scholarly journals In Vitro Drug Susceptibility of Bedaquiline, Delamanid, Linezolid, Clofazimine, Moxifloxacin, and Gatifloxacin against Extensively Drug-Resistant Tuberculosis in Beijing, China

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Yu Pang ◽  
Zhaojing Zong ◽  
Fengmin Huo ◽  
Wei Jing ◽  
Yifeng Ma ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Fluoroquinolone Resistance ◽  
Cross Resistance ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Genetic Characteristics ◽  
Acquired Drug Resistance ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant

ABSTRACT Extensively drug-resistant tuberculosis (XDR-TB) is a deadly form of TB that can be incurable due to its extreme drug resistance. In this study, we aimed to explore the in vitro susceptibility to bedaquiline (BDQ), delamanid (DMD), linezolid (LZD), clofazimine (CLO), moxifloxacin (MFX), and gatifloxacin (GAT) of 90 XDR-TB strains isolated from patients in China. We also describe the genetic characteristics of XDR-TB isolates with acquired drug resistance. Resistance to MFX, GAT, LZD, CLO, DMD, and BDQ was found in 82 (91.1%), 76 (84.4%), 5 (5.6%), 5 (5.6%), 4 (4.4%), and 3 (3.3%) isolates among the XDR-TB strains, respectively. The most frequent mutations conferring fluoroquinolone resistance occurred in codon 94 of the gyrA gene (57.8%), and the strains with these mutations (69.2%) were associated with high-level MFX resistance compared to strains with mutations in codon 90 (25.0%) (P < 0.01). All 5 CLO-resistant isolates exhibited ≥4-fold upward shifts in the BDQ MIC, which were attributed to mutations of codons 53 (60.0%) and 157 (20.0%) in the Rv0678 gene. Additionally, mutation in codon 318 of the fbiC gene was identified as the sole mutation related to DMD resistance. In conclusion, our data demonstrate that the XDR-TB strains exhibit a strikingly high proportion of resistance to the current anti-TB drugs, whereas BDQ, DMD, LZD, and CLO exhibit excellent in vitro activity against XDR-TB in the National Clinical Center on TB of China. The extensive cross-resistance between OFX and later-generation fluoroquinolones indicates that MFX and GAT may have difficulty in producing the desired effect for XDR-TB patients.

scholarly journals Early Detection of Emergent Extensively Drug-Resistant Tuberculosis by Flow Cytometry-Based Phenotyping and Whole-Genome Sequencing

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Max R. O’Donnell ◽  
Michelle H. Larsen ◽  
Tyler S. Brown ◽  
Paras Jain ◽  
Vanisha Munsamy ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Genome Sequencing ◽  
Low Frequency ◽  
Whole Genome ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Content Type ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant

ABSTRACTA critical gap in tuberculosis (TB) treatment is detection of emergent drug resistance. We hypothesized that advanced phenotyping with whole-genome sequencing (WGS) will detect low-frequencyMycobacterium tuberculosisdrug resistance. We assessed a reporter mycobacteriophage (Φ2GFP10)in vitroto detect drug-resistant subpopulations and predictM. tuberculosisbactericidal activity in this pilot study. Subsequently, we prospectively studied 20 TB patients with serial Φ2GFP10, Xpert MTB/RIF, andM. tuberculosisculture through end of treatment. WGS was performed, and single nucleotide polymorphisms (SNPs) were examined to detect mixed infection in selectedM. tuberculosisisolates. ResistantM. tuberculosisisolates were detected at 1:100,000, and changes in cytometry-gated events were predictive ofin vitroM. tuberculosisbactericidal activity using the Φ2GFP10 assay. Emergent drug resistance was detected in one patient by Φ2GFP10 at 3 weeks but not by conventional testing (M. tuberculosisculture and GeneXpert). WGS revealed a phylogeographically distinct extensively drug-resistant tuberculosis (XDR-TB) genome, identical to an XDR-TB isolate from the patient’s spouse. Variant lineage-specific SNPs were present early, suggesting mixed infection as the etiology of emergent resistance with temporal trends providing evidence for selection during treatment. Φ2GFP10 can detect low-frequency drug-resistantM. tuberculosisand with WGS characterize emergentM. tuberculosisresistance. In areas of high TB transmission and drug resistance, rapid screening for heteroresistance should be considered.

