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 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.

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 Risk factors for drug-resistant tuberculosis, the association between comorbidity status and drug-resistant patterns: a retrospective study of previously treated pulmonary tuberculosis in Shandong, China, during 2004–2019

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e044349
Author(s):  
Ning-ning Tao ◽  
Yi-fan Li ◽  
Wan-mei Song ◽  
Jin-yue Liu ◽  
Qian-yun Zhang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Drug Resistance ◽  
Retrospective Study ◽  
Pulmonary Tuberculosis ◽  
Logistic Models ◽  
Smoking History ◽  
Categorical Variables ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis

ObjectiveThis study was designed to identify the risk factors for drug-resistant tuberculosis (DR-TB) and the association between comorbidity and drug resistance among retreated pulmonary tuberculosis (PTB).DesignA retrospective study was conducted among all the 36 monitoring sites in Shandong, China, over a 16-year period. Baseline characteristics were collected from the TB Surveillance System. Categorical variables were compared by Fisher’s exact or Pearson’s χ2 test. The risk factors for drug resistance were identified using univariable analysis and multivariable logistic models. The influence of comorbidity on different types of drug resistance was evaluated by performing multivariable logistic models with the covariates adjusted by age, sex, body mass index, drinking/smoking history and cavity.ResultsA total of 10 975 patients with PTB were recorded during 2004–2019, and of these 1924 retreated PTB were finally included. Among retreated PTB, 26.2% were DR-TB and 12.5% had comorbidity. Smoking (adjusted OR (aOR): 1.69, 95% CI 1.19 to 2.39), cavity (aOR: 1.55, 95% CI 1.22 to 1.97) and comorbidity (aOR: 1.44, 95% CI 1.02 to 2.02) were risk factors for DR-TB. Of 504 DR-TB, 9.5% had diabetes mellitus, followed by hypertension (2.0%) and chronic obstructive pulmonary disease (1.8%). Patients with retreated PTB with comorbidity were more likely to be older, have more bad habits (smoking, alcohol abuse) and have clinical symptoms (expectoration, haemoptysis, weight loss). Comorbidity was significantly associated with DR-TB (aOR: 1.44, 95% CI 1.02 to 2.02), overall rifampin resistance (aOR: 2.17, 95% CI 1.41 to 3.36), overall streptomycin resistance (aOR: 1.51, 95% CI 1.00 to 2.27) and multidrug resistance (aOR: 1.96, 95% CI 1.17 to 3.27) compared with pan-susceptible patients (p<0.05).ConclusionSmoking, cavity and comorbidity lead to an increased risk of drug resistance among retreated PTB. Strategies to improve the host’s health, including smoking cessation, screening and treatment of comorbidity, might contribute to the control of tuberculosis, especially DR-TB, in China.

scholarly journals Mycobaterial interspersed repetitive units-variable number of tandem repeats analysis and pattern of drug resistance in extended drug resistant (XDR) TB isolates from pulmonary tuberculosis patients in Bangladesh

2020 ◽  
Vol 46 (1) ◽  
pp. 22-28
Author(s):  
Shirin Tarafder ◽  
Md Bayzid Bin Monir
Keyword(s):  
Drug Resistance ◽  
Molecular Typing ◽  
Tandem Repeats ◽  
Variable Number ◽  
Drug Resistant ◽  
Gyra Gene ◽  
Drug Resistant Tuberculosis ◽  
Tree Analysis ◽  
Resistant Tuberculosis ◽  
Mdr Tb

