Efficacy Of Antifungal Drugs Research Articles

Modeling of intravenous caspofungin administration using an intestine-on-chip reveals altered Candida albicans microcolonies and pathogenicity

Candida albicans is a commensal yeast of the human intestinal microbiota that, under predisposing conditions, can become pathogenic and cause life-threatening systemic infections (candidiasis). Fungal-host interactions during candidiasis are commonly studied using conventional 2D in vitro models, which have provided critical insights into the pathogenicity. However, microphysiological models with a higher biological complexity may be more suitable to mimic in vivo-like infection processes and antifungal drug efficacy. Therefore, a 3D intestine-on-chip model was used to investigate fungal-host interactions during the onset of invasive candidiasis and evaluate antifungal treatment under clinically relevant conditions. By combining microbiological and image-based analyses we quantified infection processes such as invasiveness and fungal translocation across the epithelial barrier. Additionally, we obtained novel insights into fungal microcolony morphology and association with the tissue. Our results demonstrate that C. albicans microcolonies induce injury to the epithelial tissue by disrupting apical cell-cell contacts and causing inflammation. Caspofungin treatment effectively reduced the fungal biomass and induced substantial alterations in microcolony morphology during infection with a wild-type strain. However, caspofungin showed limited effects after infection with an echinocandin-resistant clinical isolate. Collectively, this organ-on-chip model can be leveraged for in-depth characterization of pathogen-host interactions and alterations due to antimicrobial treatment.

Models for Inducing Experimental Cryptococcosis in Mice.

Cryptococcus neoformans and Cryptococcus gattii are the predominant etiological agents of cryptococcosis, a particularly problematic disease in immunocompromised individuals. The increased clinical use of immunosuppressive drugs, the inherent ability of Cryptococcus species to suppress and evade host immune responses, and the emergence of drug-resistant yeast support the need for model systems that facilitate the design of novel immunotherapies and antifungals to combat disease progression. The mouse model of cryptococcosis is a widely used system to study Cryptococcus pathogenesis and the efficacy of antifungal drugs in vivo. In this chapter, we describe three commonly used strategies to establish cryptococcosis in mice: intranasal, intratracheal, and intravenous inoculations. Also, we discuss the methodology for delivering drugs to mice via intraperitoneal injection.

Recent Advances in Understanding the Human Fungal Pathogen Hypoxia Response in Disease Progression.

Fungal-mediated disease progression and antifungal drug efficacy are significantly impacted by the dynamic infection microenvironment. At the site of infection, oxygen often becomes limiting and induces a hypoxia response in both the fungal pathogen and host cells. The fungal hypoxia response impacts several important aspects of fungal biology that contribute to pathogenesis, virulence, antifungal drug susceptibility, and ultimately infection outcomes. In this review, we summarize recent advances in understanding the molecular mechanisms of the hypoxia response in the most common human fungal pathogens, discuss potential therapeutic opportunities, and highlight important areas for future research.

Can nonsteroidal anti-inflammatory drugs (NSAIDs) be repurposed for fungal infection?

Nonsteroidal anti-inflammatory drugs (NSAIDs) are an important class of anti-inflammatory drugs widely used for the treatment of musculoskeletal disorders, mild-to-moderate pain, and fever. This review aimed to explain the functional role and possible mechanisms of the antifungal effects of NSAIDs alone or in combination with antifungal drugs in vitro and in vivo. Several studies reported that NSAIDs such as aspirin, ibuprofen, diclofenac, indomethacin, ketorolac, celecoxib, flurbiprofen, and nimesulide had antifungal activities in vitro, either fungistatic or fungicidal, against different strains of Candida, Aspergillus, Cryptococcus, Microsporum, and Trichophyton species. These drugs inhibited biofilm adhesion and development, and yeast-to-hypha conversion which may be related to a prostaglandin E2 (PGE2)/PGEx-dependent mechanism. Modulating PGE2 levels by NSAIDs during fungal infection can be introduced as a possible mechanism to overcome. In addition, some important mechanisms of the antifungal activities of NSAIDs and their new derivatives on fungi and host immune responses are summarized. Overall, we believe that using NSAIDs along with classical antifungal drugs has the potential to be investigated as a novel therapeutic strategy in clinical studies. Furthermore, combination therapy can help manage resistant strains, increase the efficacy of antifungal drugs, and reduce toxicity.