Treatment of patients with multidrug­resistant and extensively drug resistant tuberculosis depending on the composition of individualized regimens: immediate and long­term results

2021 ◽  
pp. 7-15
Author(s):  
Yu.I. Feshchenko ◽  
N.A. Litvinenko ◽  
N.V. Grankina ◽  
M.V. Pogrebna ◽  
Yu.O. Senko ◽  
...  
Keyword(s):  
Effective Treatment ◽  
Treatment Effectiveness ◽  
Individualized Treatment ◽  
Fluoroquinolone Resistance ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Treatment Regimens ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant

Objective — to study the effectiveness of treatment of MDR-TB (multidrug-resistant tuberculosis) and preXDR-TB/XDR-TB (pre-extensively and extensively drug resistant tuberculosis), depending on the composition of ITRs (individualized treatment regimens). Materials and methods. Тhe prospective observational study included 566 patients with MDR/preXDR-TB and XDR-TB during 2016—2020 on the scientific clinical bases of the SI «National Institute of Phthisiology and Pulmonology named after F.G. Yanovsky NAMS of Ukraine» and ME «Kryvyi Rih Anti-tuberculosis Dispensary» Dnipropetrovsk Regional Council Department. Patients were prescribed individualized treatment regimens in cases where short (standard or modified) regimens could not be prescribed. Patients were divided into comparison groups: 469 of them were treated with antimycobacterial therapy including bedaquiline and other effective antimycobacterial drugs groups A—C (without delamanid) — group 1. And 97 patients who were treated with the inclusion of both new antimycobacterial drugs (bedaquiline and delamanid) — group 2. Results and discussion. Regardless of whether the delamanid, in addition to bedaquiline and other drugs selected for the scheme according to WHO recommendations, «effective treatment» was found in 91.3 against 88.6 % of patients. In the remote period (6-month — 4-year follow-up period) there was no recurrence of the disease, regardless of the composition of the regime. The loss of treatment effectiveness was due to deaths from non-tuberculosis reasons and those lost for follow-up. Conclusions. For highly effective treatment, individualized regimens should include bedaquidine and linezolid from group A, and for previously ineffectively treated patients, clofazimine and carbapenems must be included (possibility to include 4 or more effective AMDs in ITR). For patients with fluoroquinolone resistance, treatment should include delamanid.

scholarly journals Evolution and Transmission Patterns of Extensively Drug-Resistant Tuberculosis in China

2014 ◽  
Vol 59 (2) ◽  
pp. 818-825 ◽  
Author(s):  
Feifei Wang ◽  
Lingyun Shao ◽  
Xiaoping Fan ◽  
Yaojie Shen ◽  
Ni Diao ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Resistance Genes ◽  
Variable Number Tandem Repeat ◽  
Resistance Mutation ◽  
Beijing Genotype ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant

ABSTRACTThe emergence and transmission of extensively drug-resistant tuberculosis (XDR-TB) pose an increasing threat to global TB control. This study aimed to identify the patterns of evolution and transmission dynamics of XDR-TB in populations in a region of China where TB is highly endemic. We analyzed a total of 95 XDR-TB isolates collected from 2003 to 2009 in Chongqing, China. Eight drug resistance genes covering 7 drugs that define XDR-TB were amplified by PCR followed by DNA sequencing. Variable-number tandem repeat 16-locus (VNTR-16) genotyping and genotypic drug resistance profiles were used to determine the evolution or transmission patterns of XDR-TB strains. Our results indicated that the Beijing genotype was predominant (85/95 [89.5%]) in XDR-TB strains, and as many as 40.0% (38/95) of the isolates were distributed into 6 clusters based on VNTR-16 genotyping and drug resistance mutation profiles. All isolates of each cluster harbored as many as six identical resistance mutations in the drug resistance genesrpoB,katG,inhApromoter,embB,rpsL, andgidB. Among the nine cases with continuous isolates from multidrug-resistant (MDR) to XDR-TB, 4 cases represented acquired drug resistance, 4 cases were caused by transmission, and 1 case was due to exogenous superinfection. The XDR-TB epidemic in China is mainly caused by a high degree of clonal transmission, but evolution from MDR to XDR and even superinfection with a new XDR strain can also occur.

