title: In vitro activity of Melaleuca alternifolia (tea tree) oil on filamentous fungi and toxicity to human cells.
abstract: Invasive fungal wound infections (IFIs) are increasingly reported in trauma patients and cause considerable morbidity and mortality despite standard of care treatment in trauma centers by experienced medical personnel. Topical agents such as oil of melaleuca, also known as tea tree oil (TTO), have been proposed for adjunctive treatment of IFIs. We evaluated the activity of TTO against filamentous fungi associated with IFIs by testing 13 clinical isolates representing nine species via time-kill assay with seven concentrations of TTO (100%, 75%, 50%, 25%, 10%, 5%, and 1%). To ascertain the safety of topical application to wounds, cell viability assays were performed in vitro using human fibroblasts, keratinocytes, osteoblasts, and umbilical vein endothelial cells with 10 concentrations of TTO (75%, 50%, 25%, 10%, 5%, and 10-fold serial dilutions from 1 to 0.0001%) at five time points (5, 15, 30, 60, and 180 min). Compatibility of TTO with explanted porcine tissues was also assessed with eight concentrations of TTO (100%, 75%, 50%, 25%, 10%, 5%, 1%, and 0.1%) at the time points used for cellular assays and at 24 h. The time-kill studies showed that fungicidal activity was variable between isolates. The effect of TTO on cell viability was primarily concentration dependent with significant cytotoxicity at concentrations of ≥ 10% and ≥ 50% for cells lines and whole tissue, respectively. Our findings demonstrate that TTO possesses antifungal activity against filamentous fungi associated with IFIs; furthermore that negligible effects on whole tissues, in contrast to individual cells, were observed following exposure to TTO. Collectively, these findings indicate a potential use of TTO as topical treatment of IFIs.
authors: Department of Medicine, Infectious Disease Service, San Antonio Military Medical Center, Fort Sam Houston, TX, USA dchomeyer@gmail.com.
authors: Diane C
authors: DC
authors: Homeyer
authors: Extremity Trauma & Regenerative Medicine Task Area, United States Army Institute of Surgical Research, Fort Sam Houston, TX, USA.
authors: Carlos J
authors: CJ
authors: Sanchez
authors: Department of Medicine, Infectious Disease Service, San Antonio Military Medical Center, Fort Sam Houston, TX, USA Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors: Katrin
authors: K
authors: Mende
authors: Department of Clinical Investigation, Brooke Army Medical Center, Fort Sam Houston, TX, USA.
authors: Miriam L
authors: ML
authors: Beckius
authors: Department of Medicine, Infectious Disease Service, San Antonio Military Medical Center, Fort Sam Houston, TX, USA.
authors: Clinton K
authors: CK
authors: Murray
authors: Extremity Trauma & Regenerative Medicine Task Area, United States Army Institute of Surgical Research, Fort Sam Houston, TX, USA.
authors: Joseph C
authors: JC
authors: Wenke
authors: Department of Medicine, Infectious Disease Service, San Antonio Military Medical Center, Fort Sam Houston, TX, USA Extremity Trauma & Regenerative Medicine Task Area, United States Army Institute of Surgical Research, Fort Sam Houston, TX, USA.
authors: Kevin S
authors: KS
authors: Akers
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D005658:Fungi / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects; D031650:Melaleuca / Q000737:chemistry*; D009181:Mycoses / Q000382:microbiology; D010006:Osteoblasts / Q000187:drug effects; D013552:Swine; D020947:Tea Tree Oil / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity*; D014946:Wound Infection / Q000382:microbiology
chemical_list: D000935:Antifungal Agents; D020947:Tea Tree Oil
keywords: Melaleuca alternifolia; cell viability; cytotoxicity; invasive fungal infection; tea tree oil