In Vitro Toxicity and Activity of Dakin's Solution, Mafenide Acetate, and Amphotericin B on Filamentous Fungi and Human Cells
ARMY INST OF SURGICAL RESEARCH FORT SAM HOUSTON TX
Pagination or Media Count:
Objectives Posttraumatic invasive fungal infections threaten critically injured combat related injuries and require a combination of extensive surgery and systemic antifungal therapy, along with topical antimicro bials used adjunctively to control the infection. We evaluated the in vitro activity of topical agents in varying combinations and concentrations against molds from patients that were responsible for wound invasive fungal infections and the topical agents toxicity to human cells. Methods Mafenide acetate solutions 2.5, 5, and 7.5, amphotericin B solutions 2 mgmL, 2 mgmL, and 20 mgmL, SMAT 5 mafenide acetate in combination with 2 mgmL, 2 mgmL, and 20 mgmL amphotericin B, and Dakin s solutions buffered sodium hypochlorite 0.5, 0.25, and 0.125 and 10 fold serial dilutions of 0.25 0.00000025 were evaluated for antifungal activity against 4 molds using a time kill assay using standard conidial suspensions of 5 104 colony forming units per milliliter. To assess cellular toxicity, confluent monolayers of human keratinocytes, dermal fibroblasts, and osteoblasts were exposed to these topical agents. Based upon efficacy and toxicity ratios, an additional 10 molds were screened with selected concentrations of the topical agents for antifungal activity and toxicity. Results All the topical agents seemed to have a dose dependent killing with only mafenide acetate showing time killing associated with prolonged contact. There was overall evidence of dose dependent cytotoxicity of the various topical agents against the various cell lines tested, but there did not seem to be increased cell death with continued exposure to the agents over time. Dakin s solution exhibited dose dependent toxicity and efficacy with 0.00025 appearing to optimize those parameters. Conclusions Mafenide acetate and amphotericin B did not seem to persistently meet the toxicity and efficacy balance as consistently as Dakin s solution.
- Medicine and Medical Research