Antifungal Treatment Research Articles

Hidden allies: how extracellular vesicles drive biofilm formation, stress adaptation, and host–immune interactions in human fungal pathogens

ABSTRACT Pathogenic fungi pose a significant threat to human health, especially given the rising incidence of invasive fungal infections and the emergence of drug-resistant strains. This requires the development of vaccines and the advancement of antifungal strategies. Recent studies have focused on the roles of fungal extracellular vesicles (EVs) in intercellular communication and host-pathogen interactions. EVs are nanosized, lipid membrane-bound particles that facilitate the transfer of proteins, lipids, and nucleic acids. Here, we review the multifaceted functions of EVs produced by different human fungal pathogens, highlighting their importance in the response of fungal cells to different environmental cues and their interactions with host immune cells. We summarize the current state of research on EVs and how leveraging this knowledge can lead to innovative approaches in vaccine development and antifungal treatment.

Targeting Candida albicans O-acetyl-L-homoserine sulfhydrylase (Met15p) in antifungal treatment.

Fungal infections are a serious threat to public health as they are becoming increasingly frequent. A major problem stems also from a rising fungal resistance to currently available antifungal therapies, therefore novel molecular targets are highly desirable. Exploration of enzymes participating in the biosynthesis pathways of essential amino acids such as L-methionine (L-Met) may provide new insights into pharmaceutical development. The MET15 gene from Candida albicans, encoding O-acetyl-L-homoserine sulfhydrylase (Met15p), an enzyme catalyzing the second step in that pathway, was cloned and expressed in two versions: as N and C-terminal oligo-His-tagged fusion proteins. The recombinant enzymes revealed appropriate activity, and catalyzed conversion of O-acetyl-L-homoserine and a sulfide ion to produce L-homocysteine. A new RP-HPLC-DAD method, using the enzymatic reaction product pre-column derivatization with 5,5'-dithio-bis-(2-nitrobenzoic acid) was developed and used by us to determine Met15p activity. Newly synthesized compounds as well as two commercially available exhibited a Met15p inhibitory effect which was related to antifungal activity. Fungal cells' sensitivity to inhibitors depending on the presence or absence of L-Met in the medium clearly indicated Met15p targeting. Moreover, the synergistic effect of the first methionine biosynthetic enzyme affecting inhibitor and Met15p inhibitors indicate that methionine biosynthesis pathway enzymes are promising molecular targets.

The distinctive pharmacokinetic profile of rezafungin, a long-acting echinocandin developed in the era of modern pharmacometrics.

Echinocandin drugs are the current first-line therapy for fungal infections caused by Candida spp. Most patients require once-daily intravenous (IV) administration in a hospital or outpatient setting for treatment, which may negatively impact their quality of life and stress healthcare resources. Similar to other echinocandins, the novel FDA-, EMA-, and Medical and Healthcare Products Regulatory Agency-approved echinocandin, rezafungin (CD101), exhibited strong antifungal activity against several fungal pathogens and a low drug-drug interaction liability, which are important for medically complex patients. A pharmacometric-based approach has been adopted throughout the development of rezafungin, which contrasts with older echinocandins where dosing regimens were largely derived empirically, and only recently based on pharmacometric guidance. This state-of-the-art approach used model-based simulations incorporating pre-clinical and clinical data as it became available to optimize the dosing regimen for rezafungin. The enhanced stability of the molecular structure and the safety profile of rezafungin allow for the administration of once-weekly IV doses, compared to the daily dosing requirement for other echinocandin drugs, with this distinctive pharmacokinetic profile of rezafungin resulting in a front-loaded dosing regimen with high exposures early in therapy for enhanced fungal killing. The long shelf-life of rezafungin makes this echinocandin more flexible in terms of storage and manufacturing. Demonstrated across clinical development, rezafungin may provide patients with next-generation first-line antifungal treatment for the treatment of candidaemia and invasive candidiasis.

Invasive Candidiasis: A Promising Approach Using Jatropha Dioica Extracts and Nanotechnology.

