Potency and stability of liposomal Amphotericin B formulated for topical management of Aspergillus spp. infections in burn patients
Alexis Laurent,
Olivier Pantet,
Lydie Laurent,
Nathalie Hirt-Burri,
Anthony de Buys Roessingh,
Wassim Raffoul,
Philippe Laurent,
Michel Monod,
Lee Ann Applegate
Affiliations
Alexis Laurent
Service of Dermatology, Laboratory of Mycology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland; Pharmacy du Gros-de-Vaud, Bercher, Switzerland
Olivier Pantet
Dept. Intensive Care, Lausanne University Hospital, Lausanne, Switzerland
Lydie Laurent
School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland; Dept. Plastic, Reconstructive & Hand Surgery, Unit of Regenerative Therapy, Lausanne University Hospital, Epalinges, Switzerland
Nathalie Hirt-Burri
Dept. Plastic, Reconstructive & Hand Surgery, Unit of Regenerative Therapy, Lausanne University Hospital, Epalinges, Switzerland
Anthony de Buys Roessingh
Dept. Plastic, Reconstructive & Hand Surgery, Unit of Regenerative Therapy, Lausanne University Hospital, Epalinges, Switzerland
Wassim Raffoul
Dept. Plastic, Reconstructive & Hand Surgery, Unit of Regenerative Therapy, Lausanne University Hospital, Epalinges, Switzerland
Philippe Laurent
School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland; Pharmacy du Gros-de-Vaud, Bercher, Switzerland
Michel Monod
Service of Dermatology, Laboratory of Mycology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
Lee Ann Applegate
Dept. Plastic, Reconstructive & Hand Surgery, Unit of Regenerative Therapy, Lausanne University Hospital, Epalinges, Switzerland; Corresponding author at: Regenerative Therapy Unit, Plastic, Reconstructive & Hand Surgery, Lausanne University Hospital, EPCR/ch. Croisettes 22, 1066 Epalinges, Switzerland.
Background: Systemic fungal infections are an important mortality factor when considering severely burned patients. Preventive topical pharmacotherapeutic management of deep fungal infections remains of secondary concern when initially treating a burn victim, despite high inherent lethal risks. Indeed, the possible subsequent invasions of newly accessible deep tissues and bone by opportunistic fungi often prove fatal. Amphotericin B is a broad-spectrum antifungal agent of choice for infections in burn victims. Intravenous administration is limited by drug-related nephrotoxicity. Novel topical Amphotericin B preparations to be applied in burn centers would therefore limit the systemic adverse effects of the active principle while preventing dissemination of sensitive pathogens and thus help reducing infectious and drug-related mortality. Objective: To establish the need for new topical pharmacotherapeutic management options to treat burn wound fungal infections and conceptually determine the applicability of liposomal Amphotericin B for such cases. Methods: Experimental liposomal Amphotericin B was prepared with commercial components and tested in vitro in our mycology laboratory to determine efficacy, stability and potential for topical application on our burn patients. Results: Data showed equivalent or superior in vitro activity of liposomal Amphotericin B versus unbound drug against Aspergillus fumigatus and superior physical and pharmacologic effect stability over time. Conclusion: Topical and relatively inexpensive liposomal Amphotericin B as described in this work is an interesting, potentially mortality-reducing candidate regarding fungal infections in early and severe burn wound management.
