Janet Herrada, Lisa Long, Erin Marie San Valentin, Fnu Samiksha, Nicole Byrnes-Shaver, Lynne Harding, Thomas S McCormick, Mahmoud Ghannoum
Candida auris frequently demonstrates resistance to multiple antifungal classes and has been classified as a critical priority pathogen by the World Health Organization and the first fungal pathogen designated an urgent threat by the U.S. Centers for Disease Control and Prevention. Patients with skin colonization face a 7%-20% risk of invasive infection, with 30-day mortality of 30%-72%. While chlorhexidine gluconate (CHG) is widely used for general skin decolonization, it fails to reliably clear C. auris from patient skin, and no proven decolonization protocol exists. We evaluated a novel chloramine-based antiseptic polymer, polyvantoin chlorine (AVA-003). In vitro CLSI broth microdilution demonstrated activity against isolates from all four major C. auris clades (I-IV), with minimum inhibitory concentrations ranging from 250 to 500 µg/mL. Two proof-of-concept experiments using a validated murine model assessed in vivo efficacy. Female BALB/c mice were inoculated with clinical isolate C. auris MRL-35368 and treated with 1.2% AVA-003, 2% CHG, or vehicle controls across two phases examining formulation and treatment duration. AVA-003 reduced fungal burden at both ear and dorsal sites compared to untreated and CHG-treated controls. Specifically, 1.2% AVA-003 reduced ear burden versus untreated controls by 3.07 log colony-forming units (CFU)/g (P = 0.003, phase I) and versus 2% CHG at 3 days by 1.42 log CFU/g (P < 0.0001, phase II); dorsal burden was reduced by 3.58 log CFU/g versus untreated controls (P < 0.0001). In phase I, 1.2% AVA-003 achieved undetectable burden (0 CFU/g) at both sites. In phase II, AVA-003 significantly reduced but did not uniformly eradicate C. auris burden. Its advantage over CHG was greater at 3 days than 7 days, likely reflecting progressive dorsal hair regrowth, a recognized limitation of the murine model. These findings support AVA-003 as a promising C. auris decolonization candidate warranting further clinical investigation.