Invasive fungal infections (IFI) represent a significant contributor to mortality among sepsis patients in the Intensive Care Unit (ICU). Early diagnosis of IFI is challenging, and currently, there are no predictive tools for identifying sepsis patients who may develop IFI. Our study aims to develop a predictive scoring system to assess the risk of IFI in patients with sepsis admitted to the ICU.

A retrospective collection of data from a total of 549 patients was conducted. Data-driven, clinically knowledge-driven, and decision tree models were used to identify predictive variables for risk of IFI in ICU patients with sepsis. Demographic data, vital signs, laboratory values, comorbidities, medication use, and clinical outcomes were all collected. The optimal model was selected based on model performance and clinical utility to establish a risk score.

Among adult patients with sepsis admitted to the ICU, 127 patients (23.1%) developed IFI. The final data-driven model included four predictive factors, the clinically knowledge-driven model included three predictive factors, and the decision tree model included two. Based on the good performance and clinical utility of the clinically knowledge-driven model, it was chosen as the optimal risk scoring model (C-statistics: 0.79 (95% confidence interval (CI): 0.75-0.83); Hosmer-Lemeshow (H-L) test P = 0.884). The ICU sepsis patient invasive fungal infection risk (AMI) score, created based on the clinically knowledge-driven model, includes mechanical ventilation, application of immunosuppressants, and the types of antibiotics used. The C-statistics for this risk score was 0.79 (95% CI:0.75-0.84) with good calibration (H-L test P = 0.992 and see calibration curve: Fig. 2). Moreover, in terms of clinical utility, the decision curve analysis for AMI showed a favorable net benefit.

The application of the AMI score can effectively distinguish whether ICU sepsis patients will develop IFI, which is beneficial for clinicians to formulate targeted and timely preventive and treatment measures based on the risk of IFI.

Our study delved into the intricate dynamics of antifungal susceptibility testing for Candida spp., employing a Design of Experiments approach. We systematically investigated the influence of pH, temperature, inoculum size, and glucose concentration on both growth patterns and inhibitory concentrations of Candida spp. Our findings underscore the nuanced interplay between these factors, revealing significant impacts on susceptibility outcomes. Notably, even minor adjustments in these parameters yielded substantial variations in growth and inhibitory concentrations, underscoring the critical importance of meticulous control over growth conditions in antifungal susceptibility testing protocols. Each Candida isolates exhibited unique susceptibility profiles, necessitating tailored culture conditions for accurate testing. Our study sheds light on the variability inherent in Candida spp. growth patterns and emphasizes the need for standardized protocols to ensure consistency across laboratories. By leveraging the design of experiments, our research provides a systematic framework for unraveling the complexities of antifungal susceptibility testing, offering valuable insights for optimizing testing protocols and informing clinical decision-making in antifungal treatment. These findings represent a significant step towards enhancing the efficacy and reliability of antifungal susceptibility testing in clinical practice.

Invasive fungal infections have been reported as complications with significant mortality and morbidity in patients hospitalized with COVID-19. This study aimed to evaluate the clinical characteristics and outcomes of candidaemia patients with COVID-19 and to investigate the association between COVID-19 and mortality in candidaemia patients.

This retrospective study included candidaemia patients aged 18 years or older admitted to four university-affiliated tertiary hospitals in South Korea between January 1, 2020, and December 31, 2022. The COVID-19 group comprised patients diagnosed with COVID-19 before the onset of candidaemia. Clinical features and outcomes were compared between the COVID-19 and non-COVID-19 groups. Multivariate logistic regression analyses were performed to identify risk factors related to 30-day mortality.

