Clinically Relevant Epithelial Lining Fluid Concentrations of Meropenem with Ciprofloxacin Provide Synergistic Killing and Resistance Suppression of Hypermutable Pseudomonas aeruginosa in a Dynamic Biofilm Model

Author:

Bilal Hajira1,Bergen Phillip J.1,Tait Jessica R.1,Wallis Steven C.2,Peleg Anton Y.3,Roberts Jason A.2456ORCID,Oliver Antonio7ORCID,Nation Roger L.8,Landersdorfer Cornelia B.1ORCID

Affiliation:

1. Centre for Medicine Use and Safety, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia

2. The University of Queensland Centre for Clinical Research, Faculty of Medicine and Centre for Translational Anti-infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia

3. Department of Infectious Diseases, The Alfred Hospital and Central Clinical School, Monash University, Melbourne, Victoria, Australia

4. Department of Pharmacy, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia

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

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

7. Hospital Universitario Son Espases, Palma de Mallorca, Spain

8. Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia

Abstract

Treatment of exacerbations of chronic Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF) is highly challenging due to hypermutability, biofilm formation, and an increased risk of resistance emergence. We evaluated the impact of ciprofloxacin and meropenem as monotherapy and in combination in the dynamic in vitro CDC biofilm reactor (CBR). Two hypermutable P. aeruginosa strains, PAOΔ mutS (MIC of ciprofloxacin [MIC ciprofloxacin ], 0.

Funder

National Health and Medical Research Council

Department of Health | National Health and Medical Research Council

MEC | Instituto de Salud Carlos III

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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