Candida albicans, a common fungal organism, often lives harmlessly in the human body. However, under certain conditions, it can turn into a dangerous pathogen, causing infections that range from mild to life-threatening. With rising resistance to antifungal treatments, understanding and controlling this opportunistic fungus has never been more crucial. This study highlights the potential of combining natural plant extracts, specifically the aqueous (JdextAq) and ethanolic (JdextEt) extracts of Jatropha dioica, with nanotechnology in the form of magnetite nanoparticles (MNPs) to combat this persistent pathogen. FTIR spectra revealed significant interactions between the metabolites and MNPs, specifically through binding to the Fe3+ and Fe2+ sites. The average size of the MNPs was 11±3 nm, and they are non-toxic even at high concentration (500 μg/ml). The same effect is observed with JdextEt; however, JdextAq is cytotoxic at this concentration. The JdextAq-MNPs hybrid is toxic even at very low concentrations (250-50 μg/ml). All materials demonstrated high inhibition against C. albicans. At safe concentrations for cell viability, MNPs (500 μg/ml) and JdextEt-MNPs (500-50 μg/ml) achieved the highest inhibition rates of 97.13 % and 97.56 %, respectively. As antifungal resistance rises, these findings pave the way for innovative therapeutic strategies against this opportunistic pathogen.

A 2-year Review of the Diagnostic Performance of Serum and Bronchoalveolar Lavage Galactomannan Testing in Lung Transplant Recipients in a National Heart and Lung Transplant Centre.

The 2015 International Society for Heart and Lung Transplant (ISHLT) fungal guidelines recommend the use of bronchoalveolar lavage (BAL) galactomannan over serum galactomannan for the diagnosis of invasive aspergillosis (IA) in lung transplant (LTx) recipients, based on limited evidence. Galactomannan testing is costly. A single-center, retrospective cohort study reviewing all 814 serum and BAL galactomannan samples received from 184 LTx recipients in our center between 2021 and 2022 and assessing their diagnostic performance in the diagnosis of IA. Over the study period, 394 serum galactomannan samples were received from 144 patients and 420 BAL galactomannan samples from 143 patients. Using a cut-off of ≥ 1.0 for BAL galactomannan, the sensitivity and specificity were 65.9% and 98.4%, respectively. In total, 30 patients had positive BAL galactomannan. Antifungal therapy was commenced or continued in 29 of these patients either as targeted or pre-emptive treatment. Using a cut-off of ≥ 0.5 for serum galactomannan, the sensitivity and specificity were 9.7% and 99.7%, respectively. In total, four patients had a positive serum galactomannan. All four patients were either already on antifungal treatment for IA or were started before the serum galactomannan result was available, supported by laboratory, clinical, and radiological findings. A positive serum galactomannan was used to monitor treatment response in one patient. Serum galactomannan is not a valuable test in the diagnosis of IA in our LTx recipients, is costly, and does not remove the need for bronchoscopy and BAL galactomannan. This supports the ISHLT recommendation.

Structure-guided design and synthesis of C22- and C32-modified FK520 analogs with enhanced activity against human pathogenic fungi.

Invasive fungal infections cause significant mortality worldwide, and current antifungal treatments are often ineffective, toxic, or face growing resistance. This research identifies calcineurin (CaN), a critical protein for fungal survival, as a potential target for developing new antifungal drugs. Although existing CaN inhibitors such as FK506 (tacrolimus) and FK520 (ascomycin) possess antifungal properties, their immunosuppressive effects limit their clinical utility. By studying the structure of human and fungal FKBP12-FK506 or FK520 complexes with CaN, we have designed and synthesized modified FK520 derivatives with strong antifungal activity and reduced immunosuppressive effects. These new derivatives are expected to have significantly improved therapeutic profiles, offering hope for more effective and safer antifungal treatments.