Of the 355 patients diagnosed with candidaemia, 39 (11.0%) had a prior diagnosis of COVID-19. The COVID-19 group exhibited greater rates of systemic corticosteroid use (20.5% vs. 8.9%, p = 0.042), central venous catheter use (74.4% vs. 57.3%, p = 0.041), and mechanical ventilation (53.8% vs. 31.6%, p = 0.006) before the onset of candidaemia. The COVID-19 group had a greater rate of septic shock at the onset of candidaemia (61.5% vs. 32.0%, p < 0.0001) and a greater 30-day mortality rate (69.2% vs. 50.9%, p = 0.031). K‒M survival analysis revealed that patients in the COVID-19 group had a lower 30-day survival rate than did those without COVID-19 (p = 0.003 by log-rank test). However, in multivariate logistic regression analysis, COVID-19 did not significantly impact 30-day mortality.

According to multivariate logistic regression analysis, COVID-19 was not an independent risk factor for mortality. However, candidaemia patients with a prior COVID-19 diagnosis were more likely to exhibit critical conditions such as mechanical ventilation and experience poor outcomes. Therefore, clinicians need to monitor and prevent candidaemia in critically ill patients with COVID-19.

The growing emergence of resistance mechanisms and side effects associated with antifungal agents highlight the need for alternative therapies. This study aims to investigate the antifungal potential of ozonated extra-virgin olive oil (EOO) against Candida albicans, with the goal of developing eco-friendly and highly effective treatments based on natural products. Antifungal activity was evaluated via cell viability and biofilm formation assays using Crystal Violet and Sytox green staining. The results showed that EOO reduced C. albicans viability in a dose-dependent manner, achieving over 90% cell death at a 3% (v/v) concentration. Transmission Electron Microscopy (TEM) revealed cell wall structural damage, and ROS levels increased by approximately 60% compared to untreated controls within 10 min of treatment. Additionally, the expression of autophagy-related genes atg-7 and atg-13was upregulated by 2- and 3.5-fold, respectively, after 15 min, suggesting a stress-induced cell death response. EOO also significantly inhibited hyphal formation and biofilm development, thus reducing C. albicans pathogenicity while preserving cell biocompatibility. EOO antifungal activity was also observed in the case of Candida glabrata. In conclusion, ozonated olive oil demonstrates potent antifungal activity against C. albicans by reducing cell viability, inhibiting hyphal and biofilm formation, and triggering oxidative stress and autophagy pathways. These findings position EOO as a promising alternative therapy for fungal infections.

A series of 6 novel ester derivatives 2-7 of natural product geodin 1 were designed and semi-synthesized through one mild step reaction with high yield. Compounds 2-7 showed strong inhibitory activities against Staphylococcus aureus in the range of 2.35-9.41 μM. Compounds 4 and 7 showed very strong inhibitory activities against antifouling bacteria Aeromonas salmonicida with MICs of 2.42 μM and 4.56 μM respectively. Most notably compounds 3-7 showed potent antifungal activities against Candida albicans in the range of 0.59-2.44 μM. Particularly, compound 3 showed the highest antifungal activity against C. albicans with a MIC value of 0.59 μM. The preliminary structure activity relationship of these derivatives showed that replacement of 4-OH group with benzoyl substituents could enhance the antibacterial and antifungal activities of geodin 1.

Candidemia is a widespread threat that can lead to significant complications in healthcare settings.

Our study aimed to identify isolates of Candida isolated from blood culture bottles of patients with candidemia and assess their antifungal susceptibility profiles.

We conducted a cross-sectional study at Cairo University tertiary care hospitals over 16 months including 90 patients. Candida isolates were collected from blood culture bottles, and identified using MALDI-TOF MS technology of VITEK MS PRIME (bioMérieux) with the corresponding database VITEK IVD Database 3.2. followed by antifungal susceptibility testing using VITEK 2 Compact system.

Candida albicans was the most common species isolated from both pediatric and adult patients with percentages of 47.3% and 36.4% respectively, followed by Candida parapsilosis with percentages of 32.6% and 25.0% respectively. Voriconazole showed the highest antifungal activity at 90.9% of isolates in adults and 95.7% in pediatrics, followed by caspofungin and micafungin. The mean hospital stays for adults ranged from 8 to 30 days and from 10 to 42 days in the pediatric group.

