ArticleThe Journal of antimicrobial chemotherapy2017
Failure of the azithromycin and ethambutol combination regimen in the hollow-fibre system model of pulmonary Mycobacterium avium infection is due to acquired resistance.
Article in The Journal of antimicrobial chemotherapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- Novel regimens for treatment ofbioRxiv : the preprint server for biology · 2026Article
- Rifamycin-, macrolide-, and ethambutol-free combinations to treatThe international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2026Article
- Association of Antimicrobial Susceptibility with Treatment Response inPathogens (Basel, Switzerland) · 2025Article
- Antibacterial action of penicillin againstIJTLD open · 2024Article
- Review
- Omadacycline efficacy in the hollow fibre system model of pulmonary Mycobacterium avium complex and potency at clinically attainable doses.The Journal of antimicrobial chemotherapy · 2022Article
- Improving the Drug Development Pipeline for Mycobacteria: Modelling Antibiotic Exposure in the Hollow Fibre Infection Model.Antibiotics (Basel, Switzerland) · 2021Review
- Therapeutic Drug Monitoring in Non-Tuberculosis Mycobacteria Infections.Clinical pharmacokinetics · 2021Review
- Comparison of Rifamycins for Efficacy AgainstFrontiers in pharmacology · 2021Article
- Preclinical Models of Nontuberculous Mycobacteria Infection for Early Drug Discovery and Vaccine Research.Pathogens (Basel, Switzerland) · 2020Review
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
objectivesTo investigate the performance of the two backbone drugs in the standard combination therapy regimen in the hollow-fibre system (HFS) model of pulmonary Mycobacterium avium complex (MAC) infection.
methodsSix HFS were inoculated with human-derived monocytes infected with MAC, and treated with 15 mg/kg of ethambutol and 500 mg of azithromycin daily for 28 days to recapitulate the concentration-time profiles seen in the lungs of humans treated with these drugs and doses. The concentration-time profiles achieved were validated by sampling the central compartment at seven timepoints over 24 h. The total MAC burden, as well as the subpopulation resistant to 3 × MIC of each drug, was identified based on sampling the peripheral compartment of each system on days 0, 3, 7, 14, 21 and 28 of therapy. The experiment was performed twice.
resultsIn non-treated control HFS, MAC grew from 5.0 to 8.53 log10 cfu/mL in 28 days. The dual therapy killed a maximum of 1.52 ± 0.43 log10 cfu/mL during the first 7 days, after which it failed. By day 28 there was no difference in MAC burden between the combination-therapy-treated and non-treated systems. Failure arose in parallel with the emergence of acquired ethambutol resistance. By day 28, 100% of the bacterial population was ethambutol resistant in the combination-therapy-treated HFS replicates.
conclusionsThe backbone combination of macrolide and ethambutol has poor MAC kill rates and is ineffective. Microbial kill is rapidly abrogated by acquired drug resistance. This backbone should be replaced.
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