Drosophila melanogaster as a model of systemic dermatophytosis.

Dermatophytosis is one of the most common fungal infections worldwide. The distribution of dermatophytes varies across continents, but the genera Trichophyton and Microsporum have emerged as the main isolated agents in humans and animals. To validate Drosophila melanogaster flies as a fast and feasible model to study dermatophytic infections. Wild-type (WT) and Toll-deficient D. melanogaster flies were infected by Trichophyton rubrum, T. mentagrophytes, Microsporum canis and Nannizzia gypsea by pricking with a needle previously dipped in inoculum concentrations ranging from 103 to 108 colony-forming units/mL. Establishment of infection was confirmed by survival curves, histopathological analysis and fungal burden. Thereafter, flies were treated with terbinafine, itraconazole and clioquinol. WT flies were predominantly resistant to the infection, whereas Toll-deficient flies succumbed to the four dermatophyte genera tested. The antifungal drugs protected flies from the infection, except for N. gypsea whose survival curves did not differ from the untreated group. This pilot study confirms that D. melanogaster is a suitable model to study the virulence and antifungal drug efficacy in dermatophyte species.

Emergence of Resistant Extensive Tinea Infections

Dermatophytosis is a contagious infection of the skin, nails, and hair that is spread by direct or indirect contact. There was a failure of standard therapy, resulting in the establishment of recurring and chronic dermatophytosis. The aim of study is to assess the extensive areas of tinea infections, the resistant and recurrent tinea infection, and the efficacy of antifungal drug on clinical cure. This is a type of cohort study was carried out at the outpatient clinic of the department of Dermatology of Salah Al-Deen General Hospital in Tikrit City in the period from October 2020 till June 2021 samples of 100 patients were included. Patients were given anti-fungal treatment and followed up for 3 months. Result is Trichophyton mentagrophytes were the most prevalent isolate. The study revealed statistically significant association between types of treatment and outcome (P = 0.001) Griseofulvin treatment had 33 % (no response) Itraconazole treatment has 9.6 % recurrent and 19.2 % no response. In conclusion the occurrence of atypical dermatophyte infections is rising and now become a Great Imitator. They become extremely extensive and late to diagnose.

Evaluation of the efficacy of heat shock protein inhibitors and antifungal drug combinations against Candida spp.

Candida species are one of the predominant causes of fungal infections and show drug-resistant infections in immune-compromised individuals. Simultaneous targeting of existing antifungal drugs with heat shock protein 90 (Hsp90) inhibitors may be an approach that increases the efficacy of antifungal drugs. Also, since most of the patients at risk for invasive fungal infections use these anticancer or immunosuppressive drugs, synergistic interaction in combination treatment can reduce the dose of antifungal drugs and create an alternative for the toxicity problem. In this study, in vitro efficacy of commonly used antifungals (amphotericin B, caspofungin, itraconazole, voriconazole, and fluconazole) in combination with four heat shock protein inhibitors geldanamycin, 17-allylamino-17-demethoxygeldanamycin, radicicol, and novobiocin against 30 clinical Candida isolates (C. albicans n = 13, C. krusei n = 7, and C. glabrata n = 10) were evaluated by time kill and checkerboard methods. The significant synergistic interaction determined especially in the combinations of geldanamycin with antifungal drugs suggests that substances with inhibitory effects on Hsp90 increase the effectiveness of antifungals or reduce the antifungal resistance. Although Hsp90 inhibitors alone did not have any significant antifungal activity, they did not show adverse interactions in combination with antifungals, and at some concentrations, they increased the effectiveness of the antifungals. These in vitro results have been found promising for the development of new therapeutic approaches in the treatment of invasive fungal infections. However, detailed studies are needed.