C. albicans remains the predominant species isolated from both pediatric and adult candidemia patients, despite a notable increase in other species. C. tropicalis and C. parapsilosis are considered the most common non-albicans Candida (NAC) species. The rise in Candida species other than albicans highlights the urgent need for effective antifungal stewardship programs. Voriconazole exhibited the higher antifungal activity followed by caspofungin and micafungin.

Acute fibrinous and organizing pneumonia (AFOP) is a rare form of pneumonia, is characterized by the deposition of fibrin in alveoli, the formation of fibrin spheres, and deposition of fibrin in alveolar junctions and bronchioles adjacent to or adjacent to the alveoli, forming institutional loose connective tissue.The clinical characteristics of AFOP lack specificity. We report a special case of AFOP that may be associated with Candida, so as to improve our understanding and diagnosis of AFOP.

In this patient who was early misdiagnosed with community-acquired pneumonia (CAP), the empirical anti-infective treatment was ineffective, and various infectious and non-infectious factors were excluded. Flexible bronchoscopy was subsequently performed, and metagenomics Next Generation Sequencing (mNGS) of Bronchoalveolar lavage fluid (BALF) showed Candida albicans, and further ultrasound interventional percutaneous and lung puncture biopsy was performed to diagnose AFOP according to pathology, while mNGS of lung pathological tissue also suggested Candid. The patient recovered well on corticosteroids.

The clinical manifestation, laboratory examination and imaging examination of AFOP has no specificity, lung biopsy and pathological examination should be carried out to make a clear diagnosis by comprehensively considering the clinical manifestations, auxiliary examination, pathology and other aspects of the patients. After definite diagnosis, it is still necessary to rule out various diseases and environmental exposure and further classify them as idiopathic or secondary, so as to choose monotherapy or combination therapy.

Fungal endophthalmitis is a chronic inflammatory condition of the eye's posterior segment that can lead to irreversible vision loss. While relatively rare in western countries, its incidence is notably higher in Asia, particularly India. The condition's prevalence is exacerbated by factors such as intravenous drug use, antibiotics, and ocular surgeries. Fungal endophthalmitis can be categorized as endogenous, arising from systemic infection, or exogenous, linked to external sources such as trauma or surgery. The fungal agents responsible vary by region, with Candida species common in the West and Aspergillus and Fusarium species more prevalent in India. Management typically involves vitrectomy and intravitreal antifungal drugs such as amphotericin B and voriconazole, though treatment is often complicated by multidrug resistance and culture-negative cases. Recent proteomic and transcriptomic analyses have highlighted the early and sustained activation of the host immune response during infection involving key inflammatory and oxidative stress-related proteins. Given the potential for excessive inflammation to cause retinal damage, targeted immunotherapies are crucial. Immunomodulation, which aims to balance the immune response, shows promise in preserving vision while effectively combating the infection. Key targets for immunomodulation include pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-17), chemokines (CCL2, CXCL8), Toll-like receptors (TLR2, TLR4), and the complement system. Additionally, modulating the activity of macrophages, neutrophils, regulatory T cells, and Th17 cells, as well as targeting inflammasomes, can help control inflammation. Biologic agents and small molecule inhibitors offer further avenues for precise immune response modulation. This review underscores the importance of a comprehensive understanding of host-pathogen interactions in the development of effective therapies for fungal endophthalmitis.

Data on the prevalence of fungal coinfections/superinfections in patients with COVID-19 are limited.

To describe the prevalence of fungal coinfections/superinfections in patients with COVID-19, as well as risk factors and demographic, clinical, and microbiological characteristics.

We included patients with a confirmed COVID-19 diagnosis and a confirmed fungal infection hospitalized in the ICU from March 2020 to December 2021. We collected data on age, sex, comorbidities, hospital length of stay (days), laboratory (ferritin) and microbiological results, treatment for COVID-19, antifungal therapy, and outcomes obtained from the clinical records.

