Therapeutic Drug Monitoring in Non-Tuberculosis Mycobacteria Infections

Jan-Willem Alffenaar^#^{1

2

3

4}, Anne-Grete Märtson^#⁵, Scott K Heysell⁶, Jin-Gun Cho^{7

8

9}, Asad Patanwala^{10

11}, Gina Burch¹², Hannah Y Kim^{10

13

14}, Marieke G G Sturkenboom⁵, Anthony Byrne¹⁵, Debbie Marriott¹⁶, Indy Sandaradura^{7

17}, Simon Tiberi^{18

19}, Vitali Sintchencko^{14

20

21

22}, Shashikant Srivastava^{23

24}, Charles A Peloquin¹²

Affiliations

¹ School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Pharmacy Building (A15), Sydney, NSW, 2006, Australia. johannes.alffenaar@sydney.edu.au.
² Westmead Hospital, Westmead, NSW, Australia. johannes.alffenaar@sydney.edu.au.
³ Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Sydney, NSW, Australia. johannes.alffenaar@sydney.edu.au.
⁴ Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. johannes.alffenaar@sydney.edu.au.
⁵ Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁶ Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA.
⁷ Westmead Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
⁸ Respiratory and Sleep Medicine, Westmead Hospital, Westmead, NSW, Australia.
⁹ Parramatta Chest Clinic, Parramatta, NSW, Australia.
¹⁰ School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Pharmacy Building (A15), Sydney, NSW, 2006, Australia.
¹¹ Royal Prince Alfred Hospital, Sydney, NSW, Australia.
¹² Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA.
¹³ Westmead Hospital, Westmead, NSW, Australia.
¹⁴ Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Sydney, NSW, Australia.
¹⁵ St. Vincent's Hospital Sydney, Heart Lung Clinic, Sydney, NSW, Australia.
¹⁶ Department of Microbiology and Infectious Diseases, St. Vincent's Hospital, Sydney, NSW, Australia.
¹⁷ Centre for Infectious Diseases and Microbiology Laboratory Services, NSW Health Pathology, Westmead Hospital, Sydney, NSW, Australia.
¹⁸ Division of Infection, Barts Health NHS Trust, Royal London Hospital, London, UK.
¹⁹ Centre for Primary Care and Public Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK.
²⁰ NSW Mycobacterium Reference Laboratory, Centre for Infectious Diseases and Microbiology Laboratory Services, NSW Health Pathology, Westmead Hospital, Wentworthville, NSW, Australia.
²¹ Centre for Infectious Diseases and Microbiology, Westmead Institute for Medical Research, Westmead, NSW, Australia.
²² Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital, Westmead, NSW, Australia.
²³ Department of Immunology, UT Southwestern Medical Center, Dallas, TX, USA.
²⁴ Department of Pulmonary Immunology, UT Health Science Center at Tyler, Tyler, TX, USA.

^# Contributed equally.

PMID: 33751415
PMCID: PMC8195771
DOI: 10.1007/s40262-021-01000-6

Review

Therapeutic Drug Monitoring in Non-Tuberculosis Mycobacteria Infections

Jan-Willem Alffenaar et al. Clin Pharmacokinet. 2021 Jun.

. 2021 Jun;60(6):711-725.

doi: 10.1007/s40262-021-01000-6. Epub 2021 Mar 10.

Authors

Affiliations

¹ School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Pharmacy Building (A15), Sydney, NSW, 2006, Australia. johannes.alffenaar@sydney.edu.au.
² Westmead Hospital, Westmead, NSW, Australia. johannes.alffenaar@sydney.edu.au.
³ Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Sydney, NSW, Australia. johannes.alffenaar@sydney.edu.au.
⁴ Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. johannes.alffenaar@sydney.edu.au.
⁵ Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁶ Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA.
⁷ Westmead Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
⁸ Respiratory and Sleep Medicine, Westmead Hospital, Westmead, NSW, Australia.
⁹ Parramatta Chest Clinic, Parramatta, NSW, Australia.
¹⁰ School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Pharmacy Building (A15), Sydney, NSW, 2006, Australia.
¹¹ Royal Prince Alfred Hospital, Sydney, NSW, Australia.
¹² Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA.
¹³ Westmead Hospital, Westmead, NSW, Australia.
¹⁴ Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Sydney, NSW, Australia.
¹⁵ St. Vincent's Hospital Sydney, Heart Lung Clinic, Sydney, NSW, Australia.
¹⁶ Department of Microbiology and Infectious Diseases, St. Vincent's Hospital, Sydney, NSW, Australia.
¹⁷ Centre for Infectious Diseases and Microbiology Laboratory Services, NSW Health Pathology, Westmead Hospital, Sydney, NSW, Australia.
¹⁸ Division of Infection, Barts Health NHS Trust, Royal London Hospital, London, UK.
¹⁹ Centre for Primary Care and Public Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK.
²⁰ NSW Mycobacterium Reference Laboratory, Centre for Infectious Diseases and Microbiology Laboratory Services, NSW Health Pathology, Westmead Hospital, Wentworthville, NSW, Australia.
²¹ Centre for Infectious Diseases and Microbiology, Westmead Institute for Medical Research, Westmead, NSW, Australia.
²² Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital, Westmead, NSW, Australia.
²³ Department of Immunology, UT Southwestern Medical Center, Dallas, TX, USA.
²⁴ Department of Pulmonary Immunology, UT Health Science Center at Tyler, Tyler, TX, USA.

