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Case Report | | Peer-Reviewed

Emergence of Non-tuberculous Mycobacteria Infections in Patients with Drug-Resistant Tuberculosis (DR-TB) During Bedaquiline - Containing Treatment

Mustofa Hassen Yesuf*,  Abdurehman Seid Mohammed,  Nesredin Hassen Yesuf,  Simret Arega Semaga,  Rani Seid Oumer,  Mahlet Girma Tilahun
Published in European Journal of Clinical and Biomedical Sciences (Volume 11, Issue 1)
Received: 29 December 2024     Accepted: 13 January 2025     Published: 11 February 2025
Views:       Downloads:
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Abstract

Introduction: Environmental microorganisms known as non-tuberculous mycobacteria (NTM) are frequently found in soil and water, originating from both natural and man-made sources. All mycobacteria species are included in this group, with the exception of Mycobacterium leprae, which causes leprosy, and Mycobacterium tuberculosis complex, which causes tuberculosis. NTM consists of a diverse array of over 190 distinct species. Mycobacterium avium complex (MAC), which consists of Mycobacterium avium and Mycobacterium intracellulare, is the most common pathogen that causes disease in humans. Mycobacterium abscessus (MAB) is the next most common pathogen. Methods: The centre, Saint Peter’s Specialized Hospital, is the pioneering TB specialized hospital in Ethiopia. Both conventional and molecular drug susceptibility testing were used to diagnose the patients with DR-TB. NTM-infected patients received therapy for their DR-TB using regimens containing bedaquiline, and they were monitored once treatment started. Sputum samples were gathered in order to evaluate the effectiveness of the treatment using mycobacterial culture. We have already come across two NTM cases. Result: Concerns have been raised about the occurrence of nontuberculous mycobacteria (NTM) infections in patients with drug-resistant tuberculosis (DR-TB) using bedaquiline-containing regimens. In a recent study, six cases of NTM infection were documented among patients undergoing treatment with Bedaquiline. The final treatment outcomes for these cases were cured. Bedaquiline is a prospective treatment option for NTM infections because it has shown excellent antibacterial action against a variety of NTM species. However, while effective against extra pulmonary NTM infections; its efficacy in pulmonary infections remains less clear. The increasing incidence of NTM infections in this patient population highlights the need for careful monitoring and potential adjustments in treatment strategies to address the complications arising from these co-infections. Conclusion: These outcomes underscore the complexity of managing co-infections in patients already burdened by DR-TB. It suggest that while Bedaquiline shows promise in treating DR-TB, its role in managing concurrent NTM infections requires careful consideration. The emergence of NTM during treatment may be influenced by factors such as the pharmacokinetics of Bedaquiline and the intrinsic resistance of various NTM species. This situation necessitates ongoing monitoring and potentially revised therapeutic strategies to address these co-infections effectively. As the incidence of NTM infections continues to rise globally, it is crucial for healthcare providers to remain vigilant in identifying and managing these infections in patients undergoing treatment for DR-TB.

Published in European Journal of Clinical and Biomedical Sciences (Volume 11, Issue 1)
DOI 10.11648/j.ejcbs.20251101.12
Page(s) 11-15
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

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Copyright © The Author(s), 2025. Published by Science Publishing Group
Previous article
Keywords