Only 11 out of 740 patients met the inclusion criteria. The coinfection rate was 0.3% and the superinfection was 1.2%. The most affected population was male adults. The coinfections/superinfections diagnosed were candiduria and candidemia, caused by Candida albicans, C. tropicalis, C. glabrata, C. lusitaniae, and Kluyveromyces marxianus (C. kefyr). In addition, tracheobronchitis due to Aspergillus fumigatus was found. The most used antifungals were fluconazole and caspofungin. The lethality in patients with fungal coinfections was 50% and superinfections, 22%. The length of hospital stay was 11-65 days. Eight patients required mechanical ventilation and six received corticosteroids. The main comorbidity was diabetes mellitus (81.8%).

The rate of fungal coinfections/superinfections in COVID-19 patients was low, but the lethality found urges for routine fungal screening in patients with severe COVID-19 to timely detect fungal infections that may further compromise the patient’s life.

Candida albicans, an opportunistic oral pathogen, synergizes with Staphylococcus aureus, allowing bacteria to co-invade and systemically disseminate within the host. Studying human-microbe interactions creates the need for a universal culture medium that supports fungal, bacterial, and human cell culturing, while allowing sensitive analytical approaches such as OMICs and chromatography techniques. In this study, we established a fully defined, customizable adaptation of Dulbecco's modified Eagle medium (DMEM), allowing multi-kingdom culturing of S. aureus, C. albicans, and human oral cell lines, whereas minimal version of DMEM (mDMEM) did not support growth of S. aureus, and neither did supplementation with dextrose, MEM non-essential amino acids, pyruvate, and Glutamax. This new medium composition, designated as "mDMEM-DMP," promoted growth of all tested S. aureus strains. Addition of 25 mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) further improved growth, while higher concentrations did not improve growth any further. Higher concentrations of HEPES did result in prolonged stabilization of medium pH. mDMEM-DMP promoted (hyphal) C. albicans monoculturing and co-culturing on both solid and semi-solid surfaces. In contrast to S. aureus, addition of HEPES reduced C. albicans maximum culture optical density (OD). Finally, only buffered mDMEM-DMP (100 mM HEPES) was successful in maintaining the metabolic activity of human oral Ca9-22 and HO1N1 cell lines for 24 hours. Altogether, our findings show that mDMEM-DMP is a versatile and potent culture medium for both microbial and human cell culturing, providing a customizable platform to study human as well as microbial molecular physiology and putative interactions.

Interaction between microbes and the host are in the center of interest both in disease and in health. In order to study the interactions between microbes of different kingdoms and the host, alternative media are required. Synthetic media are useful as they allow addition of specific components. In addition, well-defined media are required if high-resolution analyses such as metabolomics and proteomics are desired. We describe the development of a synthetic medium to study the interactions between C. albicans, S. aureus, and human oral epithelial cells. Our findings show that mDMEM-DMP is a versatile and potent culture medium for both microbial and human cell culturing, providing a customizable platform to study human as well as microbial molecular physiology and putative interactions.

Heteroleptic metal complexes containing CuII, CoII, and ZnII, incorporating curcumin and a Schiff base ligand (L), were synthesized and characterized, and their antifungal activity was evaluated. Their antifungal activities were investigated individually and in combination with fluconazole. Utilizing various analytical techniques such as UV-Vis, FT-IR, NMR, ESI-MS, TGA-DTG, elemental analyses, conductance, and magnetic susceptibility measurements, complex C1 ([Cu(Cur)LCl(H2O)]) was assigned a distorted octahedral geometry, while complexes C2 ([Co(Cur)LCl(H2O)]) and C3 ([Zn(Cur)LCl(H2O)]) were assigned octahedral geometries. Among these complexes, C2 exhibited the highest inhibitory activity against both FLC-susceptible and resistant strains of Candida albicans. Furthermore, C2 demonstrated candidicidal activity and synergistic interactions with fluconazole, effectively inhibiting the growth and survival of both FLC-resistant and FLC-sensitive C. albicans strains. The complex displayed a dose-dependent inhibition of drug efflux pumps in FLC-resistant C. albicans strains, indicating its potential to disrupt the cell membrane of these strains. The significant role of membrane efflux transporters in the development of antifungal drug resistance within Candida species has been extensively documented and our findings indicate that complex C2 specifically targets this crucial factor, thereby playing a pivotal role in mitigating drug resistance in C. albicans.