Background: To investigate the spread of specific genotypes in a defined geographical area and to determine any relationship of these genotypes with drug resistance the most essential method is molecular typing. It allows a rapid and precise species differentiation. Objective: This study was intended to observe the genotypes of XDR mycobacterium tuberculosis by determining 24 loci MIRU-VNTR analysis. Methods: To gain an insight about molecular typing of MTB and drug resistance-associated mutations in XDR-TB isolates a total of 98 multi drug resistant tuberculosis (MDR-TB) isolates collected through Xpert MTB/RIF assay. They were subjected to 2nd line (Fluoroquinolones, kanamycin, capreomycin and amikacin) drug susceptibility testing through line probe assay (LPA) in a view to detect extensively drug resistant tuberculosis (XDR-TB). Genotyping was done for XDR-TB isolates using 24 loci Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) using the online tool at http://www.MIRU-VNTRplus.org.. Out of 98 MDR-TB isolates 11(11.23%)  XDR-TB isolates were typed and analysed. Results: Twenty four loci MIRU-VNTR genotyping involving similarity searching and phylogenetic tree analysis revealed that six (54.60%) XDR-TB isolates belonged to Beijing strain, Other MTB strain also detected were Delhi/CAS two(18.20%), Haarlem two(18.20%) and New-1, one (9.10%) in number. Minimum spanning tree analysis showed two strain of Beijing family form a clonal complex. Beijing strains were more common among younger age group and within urban population. Beijing strains were also predominant in treatment failure patient. Only one new case of XDR-TB belongs to Delhi/CAS family. Second line mycobacterial drug resistance (MTBDRsl) detected by LPA showed the most prevalent mutations involved in Fluoroquinolones drug resistance (FQ) was Asp94Gly in gyrA gene (54.55%) in quinolone resistance determining region (QRDR) and for Injectable 2nd line Drug resistance (ISL) was A1401G, C1402T in 16S rrs gene (100%)..  All XDR-TB isolates showed resistance to Levofloxacin in 2nd line LPA but Moxifloxacin showed low level resistance to some cases. Conclusion: Molecular typing of XDR- TB isolates and pattern of drug resistance associated mutations in XDR-TB isolates in Bangladesh have not been reported previously. The result of this study highlights the need to reinforce the TB policy in Bangladesh with regard to control the spread and transmission as well as detection and treatment strategies regarding XDR-TB. Bangladesh Med Res Counc Bull 2020; 46(1): 22-28

scholarly journals Evaluation of Nitrate Reductase Assay (NRA) for rapid detection of druc resistant tuberculosis at National Tuberculosis Centre, Nepal

1970 ◽  
Vol 7 (1) ◽  
pp. 26-30
Author(s):  
PK Mandal ◽  
S Basnyat ◽  
DK Khadka ◽  
DR Bhatta
Keyword(s):  
Drug Resistance ◽  
Nitrate Reductase ◽  
Sensitivity And Specificity ◽  
Drug Susceptibility ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
National Tuberculosis ◽  
Nitrate Reductase Assay ◽  
Hiv Aids

Background: Treatment of drug-resistant tuberculosis is often based on drug susceptibility testing results. Thus simple, rapid and economic test is very important for diagnosis of drug resistant tuberculosis and such method aids in TB control effectively. One such method is a Nitrate Reductase Assay (NRA). Objective: To evaluate feasibility and performance of Nitrate Reductase Assay in the screening of drug-resistant tuberculosis. Setting: National Tuberculosis Centre and SAARC TB and HIV/AIDS Centre, Thimi, Bhaktapur, Nepal from April 2008 to March 2009. Methods: A prospective study comparing the sensitivity and specificity of the Nitrate Reductase Assay with the gold standard Lowenstein Jensen proportion method in determining drug susceptibility pattern to four primary anti-tubercular drugs i.e. isoniazid, rifampicin, streptomycin and ethambutal among clinical isolates.Results: Among 121 specimens , the sensitivity and specificity of the Nitrate Reductase Assay for detection of Isoniazid resistance was 100% and 91%, for rifampicin was 100% and 98.95%, for streptomycin was 96% and 91.66% and for ethambutal was 100% and 98% respectively.Conclusions: The Nitrate Reductase Assay is sensitive and specific enough for the detection of drug resistant tuberculosis. It is rapid, easy to use and inexpensive, making it suitable for developing countries. Its usefulness for national drug resistance surveys should be assessed. Keywords: diagnosis; drug resistance; sensitivity; specificity; NRADOI: 10.3126/saarctb.v7i1.3960SAARC J. TUBER. LUNG DIS. HIV/AIDS 2010 VII(1) 26-30

scholarly journals Socio-demographic Profile and Drug Sensitivity Pattern of Suspected Drug Resistant Tuberculosis among Patients in Regional Tuberculosis Reference Laboratory (R.T.R.L) of a Tertiary Hospital

2017 ◽  
Vol 18 (2) ◽  
pp. 62-67 ◽  
Author(s):  
Ummay Fatema Khatun ◽  
Robed Amin ◽  
Muna Islam ◽  
Abdur Rob ◽  
Abdur Rahim
Keyword(s):  
Drug Resistance ◽  
Drug Sensitivity ◽  
Reference Laboratory ◽  
Drug Resistant ◽  
Suspected Drug ◽  
Drug Resistant Tuberculosis ◽  
Demographic Profile ◽  
Resistant Tuberculosis ◽  
Sensitivity Pattern ◽  
Mdr Tb

