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Tytuł:
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Variations in rifampicin and isoniazid resistance associated genetic mutations among drug naïve and recurrence cases of pulmonary tuberculosis.
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Autorzy:
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Kabir S; Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore, 54590, Pakistan; Department of Microbiology, University of the Central Punjab, Lahore Pakistan.
Junaid K; College of Applied Medical Sciences, Jouf University, Sakaka, Al Jouf, Saudi Arabia.
Rehman A; Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore, 54590, Pakistan. Electronic address: .
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Źródło:
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International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases [Int J Infect Dis] 2021 Feb; Vol. 103, pp. 56-61. Date of Electronic Publication: 2020 Nov 09.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Publication: Hamilton, ON : Elsevier
Original Publication: Hamilton, ON : Decker, c1996-
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MeSH Terms:
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Antitubercular Agents/*pharmacology
Isoniazid/*pharmacology
Mycobacterium tuberculosis/*genetics
Rifampin/*pharmacology
Tuberculosis, Multidrug-Resistant/*microbiology
Tuberculosis, Pulmonary/*microbiology
Adult ; Antitubercular Agents/therapeutic use ; Drug Resistance, Multiple, Bacterial/genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Mycobacterium tuberculosis/drug effects ; Mycobacterium tuberculosis/isolation & purification ; Reinfection/microbiology ; Treatment Failure ; Tuberculosis, Multidrug-Resistant/drug therapy ; Tuberculosis, Pulmonary/drug therapy ; Young Adult
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Contributed Indexing:
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Keywords: MDR-TB; MTBDR plus assay; Mycobacterium tuberculosis; Rifampicin and isoniazid resistance
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Substance Nomenclature:
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0 (Antitubercular Agents)
V83O1VOZ8L (Isoniazid)
VJT6J7R4TR (Rifampin)
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Entry Date(s):
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Date Created: 20201112 Date Completed: 20210330 Latest Revision: 20210330
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Update Code:
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20240105
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DOI:
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10.1016/j.ijid.2020.11.007
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PMID:
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33181327
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Background: The resistance to first-line drugs can increase the risk of treatment failure and development of resistance to other anti-TB drugs. In TB endemic settings, a considerable rate of recurrence cases exhibited each, year which adds significant burden to the prevalence of disease worldwide.
Methods: A total of 562 sputum samples were collected from presumptive positive clinical cases of MDR tuberculosis. Treatment history and demographic data of the patients were obtained after informed consent. Xpert MTB/RIF assay was performed for simultaneous detection of MTB and rifampicin resistance. The mutation patterns of isoniazid and rifampicin were observed after multiplex PCR and reverse hybridization by Genotype® MTBDRplus version 2.0 assay.
Results: A total of 73 of 97 cases (75.2%) of treatment failure were found positive for MDR-TB, whereas 79.6% newly diagnosed and 72.9% default cases were MDR in our isolates. The mutation of rpoB S531L was slightly higher in new treatment cases (89.3%) as compared to the default (80.4%) and failure cases (84.8%), whereas rpoB D516V mutation was more prevalent in default cases (19.6%) with complete absence of rpoB 526 mutation, which was observed in the other two types of cases. The mutation pattern of katG resistance differed among drug naïve and recurrence cases. The resistance in newly diagnosed cases was mostly conferred by katG 315 (49.1%) whereas in default (70.8%) and failure cases (63.3%) isoniazid resistance was commonly associated with katG S315T1 mutation. Mutations in inhA promoter region occurred at nucleotide position -8 and -15. In new cases the rate of mutation of C-15T was 3.7% and T-8A was 1.5% while in treatment failure cases the frequency for C-15T and T-8C was 2.5 and 3.8% respectively. However, no inhA promoter region mediated mutations were detected in default treatment cases.
Conclusion: Retreated cases are at more risk of developing hot spot mutations. An unusual difference in mutation pattern was determined in naïve and recurrence cases. Some mutations were exclusively associated with the retreatment of 35anti-TB drugs which suggest the increased risk of resistance with poor treatment outcome.
(Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)
