Phase 1 safety trial of a natural product cocktail with antibacterial activity in human volunteers

Abstract

New antibiotics are urgently needed to reduce the health burden of antibiotic-resistant bacterial infection. Natural products (NPs) derived from plants and animals are a current focus of research seeking to discover new antibacterial molecules with clinical potential. A cocktail of NPs based on a medieval remedy for eye infection eliminated biofilms of several highly antibiotic-resistant bacterial species in laboratory studies, and had a promising safety profile in vitro and in a mouse model. A necessary prelude to refining this remedy into a defined, synthetic mixture suitable for testing with wound infections is to firstly establish safety when applied to healthy human skin. We aimed to assess skin-related outcomes of the preparation in a sample of healthy volunteers. This prospective, single arm, non-randomised Phase I clinical trial consisted of a single patch test intervention with 48-h follow-up. Volunteers were staff, students and members of the public recruited from the University of Warwick and surrounding locality. Adults aged 18–79 years, with no history of severe immunity-related disease, diabetes, recent infection, or known pregnancy were eligible. A 100 µl application of a filter-sterilised NP mixture, comprising ground garlic, onion, white wine and bovine bile, was applied to skin on the upper arm and covered with a dressing. The primary outcome was skin-related adverse events over 48 h. Digital photographs were captured where bothersome, salve-related events were reported. 109 volunteers, aged 18–77 years, were recruited between June and July 2021. Sample mean age was 37.6 (SD 16.1) years, and 63 (58%) participants were female. Outcome data were obtained for 106/109 (97%); two participants were lost to follow-up and one removed the skin patch after nine hours due to a bothersome garlic odour. Twenty-one (19.8%) participants reported any patch-test related sign or symptom; of these 14 (13.2%) participants reported minor events related to the salve, including itchiness, redness, or garlic odour. No serious events were reported. We found no evidence of serious skin-related adverse events related to the NP preparation. Trial registration: International Standard Randomised Controlled Trial Number (ISRCTN10773579). Date registered: 08/01/2021.