Antimicrobial Activity Of Aerosolized Liposomal Cycloporine (l-Csa) To Different Opportunistic Microorganism

J. M. Schierholz , O. Denk , I. Fischer , A. Schwarzkopf , M. Keller

Author address: 

PARI Pharma GmbH, Graefelfing, Germany, University of Tuebingen, Tuebingen, Germany, Labor L+S, Aura an der Saale, Germany

Abstract: 

Introduction: Pulmonary infections are caused by nosocomial organisms, largely Aspergillus and Candida spp. associated with a high mortality in the first month after transplantation. Aerosolized liposomal 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 lung infections. Materials and Methods: Enriched sheep blood agar without di- and monosaccharides was chosen to simulate the anastomoses site which are the primary site of clinically apparent infection. Each Petri dish thus simulates 0.254 m of wound surface. The test strains 2 represented yeasts (Candida albicans, ATCC 10231) and molds (Aspergillus niger, ATCC 16404, Aspergillus fumigatus ATCC 9197), Pseudomonas (Pseudomonas aeruginosa ATCC 27853) and Streptococcus (Streptococcus pneumoniae ATCC 33400). Agar plates were overlaid with L-CsA and microorganisms (100 μl of suspension with about 3,5 x103 CFU),incubated at 36°C +/- 1 °C and colony counts were observed and documented at day 1, 2, 3, 4 and 5. Results: The L-CsA inhibited the harmful pathogen Aspergillus niger in this simulation and slowed the evident growth of A. fumigatus. The yeast Candida albicans showed less colony counts. Streptococcus pneumoniae was inhibited over time und L-CsA showed classical dose-response relationships. Conclusion: Cyclosporine as a calcineurin-inhibitor has shown some activity towards opportunistic pathogens such as Aspergillus niger and fumigatus, Cryptococcus neoformans and some Candida strains as well as in combination with azoles. Locally high concentrations of liposomal CsA may prevent colonization as well as infection of the lung of transplanted patients even in combination with systemic antimicrobial drugs.
2011

abstract No: 

B58

Full conference title: 

American Thoracic Society
    • ATS 2011