Are Plants the Answer to the Global Antibiotic Resistance Crisis? Novel application of natural plant extracts into a topical gel formulation for the treatment of skin and soft tissue infections

Abstract

Antimicrobial resistant infections are one of the biggest threats to human health worldwide, causing enormous losses to human life and productivity every year. Among developed nations, New Zealand has one of the highest incidences of skin and soft tissue infections (SSTIs), primarily caused by increasingly drug-resistant Staphylococcus aureus but other organisms such as Escherichia coli, Candida albicans and Candida auris pose considerable risks to the healthcare system as well. Plant-sourced extracts have been used extensively throughout history for their medicinal properties, and with much of nature’s reservoir yet to be studied for their antimicrobial capabilities, this project aimed to identify from a panel of 12 unknown plant extracts and solvents, candidates which were rapidly microbicidal that could be incorporated into a fast-killing topical gel to treat drug sensitive and resistant SSTI pathogens. Based on CLSI methodology, broth microdilution testing was carried out to determine which plant extracts possessed antimicrobial activity against drug-sensitive bacteria and fungi, with those showing killing selected for further studies against drug-resistant pathogen strains. Experimental outcomes revealed that the best plant extract, with the broadest spectrum of interdomain activity against both bacterial and fungal pathogens was “AF1” which exhibited lethal activity at sub 1% v/v concentration against all tested pathogens except C. auris 21092 which was not tested for commercial reasons and E. coli. Extract candidates “P1” and “P2” were only active against the yeasts C. albicans 10231 and C. auris 21092, but outperformed the clinical antifungal amphotericin B by having a faster time-to-kill and more strongly suppressing yeast re-growth over time which AF1 also achieved against the former. Although rheology testing showed that plant extracts were suitable for incorporation within a 2% w/v chitosan gel base, the final AF1-chitosan formulation had a reduced rate of microbicidal activity compared to the active crude extracts alone which had achieved a 3-log reduction or ≥ 99.9% killing of added C. albicans 10231 and C. auris 21092 inoculums within 10 minutes. Ultimately, the outcomes of this project supported the hypotheses that plant extracts possessed the capability to rapidly kill some drug-sensitive and drug-resistant strains of bacterial and fungal pathogens implicated in SSTIs, and also exhibited desirable rheology properties when incorporated within a chitosan gel. However, further work and testing for stability, toxicity and improvements upon the antimicrobial potency of the topical formulation will be needed for it to become more suitable for human applications.