Antimicrobial properties of aerosolized liposomal cyclosporine (L-CsA) in lung transplantation patients An in vitro study

Joerg Schierholz, Andreas Schwarzkopf, Oliver Denk, Imma Fischer, Manfred Keller.

Author address: 

PARI Pharma GmbH, Aerosol Research Institute, Graefelfing, Germany 2Facharzt für Mikrobiologie und Infektionsepidemiologie, Ö. b. u. b. Sachverständiger für Krankenhaushygiene, Aura an der Saale, Germany 3Biostatistik Tuebingen, University of Tuebi

Abstract: 

Approximately 40% of all deaths after lung transplantation are caused by infections and 60 to 80% of these infections are respiratory. Aerosolized liposomal cyclosporine is currently being tested in a Phase II clinical trial for the prevention of bronchiolitis obliterans in lung transplant patients. Here we present the efficacy of L-CsA to inhibit the growth of lung pathogens. Materials and Methods Enriched sheep blood agar without di- and monosaccharides was chosen to simulate the anastomoses site. Each Petri dish thus simulates 0.254 m² of wound surface compared to 100 m² lung surface. Due to the lack of any defense mechanisms this study represents a worst case scenario. Test strains: Candida albicans ATCC 10231, Aspergillus niger ATCC 16404, Aspergillus fumigatus ATCC 9197, Pseudomonas aeruginosa ATCC 27853, Streptococcus pneumoniae ATCC 33400. Agar plates were overlaid with L-CsA and microorganisms (100 μl of suspension with about 3.5 x 103 CFU), than incubated at 36°C +/- 1 °. Colony counts were documented at day 1, 2, 3, 4 and 5. Results In comparison to control media L-CsA inhibited the harmful pathogen Aspergillus niger in this simulation and slowed evident the growth of A. fumigatus. The yeast Candida albicans showed less colony counts. The Pseudomonas colonies grew without signs of inhibition and Streptococcus pneumoniae was inhibited completely over time. The controls showed normal growth. Conclusion Aerosolized L-CsA, even targeted delivered and locally high concentrated, may have the impact for both the prevention of the development of BOS as well as the prevention of some opportunistic pulmonal infections.
2010

abstract No: 

E3489

Full conference title: 

20th European Respiratory Society conference
    • ERS 20th (2010)