Candida albicans is one of the most dangerous pathogenic fungi in the world, according to the classification of the World Health Organization, due to the continued development of its resistance to currently available anticandidal agents. To overcome this problem, the current work provided a simple, one-step, cost-effective, and safe technique for the biosynthesis of new functionalized anticandidal selenium nanoparticles (Se NPs) against C. albicans ATCC10231 using the cell-free supernatant of Limosilactobacillus fermentum (OR553490) strain. The bacterial strain was isolated from yogurt samples available in supermarkets, in Damietta, Egypt. The mixing ratio of 1:9 v/v% between cell-free bacterial metabolites and sodium selenite (5 mM) for 72 h at 37 °C were the optimum conditions for Se NPs biosynthesis. Ultraviolet-visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), X-ray diffraction (XRD), Zeta analyses, and elemental analysis system (EDS) were used to evaluate the optimized Se NPs. The Se NPs absorption peak appeared at 254 nm. Physicochemical analysis of Se NPs revealed the crystalline-shaped and well-dispersed formation of NPs with an average particle size of 17-30 nm. Se NPs have - 11.8 mV, as seen by the zeta potential graph. FT-IR spectrum displayed bands of symmetric and asymmetric amines at 3279.36 cm-1 and 2928.38 cm-1, aromatic and aliphatic (C-N) at 1393.32 cm-1 and 1237.11.37 cm-1 confirming the presence of proteins as stabilizing and capping agents. Se NPs acted as a superior inhibitor of C. albicans with an inhibition zone of 26 ± 0.03 mm and MIC value of 15 µg/mL compared to one of the traditional anticandidal agent, miconazole, which revealed 18 ± 0.14 mm and 75 µg/mL. The cytotoxicity test shows that Se NPs have a low toxic effect on the normal keratinocyte (IC50 ≈ 41.5 μg/mL). The results indicate that this green synthesis of Se NPs may have a promising potential to provide a new strategy for drug therapy.

Candida auris is a recently discovered yeast with a multi-drug resistant profile associated with high mortality rates. The rapid identification of Candida auris in hospital settings is crucial to allow appropriate therapeutic and rapid implementation of infection management measures. The aim of this study was to develop a lateral flow immunoassay (LFIA) for the rapid identification of Candida auris.

Highly specific monoclonal antibodies were obtained by immunizing mice with membrane proteins from Candida auris which were then used to develop a LFIA whose performance was assessed by testing 12 strains of Candida auris and 37 strains of other Candida species. Isolates were grown on either Sabouraud dextrose, CHROMagarTM Candida Plus or HardyCHROMTM Candida + auris agar plates. The strains were also cultured on salt sabouraud-dextrose with chloramphenicol or a commercially available Salt-Sabouraud Dulcitol Broth with chloramphenicol and gentamicin, and processed using a simple centrifugation protocol to recover a pellet. Finally, the colonies or yeast extract were transferred to the LFIA to determine the specificity and sensitivity of the assay.

The LFIA reached 100% specificity and sensitivity from solid agar plates. For both enrichment broths, some Candida non-auris species were able to grow, but the LFIA remained 100% specific. The use of a dextrose-based sabouraud broth resulted in earlier identification with the LFIA, with most of the Candida auris strains detected at 24 h.