Background: Drug resistant tuberculosis has been reported in all regions of the world. In this study we address the socio-demographic profile and drug sensitivity pattern as well as prevalence of drug resistance tuberculosis in a tertiary center (regional TB reference laboratory) in Bangladesh.Method: This Study was carried out in R.T.R.L. (Regional TB Reference Laboratory) in 250 bedded Chittagong General Hospital. Patients who were referred to R.T.R.L during the period July 2012 to July 2013 were included in the study. Total 100 patients with suspected drug resistant tuberculosis (TB) who had any one of 9 criteria of NTP (National Tuberculosis Control Programme) were selected consecutively. Gene xpert MTB/RIF (Rifampicin resistance) test for all sputum positive cases were performed. Sputum sample of Patients with positive microscopy for AFB or positive Xpert/MTB was sent for culture. The samples with positive sputum culture were sent for drug sensitivity test for 1st line anti- tubercular drug.Result: Among 100 patients 78 were male and 22 were female, majority of the patients (64) were between 15-45 years with poor socio economic condition (73%) and primarily educated. Analysis of our Study result showed that 18% of patients were mono-drug resistant. Among them 13% showed resistance to isoniazid (INH), 4% to streptomycin and only 2% to rifampicin. No patient was found resistant to pyrazinamide (PNZ) and 38% of patient with suspected drug – resistant TB was found to have no drug resistance. 18% of patient had multidrug resistant tuberculosis (MDR-TB) among which 56% were relapse cases (48% after cat -I, 8% after cat II), 24% were non – converter of cat –I, 12% belonged to failure of cat –I, 3% failure of cat –II, 2% return after default and others. 1% of patient had history of contact with MDR –TB patient.Conclusion: Drug-resistance tuberculosis especially MDR-TB, was higher in patients with previously incomplete anti-tuberculosis treatment. A high level of drug resistance among the re-treatment TB patients poses a threat of transmission of resistant strains to susceptible persons in the community. For this reason proper counseling of patients and attention towards the completion of the anti-TB treatment are needed.J MEDICINE July 2017; 18 (2) : 62-67

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 Evaluation of MTBDRplusand MTBDRslin Detecting Drug-Resistant Tuberculosis in a Chinese Population

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Wei Lu ◽  
Yan Feng ◽  
Jianming Wang ◽  
Limei Zhu
Keyword(s):  
Drug Resistance ◽  
Chinese Population ◽  
Sequencing Analysis ◽  
Drug Resistant ◽  
Line Probe Assay ◽  
Drug Resistant Tuberculosis ◽  
Additional Tool ◽  
Resistant Tuberculosis ◽  
Probe Assay ◽  
Mycobacteria Tuberculosis

Background. This study aims to evaluate GenoType MTBDRplusand GenoType MTBDRslfor their ability to detect drug-resistant tuberculosis in a Chinese population.Methods. We collected 112Mycobacteria tuberculosisstrains from Jiangsu province, China. The conventional DST and line probe assay were used to detect drug resistance to rifampicin (RFP), isoniazid (INH), ofloxacin (OFX), kanamycin (Km), and ethambutol (EMB).Results. The sensitivity and specificity were 100% and 50% for RFP and 86.11% and 47.06% for INH, respectively. The most common mutations observed in MTBDRpluswererpoBWT8 omission + MUT3 presence,katGWT omission + MUT1 presence, andinhAWT1 omission + MUT1 presence. For drug resistance to OFX, Km, and EMB, the sensitivity of MTBDRslwas 94.74%, 62.50%, and 58.82%, respectively, while the specificity was 92.59%, 98.81%, and 91.67%, respectively. The most common mutations weregyrAWT3 omission + MUT3C presence,rrsMUT1 presence,embBWT omission + MUT1B presence, andembBWT omission + MUT1A presence. Sequencing analysis found several uncommon mutations.Conclusion. In combination with DST, application of the GenoType MTBDRplusand GenoType MTBDRslassays might be a useful additional tool to allow for the rapid and safe diagnosis of drug resistance to RFP and OFX.

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