Nanoparticle-Mediated Delivery of Deferasirox: A Promising Strategy Against Invasive Aspergillosis

Background: Invasive aspergillosis (IA) is a deadly fungal lung infection. Antifungal resistance and treatment side effects are major concerns. Iron chelators are vital for IA management, but systemic use can cause side effects. We developed nanoparticles (NPs) to selectively deliver the iron chelator deferasirox (DFX) for IA treatment. Methods: DFX was encapsulated in poly(lactic-co-glycolic acid) (PLGA) NPs using a single emulsion solvent evaporation method. The NPs were characterized by light scattering and electron microscopy. DFX loading efficiency and release were assessed spectrophotometrically. Toxicity was evaluated using SRB, luciferase, and XTT assays. Therapeutic efficacy was tested in an IA mouse model, assessing fungal burden by qPCR and biodistribution via imaging. Results: DFX-NPs had a size of ~50 nm and a charge of ~−30 mV, with a loading efficiency of ~80%. Release kinetics showed DFX release via diffusion and bioerosion. The EC50 of DFX-NPs was significantly lower (p < 0.001) than the free drug, and they were significantly less toxic (p < 0.0001) in mammalian cell cultures. In vivo, NP treatment significantly reduced Af burden (p < 0.05). Conclusion: The designed DFX-NPs effectively target and kill Af with minimal toxicity to mammalian cells. The significant in vivo therapeutic efficacy suggests these NPs could be a safe and effective treatment for IA.

Applications of Nanotechnology in Combating Fungal Diseases in Humans: An Updated Review

In recent years, fungal infections caused by filamentous fungi have posed a serious threat to public health worldwide. Fungi such as Aspergillus, Coccidioides, and Mucorales (the most common filamentous fungi), as well as Candida auris (a non-filamentous fungus), can cause infections in humans. It can cause serious life-threatening diseases in individuals with weakened immune systems, patients infected with HIV/AIDS, uncontrolled diabetes, blood disorders, organ transplants, and chemotherapy. In this review, we describe the available nan formulations (metallic and polymeric nanoparticles) that have been developed to enhance efficacy and reduce the number of adverse effects following the administration of conventional antifungals. The burden posed by fungal infections on human health is increasing worldwide. Fungi such as Aspergillus, Candida, and Cryptococcus are among the most common pathogens responsible for human diseases, accounting for over 90% of infection-related deaths. Moreover, effective antifungal treatments are not available, primarily due to host toxicity, pathogen resistance, and immunodeficiency. In recent years, nanomaterials have proven to be not only more efficient antifungal therapeutic agents but also capable of overcoming fungal drug resistance".

The first report of rhinosinusitis by Rhizopus delemar in a patient with severe COVID-19 in Iran: a case report

BackgroundMucormycosis is a severe and fatal fungal infection in patients with coronavirus disease 2019 caused by Mucorales. Here we present a case of a 63-year-old man with coronavirus disease 2019 infection, along with rhinosinusitis mucormycosis caused by Rhizopus delemar.Case presentationA 63-year-old Iranian man suffering from a coronavirus disease 2019 infection with symptoms of cough, shortness of breath, and generalized body pain. On the basis of the clinical manifestations, such as headache, a history of black nasal discharge, nasal hypoesthesia, facial swelling, numbness, nasal obstruction, presence of necrotic lesions on the nasal passages on physical examination, and abnormal computed tomography scans of paranasal sinuses, the patient underwent surgical debridement. Direct microscopy of specimens obtained from the paranasal sinuses, and subsequent isolation and identification, revealed a rhinosinusitis mucormycosis caused by R. delemar. Despite therapeutic measures, such as sinus debridement surgery and antifungal therapy with amphotericin B injection (50 mg/day), the patient died after 35 days of hospitalization.ConclusionIn this report, we present the first documented case of human infection with R. delemar in a patient with coronavirus disease 2019 infection, who also exhibited rhinosinusitis mucormycosis. R. delemar appears to be an emerging agent of rhinosinusitis mucormycosis in this region. Furthermore, prompt diagnosis and the exploration of alternative antifungal treatments, beyond amphotericin B, may be crucial for effectively managing patients with R. delemar infections.

