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A chloramine-based antiseptic polymer improves Candida auris skin decolonization compared to chlorhexidine in a
Janet Herrada1, Lisa Long1, Erin Marie San Valentin1
1Department of Dermatology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
Abstract:
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.
Insights
A new chloramine-based antiseptic, polyvantoin chlorine (AVA-003), shows promise for decolonizing skin of the critical pathogen Candida auris. AVA-003 demonstrated superior efficacy compared to chlorhexidine gluconate in reducing fungal burden in a murine model.
Area of Science:
- Infectious Diseases
- Antimicrobial Resistance
- Medical Mycology
Background:
- Candida auris is a critical priority pathogen due to its frequent multidrug resistance and high mortality rates.
- Skin colonization by C. auris poses a significant risk for invasive infection, yet current decolonization methods like chlorhexidine gluconate (CHG) are unreliable.
- There is an urgent need for effective C. auris decolonization protocols.
Purpose of the Study:
- To evaluate the efficacy of a novel chloramine-based antiseptic polymer, polyvantoin chlorine (AVA-003), for C. auris decolonization.
- To compare the effectiveness of AVA-003 against CHG in a validated murine model.
Main Methods:
- In vitro broth microdilution assessed AVA-003 activity against C. auris isolates from all four major clades.
- In vivo efficacy was evaluated in a murine model inoculated with C. auris.
- Mice were treated with 1.2% AVA-003, 2% CHG, or vehicle controls across two phases examining formulation and treatment duration.
Main Results:
- AVA-003 demonstrated in vitro activity against all tested C. auris clades (MICs 250-500 µg/mL).
- In vivo, AVA-003 significantly reduced C. auris fungal burden on both ear and dorsal skin compared to untreated and CHG-treated controls.
- AVA-003 achieved undetectable fungal burden in phase I and significantly reduced burden in phase II, showing greater advantage over CHG at 3 days.
Conclusions:
- Polyvantoin chlorine (AVA-003) is a promising candidate for C. auris decolonization.
- AVA-003 shows superior efficacy compared to CHG in reducing C. auris burden in a murine model.
- Further clinical investigation of AVA-003 for C. auris decolonization is warranted.
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