scholarly journals Drug-resistant Tuberculosis: First Line Drug Resistance Pattern among Mycobacterium Tuberculosis Strains Isolated from a Reference Laboratory in Kerala State, India

Author(s):  
Neetha S Murthy ◽  
Sanjeev Nair ◽  
PK Ramya ◽  
Renu Susan George ◽  
B Ravikrishnan ◽  
...  

Resistance to antimycobacterial agents consistently remains a major obstacle to end TB in India. Geographical prevalence data regarding drug-resistant evolutionary genetics of M. tuberculosis (MTB) remains sparse in India. Our objective was to determine the genotypic drug resistance mutation pattern for Rifampicin and Isoniazid of MTB isolates to gain an understanding of the prevailing molecular epidemiology of drug-resistant tuberculosis. In this study 2528 M. tuberculosis DNA isolates from presumptive DRTB suspects received at the nodal TB reference laboratory in Kerala were tested for Rifampicin and Isoniazid resistance by sequence-based diagnostic Line Probe assay (LPA). Geographical prevalence and associations of rpoB, katG, inhA resistance codons was analyzed from January 2019 to March 2020. Among the 2528 DNA samples subjected for Rifampicin and Isoniazid resistance determination by LPA, 146 (5.8%) isolates were resistant to both drugs. Isoniazid mono-resistance was found in 164 (6.5%) and Rifampicin mono-resistance in 38 (1.5%) isolates. The most frequent rpoB mutation was S531L (60.32%) followed by S531W/L533P mutations seen in 8.15% of the isolates. S315T1 KatG mutation was seen in 97.33% of Isoniazid resistant isolates. 84.68% isolates with rpoB S531L mutation were found to be multidrug-resistant. 82.9% of isolates with rpoB S531L mutation showed katG S315T1 mutation. Mono isoniazid-resistant isolates were significantly higher compared to mono rifampicin-resistant isolates among the DNA isolates studied in our region. The molecular epidemiological pattern most frequently associated with multidrug resistance was rpoB S531L which was significantly associated with the co-presence of S315T1 mutation.

2017 ◽  
Vol 18 (2) ◽  
pp. 62-67 ◽  
Author(s):  
Ummay Fatema Khatun ◽  
Robed Amin ◽  
Muna Islam ◽  
Abdur Rob ◽  
Abdur Rahim

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


2014 ◽  
Vol 59 (2) ◽  
pp. 818-825 ◽  
Author(s):  
Feifei Wang ◽  
Lingyun Shao ◽  
Xiaoping Fan ◽  
Yaojie Shen ◽  
Ni Diao ◽  
...  

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.


2010 ◽  
Vol 3 (2) ◽  
pp. 13-17 ◽  
Author(s):  
ABM Abdul Wadud ◽  
ASM Matiur Rahman ◽  
Md Ruhul Amin Miah ◽  
Ahmed Abu Saleh

This study was carried out to isolate M. tuberculosis from smear positive sputum samples by MB/BacT automated culture system and investigate the drug resistance pattern. Among 101 smear positive cases 96 (95.05 %) yielded growth of Mycobacteria, 3 (02.97 %) were contaminated and 2 (01.98 %) showed no growth. Culture positive detection time for M. tuberculosis was lowest 7 days and highest 36.3 days and average detection time was11.3 days. Detection time for NTM was 19.2 days. Among 96 isolates 95 (98.96 %) were M. tuberculosis and remaining 1 (1.04 %) was photochromogen Non-tuberculous Mycobacteria (NTM). Out of 95 M. tuberculosis 51 (53.84 %) were resistant to at least one drug, 38 (40.00 %) to INH, 31 (32.63%) to RMP, 13(13.68 %) to SM, 11 (11.58 %) to EMB and 10 (10.53 %) to PZA and multi-drug resistant tuberculosis (MDR-TB) was 21 (22.11 %). Resistance to one drug was 21 (22.11%), two drugs 15 (15.79 %), to three drugs 10 (10.53 %) and resistant to four or more drugs 5(5.26 %) cases.Bangladesh J Med Microbiol 2010; 03 (02): 13-17


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 ◽  
...  

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.


2020 ◽  
Vol 46 (1) ◽  
pp. 22-28
Author(s):  
Shirin Tarafder ◽  
Md Bayzid Bin Monir

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


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