In Vitro and In Vivo Antifungal Activity of AmBisome Compared to Conventional Amphotericin B and Fluconazole against Candida auris.

Antifungal activity of AmBisome against Candida auris was determined in vitro and in vivo AmBisome showed MIC50 and MIC90 values of 1 and 2 µg/ml, respectively. Unlike conventional amphotericin B, significant in vivo efficacy was observed in the AmBisome 7.5 mg/kg treatment group in survival and reduction of kidney tissue fungal burden compared to the untreated group. Our data show that AmBisome has significant antifungal activity against C. auris infection in vitro and in vivo.

Efficacy of Voriconazole, Isavuconazole, Fluconazole, and Anidulafungin in the Treatment of Emerging Candida auris Using an Immunocompromised Murine Model of Disseminated Candidiasis.

Antifungal activity of anidulafungin, voriconazole, isavuconazole, and fluconazole in the treatment of Candida auris was determined in vitro and in vivo. MICs for anidulafungin, voriconazole, isavuconazole, fluconazole, and amphotericin B were 0.5, 1, >64, 0.25, and 4 µg/ml, respectively. Significant in vivo efficacy was observed in the anidulafungin- and voriconazole-treated groups in survival and reduction in kidney tissue fungal burden compared to that in the untreated group (P values of <0.001 and 0.044, respectively). Our data showed that anidulafungin and voriconazole had comparable efficacies against C. auris, whereas isavuconazole did not show significant in vivo activity.

Candida tropicalis Affects Candida albicans Virulence by Limiting Its Capacity to Adhere to the Host Intestinal Surface, Leading to Decreased Susceptibility to Colitis in Mice.

Candida (C.) infections represent a serious health risk for people affected by inflammatory bowel disease. An important fungal virulence factor is the capacity of the fungus to form biofilms on the colonized surface of the host. This research study aimed to determine the effect of a C. tropicalis and C. albicans co-infection on dextran sodium sulfate (DSS)-induced colitis in mice. The colitis severity was evaluated using histology and a colonoscopy. The mice were mono-inoculated with C. albicans or C. tropicalis or co-challenged with both species. The mice were administered 3% DSS to induce acute colitis. The biofilm activity was assessed using (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl] 2H-tetrazoliumhydroxide (XTT) and dry-weight assays. The abundance of C. albicans in the colon tissues was assessed by immunohistochemistry. The co-challenged mice showed a decreased colitis severity compared to the mono-inoculated mice. The dry-weight assay demonstrated a marked decrease in C. albicans biofilm production in a C. albicans culture incubated with C. tropicalis supernatant. Immunohistochemical staining showed that C. albicans was more abundant in the mucosa of C. albicans mono-inoculated mice compared to the co-inoculated group. These data indicate an antagonistic microbial interaction between the two Candida species, where C. tropicalis may produce molecules capable of limiting the ability of C. albicans to adhere to the host intestinal surface, leading to a reduction in biofilm formation.

Efficacy of chlorhexidine in advanced performance technology formulation in decolonizing the skin using Candida auris skin colonization mouse model.

The incidence of Candida auris, an emerging multidrug resistant fungal species, is increasing. The ability of this yeast to colonize the human skin could lead to infections. Identifying agents to reduce the skin fungal burden is critical. Chlorhexidine formulated in a new Advanced Performance Technology formulation (APT-CH) was significantly more effective than untreated controls. Additional studies are warranted.

In Vivo Skin Colonization and Decolonization Models for Candida auris.

Candida auris infections present a critical problem to the healthcare system in many parts of the world. This yeast clinically manifests as a disseminated candidiasis which can be life-threating for susceptible individuals, as well as cutaneous and wound infections. Moreover, C. auris can colonize the skin and act as a nidus of infection. Importantly, this emerging yeast unlike other Candida spp. has demonstrated multidrug resistance; thus its eradication can be challenging. Animal models are important to gain insight into the pathogenesis of this infection, as well as play a significant role in drug development. In this chapter, we describe two C. auris animal models: a cutaneous infection guinea pig model and a skin decolonization mouse model.

An Immunocompromised Mouse Model of Candida auris Systemic Infection.

With the recent emergence of multidrug-resistant Candida auris, there is an urgent need for new antifungal compounds with novel pharmacodynamic and pharmacokinetic properties that can treat systemic fungal infections caused by this emerging yeast. Historically, testing the efficacy of treatment for disseminated candidiasis was accomplished using a diverse array of in vivo animal models, including mice which offer an advantage both in their similarities to humans and their lower cost of maintenance. However, in order to create effective in vivo models for testing new antifungal compounds designed to treat systemic infections, it is important that these models also mimic several of the relevant predisposing conditions that can lead to disseminated candidiasis. Here, we describe an immunocompromised mouse model of hematogenously disseminated C. auris infection, which may have utility to test the efficacy of candidate antifungal compounds.