The Use of Galleria mellonella Larvae to Study the Pathogenicity and Clonal Lineage-Specific Behaviors of the Emerging Fungal Pathogen Candida auris.

Candida species are the most common fungal causes of disseminated infections in humans. Although such infections are associated with high morbidity and mortality, it is widely accepted that virulence, antifungal susceptibility, and disease outcome vary according to individual Candida species. In this respect, the emerging pathogen Candida auris has received much attention due to its propensity to cause widespread nosocomial outbreaks, to exhibit high virulence in several infection models, and to develop resistance to multiple classes of antifungal drugs. Although mammalian models of infection have long been viewed as the gold standard for studies on fungal virulence, comparative pathogenicity, and evaluation of antifungal drug efficacy, the larvae of the greater wax moth Galleria mellonella have shown considerable promise as an alternative invertebrate model of infection. Galleria larvae are inexpensive, are easily maintained in the laboratory, tolerate incubation at human physiological temperatures, possess cellular and humoral immune systems that share many features with mammals, and allow investigation of pathogenicity/virulence using multiple different reading endpoints. Here, I describe in detail the methods that can be used to study the virulence/pathogenicity of Candida auris in G. mellonella.

Clinical efficacy and safety of antifungal drugs for the treatment of Candida parapsilosis infections: a systematic review and network meta-analysis.

Antifungal drugs have already been established as an effective treatment option for Candida parapsilosis infections, but there is no universal consensus on the ideal target for clinical efficacy and safety of antifungal drugs for the treatment of C. parapsilosis infections. Few studies have directly compared the efficacies of antifungal drugs for the treatment of C. parapsilosis infections. We hypothesize that different antifungal drugs offer differing clinical efficacy and safety for the treatment of C. parapsilosis infections. We performed a comprehensive network meta-analysis on different strategies for C. parapsilosis infection treatment and compared the clinical efficacy and safety of antifungal drugs as interventions for C. parapsilosis infections. The Cochrane Database of Systematic Reviews, Medline, Embase, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Technology of Chongqing VIP database, Wan Fang Data, and SinoMed databases were searched to identify appropriate randomized trials. Among the extracted C. parapsilosis cases, the survival and death rates with treatment of C. parapsilosis infection were compared among groups treated with different antifungal drugs. According to the evidence-network analysis, echinocandins were a better choice than other drugs for treating C. parapsilosis infections, and more importantly, caspofungin showed a more preferable effect for decreasing the risk of 30 day mortality. In conclusion, this study systematically evaluated the effectiveness and safety of antifungal drugs for the purpose of helping clinicians choose the most appropriate antifungal drugs. Future studies with larger samples are needed to evaluate the effects of patient factors on the clinical efficacy and safety of antifungal drugs for C. parapsilosis infections.

Secondary Infections After Diagnosis of Severe Radiation Pneumonitis (SRP) Among Patients With Non-Small Cell Lung Cancer: Pathogen Distributions, Choice of Empirical Antibiotics, and the Value of Empirical Antifungal Treatment

