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Kim, Huh, Park, Kim, and Sohn: Comparative evaluation of critical concentrations for detecting borderline rifampin resistance in Mycobacterium tuberculosis
Original article

Ann Clin Microbiol 2023;26(4):139-145.

Published online: 20 December 2023

DOI: https://doi.org/10.5145/ACM.2023.26.4.139

Comparative evaluation of critical concentrations for detecting borderline rifampin resistance in Mycobacterium tuberculosis

Chang-Ki Kim1, Hee Jae Huh2, Jeong Su Park3, Taesoung Kim1, Jae Han Sohn1

1Department of Laboratory Medicine, Seoul Clinical Laboratories, Yongin

2Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul

3Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Korea

Corresponding author: Chang-Ki Kim E-mail: psoas95@gmail.com

Received 4 December 2023       Revised 18 December 2023       Accepted 18 December 2023

© Korean Society of Clinical Microbiology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background: Rifampin plays an important role in tuberculosis treatment. In recent years, the introduction of molecular testing techniques has enabled the rapid detection of rifampin resistance, leading to discrepancies with conventional methods. The World Health Organization (WHO) has analyzed mutations in the rpoB gene that induce rifampin resistance and identified certain mutations causing borderline resistance, which are often undetected using conventional tests. Consequently, the WHO has lowered the rifampin resistance criterion concentration from 1.0 to 0.5 μg/mL in 7H10 and MGIT 960. The present study aimed to evaluate the impact of this change in critical concentration on the detection of borderline rifampin resistance in Mycobacterium tuberculosis. Methods: Tuberculosis strains submitted for antituberculosis drug susceptibility testing from May 2021–2022 were analyzed. Three institutions participated; the Seoul Clinical Laboratories used the agar proportion method, whereas the Samsung Medical Center and Seoul National University Bundang Hospital utilized the MGIT 960 system to test both the original and revised concentrations. Mutations were confirmed through rpoB gene sequencing for strains showing discrepancies. Results: A total of 1,596 valid susceptibility tests were conducted during the study period. Rifampin resistance was detected in 35 cases (2.19%) at 1.0 μg/mL and in 38 cases (2.38%) at 0.5 μg/mL, whereas isoniazid resistance was observed in 158 cases (9.90%). Among the three rifampin discrepancy strains, one harbored an H445L mutation, whereas the remaining two exhibited an L452P mutation. These mutations were classified as borderline resistant. Conclusion: Applying the new rifampin critical concentration resulted in a 0.19% increase in resistance rate and an 8.57% increase in detection cases. Additionally, despite testing with large number of rifampin-susceptible strains, no false resistance results were obtained. Therefore, the application of the new critical concentration is considered beneficial for the management of rifampin-resistant tuberculosis..

Keywords: Tuberculosis, Rifampin, Borderline resistance

[in Korean]

Ethics statement

It is not a human population study; therefore, approval by the institutional review board or the obtainment of informed consent is not required.

Conflicts of interest

No potential conflicts of interest relevant to this article were reported.

Funding

This study was conducted with support from the Korea Disease Control and Prevention Agency.

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Table 1
DST results from three institutes
ACM-2604-06-t1.png

Abbreviations: DST, drug susceptibility testing; CCs, critical concentrations; SMC, Samsung Medical Center; SNUBH, Seoul National University Bundang Hospital; SCL, Seoul Clinical Laboratories; RIF, rifampin; INH, isoniazid; S, susceptible; R, resistant.

Table 2
Conventional DST results and rpoB gene sequencing data of three rifampin resistant isolates with new critical concentration
ACM-2604-06-t2.png

Abbreviations: DST, drug susceptibility testing; TB, tuberculosis; CC, critical concentration; INH, isoniazid; SM, streptomycin; EMB, ethambutol; ETH, ethionamide; CAP, capreomycin; KM, kanamycin; AMK, amikacin; OFL, ofloxacin; LEV, levofloxacin; MOX, moxifloxacin; PAS, para-aminosalicylic acid; RBT, rifabutin; LIN, linezolid; PZA, pyrazinamide; S, susceptible; R, resistant.

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