Non-tuberculous Mycobacteria, Drug-resistant Tuberculosis, Addis Ababa, Ethiopia

1. Introduction
Globally, tuberculosis (TB) continues to be the primary cause of mortality from infectious diseases
[1]
. The rise of drug-resistant TB significantly threatens global TB management and is a critical public health concern in numerous nations. The Global TB Report 2022 indicated that approximately 10.6 million individuals fell ill with TB that year
[2, 3]
In 2021, TB caused around 1.6 million deaths, including 1.4 million among HIV-negative persons and 187,000 among those with HIV. Additionally, in 2021, an expected 450,000 new cases of TB emerged, with 3.6% of new cases and 18% of previously treated patients being found to be multidrug-resistant or rifampicin-resistant
[4, 5]
. Drug-resistant tuberculosis (DR-TB) is difficult and complicated to treat. It involves the use of highly toxic anti-TB medications, which raises the risk of adverse effects, extends the duration of treatment, and incurs significant medical expenses
[6]
. As a result, only about half of the patients experience positive outcomes after receiving these treatments
[7]
.
New anti-TB drugs that are efficient against Mycobacterium tuberculosis (MTB) must be developed immediately and operate through novel mechanisms of action
[8]
. Bedaquiline, a diarylquinoline, has been approved by the FDA for treating drug-resistant TB (DR-TB)
[9]
. As a promising new treatment for MTB, Bedaquiline shows potential for effectively addressing this challenging disease when properly optimized
[10]
. The World Health Organization endorses Bedaquiline for creating effective combination therapies against DR-TB
[11]
, and its inclusion has shown significant efficacy in treating DR-TB patients
[10, 12]
. Through a nationwide trial program, Bedaquiline has been accessible to DR-TB patients in China since 2018
[13]
.
Environmental microorganisms known as non-tuberculous mycobacteria (NTM) are frequently found in soil and water, originating from both natural and man-made sources. All mycobacteria species are included in this group, with the exception of Mycobacterium leprae, which causes leprosy, and Mycobacterium tuberculosis complex, which causes tuberculosis. NTM consists of a diverse array of over 190 distinct species
[14]
. Mycobacterium avium complex (MAC), which consists of Mycobacterium avium and Mycobacterium intracellulare, is the most common pathogen that causes disease in humans. Mycobacterium abscessus (MAB) is the next most common pathogen
[15]
.
Since non-tuberculous mycobacteria (NTM) infections are not considered notifiable diseases in many areas, it is challenging to collect reliable statistics on the prevalence. Over the previous ten years, the number of reported cases more than doubled in Queensland, Australia, where NTMs are notifiable, from 672 in 2012 to 1,490 in 2022
[16]
. By 2040, NTM infections may triple, according to projections
[17]
. Mycobacterium tuberculosis isolates are currently eight times less common than NTM isolates; in 2023, 191 TB cases were reported, compared to 1,565 NTM isolates
[18]
. The clinical importance of NTM isolation and the choice to start treatment are more controversial, even if isolating M. tuberculosis suggests clinical disease. The ATS/IDSA guidelines help differentiate between NTM pulmonary disease and mere colonization based on clinical, microbiological, and radiological criteria
[19]
.
Several theories have been proposed to explain the rising incidence of non-tuberculous mycobacteria (NTM) infections in recent years. Advances in diagnostic techniques have made it easier to accurately identify NTM infections, with faster and more specific tests available. Additionally, the number of immunocompromised individuals, who are more susceptible to NTM infections, is increasing. A survey by the National Health Insurance Service (NHIS) indicated a rise in immunocompromised individuals from 2.7% in 2013 to 6.6% in 2021
[20]
. Furthermore, individuals with cystic fibrosis (CF), who are fortunately living longer, are also at a heightened risk for developing NTM infections
[21]
.
Even though NTM infections are becoming more common, misdiagnosis is still a major problem. Clinically, non-specific symptoms like fever, fatigue, weight loss, and persistent cough are seen with NTM infections
[19]
. Clinical symptoms, imaging demonstrating nodular or cavity opacities, and positive cultures from sputum, bronchial washings, or lung biopsies with mycobacterial histological characteristics are all necessary for the diagnosis, which also requires microbiological confirmation
[19, 22]
. Importantly, depending on the risk factors of each patient, a positive NTM isolation may not always mean an active infection or disease, making it more difficult to decide whether to start treatment or keep monitoring up.
Mycobacterium avium and other non-tuberculous mycobacteria (NTMs) are frequently encountered by the general public while they go about their daily lives. Showerheads are a frequent exposure source because they can aerosolize and inhale microorganisms from municipal water
[22]
. NTMs can also be present in soil during gardening and may be isolated from hospital equipment
[15]
.
1.1. Challenges of Current Treatment Options
Currently, at least three medications are used to treat non-tuberculous mycobacterial (NTM) infections. Most regimens consist of rifampicin and ethambutol in addition to a macrolide, such as azithromycin or clarithromycin
[19]
. However, research shows that within 6 to 12 months of completing initial medication, 10% to 60% of patients develop relapse or reinfection
[23]
. Antibiotic pharmacokinetic interactions could be one cause of these unfavorable results. Rifampicin dramatically lowered peak serum concentrations of macrolides, according to research by van Ingen et al., with levels of azithromycin and clarithromycin dropping by up to 23% and 68%, respectively
[24]
. Whether this drop in blood concentration has an impact on the macrolides' ability to eradicate lung bacteria is still unknown. Despite macrolides' high tissue penetration, the treatment regimen's overall efficacy may be lowered if these antibiotics don't work well together
[25]
.
1.2. Determination of the Current Treatment Regimen
The first "American Thoracic Society (ATS) declaration for the identification and treatment of nontuberculous mycobacteria" was issued in 1990 and recommended a four-drug regimen. For the first two months of treatment, this regimen consisted of 300 mg of isoniazid, 600 mg of rifampin, and 25 mg/kg of ethambutol; for the remaining months, the dose reduced to 15 mg/kg. Furthermore, streptomycin recommended for the first three to six months of treatment
[26]
.
Table 1. Emergence of nontuberculous mycobacteria infections during anti-tuberculosis therapy, 2024.