This study aimed to assess pathogen distributions and antimicrobial sensitivity characteristics in patients with non-small cell lung cancer (NSCLC) with severe radiation pneumonitis (SRP) and secondary infections. Data from 1746 patients with NSCLC and SRP after thoracic radiation therapy from January 2009 to December 2020 were retrospectively analyzed. Pneumonia incidence, causative pathogens, and antibiotic resistance characteristics in patients with secondary lung infections were analyzed. Risk factors associated with mortality were identified through univariate and multivariate analyses. Antifungal drug efficacy and duration-related effects were assessed with Forest plots and receiver operating characteristic curves. Overall, 44.5% of patients with NSCLC and SRP (777 of 1746 patients) were diagnosed with secondary lung infections. In total, 899 bacterial strains were isolated from these patients, with Acinetobacter baumannii (n=206; 27%), Klebsiella pneumonia (n=200; 26.2%), and Pseudomonas aeruginosa (n=104; 13.6%) being the most common. Carbapenem and cefoperazone-sulbactam resistance rates of 52.7% and 32.2%, 28.8% and 26.4%, and 23.7% and 20.2% were observed for these isolates, respectively. Infection-related deaths occurred in 22.4% of patients with SRP. Independent risk factors for infection-related death included poor performance status scores, inappropriate empirical antimicrobial treatment, bacteria/fungal coinfection, and lack of empirical antifungal treatment. Receiver operating characteristic curves showed that the cutoff value of empirical antifungal treatment duration was 9 (area under the curve: 0.819). For patients with SRP and secondary lung infections, appropriate empirical antimicrobial treatment could decrease infection-related mortality, and cefoperazone-sulbactam may be an appropriate antibacterial drug. Empirical antifungal treatment for a minimum of 9 days might contribute to better outcomes. Although this represents a promising treatment approach for patients with SRP and secondary lung infections before antibacterial susceptibility testing, further prospective validation is essential.

CD23 mediated the induction of pro-inflammatory cytokines Interleukin-1 beta and tumor necrosis factors-alpha in Aspergillus fumigatus keratitis.

CD23 mediated the induction of pro-inflammatory cytokines Interleukin-1 beta and tumor necrosis factors-alpha in Aspergillus fumigatus keratitis.

FbD directed fabrication and investigation of luliconazole based SLN gel for the amelioration of candidal vulvovaginitis: a 2T (thermosensitive & transvaginal) approach.

Candidal vulvovaginitis (CVV), is the second most leading vaginal infection (global prevalence > 75%), caused due to excessive growth of Candida spp., predominantly Candida albicans (>95% cases). The current treatment regimens for CVV are marred with the challenges of fungal resistance & infection recurrence, subsequently leading to the compromised therapeutic efficacy of anti-fungal drugs, prolonged treatment and low patient compliance. The core of the present research was the fabrication & investigation of 2 T-SLN (solid lipid nanoparticles) gel carrying luliconazole for the amelioration of CVV. ‘2T’ symbolizes transvaginal & thermosensitive attributes of the present formulation. SLNs were prepared by a modified melt emulsification-ultra sonication method using a combination of solid lipids (Gelucire 50/13 & Precirol ATO 5), surfactant (Tween 80) and co-surfactant (Kolliphor). Formulation by design (FbD) approach was adopted to obtain appropriately screened and tailored SLNs. The optimized SLNs yielded a particle size, polydispersity index & entrapment efficiency of 62.18 nm, 0.263 & 81.5% respectively. To formulate the 2 T-gel, the final SLNs were loaded into Carbopol 971P-NF and Triethanolamine based gel. The 2 T-SLN gel was found to be easily spreadable and homogenous with mean extrudability (15 ± 0.4 g/cm2), viscosity (696.42 ± 2.34 Pa·s) and %drug content (93.24 ± 0.73%) values.. The pH of the prepared 2 T-SLN gel (4.5 ± 0.5) was in concordance with the vaginal pH (normal conditions). For in-vitro characterization of an optimized 2 T-SLN gel the release kinetics & anticandidal activity were assessed which offers a %cumulative drug release of 62 ± 0.5% in 72 h and 37.3 ± 1.5 mm zone of inhibition in 48 h. The visual appearance & dimensions were determined using fluorescent microscopy (spherical shape) & transmission electron microscopy (90–120 nm) respectively. The optimized 2 T-SLN gel showcases a skin-friendly profile with no significant signs of erythema and oedema and was found to be stable at room temperature for 2 months without any visual non-uniformity/cracking/breaking. In conclusion, the current research serves a new therapeutic perspective in assessing the activity of luliconazole for vaginal drug delivery using a 2 T-SLN gel system.