The developed LFIA prototype represents a powerful tool to fight the emerging threat of Candida auris. Clinical validation represents the next step.

Head and Neck Cancer (HNC) patients receiving radiotherapy (RT) often suffer from xerostomia and/or hyposalivation. As saliva plays an important antimicrobial and cleansing roles, these patients are at higher risks of opportunistic infections. This narrative review aims to provide an overview of current evidence on oral Candida colonisation and infection in these patients.

A literature review of clinical studies on oral Candida colonisation and candidiasis in HNC patients receiving radiotherapy/chemoradiotherapy was conducted.

Many clinical studies found high levels of Candida colonisation and a substantial proportion of post-RT HNC patients suffering from oropharyngeal candidiasis (OPC). Importantly, oral Candida could be a reservoir for life-threatening systemic infection in immunocompromised patients. The rising prevalence of non-albicans Candida species and drug-resistant infections has made identification of Candida species and antifungal susceptibility more important. Recent advances in oral microbiome and its interactions with Candida are discussed. This review also offers perspectives on limitations of current evidence and suggestions for future research.

Further research to better understand Candida carriage, microbiome, OPC, and xerostomia/hyposalivation post-RT would aid in devising a more comprehensive long-term management plan and novel therapeutic approaches for HNC patients to achieve the full benefits of RT while minimising side effects.

SUMMARYA significant increase in the incidence of Candida-mediated infections has been observed in the last decade, mainly due to rising numbers of susceptible individuals. Recently, the World Health Organization published its first fungal pathogen priority list, with Candida species listed in medium, high, and critical priority categories. This review is a synthesis of information and recent advances in our understanding of two of these species-Candida albicans and Candida glabrata. Of these, C. albicans is the most common cause of candidemia around the world and is categorized as a critical priority pathogen. C. glabrata is considered a high-priority pathogen and has become an increasingly important cause of candidemia in recent years. It is now the second most common causative agent of candidemia in many geographical regions. Despite their differences and phylogenetic divergence, they are successful as pathogens and commensals of humans. Both species can cause a broad variety of infections, ranging from superficial to potentially lethal systemic infections. While they share similarities in certain infection strategies, including tissue adhesion and invasion, they differ significantly in key aspects of their biology, interaction with immune cells, host damage strategies, and metabolic adaptations. Here we provide insights on key aspects of their biology, epidemiology, commensal and pathogenic lifestyles, interactions with the immune system, and antifungal resistance.

Aim: The objective of this study was to evaluate the clinical and epidemiological aspects of Candida infections. Methods: The study relied on the analysis of electronic medical records. Results: Among 183 patients with positive fungal infections, 57 were from the community and 126 from hospitals. Females predominated in both groups (82.4% in the community, 54.7% in hospitals). Non-albicans Candida spp. accounted for 62.8% of cases. Antifungal therapy was prescribed for 67 patients, with a 55.6% mortality rate. Conclusion: The increasing prevalence of non-albicans Candida species highlights the need for better candidiasis monitoring and control, especially concerning antifungal use amidst rising antimicrobial resistance, particularly in empirical therapy scenarios.

Pathogenic fungal species can cause superficial and mucosal infections, to potentially fatal systemic or invasive infections in humans. These infections are more common in immunocompromised or critically ill patients and have a significant morbidity and fatality rate. Fungal pathogens utilize several strategies to adapt the host environment resulting in efficient and comprehensive alterations in their cellular metabolism. Fungal virulence is regulated by several factors and post-transcriptional regulation mechanisms involving mRNA molecules are one of them. Post-transcriptional controls have emerged as critical regulatory mechanisms involved in the pathogenesis of fungal species. The untranslated upstream and downstream regions of the mRNA, as well as RNA-binding proteins, regulate morphogenesis and virulence by controlling mRNA degradation and stability. The limited number of available therapeutic drugs, the emergence of multidrug resistance, and high death rates associated with systemic fungal illnesses pose a serious risk to human health. Therefore, new antifungal treatments that specifically target mRNA pathway components can decrease fungal pathogenicity and when combined increase the effectiveness of currently available antifungal drugs. This review summarizes the mRNA degradation pathways and their role in fungal pathogenesis.