scholarly journals Beta-lactam antibiotics as reserve medications for the treatment of drug-resistant tuberculosis

2021 ◽  
Vol 66 (5-6) ◽  
pp. 78-85
Author(s):  
G. N. Mozhokina ◽  
A. G. Samoilova ◽  
I. A. Vasilyeva
Keyword(s):  
Drug Resistance ◽  
Review Article ◽  
Drug Resistant ◽  
Beta Lactam ◽  
Drug Resistant Tuberculosis ◽  
Beta Lactam Antibiotics ◽  
Resistant Tuberculosis ◽  
Extensive Drug Resistance ◽  
Tuberculosis Activity

The review article presents an analysis of literature data on the necessity to expand the range of medications possessing anti-tuberculosis activity for the treatment of the most severe forms of drug-resistant tuberculosis through the use of beta-lactam antibiotics in chemotherapy regimens. The mechanism of action of beta- lactam antibiotics on mycobacterium tuberculosis is shown, and the results of in vitro studies to assess their anti-tuberculosis activity are presented. Clinical studies on the use of carbapenems prove the feasibility of their use for the treatment of patients with tuberculosis with multiple and extensive drug resistance of the pathogen.

scholarly journals Drug resistance profile among multi-drug resistant tuberculosis patients at diagnosis and correlation with history of anti-tubercular treatment in a tertiary care center

2019 ◽  
Vol 6 (6) ◽  
pp. 1918
Author(s):  
Rahul Kumar ◽  
Rajiv Garg ◽  
Silpa Kshetrimayum ◽  
Amita Jain
Keyword(s):  
Drug Resistance ◽  
Drug Sensitivity ◽  
Drug Resistant ◽  
Second Line ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Primary Drug Resistance ◽  
Mdr Tb ◽  
History Of

Background: Drug Resistant Tuberculosis (DR-TB) is a major threat to the realization of the goal of a TB free world in the near future. It is important to study the reasons for the increasing number of such cases so that effective action can be taken to control this growing epidemic.Methods: Sputum from 36 patients diagnosed with acquired pulmonary Multidrug Resistant Tuberculosis (MDR-TB) were subjected to first- and second-line Drug Sensitivity Testing (DST) after liquid culture in mycobacterium growth Indicator Tube (MGIT). Primary MDR-TB cases were excluded. The relation of the drug sensitivity profile with the history of prior treatment taken was statistically analysed.Results: Majority of the patients had received appropriate treatment, and most had adhered to prescribed treatment. Among the 36 patients, 24(66.7%) were found to be Pre-Extensively Drug Resistant (Pre-XDR-TB) and 4(11.1%) were extensively drug resistant XDR-TB cases. Inappropriate prescription of fluoroquinolone (FQ) was found to be most common. Prior intake of any drug was not found to significantly affect subsequent resistance to that drug.Conclusions: Fluoroquinolone resistance is quite common in patients with DR-TB (66.7%). This study did not find the prior use of FQ or any other drug to significantly affect subsequent resistance to the drug. Primary drug resistance is thus a major concern. 11.1% patients were found to be XDR-TB cases. Hence DST for first- and second-line drugs should be done at the time of diagnosis to avoid failure of treatment with a predesigned regimen.

scholarly journals Drug resistance beyond extensively drug-resistant tuberculosis: individual patient data meta-analysis

2012 ◽  
Vol 42 (1) ◽  
pp. 169-179 ◽  
Author(s):  
Giovanni Battista Migliori ◽  
Giovanni Sotgiu ◽  
Neel R. Gandhi ◽  
Dennis Falzon ◽  
Kathryn DeRiemer ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Patient Data ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant
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