Tobacco Hornworm (Manduca sexta) caterpillars as a novel host model for the study of fungal virulence and drug efficacy

ABSTRACT The two leading yeast pathogens of humans, Candida albicans and Cryptococcus neoformans, cause systemic infections in >1.4 million patients worldwide with mortality rates approaching 75%. It is thus imperative to study fungal virulence mechanisms, efficacy of antifungal drugs, and host response pathways. While this is commonly done in mammalian models, which are afflicted by ethical and practical concerns, invertebrate models, such as wax moth larvae and nematodes have been introduced over the last two decades. To complement existing invertebrate host models, we developed fifth instar caterpillars of the Tobacco Hornworm moth Manduca sexta as a novel host model. These caterpillars can be maintained at 37°C, are suitable for injections with defined amounts of yeast cells, and are susceptible to the most threatening yeast pathogens, including C. albicans, C. neoformans, C. auris, and C. glabrata. Importantly, fungal burden can be assessed daily throughout the course of infection in a single caterpillar’s feces and hemolymph. Infected caterpillars can be rescued by treatment with antifungal drugs. Notably, these animals are large enough for weight to provide a reliable and reproducible measure of fungal disease and to facilitate host tissue-specific expression analyses. M. sexta caterpillars combine a suite of parameters that make them suitable for the study of fungal virulence.

A novel silkworm infection model with fluorescence imaging using transgenic Trichosporon asahii expressing eGFP

Trichosporon asahii is a pathogenic fungus that causes deep mycosis in patients with neutropenia. Establishing an experimental animal model for quantitatively evaluating pathogenicity and developing a genetic recombination technology will help to elucidate the infection mechanism of T. asahii and promote the development of antifungal drugs. Here we established a silkworm infection model with a transgenic T. asahii strain expressing eGFP. Injecting T. asahii into silkworms eventually killed the silkworms. Moreover, the administration of antifungal agents, such as amphotericin B, fluconazole, and voriconazole, prolonged the survival time of silkworms infected with T. asahii. A transgenic T. asahii strain expressing eGFP was obtained using a gene recombination method with Agrobacterium tumefaciens. The T. asahii strain expressing eGFP showed hyphal formation in the silkworm hemolymph. Both hyphal growth and the inhibition of hyphal growth by the administration of antifungal agents were quantitatively estimated by monitoring fluorescence. Our findings suggest that a silkworm infection model using T. asahii expressing eGFP is useful for evaluating both the pathogenicity of T. asahii and the efficacy of antifungal drugs.

Improved efficacy of antifungal drugs in combination with monoterpene phenols against Candida auris

Emergence of Candida auris has been described as a global health threat due to its ability to cause invasive infections with high mortality rate and multidrug resistance. Novel drugs and therapies are required to target this organism and its pathogenicity. Anti-virulence approach and combination therapy have been proposed as alternatives in recent years. This study evaluated the virulence factors in C. auris, combination antifungal activity of phenolic compounds with antifungal drugs and determined effect of the most active compound on positive pathogenicity markers of C. auris. Antifungal susceptibility profile of 25 clinical isolates of C. auris against antifungal agents as well as against phenolic compounds was obtained using CLSI guidelines. Combination of the most active phenolic compound with antifungal drugs was determined. Effect of carvacrol on the virulence factors was also studied. Carvacrol was the most active phenol with median MIC of 125 µg/ml and its combination with fluconazole, amphotericin B, nystatin and caspofungin resulted synergistic and additive effects in 68%, 64%, 96% and 28%, respectively. Combination also reduced the MIC values of the drugs. All test strains showed adherence ability to epithelial cells and 96% of strains produced proteinase. None of the strains produced hyphae and phospholipase. At low concentrations, carvacrol significantly inhibited the adherence ability and proteinase production (both p < 0.01). Carvacrol has antifungal and anti-virulence activity against C. auris. It also showed an enhanced antifungal activity in combination with antifungal agents. Therefore it has potential to be developed into a novel antifungal agent.