Mycotic Necrotizing Fasciitis of the Face: A Case Report and Review of Literature

Necrotizing fasciitis is a rare but potentially serious and fatal infection. It is a dermo-hypodermitis with necrosis of the superficial fascia, typically caused by Streptococcus pyogenes. However, rare cases of fungal necrotizing fasciitis have been reported. We report the case of a 65-year-old type II diabetic patient who developed necrotizing cellulitis of the right hemiface with homolateral orbito-palpebral extension. The initial management was based on drainage of purulent collections with resection of necrotic tissues associated with parenteral antibiotherapy without clinical improvement. Bacteriological sampling revealed the presence of yeast. The mycological examination was positive for Candida albicans resistant to fluconazole. Antifungal treatment with intravenous amphotericin B was initiated with good clinical progression and complete remission after 1 month. The aim of this paper is to highlight the importance of promptly considering this diagnosis and extending the initial assessment of necrotic skin lesions to include mycological examination to detect severe forms of cutaneous candidiasis.

Selenium nanoparticles: effect of autoclave treatment on size, shape, phase and antimicrobial properties

Amorphous selenium nanoparticles have been synthesized by pulsed laser ablation in liquids. After undergoing a thermal treatment at 121°C for 60 minutes, the amorphous nanoparticles crystallized into trigonal ones. The antimicrobial properties of both amorphous and trigonal nanoparticles have been compared; and the amorphous ones displayed better antibacterial and antifungal properties compared to the trigonal ones. Specifically, Methicillin-resistant Staphylococcus aureus (MRSA), Ampicillin-resistant Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Candida albicans were almost completely inhibited in the presence of amorphous selenium nanoparticles at 0.025 microgram/ml concentrations after 24 hours of in vitro culture, compared to controls (no nanoparticles). In summary, such a high sensitivity of these bacterial and fungal strains to low concentrations of amorphous selenium nanoparticles warrants further investigation to develop efficient anti-bacterial and anti-fungal treatments.

Tenebrio molitor (Coleoptera: Tenebrionidae) as an alternative host for the study of pathogenicity in Candida auris

BackgroundCandida auris, a multidrug-resistant fungal pathogen, has emerged as a significant global health threat due to its high transmission and mortality rates, especially in healthcare settings. ObjectiveThis study aimed to establish the larvae of the coleopteran Tenebrio molitor (mealworm) as an in vivo model to evaluate the virulence of different C. auris strains. MethodsT. molitor larvae were inoculated with varying doses and strains of C. auris. Mortality rates were monitored, melanization responses, and phenoloxidase activity were assessed. Histopathological analyses were conducted to observe tissue invasion by the yeast cells. Additionally, a biofilm formation test was included as a complementary analysis to determine if biofilm production would influence the virulence of the C. auris strains. ResultsA dose-dependent increase in mortality was observed, with the highest fungal load leading to the highest mortality rates. The study also revealed significant differences in virulence among the strains, with those from Kuwait and the reference strain CBS 10913 showing the highest pathogenicity. Melanization rates were significantly higher in infected larvae, indicating an active immune response. The histopathological analysis revealed the presence of C. auris cells within the tissue of T. molitor larvae. However, the biofilm formation complementary test did not show a significant difference in virulence among the different clades of C. auris. ConclusionThe T. molitor model effectively demonstrated the pathogenic potential and virulence differences of C. auris strains. Strains from Kuwait and the reference strain CBS 10913 exhibited the highest virulence, causing 100% mortality within 24 hours. The model also highlighted significant biofilm formation and melanization responses, correlating with fungal burden. This insect model provides a valuable and cost-effective tool for preliminary virulence screening of clinical yeast strains, offering insights into host-pathogen interactions and the potential for evaluating antifungal treatments in vivo.

