1146. In Vitro Activity of Manuka Honey and Polyhexamethylene Biguanide on Filamentous Fungi and Toxicity to Human Cells
Session: Poster Abstract Session: Pharmacological Studies of Antifungals
Friday, October 9, 2015
Room: Poster Hall
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 5min and 24hrs.  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. Exophiala and Fusarium growth was completely suppressed at 5min for all PHMB concentrations, and at 12hrs and 6hrs, respectively, for all MH concentrations.  PHMB failed to completely suppress A. flavus, A. 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 24hrs.  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.

Joseph Yabes Jr., MD1, Brian White, DO2, Katrin Mende, PhD3, Kevin S. Akers, MD, FIDSA4, Carlos Sanchez Jr., PhD4, Joseph Wenke, PhD5, Miriam Beckius, MPH3, Wendy Zera, BS6 and Clinton K. Murray, MD, FIDSA7, (1)Internal Medicine, San Antonio Military Medical Center, Fort Sam Houston, TX, (2)Infectious Disease Service, San Antonio Military Medical Center, Fort Sam Houston, TX, (3)Department of Clinical Investigation, San Antonio Military Medical Center, Fort Sam Houston, TX, (4)Extremity Trauma and Regenerative Medicine, US Army Institute of Surgical Research, Fort Sam Houston, TX, (5)Extremity Trauma & Regenerative Medicine, United States Army Institute of Surgical Research, Fort Sam Houston, TX, (6)Department of Medicine, San Antonio Military Medical Center, Fort Sam Houston, TX, (7)Infectious Disease Service, Brooke Army Medical Center, Fort Sam Houston, TX

Disclosures:

J. Yabes Jr., None

B. White, None

K. Mende, None

K. S. Akers, None

C. Sanchez Jr., None

J. Wenke, None

M. Beckius, None

W. Zera, None

C. K. Murray, None

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