Development of nose-to-brain delivery of ketoconazole by nanostructured lipid carriers against cryptococcal meningoencephalitis in mice

Cryptococcus neoformans-mediated meningoencephalitis is a critical infectious disorder of the human central nervous system. However, efficient treatment for the disease is limited due to the poor penetration across the blood brain barrier (BBB). Here, we develop a nose-to-brain drug delivery system utilizing nanostructured lipid carriers (NLCs). We demonstrated that fluorescent-dye-loaded NLCs efficiently uptake into the cytoplasm of encapsulated C. neoformans cells. In comparison with current antifungal drugs, the ketoconazole (keto)-NLCs show significantly increased antifungal activity against C. neoformans in vivo under various growth conditions. The NLCs show enhanced tissue colonization properties. Importantly, using animal imaging analyses, NLCs are able to enter brain tissues via the olfactory bulb region by intranasal administration, bypassing the BBB. In addition, NLCs maintain prolonged residence in tissues. In mouse brain tissue, keto-NLCs showed significantly enhanced antifungal activity when administered intranasally, drastically dampening the C. neoformans burden. Taken together, NLCs not only improve the ketoconazole penetration efficiency against capsulated C. neoformans cells, but also boost the efficacy of antifungal drugs. Most importantly, keto-NLCs significantly contribute to the treatment of cryptococcal meningoencephalitis in mice by bypassing the BBB via the olfactory system.

Candida parapsilosis: from Genes to the Bedside.

Patients with suppressed immunity are at the highest risk for hospital-acquired infections. Among these, invasive candidiasis is the most prevalent systemic fungal nosocomial infection. Over recent decades, the combined prevalence of non-albicans Candida species outranked Candida albicans infections in several geographical regions worldwide, highlighting the need to understand their pathobiology in order to develop effective treatment and to prevent future outbreaks. Candida parapsilosis is the second or third most frequently isolated Candida species from patients. Besides being highly prevalent, its biology differs markedly from that of C. albicans, which may be associated with C. parapsilosis' increased incidence. Differences in virulence, regulatory and antifungal drug resistance mechanisms, and the patient groups at risk indicate that conclusions drawn from C. albicans pathobiology cannot be simply extrapolated to C. parapsilosis Such species-specific characteristics may also influence their recognition and elimination by the host and the efficacy of antifungal drugs. Due to the availability of high-throughput, state-of-the-art experimental tools and molecular genetic methods adapted to C. parapsilosis, genome and transcriptome studies are now available that greatly contribute to our understanding of what makes this species a threat. In this review, we summarize 10 years of findings on C. parapsilosis pathogenesis, including the species' genetic properties, transcriptome studies, host responses, and molecular mechanisms of virulence. Antifungal susceptibility studies and clinician perspectives are discussed. We also present regional incidence reports in order to provide an updated worldwide epidemiology summary.

Pre-Existing Liver Disease and Toxicity of Antifungals.

Pre-existing liver disease in patients with invasive fungal infections further complicates their management. Altered pharmacokinetics and tolerance issues of antifungal drugs are important concerns. Adjustment of the dosage of antifungal agents in these cases can be challenging given that current evidence to guide decision-making is limited. This comprehensive review aims to evaluate the existing evidence related to antifungal treatment in individuals with liver dysfunction. This article also provides suggestions for dosage adjustment of antifungal drugs in patients with varying degrees of hepatic impairment, after accounting for established or emerging pharmacokinetic–pharmacodynamic relationships with regard to antifungal drug efficacy in vivo.

Generation of A Mucor circinelloides Reporter Strain-A Promising New Tool to Study Antifungal Drug Efficacy and Mucormycosis.

