ArticleAntimicrobial agents and chemotherapy2015
Amikacin Pharmacokinetics/Pharmacodynamics in a Novel Hollow-Fiber Mycobacterium abscessus Disease Model.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Systematic and quantitative analyses of hollow fiber model ofMicrobiology spectrum · 2026Pooled it
- Falling short: Inadequate target attainment in guideline-based therapy of nontuberculous mycobacterial disease.medRxiv : the preprint server for health sciences · 2026Article
- Sulbactam-durlobactam plus ceftriaxone dosing and novel treatment regimens forAntimicrobial 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
- Eravacycline pharmacokinetics/pharmacodynamics in the hollow fiber system model ofMicrobiology spectrum · 2026Article
- Enhanced activity of apramycin and apramycin-based combinations against Mycobacteroides abscessus.The Journal of antimicrobial chemotherapy · 2026Article
- Review of the Canadian Nontuberculous Mycobacterial Disease Landscape-Challenges and Opportunities.Tropical medicine and infectious disease · 2025Review
- Article
- Sulbactam-Durlobactam Plus Ceftriaxone Dosing and Novel Treatment Regimens forbioRxiv : 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
- In Vitro Activity of Imipenem/Relebactam Alone and in Combination Against Cystic Fibrosis Isolates ofAntibiotics (Basel, Switzerland) · 2025Article
- Effective killing ofMicrobiology spectrum · 2025Article
- Durlobactam in combination with β-lactams to combatAntimicrobial agents and chemotherapy · 2025Article
- Time-dependent pharmacodynamics of amikacin onMicrobiology spectrum · 2024Article
- Metabolic Rewiring ofMetabolites · 2024Review
- Successful addition of topical antibiotic treatment after surgery in treatment-refractory nontuberculous mycobacterial skin and soft tissue infections.Antimicrobial agents and chemotherapy · 2023Article
- Omadacycline pharmacokinetics/pharmacodynamics in the hollow fiber model and clinical validation of efficacy to treat pulmonary Mycobacterium abscessus disease.International journal of antimicrobial agents · 2023Article
- Review
- Liposomal drug delivery to manage nontuberculous mycobacterial pulmonary disease and other chronic lung infections.European respiratory review : an official journal of the European Respiratory Society · 2021Review
- Clinical Pharmacokinetic and Pharmacodynamic Considerations in the Drug Treatment of Non-Tuberculous Mycobacteria in Cystic Fibrosis.Clinical pharmacokinetics · 2021Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
The treatment of pulmonary Mycobacterium abscessus disease is associated with very high failure rates and easily acquired drug resistance. Amikacin is the key drug in treatment regimens, but the optimal doses are unknown. No good preclinical model exists to perform formal pharmacokinetics/pharmacodynamics experiments to determine these optimal doses. We developed a hollow-fiber system model of M. abscessus disease and studied amikacin exposure effects and dose scheduling. We mimicked amikacin human pulmonary pharmacokinetics. Both amikacin microbial kill and acquired drug resistance were linked to the peak concentration-to-MIC ratios; the peak/MIC ratio associated with 80% of maximal kill (EC80) was 3.20. However, on the day of the most extensive microbial kill, the bacillary burden did not fall below the starting inoculum. We performed Monte Carlo simulations of 10,000 patients with pulmonary M. abscessus infection and examined the probability that patients treated with one of 6 doses from 750 mg to 4,000 mg would achieve or exceed the EC80. We also examined these doses for the ability to achieve a cumulative area under the concentration-time curve of 82,232 mg · h/liter × days, which is associated with ototoxicity. The standard amikacin doses of 750 to 1,500 mg a day achieved the EC80 in ≤ 21% of the patients, while a dose of 4 g/day achieved this in 70% of the patients but at the cost of high rates of ototoxicity within a month or two. The susceptibility breakpoint was an MIC of 8 to 16 mg/liter. Thus, amikacin, as currently dosed, has limited efficacy against M. abscessus. It is urgent that different antibiotics be tested using our preclinical model and new regimens developed.
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