile Range, IQR 33–48) reporting having sex with other men, MSM (51%). Conclusion A high rate of clustered transmission of subtype B drug-sensitive strains to reverse transcriptase and protease inhibitors was observed among MSM. Twenty-eight out of forty-one MSM study subjects (68.0%) infected were implicated in five transmission clusters, two of which are subtype A1 and three subtype B strains. The two largest MSM subtype B clusters included nine and eight Cypriot men, respectively, living in all major cities in Cyprus. There were only three newly diagnosed patients with transmitted drug resistant HIV-1 strains, one study subject from the United Kingdom infected with subtype B strain and one from Romania with subtype A2 strain, both with the PI drug resistance mutation M46L and one patient from Greece with subtype A1 strain with the NNRTI drug resistance mutation K103N. Disclosures All authors: No reported disclosures.

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