Sex

Age (years)

Patient Category

Drug Susceptibility

Comorbidity

Time of culture conversion

Time of NTM emergence

Treatment regimen

Outcome

F

30

Relapse

RR-PTB

NO

5th month

18th month

(All oral) longer regimen

cured

M

51

Relapse

MDR-PTB

NO

1st Month

6th month

BPaLM

Cured
2. Method
The center, Saint Peter’s Specialized Hospital, is the pioneering TB specialized hospital in Ethiopia. Both conventional and molecular drug susceptibility testing were used to diagnose the patients with DR-TB. NTM-infected patients received therapy for their DR-TB using regimens containing bedaquiline, and they were monitored once treatment started. Sputum samples were gathered in order to evaluate the effectiveness of the treatment using mycobacterial culture. We have already come across two NTM cases. The period of time between the start of treatment and the negative sputum culture results was known as the "time to sputum culture conversion." Clinical and demographic data were gathered from medical records. The study received ethical approval from Saint Peter's Specialized Hospital's Institutional Review Board (IRB).
3. Results
The urgent need to create novel anti-TB drugs that are effective against Mycobacterium tuberculosis (MTB) and have a different mode of action
[8]
. The Food and Drug Administration has authorized bedaquiline, a drug belonging to the diarylquinoline class, for the treatment of DR-TB
[9]
. When properly optimized, bedaquiline, a new drug against MTB, has the potential to be used to fight this challenging disease
[10]
. The World Health Organization advises using bedaquiline to create combination regimens that effectively combat DR-TB
[11]
. Incorporating bedaquiline into the therapy of DR-TB patients has shown encouraging results
[10, 12]
. Since late 2016, DR-TB patients in Ethiopia have had clinical access to bedaquiline through a nationwide pilot program
[13]
.
Concerns have been raised about the occurrence of nontuberculous mycobacteria (NTM) infections in patients with drug-resistant tuberculosis (DR-TB) using bedaquiline-containing regimens. In a recent study, two cases of NTM infection were documented among patients undergoing treatment with bedaquiline. The final treatment outcomes for these cases were cured. Bedaquiline is a prospective treatment option for NTM infections because it has shown excellent antibacterial action against a variety of NTM species. However, while effective against extra pulmonary NTM infections; its efficacy in pulmonary infections remains less clear. The increasing incidence of NTM infections in this patient population highlights the need for careful monitoring and potential adjustments in treatment strategies to address the complications arising from these co-infections.
4. Discussion
Concerns have been raised about the occurrence of nontuberculous mycobacteria (NTM) infections in patients with drug-resistant tuberculosis (DR-TB) using bedaquiline-containing regimens.
The increasing incidence of NTM infections in patients undergoing therapy for DR-TB may be attributed to several factors. First, while bedaquiline has shown promising antibacterial activity against various NTM species, its efficacy appears to be limited primarily to extra pulmonary infections rather than pulmonary ones. This limitation can complicate treatment strategies, especially in cases where patients present with both DR-TB and NTM infections.
Furthermore, the intrinsic resistance of many NTM species to standard antibiotics poses significant challenges. The presence of NTM infections during bedaquiline therapy may indicate a failure of the immune system to control these opportunistic pathogens, particularly in immunocompromised patients. Our findings align with previous studies that have reported high rates of relapse or reinfection in patients treated for NTM infections, highlighting the need for vigilant monitoring and potential adjustments in therapeutic approaches.