Candida parapsilosis keratitis: A case series

Purposeto describe the diagnosis and management of Candida parapsilosis keratitis Designa retrospective, observational case series. Methodsthis study was carried out in a single-centre tertiary referral eye hospital and includes 20 eyes of 19 patients. Electronic case notes and in vivo confocal microscopy (IVCM) records were searched for the keyword ‘parapsilosis’, with inclusion if there was keratitis with either a corresponding positive polymerase chain reaction (PCR) or microbial culture result for Candida parapsilosis. Individual case notes were reviewed to obtain information regarding diagnosis, treatment, and final visual outcomes. Cases were excluded if a patient was lost to follow-up before the end of antifungal treatment. Resultsthe risk factors for C. parapsilosis keratitis were: ocular surface disease, concurrent topical steroid use, previous corneal surgery and long-term contact lens wear. The mean presenting corrected distance visual acuity (CDVA) was LogMAR 1.49 (range 0.2 – 2.3), with a final CDVA of LogMAR 1.11 (-0.2 – 2.3). Where used, microbiological culture was positive in 19 out of 20 cases, PCR in 6 out of 11 cases, and IVCM in 8 out of 13 cases. Two-thirds of cases were managed with either topical voriconazole or amphotericin B, with four cases surgically managed by therapeutic keratoplasty and two cases requiring evisceration. ConclusionsPatients presenting with microbial keratitis with risk factors for C. parapsilosis keratitis should be managed with a high degree of clinical suspicion. Post-infection visual outcomes are poor but reflect pre-existing ocular comorbidities. Delays in diagnosis can be reduced by through the use of ICVM and PCR.

Pulmonary Aspergillosis: An Observation from a Tertiary Care Hospital of Western Uttar Pradesh

Background: Aspergillus is the most frequently occurring fungal infection in immunocompromised patients with a high mortality rate. Invasive pulmonary aspergillosis is the most serious entity on the spectrum of pulmonary aspergillosis. Limited studies on the occurrence of pulmonary aspergillosis from this geographical area prompted us to carry out this study. Materials and Methods: This hospital-based cross-sectional observational study was carried out in the Postgraduate Department of Microbiology of a tertiary care medical teaching hospital in western Uttar Pradesh for one year. A total of 1032 respiratory samples were subjected for isolation and identification of fungal pathogens by direct microscopic examination (KOH mount) and culture on Sabouraud dextrose agar. Results: The isolation rate of pulmonary aspergilli was 6.97%. The majority of the respiratory samples received were sputum 900 (87.2%) followed by bronchoalveolar lavage fluid 132 (12.7%). The pulmonary pathology was predominantly seen in the age group of 41–50 years (25%). Male patients (69%) were predominant. The majority of the samples (50%) were from the respiratory medicine ward followed by the respiratory medicine ICU (25%). Aspergillus fumigatus (58%) was the predominant species isolated followed by Aspergillus flavus (25%). Conclusion: Isolation of Aspergillus species from patients of pulmonary pathology needs to be correlated clinically to rule out colonization as they may need proper antifungal treatment. Indiscriminate use of antifungals may lead to the emergence of antifungal drug resistance.

Clinical Evaluation of a Novel CRISPR-Cas12a-Based RID-MyC Assay for the Diagnosis of Fungal Endophthalmitis

