Novel Bacteriophage Cocktail, Endolysin-Hydroxyethyl Cellulose Gel, and Mixture Gel Therapy for Acne Vulgaris Caused by Multidrug Resistant Propionibacterium (Cutibacterium) acnes

Background: Propionibacterium (Cutibacterium) acnes ( P. acnes ) is a bacterium closely associated with the pathophysiology of acne vulgaris. Objectives: First to prepare a hydroxyethyl cellulose (HEC) gel containing Propionibacterium-specific cocktail of lytic bacteriophages along with Propionibacterium-specific phage endolysin, and second to test the efficacy of the prepared gel using in vitro antibacterial validation tests and in vivo clinical trials targeting facial multidrug resistant (MDR) P. acnes by applying the gel topically on moderate-severe acne lesions. Materials and Methods: Thirteen isolates of MDR P. acnes bacteria were obtained from acne lesions of human skin by using comedone extractor. Two isolates of bacteriophages with specific lytic activity to MDR P. acnes were isolated by conventional microbiological methods and bacteriophage cocktail was accordingly prepared; moreover, a purified endolysin extracted from one of the isolated bacteriophages was used with the phage cocktail. Gel-based formulation from bacteriophage cocktail and endolysin-HEC was prepared. In vitro validation tests, namely spot lysis, top layer plaque, and antibacterial activity assays were performed. In vivo topical application of the prepared gel for 30 minutes three times daily for 1 week on moderate-severe facial acne lesions of volunteers aged above 25 years old caused by MDR P. acnes. Results: Gel-based formulations showed 100% in vitro spectrum of lysis against MDR P. acnes isolates. No allergic reaction was found from the topical therapy of the prepared gel; moreover, a remarkable clinical improvement was observed in terms of decreased inflammatory signs, size, and number of comedones, along with complete decolonization of MDR P. acnes in gel-treated acne lesions when compared to the untreated acne lesions (control). Conclusion: Bacteriophage cocktail, endolysin-HEC gel, and mixture gel therapy may offer a real chance for patients with chronic acne lesions caused by MDR P. acnes and may protect teenagers and young adults from antibiotic overuse, anxiety, and depression.