The emergence of NTM infections during bedaquiline therapy necessitates further research into optimal treatment regimens and the mechanisms underlying these co-infections. Understanding the pharmacokinetics and potential interactions between bedaquiline and other anti-mycobacterial agents is crucial in developing effective treatment strategies. Additionally, as the prevalence of NTM infections continues to rise globally, healthcare providers must remain vigilant in recognizing and managing these infections in patients undergoing treatment for DR-TB.
5. Conclusion and Recommendations
Concerns have been raised about the occurrence of nontuberculous mycobacteria (NTM) infections in patients with drug-resistant tuberculosis (DR-TB) using bedaquiline-containing regimens. In our case study, we documented two instances of NTM infections, with both patients achieving cure. The findings suggest that while bedaquiline shows promise in treating DR-TB, its role in managing concurrent NTM infections requires careful consideration. The emergence of NTM during treatment may be influenced by factors such as the pharmacokinetics of bedaquiline and the intrinsic resistance of various NTM species. This situation necessitates ongoing monitoring and potentially revised therapeutic strategies to address these co-infections effectively.
As the incidence of NTM infections continues to rise globally, it is crucial for healthcare providers to remain vigilant in identifying and managing these infections in patients undergoing treatment for DR-TB. Future research should focus on optimizing treatment regimens that incorporate bedaquiline while addressing the challenges posed by NTM, ultimately aiming to improve patient outcomes in this vulnerable population.
Abbreviation

BPaLM

Bedaquiline, Pretomanid, Linezolid and Moxifloxacin

CF

Cystic Fibrosis

DR-TB

Drug- resistant Tuberculosis

NHIS

National Health Insurance Service

MAB

Mycobacterium Abscessus

MAC

Mycobacterium Avium Complex

NTM

Non-tuberculous Mycobacteria

TB

Tuberculosis
Acknowledgments
We would like to thank all multidrug resistance patient treatment team who are participated in the care of the patients.
Authors’ Contribution
Mustofa Hassen Yesuf: Conceptualization, Data curation, Investigation, Methodology, Supervision, Validation, Writing – original draft, Writing – review & editing
Abdurehman Seid Mohamed: Data curation, Investigation, Methodology, Supervision, Validation, Writing – original draft, Writing – review & editing
Nesredin Hassen Yesuf: Data curation, Validation, Writing – review & editing
Rani Seid Oumer: Data curation, Writing – review & editing
Simret Arega Semaga: Investigation, Validation, Writing – review & editing
Mahlet Girma Tilahun: Methodology, Validation, Writing – review & editing
Each author certifies that they fulfill the most recent ICMJE Authorship requirements.
Ethical Approval and Informed Consent
All patients gave their informed consent before the study was published. The study received ethical approval from Saint Peter's Specialized Hospital's Institutional Review Board (IRB).
Data Avaiablity Statement
The data are available with corresponding author upon reasonable request will provide.
Funding
No grant from a public, private or nonprofit organization.
Conflicts of Interest
The authors state that none of the work described in this study could have been influenced by any known competing financial interests or personal relationships.
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    Yesuf, M. H., Mohammed, A. S., Yesuf, N. H., Semaga, S. A., Oumer, R. S., et al. (2025). Emergence of Non-tuberculous Mycobacteria Infections in Patients with Drug-Resistant Tuberculosis (DR-TB) During Bedaquiline - Containing Treatment. European Journal of Clinical and Biomedical Sciences, 11(1), 11-15. https://doi.org/10.11648/j.ejcbs.20251101.12

