Correlation of drug exposure and bacterial susceptibility with treatment response for Mycobacterium avium complex lung disease: protocol for a prospective observational cohort study

IntroductionThe burden of Mycobacterium avium complex (MAC) lung disease is increasing globally and treatment outcome is in general poor. Therapeutic drug monitoring has the potential to improve treatment outcome by ensuring adequate drug exposure. However, very limited population-based studies exis...

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Vydané v:BMJ open Ročník 13; číslo 10; s. e075383
Hlavní autori: Zheng, Xubin, Wang, Li, Davies Forsman, Lina, Zhang, Yangyi, Chen, Yuhang, Luo, Xuejiao, Liu, Yidian, Bruchfeld, Judith, Hu, Yi, Alffenaar, Jan-Willem C, Sha, Wei, Xu, Biao
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: London British Medical Journal Publishing Group 03.10.2023
BMJ Publishing Group LTD
BMJ Publishing Group
Edícia:Protocol
Predmet:
Antibiotics
Clinical outcomes
CLINICAL PHARMACOLOGY
Cohort analysis
Drug dosages
Epidemiology
Hospitals
Infections
Infectious Diseases
Lung diseases
MICROBIOLOGY
Observational studies
Pharmacokinetics
Public health
Sample size
Tuberculosis
Whole genome sequencing
China
ISSN:2044-6055, 2044-6055
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Shrnutí:IntroductionThe burden of Mycobacterium avium complex (MAC) lung disease is increasing globally and treatment outcome is in general poor. Therapeutic drug monitoring has the potential to improve treatment outcome by ensuring adequate drug exposure. However, very limited population-based studies exist for MAC lung disease. This study aims to describe the distribution of drug exposure for key antimycobacterial drugs at population level, and to analyse them in relationship to treatment outcome in patients with MAC lung disease.Methods and analysisA prospective cohort aiming to include 100 adult patients diagnosed with and treated for MAC lung disease will be conducted in Shanghai Pulmonary Hospital, China. Blood samples will be collected after 1 month MAC treatment for measurement of macrolides, rifamycin, ethambutol, amikacin and/or fluoroquinolones, using a validated liquid-chromatography tandem mass spectrometry method. Respiratory samples will be collected at inclusion and once every 3 months for mycobacterial culture until treatment completion. Minimum inhibitory concentration (MIC) determination will be performed using a commercial broth microdilution plate. In addition to mycobacterial culture, disease severity and clinical improvement will be assessed from the perspective of lung function, radiological presentation and self-reported quality of life. Whole genome sequencing will be performed for any longitudinal isolates with significant change of MIC to explore the emergence of drug resistance-conferring mutations. The relationship between drug exposure and treatment outcome will be analysed and potential confounders will be considered for adjustment in multivariable models. Meanwhile, the associations between drug exposure in relation to MIC and markers of treatment response will be explored using Cox proportional hazards or binary logistic regression models, as appropriate.Ethics and disseminationThis study has been approved by the ethics committee of Shanghai Pulmonary Hospital (No. K22-149Z). Written and oral informed consent will be obtained from all participants. The study results will be submitted to a peer-reviewed journal.Trial registeration numberNCT05824988.
Bibliografia:Protocol
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ISSN:2044-6055
2044-6055
DOI:10.1136/bmjopen-2023-075383