ObjectiveThis study evaluates the RID-MyC (Rapid Identification of Mycoses using CRISPR) assay, a CRISPR/Cas12a-based diagnostic tool, for its efficacy in diagnosing fungal endophthalmitis (FE), comparing it with panfungal PCR and culture methods. DesignA comparative cross-sectional study assessing the performance of the RID-MyC assay against established diagnostic modalities for FE. SubjectsThe study included 133 intraocular samples from 117 patients with suspected microbial endophthalmitis. MethodsThe study compared the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the RID-MyC assay against panfungal PCR and culture. The Limit of Detection (LoD) for Aspergillus flavus and Candida albicans was determined for both RID-MyC and panfungal PCR across three different media: nuclease-free water (NFW), aqueous humor (AH), and vitreous humor (VH). Discrepancy analysis was conducted for discordant results, incorporating clinical outcomes and responses to antifungal treatment. Main Outcome MeasuresThe study primarily assessed the sensitivity, specificity, PPV, and NPV for clinical samples. Time to diagnosis was also evaluated. ResultsThe RID-MyC assay demonstrated a sensitivity of 88.24% (CI: 63.56% to 98.54%) and specificity of 93.1% (CI: 86.86% to 96.98%), with PPV and NPV of 65.22% (CI: 48.45% to 78.91%) and 98.18% (CI: 93.62% to 99.50%), respectively. Discrepancy analysis enhanced sensitivity to 90.48% (CI: 69.62% to 98.83%) and specificity to 96.43% (CI: 91.11% to 99.02%). The RID-MyC assay was 10 to 1000-fold more sensitive than panfungal PCR in detecting Aspergillus flavus and Candida albicans in intraocular specimens. The time to diagnosis with the RID-MyC assay was consistently under two hours. ConclusionsThe RID-MyC assay may advance the rapid and precise diagnosis of FE, with possible relevance to other invasive fungal conditions.

Mucormycosis and COVID-19: Unraveling the Interplay of Fungal Infection in a Global Health Crisis: An Overview.

The healthcare system has been greatly affected by the COVID-19 pandemic, result-ing in an increase in secondary and co-infections among patients. Factors like pulmonary dam-age and weakened immune systems make patients more susceptible to fungal infections. Mu-cormycosis, an opportunistic fungal infection, prospers in environments with limited oxygen, and elevated glucose levels due to conditions such as diabetes and steroid use, as well as in acidic environments from metabolic acidosis and diabetic ketoacidosis, where it demonstrates heightened germination ability. Recognizing these complications is critical to minimize harm to patients. The insights gained from this review can improve our understanding of how fungal infections develop in connection to COVID-19, leading to better predictive algorithms, tailored care plans, enhanced antifungal treatments, quicker diagnostics, and improved management strategies.

Crushed posaconazole delayed-release tablets for antifungal prophylaxis and treatment in children.

Therapeutic drug monitoring (TDM) is recommended for posaconazole to achieve target concentrations of ≥0.7 mg/L and ≥1.0 mg/L for prophylaxis and treatment of invasive fungal infection (IFI), respectively. However, target attainment is challenging with the oral suspension, particularly in children. Here, we describe our experience using crushed delayed-release tablet (DRT) in a paediatric cohort, with a focus on TDM. We undertook a retrospective audit of crushed posaconazole DRT administration via enteral feeding tubes (EFTs) for patients aged ≤18 years over 18 months at The Royal Children's Hospital Melbourne who had at least one trough concentration measured at steady state. Details of patient demographics, posaconazole dosing, monitoring and adverse effects were recorded. Twelve patients with a median age of 9 years (range 2 to 14) received posaconazole DRT via EFT for prophylaxis (n = 8) or treatment (n = 4). All children achieved target concentration, with a median dose of 7 mg/kg/day (range 5 to 11) for prophylaxis and 13 mg/kg/day (range 9 to 20) for treatment. The median time to reach therapeutic levels was 7 days (range 5 to 14) for prophylaxis and 20 days (range 15 to 35) for treatment. One child had blockage of their EFT, which was attributed to posaconazole. No other adverse effects were observed. Crushed posaconazole DRT administered via EFT may be used as a method of attaining therapeutic posaconazole concentrations in children for antifungal prophylaxis and treatment.

Rosmarinic Acid Exhibits Antifungal and Antibiofilm Activities Against Candida albicans: Insights into Gene Expression and Morphological Changes