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    Yesuf, M. H.; Mohammed, A. S.; Yesuf, N. H.; Semaga, S. A.; Oumer, R. S., et al. Emergence of Non-tuberculous Mycobacteria Infections in Patients with Drug-Resistant Tuberculosis (DR-TB) During Bedaquiline - Containing Treatment. Eur. J. Clin. Biomed. Sci. 2025, 11(1), 11-15. doi: 10.11648/j.ejcbs.20251101.12

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    AMA Style

    Yesuf MH, Mohammed AS, Yesuf NH, Semaga SA, Oumer RS, et al. Emergence of Non-tuberculous Mycobacteria Infections in Patients with Drug-Resistant Tuberculosis (DR-TB) During Bedaquiline - Containing Treatment. Eur J Clin Biomed Sci. 2025;11(1):11-15. doi: 10.11648/j.ejcbs.20251101.12

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  • @article{10.11648/j.ejcbs.20251101.12,
  author = {Mustofa Hassen Yesuf and Abdurehman Seid Mohammed and Nesredin Hassen Yesuf and Simret Arega Semaga and Rani Seid Oumer and Mahlet Girma Tilahun},
  title = {Emergence of Non-tuberculous Mycobacteria Infections in Patients with Drug-Resistant Tuberculosis (DR-TB) During Bedaquiline - Containing Treatment},
  journal = {European Journal of Clinical and Biomedical Sciences},
  volume = {11},
  number = {1},
  pages = {11-15},
  doi = {10.11648/j.ejcbs.20251101.12},
  url = {https://doi.org/10.11648/j.ejcbs.20251101.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ejcbs.20251101.12},
  abstract = {Introduction: Environmental microorganisms known as non-tuberculous mycobacteria (NTM) are frequently found in soil and water, originating from both natural and man-made sources. All mycobacteria species are included in this group, with the exception of Mycobacterium leprae, which causes leprosy, and Mycobacterium tuberculosis complex, which causes tuberculosis. NTM consists of a diverse array of over 190 distinct species. Mycobacterium avium complex (MAC), which consists of Mycobacterium avium and Mycobacterium intracellulare, is the most common pathogen that causes disease in humans. Mycobacterium abscessus (MAB) is the next most common pathogen. Methods: The centre, Saint Peter’s Specialized Hospital, is the pioneering TB specialized hospital in Ethiopia. Both conventional and molecular drug susceptibility testing were used to diagnose the patients with DR-TB. NTM-infected patients received therapy for their DR-TB using regimens containing bedaquiline, and they were monitored once treatment started. Sputum samples were gathered in order to evaluate the effectiveness of the treatment using mycobacterial culture. We have already come across two NTM cases. Result: Concerns have been raised about the occurrence of nontuberculous mycobacteria (NTM) infections in patients with drug-resistant tuberculosis (DR-TB) using bedaquiline-containing regimens. In a recent study, six cases of NTM infection were documented among patients undergoing treatment with Bedaquiline. The final treatment outcomes for these cases were cured. Bedaquiline is a prospective treatment option for NTM infections because it has shown excellent antibacterial action against a variety of NTM species. However, while effective against extra pulmonary NTM infections; its efficacy in pulmonary infections remains less clear. The increasing incidence of NTM infections in this patient population highlights the need for careful monitoring and potential adjustments in treatment strategies to address the complications arising from these co-infections. Conclusion: These outcomes underscore the complexity of managing co-infections in patients already burdened by DR-TB. It suggest that while Bedaquiline shows promise in treating DR-TB, its role in managing concurrent NTM infections requires careful consideration. The emergence of NTM during treatment may be influenced by factors such as the pharmacokinetics of Bedaquiline and the intrinsic resistance of various NTM species. This situation necessitates ongoing monitoring and potentially revised therapeutic strategies to address these co-infections effectively. As the incidence of NTM infections continues to rise globally, it is crucial for healthcare providers to remain vigilant in identifying and managing these infections in patients undergoing treatment for DR-TB.},
 year = {2025}
}