^# Contributed equally.

PMID: 33751415
PMCID: PMC8195771
DOI: 10.1007/s40262-021-01000-6

Abstract

Nontuberculous mycobacteria can cause minimally symptomatic self-limiting infections to progressive and life-threatening disease of multiple organs. Several factors such as increased testing and prevalence have made this an emerging infectious disease. Multiple guidelines have been published to guide therapy, which remains difficult owing to the complexity of therapy, the potential for acquired resistance, the toxicity of treatment, and a high treatment failure rate. Given the long duration of therapy, complex multi-drug treatment regimens, and the risk of drug toxicity, therapeutic drug monitoring is an excellent method to optimize treatment. However, currently, there is little available guidance on therapeutic drug monitoring for this condition. The aim of this review is to provide information on the pharmacokinetic/pharmacodynamic targets for individual drugs used in the treatment of nontuberculous mycobacteria disease. Lacking data from randomized controlled trials, in vitro, in vivo, and clinical data were aggregated to facilitate recommendations for therapeutic drug monitoring to improve efficacy and reduce toxicity.

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Conflict of interest statement

Anne-Grete Märtson was funded by Marie Skłodowska-Curie Actions (grant agreement no. 713660-PRONKJEWAIL-H2020-MSCA-COFUND-2015). Scott K Heysell was supported by NIH R01 AI137080. Shashikant Srivastava received supported by the ATS Foundation/Insmed Research Award in Non-Tuberculous Mycobacteria Lung Disease and NIH 1 R21 AI148096-01. Jan-Willem Alffenaar, Jin-Gun Cho, Asad Patanwalla, Gina Burch, Hannah Y Kim, Marieke GG Sturkenboom, Anthony Byrne, Debbie Marriott, Indy Sandaradura, Simon Tiberi, Vitali Sintchencko, and Charles A Peloquin have no conflicts of interest that are directly relevant to the content of this article.

Figures

**Fig. 1**
In vitro infection models (created with BioRender.com). a Time-kill kinetic models study the bactericidal effect of static drug concentrations in time. The dashed line shows the decline in concentration as a function of chemical degradation due to instability of the compound. b The response of in vitro models is reflected by the number of colony-forming units (CFUs). An increase is observed for inactive compounds and a control situation (growth in medium). c Hollow fiber infection models study the bactericidal effect of dynamic drug concentrations (mimicking human pharmacokinetics) in time. The hollow fiber infection model (HF) can facilitate experiments with extracellular bacteria, intracellular bacteria, and immune cells, thereby accounting for the different conditions of nontuberculous mycobacteria infections

See this image and copyright information in PMC

References

1. Cowman S, van Ingen J, Griffith DE, Loebinger MR. Non-tuberculous mycobacterial pulmonary disease. Eur Respir J. 2019;54:190025. - PubMed
1. Prevots DR, Marras TK. Epidemiology of human pulmonary infection with nontuberculous mycobacteria: a review. Clin Chest Med. 2015;36:13–34. - PMC - PubMed
1. Haworth CS, Banks J, Capstick T, Fisher AJ, Gorsuch T, Laurenson IF, et al. British Thoracic Society guideline for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD) BMJ Open Respir Res. 2017;4:e000242. - PMC - PubMed
1. Daley CL, Iaccarino JM, Lange C, Cambau E, Wallace RJJ, Andrejak C, et al. Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline. Eur Respir J. 2020;56:2000535. - PMC - PubMed
1. Honda JR, Knight V, Chan ED. Pathogenesis and risk factors for nontuberculous mycobacterial lung disease. Clin Chest Med. 2015;36:1–11. - PubMed

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Therapeutic Drug Monitoring in Non-Tuberculosis Mycobacteria Infections

Affiliations

Therapeutic Drug Monitoring in Non-Tuberculosis Mycobacteria Infections

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical