ArticleAntimicrobial agents and chemotherapy2016
Amikacin Optimal Exposure Targets in the Hollow-Fiber System Model of Tuberculosis.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Lesion Penetration and Activity Limit the Utility of Second-Line Injectable Agents in Pulmonary Tuberculosis.Antimicrobial agents and chemotherapy · 2021Pooled it
- Falling short: Inadequate target attainment in guideline-based therapy of nontuberculous mycobacterial disease.medRxiv : the preprint server for health sciences · 2026Article
- Therapeutic drug monitoring in tuberculosis.European journal of clinical pharmacology · 2024Review
- Role of therapeutic drug monitoring in the treatment of multi-drug resistant tuberculosis.Journal of clinical tuberculosis and other mycobacterial diseases · 2024Article
- Omadacycline pharmacokinetics/pharmacodynamics and efficacy against multidrug-resistantAntimicrobial agents and chemotherapy · 2024Article
- Meropenem-vaborbactam restoration of first-line drug efficacy and comparison of meropenem-vaborbactam-moxifloxacin versus BPaL MDR-TB regimen.International journal of antimicrobial agents · 2023Article
- Hollow-fibre system model of tuberculosis reproducibility and performance specifications for best practice in drug and combination therapy development.The Journal of antimicrobial chemotherapy · 2023Article
- Pharmacokinetics and pharmacodynamics of anti-tuberculosis drugs: An evaluation ofFrontiers in pharmacology · 2022Review
- Improving the Drug Development Pipeline for Mycobacteria: Modelling Antibiotic Exposure in the Hollow Fibre Infection Model.Antibiotics (Basel, Switzerland) · 2021Review
- Clinical Pharmacokinetic and Pharmacodynamic Considerations in the Drug Treatment of Non-Tuberculous Mycobacteria in Cystic Fibrosis.Clinical pharmacokinetics · 2021Review
- Population Pharmacokinetics and Bayesian Dose Adjustment to Advance TDM of Anti-TB Drugs.Clinical pharmacokinetics · 2021Review
- Prevention of acquired sensorineural hearing loss in mice by in vivo Htra2 gene editing.Genome biology · 2021Article
- Low-dose amikacin in the treatment of Multidrug-resistant Tuberculosis (MDR-TB).BMC infectious diseases · 2021Article
- DifferentialAntimicrobial agents and chemotherapy · 2021Article
- A Review of Clinical Pharmacokinetic and Pharmacodynamic Relationships and Clinical Implications for Drugs Used to Treat Multi-drug Resistant Tuberculosis.European journal of drug metabolism and pharmacokinetics · 2020Review
- Integrating Pharmacokinetics and Pharmacodynamics in Operational Research to End Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020Article
- Towards tailored regimens in the treatment of drug-resistant tuberculosis: a retrospective study in two Italian reference Centres.BMC infectious diseases · 2019Article
- Transformation Morphisms and Time-to-Extinction Analysis That Map Therapy Duration From Preclinical Models to Patients With Tuberculosis: Translating From Apples to Oranges.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Article
- Ethionamide Pharmacokinetics/Pharmacodynamics-derived Dose, the Role of MICs in Clinical Outcome, and the Resistance Arrow of Time in Multidrug-resistant Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Article
- Pharmacokinetic/Pharmacodynamic Background and Methods and Scientific Evidence Base for Dosing of Second-line Tuberculosis Drugs.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
Abstract
Aminoglycosides such as amikacin are currently used for the treatment of multidrug-resistant tuberculosis (MDR-TB). However, formal pharmacokinetic/pharmacodynamic (PK/PD) studies to identify amikacin exposures and dosing schedules that optimize Mycobacterium tuberculosis killing have not been performed. It is believed that aminoglycosides do not work well under acidic conditions, which, if true, would mean poor sterilizing activity against semidormant bacilli at low pH. We performed time-kill studies to compare the bactericidal effect of amikacin in log-phase-growth bacilli with the sterilizing effect in semidormant bacilli at pH 5.8 in broth. In log-phase M. tuberculosis at normal pH versus semidormant M. tuberculosis at pH 5.8, the maximal kill (Emax) estimate and 95% confidence interval (CI) were 5.39 (95% CI, 4.91 to 5.63) versus 4.88 (CI, 4.46 to 5.22) log10 CFU/ml, while the concentration mediating 50% of Emax (EC50) was 1.0 (CI, 0. 0.86 to 1.12) versus 0.60 (CI, 0.50 to 0.66) times the MIC, respectively. Thus, the optimal exposures and kill rates identified for log-phase M. tuberculosis will be optimal even for semidormant bacilli. Next, we performed exposure-response and dose-scheduling studies in the hollow-fiber system model of tuberculosis using log-phase M. tuberculosis We recapitulated the amikacin concentration-time profiles observed in lungs of patients treated over 28 days. The PK/PD index linked to M. tuberculosis kill was the peak concentration (Cmax)-to-MIC ratio (r(2) > 0.99), closely followed by the area under the concentration-time curve from 0 to 24 h (AUC0-24)-to-MIC ratio (r(2) = 0.98). The EC90 was a Cmax/MIC ratio of 10.13 (95% CI, 7.73 to 12.48). The EC90 is the dosing target for intermittent therapy that optimizes cure in TB programs for MDR-TB patients.
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