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  • TY  - JOUR
T1  - Emergence of Non-tuberculous Mycobacteria Infections in Patients with Drug-Resistant Tuberculosis (DR-TB) During Bedaquiline - Containing Treatment
AU  - Mustofa Hassen Yesuf
AU  - Abdurehman Seid Mohammed
AU  - Nesredin Hassen Yesuf
AU  - Simret Arega Semaga
AU  - Rani Seid Oumer
AU  - Mahlet Girma Tilahun
Y1  - 2025/02/11
PY  - 2025
N1  - https://doi.org/10.11648/j.ejcbs.20251101.12
DO  - 10.11648/j.ejcbs.20251101.12
T2  - European Journal of Clinical and Biomedical Sciences
JF  - European Journal of Clinical and Biomedical Sciences
JO  - European Journal of Clinical and Biomedical Sciences
SP  - 11
EP  - 15
PB  - Science Publishing Group
SN  - 2575-5005
UR  - https://doi.org/10.11648/j.ejcbs.20251101.12
AB  - Introduction: Environmental microorganisms known as non-tuberculous mycobacteria (NTM) are frequently found in soil and water, originating from both natural and man-made sources. All mycobacteria species are included in this group, with the exception of Mycobacterium leprae, which causes leprosy, and Mycobacterium tuberculosis complex, which causes tuberculosis. NTM consists of a diverse array of over 190 distinct species. Mycobacterium avium complex (MAC), which consists of Mycobacterium avium and Mycobacterium intracellulare, is the most common pathogen that causes disease in humans. Mycobacterium abscessus (MAB) is the next most common pathogen. Methods: The centre, Saint Peter’s Specialized Hospital, is the pioneering TB specialized hospital in Ethiopia. Both conventional and molecular drug susceptibility testing were used to diagnose the patients with DR-TB. NTM-infected patients received therapy for their DR-TB using regimens containing bedaquiline, and they were monitored once treatment started. Sputum samples were gathered in order to evaluate the effectiveness of the treatment using mycobacterial culture. We have already come across two NTM cases. Result: Concerns have been raised about the occurrence of nontuberculous mycobacteria (NTM) infections in patients with drug-resistant tuberculosis (DR-TB) using bedaquiline-containing regimens. In a recent study, six cases of NTM infection were documented among patients undergoing treatment with Bedaquiline. The final treatment outcomes for these cases were cured. Bedaquiline is a prospective treatment option for NTM infections because it has shown excellent antibacterial action against a variety of NTM species. However, while effective against extra pulmonary NTM infections; its efficacy in pulmonary infections remains less clear. The increasing incidence of NTM infections in this patient population highlights the need for careful monitoring and potential adjustments in treatment strategies to address the complications arising from these co-infections. Conclusion: These outcomes underscore the complexity of managing co-infections in patients already burdened by DR-TB. It suggest that while Bedaquiline shows promise in treating DR-TB, its role in managing concurrent NTM infections requires careful consideration. The emergence of NTM during treatment may be influenced by factors such as the pharmacokinetics of Bedaquiline and the intrinsic resistance of various NTM species. This situation necessitates ongoing monitoring and potentially revised therapeutic strategies to address these co-infections effectively. As the incidence of NTM infections continues to rise globally, it is crucial for healthcare providers to remain vigilant in identifying and managing these infections in patients undergoing treatment for DR-TB.
VL  - 11
IS  - 1
ER  -

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