Isoniazid Resistance Level and Associated Resistance Conferring-mutations in Rifampicin Resistant Mycobacterium tuberculosis

Rifampicin resistant Mycobacterium tuberculosis

Authors

  • Naomee Shareef Department of Microbiology, Mugda Medical College Hospital, Dhaka, Bangladesh
  • Shaheda Anwar Department of Microbiology and Immunology, Bangabandhu Sheikh Mujib Medical University, Dhaka
  • Abu Naser Ibne Sattar Department of Microbiology and Immunology, Bangabandhu Sheikh Mujib Medical University, Dhaka
  • ASM Rayahanul Hoque Department of Anesthesiology, Shaheed Suhrawardy Medical College Hospital, Dhaka, Bangladesh
  • Mohammad Jobayer National Center for Control of Rheumatic Fever & Heart Disease, Dhaka, Bangladesh
  • Ahmed Abu Saleh Department of Microbiology and Immunology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

DOI:

https://doi.org/10.3329/bmrcb.v49i2.66004

Keywords:

MDR-TB, INH resistance, katG, inhA, High level INH resistance, Low level INH resistance.

Abstract

Background: Multidrug resistant tuberculosis (MDR-TB) is a global public health problem causing treatment failure. Rifampicin (RIF) resistance has been used as a surrogate marker for MDR-TB diagnosis, but level of isoniazid (INH) resistance and associated resistance conferring mutations for INH in rifampicin-resistant TB cases are little known.

Objective: The objective of this study was to determine level of isoniazid resistance and associated resistance conferring mutations in rifampicin resistant Mycobacterium tuberculosis (MTB) in sputum samples.

Methods: A total 53 RIF resistant MTB isolates in sputum, detected by Xpert-MTB RIF assay were enrolled in the study. Culture positive samples were tested by BACTEC MGIT 960 system and level of isoniazid resistance was determined, defined as minimum inhibitory concentration of INH of >0.4 µg/mL and 0.1-0.4 µg/mL as high level and low level INH resistance respectively. Distribution of mutation in katG (codon 315) and inhA promoter (-5, -8, -15 and -16) genes by Real-time PCR among the different degrees of INH resistance was investigated.

Results: Among the growth positive isolates, 68.8% of the resistant isolates had high level INH resistance, where katG was found to be the prominent mutation, with or without combined with inhA mutation. Positive predictive value (PPV) of katG mutation was 84.6% in detecting a high level of INH resistance. Low level resistance was present in 31.3% isolates, conferring mutation in inhA and katG in equal percentage (40%), but no detectable mutations were found in 20% low level INH resistant MTB isolates. The PPV of inhA mutation was 33.3% in detection low level resistance.

Conclusion: Most of the INH resistant isolates conferred high level resistance and were associated with katG mutation. Evaluation of level INH resistance before using high dose INH will help to avoid dose dependent toxicity and to determine an appropriate treatment regimen.

Bangladesh Medical Res Counc Bull 2023; 49(2): 120-125

 

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Published

2023-08-01

How to Cite

Shareef , N. ., Anwar, S. ., Sattar, A. N. I. ., Hoque, A. R. ., Jobayer, M., & Saleh, A. A. . (2023). Isoniazid Resistance Level and Associated Resistance Conferring-mutations in Rifampicin Resistant Mycobacterium tuberculosis: Rifampicin resistant Mycobacterium tuberculosis. Bangladesh Medical Research Council Bulletin, 49(2), 120–125. https://doi.org/10.3329/bmrcb.v49i2.66004

Issue

Vol. 49 No. 2 (2023)

Section

Research Papers

License

Copyright (c) 2023 Naomee Shareef , Shaheda Anwar; Abu Naser Ibne Sattar; ASM Rayahanul Hoque, Mohammad Jobayer, Ahmed Abu Saleh

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