In Vitro Activity of Manuka Honey and Polyhexamethylene Biguanide on Filamentous Fungi and Toxicity to Human Cells

Joseph Yabes, Jr., MD Brian White, DO Katrin Mende, PhD Kevin S. Akers, MD, FIDSA Carlos Sanchez, Jr., PhD Joseph Wenke, PhD Miriam Beckius, MPH Wendy Zera, BS Clinton K. Murray, MD, FIDSA


Background. Invasive fungal infections after combat-related traumatic injuries complicate clinical care, requiring aggressive surgical debridement and systemic antifungal therapy. The purpose of the study was to evaluate the antifungal effect and the toxicity of two topical agents; Manuka honey (MH) and polyhexamethylene biguanide (PHMB).

Methods. The activities of various concentrations of MH (40%, 60%, 80%) and PHMB (0.01%, 0.04%, 0.1%) against 13 clinical mold isolates (1 Lichtheimia sp., 3 Aspergillus flavus, 1 Aspergillus fumigatus, 1 Aspergillus terreus, 2 Mucor spp., 1 Fusarium sp., 1 Exophiala sp., 1 Apophysomyces sp., 2 Actinomucor elegans) were evaluated using an established time kill assay at time points between 5 min and 24 hrs. Cell viability was examined by exposing confluent monolayers of human epidermal keratinocytes, dermal fibroblasts and osteoblasts to identical concentrations of the agents at the same time points, allowing determination of the 50% viability (LD50) concentration.

Results. Overall antifungal activity more closely correlated with exposure time than concentration. Exophialaand Fusarium growth was completely suppressed at 5 min for all PHMB concentrations, and at 12 hrs and 6 hrs, respectively, for all MH concentrations. PHMB failed to completely suppress A. flavusA. terreus and Apophysomyces growth but was able to kill >75%, >70%, and >90%, respectively, compared to the control. MH was unable to completely suppress growth of either Mucor isolate but killed >90%. Only Lichtheimia had persistent growth to both agents at 24 hrs. PHMB viability assays displayed concentration and time dependent toxicity, but only time was a predictor for fibroblasts. For MH, neither concentration nor time predicted toxicity for individual cell types, but when all cell types were reviewed in aggregate, time was a predictor.

Conclusion. The study demonstrated that MH and PHMB possess primarily time-dependent antifungal activity but had highly toxic effects on cells. Cellular toxicity at the same concentrations and longer exposure times may limit clinical benefit; however, the concentrations tested are currently in clinical use. Further research is needed to evaluate effects on whole tissues versus cell cultures.

Disclosures.All authors: No reported disclosures.


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