ArticleThe Journal of antimicrobial chemotherapy2022
Omadacycline efficacy in the hollow fibre system model of pulmonary Mycobacterium avium complex and potency at clinically attainable doses.
Article in The Journal of antimicrobial chemotherapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- A systematic review of tetracyclines for nontuberculous mycobacteria: focus on rapidly growing mycobacteria.European respiratory review : an official journal of the European Respiratory Society · 2025Pooled it
- Macrolide-resistantJournal of clinical tuberculosis and other mycobacterial diseases · 2026Review
- 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
- Preclinical pharmacokinetics/pharmacodynamics studies defining the role of ethambutol inAntimicrobial agents and chemotherapy · 2026Article
- Preclinical evaluation of epetraborole in the hollow fibre system model of Mycobacterium abscessus lung disease.The Journal of antimicrobial chemotherapy · 2026Article
- Omadacycline as a drug candidate for Mycobacterium avium infections: in vitro insights on single and combination therapies.The Journal of antimicrobial chemotherapy · 2026Article
- Eravacycline pharmacokinetics/pharmacodynamics in the hollow fiber system model ofMicrobiology spectrum · 2026Article
- Pharmacodynamic evidence for tedizolid use inIJTLD open · 2026Article
- Article
- Omadacycline for peritoneal dialysis-associated peritonitis caused byFrontiers in medicine · 2026Article
- Efficacy of drug regimens containing omadacycline in a murine model ofFrontiers in microbiology · 2026Article
- Article
- Tigecycline pharmacodynamics in the hollow fiber system ofbioRxiv : the preprint server for biology · 2025Article
- Imipenem Pharmacokinetics/Pharmacodynamics in Preclinical Hollow Fiber Model, Dose Finding in Virtual Patients, and Clinical Evidence of Efficacy for Mycobacterium abscessus Lung Disease.The Journal of infectious diseases · 2025Article
- Comparative efficacy of tetracyclines against isolates ofIJTLD open · 2025Article
- Tigecycline pharmacodynamics in the hollow fiber system ofFrontiers in pharmacology · 2025Article
- Mycobacterium abscessus strain variability in preclinical drug development: does it really matter?The Journal of antimicrobial chemotherapy · 2024Article
- Ertapenem's therapeutic potential for Mycobacterium avium lung disease in the hollow fibre model.International journal of antimicrobial agents · 2024Article
- Ceftriaxone Efficacy for Mycobacterium avium Complex Lung Disease in the Hollow Fiber and Translation to Sustained Sputum Culture Conversion in Patients.The Journal of infectious diseases · 2024Article
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Authors and funding
7 authors.
Funding
Abstract
objectivesThe standard of care (SOC) for the treatment of pulmonary Mycobacterium avium complex (MAC) disease (clarithromycin, rifabutin, and ethambutol) achieves sustained sputum conversion rates of only 54%. Thus, new treatments should be prioritized.
methodsWe identified the omadacycline MIC against one laboratory MAC strain and calculated drug half life in solution, which we compared with measured MAC doubling times. Next, we performed an omadacycline hollow fibre system model of intracellular MAC (HFS-MAC) exposure-effect study, as well as the three-drug SOC, using pharmacokinetics achieved in patient lung lesions. Data was analysed using bacterial kill slopes (γ-slopes) and inhibitory sigmoid Emax bacterial burden versus exposure analyses. Monte Carlo experiments (MCE) were used to identify the optimal omadacycline clinical dose.
resultsOmadacycline concentration declined in solution with a half-life of 27.7 h versus a MAC doubling time of 16.3 h, leading to artefactually high MICs. Exposures mediating 80% of maximal effect changed up to 8-fold depending on sampling day with bacterial burden versus exposure analyses, while γ-slope-based analyses gave a single robust estimate. The highest omadacycline monotherapy γ-slope was -0.114 (95% CI: -0.141 to -0.087) (r2 = 0.98) versus -0.114 (95% CI: -0.133 to -0.094) (r2 = 0.99) with the SOC. MCEs demonstrated that 450 mg of omadacycline given orally on the first 2 days followed by 300 mg daily would achieve the AUC0-24 target of 39.67 mg·h/L.
conclusionsOmadacycline may be a potential treatment option for pulmonary MAC, possibly as a back-bone treatment for a new MAC regimen and warrants future study in treatment of this disease.
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