Invasive fungal infections caused by Mucorales (mucormycosis) have increased worldwide. These life-threatening infections affect mainly, but not exclusively, immunocompromised patients, and are characterized by rapid progression, severe tissue damage and an unacceptably high rate of mortality. Still, little is known about this disease and its successful therapy. New tools to understand mucormycosis and a screening method for novel antimycotics are required. Bioluminescent imaging is a powerful tool for in vitro and in vivo approaches. Hence, the objective of this work was to generate and functionally analyze bioluminescent reporter strains of Mucor circinelloides, one mucormycosis-causing pathogen. Reporter strains were constructed by targeted integration of the firefly luciferase gene under control of the M. circinelloides promoter Pzrt1. The luciferase gene was sufficiently expressed, and light emission was detected under several conditions. Phenotypic characteristics, virulence potential and antifungal susceptibility were indifferent to the wild-type strains. Light intensity was dependent on growth conditions and biomass, being suitable to determine antifungal efficacy in vitro. This work describes for the first time the generation of reporter strains in a basal fungus that will allow real-time, non-invasive infection monitoring in insect and murine models, and the testing of antifungal efficacy by means other than survival.

380. Drosophila melanogaster as a Facile Model for Large-Scale Studies of Virulence Mechanisms and Antifungal Drug Efficacy in Candida auris Candidiasis

Background Candida auris is an emerging multi-drug-resistant human pathogen. Experimental data on the pathogenicity of C. auris is scarce, especially regarding its virulence compared with C. albicans. Additionally, studies of drug efficacy against C. auris rely on conventional animal models that are laborious and low throughput; alternative, less cumbersome models are desirable. To that end, we developed a C. auris fly infection model.MethodsWe injected 2-week-old TollI-RXA/Tollr632 female flies with a needle dipped in Candida solutions (108 yeast cells/mL) in the dorsal side of the thorax. Flies were infected with 10 different C. auris strains (source: CDC/FDA) and a C. albicansclinical strain. For drug protection studies, C. auris isolate AR-BANK#0386 [MICs: fluconazole (FLC) > 64, posaconazole (POSA) 0.125–0.25, isavuconazole (ISA) 0.25–1, voriconazole (VRC) 0.5–2 µg/mL)] was used. We assessed survival differences associated with different inocula (107 to 1010 yeast cells/mL) and yeast strains. Moreover, protection conferred by addition of FLC, VRC, ISA, POSA, or FLC combined with 5-FC (flucytosine) and/or nikkomycin Z (NikZ) to fly food was studied. Three independent runs were performed for each experiment.ResultsA) All C. auris strains and C. albicans exhibited comparable in vitro growth rates. B) All strains of C. auris were similarly more virulent than C. albicans (P < 0.0001), with all flies dying by day 7 post-infection. C) FLC, VRC, ISA, FLC+5-FC, FLC+NikZ, or FLC+NikZ+5-FC-fed flies infected with C. auris #0386 had comparably poor survival outcomes compared with untreated C. auris #0386-infected flies. Interestingly, survival rates were improved in POSA-fed infected flies compared with FLC-treated or untreated infected flies (P < 0.0001). As POSA is a cell-associated drug, we are conducting C. auris phagocytosis assays with Drosophila hemocytes that are co-incubated or not with POSA.Conclusion Drosophila is a promising, fast, and inexpensive in-vivo model to study pathogenesis and drug activity in C. auris candidiasis.Disclosures N. Beyda, Astellas: Scientific Advisor, Grant recipient. D. P. Kontoyiannis, Merck: Consultant, Research support and Speaker honorarium. Pfizer: Consultant, Research support. Astellas: Consultant, Research support and Speaker honorarium. Gilead: Speaker’s Bureau, Speaker honorarium. F2G Inc.: Speaker’s Bureau, Speaker honorarium. Cidara Inc.: Speaker’s Bureau, Speaker honorarium. Jazz Pharmaceuticals: Speaker’s Bureau, Speaker honorarium.