Candida species, opportunistic pathogens that cause various infections, pose a significant threat due to their ability to form biofilms that resist antifungal treatments and immune responses. The increasing resistance of Candida spp. and the limited availability of effective treatments have prompted the research of natural compounds as alternative therapies. This study assessed the antifungal properties of RA against Candida species, focusing on its impact on C. albicans biofilms and the underlying mechanisms. The antifungal efficacy of RA was evaluated using the CLSI M27-A3 microdilution method on both fluconazole-susceptible and -resistant strains. Biofilm formation by C. albicans was assessed through a crystal violet assay, while its antibiofilm activity was analyzed using an MTT assay and field emission scanning electron microscopy (FESEM). Gene expression related to biofilm formation was studied using quantitative real-time PCR (qRT-PCR), and statistical analysis was performed with an ANOVA. Among the 28 Candida strains tested, RA exhibited minimum inhibitory concentration (MIC) values ranging from 160 to 1280 μg/mL. At a 640 μg/mL concentration, it significantly reduced the expression of genes associated with adhesion (ALS3, HWP1, and ECE1), hyphal development (UME6 and HGC1), and hyphal cAMP-dependent protein kinase regulators (CYR1, RAS1, and EFG1) in RAS1-cAMP-EFG1 pathway (p < 0.05). FESEM analysis revealed a reduction in hyphal networks and disruptions on the cell surface. Our study is the first to demonstrate the effects of RA on C. albicans adhesion, hyphae development, and biofilm formation through gene expression analysis with findings supported by FESEM. This approach distinguishes our study from previous studies on the effect of RA on Candida. However, the high MIC values of RA limit its antifungal potential. Therefore, more extensive research using innovative methods is required to increase the antifungal effect of RA.

Collateral sensitivity counteracts the evolution of antifungal drug resistance in Candida auris.

Antifungal drug resistance represents a serious global health threat, necessitating new treatment strategies. Here we investigated collateral sensitivity (CS), in which resistance to one drug increases sensitivity to another, and cross-resistance (XR), in which one drug resistance mechanism reduces susceptibility to multiple drugs, since CS and XR dynamics can guide treatment design to impede resistance development, but have not been systematically explored in pathogenic fungi. We used experimental evolution and mathematical modelling of Candida auris population dynamics during cyclic and combined drug exposures and found that especially CS-based drug cycling can effectively prevent the emergence of drug resistance. In addition, we found that a CS-based treatment switch can actively select against or eradicate resistant sub-populations, highlighting the potential to consider CS in therapeutic decision-making upon resistance detection. Furthermore, we show that some CS trends are robust among different strains and resistance mechanisms. Overall, these findings provide a promising direction for improved antifungal treatment approaches.

The Candida auris Infection After the COVID-19 Pandemic Seems to be an Urgent Public Health Emergency: A Call to Attention.

Inconsequential diseases can sometimes become extremely dangerous through mutation. Antifungal resistance has increased by 24%, and resistance only due to Candida auris (C. auris) species have increased by 60%. Here, we aimed to assess the knowledge of antifungal treatment and preventative measures to mitigate the consequences of infections caused by C. auris. We performed a comprehensive literature search and gathered information for this review from publicly available published articles. We used C. auris, C. auris infection, mycoses, and antifungal resistance as search terms in Google Scholar, PubMed, and Scopus. We extracted the relevant information from the available article after careful evaluation. The genus C. auris was especially difficult to diagnose, as it was often mistaken for other types of yeast and led to incorrect treatment. The only effective method for diagnosing C. auris is through blood culture testing in laboratories and PCR tests. Because of its mutation, C. auris has grown increasingly resistant to all three classes of antifungals, with almost all strains resistant to fluconazole. These resistances were traced back to multiple-point mutations in certain genes, such as ERG11 in the case of fluconazole and amphotericin B. In addition, C. auris is phylogenetically related to C. haemulonii, an emerging pathogen notably resistant to antifungals. So, it may be an evolutionary resistance that occurred earlier but has only begun to spread now. Echinoderm, a reliable treatment for C. auris infections showed ineffectively against FKS1 and ERG3 gene mutated Candida strains. Newly developed antifungal agents, like Ibrexafungerp, showed promising results against echinocandin-resistant strains in clinical trials. Without vaccines and effective treatment, its capacity to mutate and spread has detrimental effects on humans. Therefore, extensive research on drug development, quick, reliable diagnosis, and effective strategies for disease prevention and treatment are required to mitigate the health impact of C. auris.