Pharmacodynamic Evaluation of Plasma and Epithelial Lining Fluid Exposures of Amikacin against Pseudomonas aeruginosa in a Dynamic In Vitro Hollow-Fiber Infection Model

Author:

Heffernan Aaron J.12ORCID,Sime Fekade B.23ORCID,Sarovich Derek S.4,Neely Michael5,Guerra-Valero Yarmarly3,Naicker Saiyuri23,Cottrell Kyra3,Harris Patrick36ORCID,Andrews Katherine T.7,Ellwood David18,Wallis Steven C.3,Lipman Jeffrey3910,Grimwood Keith111,Roberts Jason A.23910ORCID

Affiliation:

1. School of Medicine, Griffith University, Gold Coast, Queensland, Australia

2. Centre for Translational Anti-Infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia

3. University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia

4. GeneCology Research Centre, University of the Sunshine Coast, Sippy Downs, Queensland, Australia

5. Children’s Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, California, USA

6. Department of Microbiology, Pathology Queensland, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia

7. Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland, Australia

8. Department of Maternal and Fetal Medicine, Gold Coast Health, Southport, Queensland, Australia

9. Department of Intensive Care Medicine, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia

10. Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France

11. Department of Paediatrics, Gold Coast Health, Southport, Queensland, Australia

Abstract

Given that aminoglycosides, such as amikacin, may be used for multidrug-resistant Pseudomonas aeruginosa infections, optimization of therapy is paramount for improved treatment outcomes. This study aims to investigate the pharmacodynamics of different simulated intravenous amikacin doses on susceptible P. aeruginosa to inform ventilator-associated pneumonia (VAP) and sepsis treatment choices. A hollow-fiber infection model with two P. aeruginosa isolates (MICs of 2 and 8 mg/liter) with an initial inoculum of ∼10 8 CFU/ml was used to test different amikacin dosing regimens.

Funder

Department of Health | National Health and Medical Research Council

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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