In Vitro activity of Manuka Honey and polyhexamethylene biguanide on filamentous fungi and toxicity to human cell lines.
Soft-tissue invasive fungal infections are increasingly recognized as significant entities directly contributing to morbidity and mortality. They complicate clinical care, requiring aggressive surgical debridement and systemic antifungal therapy. To evaluate new topical approaches to therapy, we examined the antifungal activity and cytotoxicity of Manuka Honey (MH) and polyhexamethylene biguanide (PHMB). The activities of multiple concentrations of MH (40%, 60%, 80%) and PHMB (0.01%, 0.04%, 0.1%) against 13 clinical mould isolates were evaluated using a time-kill assay between 5 min and 24 h. Concentrations were selected to represent current clinical use. Cell viability was examined in parallel for human epidermal keratinocytes, dermal fibroblasts and osteoblasts, allowing determination of the 50% viability (LD50) concentration. Antifungal activity of both agents correlated more closely with exposure time than concentration. Exophiala and Fusarium growth was completely suppressed at 5 min for all PHMB concentrations, and at 12 and 6 h, respectively, for all MH concentrations. Only Lichtheimia had persistent growth to both agents at 24 h. Viability assays displayed concentration-and time-dependent toxicity for PHMB. For MH, exposure time predicted cytotoxicity only when all cell types were analyzed in aggregate. This study demonstrates that MH and PHMB possess primarily time-dependent antifungal activity, but also exert in vitro toxicity on human cells which may limit clinical use. Further research is needed to determine ideal treatment strategies to optimize antifungal activity against moulds while limiting cytotoxicity against host tissues in vivo.
San Antonio Military Medical Center, Fort Sam Houston, TX, USA.
Joseph M
JM
Yabes
San Antonio Military Medical Center, Fort Sam Houston, TX, USA.
Brian K
BK
White
San Antonio Military Medical Center, Fort Sam Houston, TX, USA.
Clinton K
CK
Murray
United States Army Institute of Surgical Research, Fort Sam Houston, TX, USA.
Carlos J
CJ
Sanchez
San Antonio Military Medical Center, Fort Sam Houston, TX, USA.|Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.|The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD USA.
Katrin
K
Mende
San Antonio Military Medical Center, Fort Sam Houston, TX, USA.
Miriam L
ML
Beckius
San Antonio Military Medical Center, Fort Sam Houston, TX, USA.|Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.|The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD USA.
Wendy C
WC
Zera
United States Army Institute of Surgical Research, Fort Sam Houston, TX, USA.
Joseph C
JC
Wenke
United States Army Institute of Surgical Research, Fort Sam Houston, TX, USA.
Kevin S
KS
Akers
D001645:Biguanides / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004202:Disinfectants / Q000494:pharmacology* / Q000633:toxicity; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology; D005658:Fungi / Q000187:drug effects* / Q000502:physiology; D006722:Honey; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000502:physiology; D007928:Lethal Dose 50; D008826:Microbial Sensitivity Tests; D010006:Osteoblasts / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
D001645:Biguanides; D004202:Disinfectants; C031233:polihexanide
Mucorales; Topical; cytotoxicity; manuka honey; polyhexamethylene biguanide; polyhexanide