The fungal component of the microbiota, the mycobiota, has been neglected for a long time due to its poor richness compared to bacteria. Limitations in fungal detection and taxonomic identification arise from using metagenomic approaches, often borrowed from bacteriome analyses. However, the relatively recent discoveries of the ability of fungi to modulate the host immune response and their involvement in human diseases have made mycobiota a fundamental component of the microbial communities inhabiting the human host, deserving some consideration in host-microbe interaction studies and in metagenomics. Here, we reviewed recent data on the identification of yeasts of the Ascomycota phylum across human body districts, focusing on the most representative genera, that is, Saccharomyces and Candida. Then, we explored the key factors involved in shaping the human mycobiota across the lifespan, ranging from host genetics to environment, diet, and lifestyle habits. Finally, we discussed the strengths and weaknesses of culture-dependent and independent methods for mycobiota characterization. Overall, there is still room for some improvements, especially regarding fungal-specific methodological approaches and bioinformatics challenges, which are still critical steps in mycobiota analysis, and to advance our knowledge on the role of the gut mycobiota in human health and disease. This article is categorized under: Immune System Diseases > Genetics/Genomics/Epigenetics Immune System Diseases > Environmental Factors Infectious Diseases > Environmental Factors.

The incidence of candidemia in healthcare centers is associated with high morbidity and mortality. Frequency varies significantly among regions, with some species being more prevalent than others in Latin America. In this study, 191 clinical Candida isolates were collected from a major hospital in Ecuador from January 2019 to February 2020 aiming to assess their prevalence and distribution. After data processing, 168 isolates characterized by the VITEK 2 system were subsequently identified by ITS sequencing. Results showed diverse Candida species distributions, with C. albicans and C. tropicalis being the most prevalent across different clinical sources. In hospitalized individuals, C. tropicalis (38%) and C. albicans (37%) were the most prevalent, followed by, C. parapsilosis (16%), C. glabrata (5%), and other non-Candida albicans (NCA) species (6%). Conversely, C. parapsilosis (48%), C. albicans (20%), and C. glabrata (14%), associated with candidemia, were the most common in blood and CSF. Additionally, uncommon NCA species such as C. haemulonii, C. kefyr, and C. pelliculosa were identified in Ecuador for the first time. Discrepancies in species identification were observed between the VITEK 2 system and ITS sequencing, coinciding at 85%. This highlights the need for ongoing surveillance and identification efforts in Ecuador's clinical and epidemiological settings.

Cutaneous candidiasis, caused by Candida albicans, is a severe and frustrating condition, and finding effective treatments can be challenging. Therefore, the development of farnesol-loaded nanoparticles is an exciting breakthrough. Ethosomes are a novel transdermal drug delivery carrier that incorporates a certain concentration (10-45%) of alcohols into lipid vesicles, resulting in improved permeability and encapsulation rates compared to conventional liposomes. Farnesol is a quorum-sensing molecule involved in morphogenesis regulation in C. albicans, and these ethosomes offer a promising new approach to treating this common fungal infection. This study develops the formulation of farnesol-loaded ethosomes (farnesol-ethosomes) and assesses applications in treating cutaneous candidiasis induced by C. albicans in vitro and in vivo. Farnesol-ethosomes were successfully developed by ethanol injection method. Therapeutic properties of farnesol-ethosomes, such as particle size, zeta potential, and morphology, were well characterized. According to the results, farnesol-ethosomes demonstrated an increased inhibition effect on cells' growth and biofilm formation in C. albicans. In Animal infection models, treating farnesol-ethosomes by transdermal administration effectively relieved symptoms caused by cutaneous candidiasis and reduced fungal burdens in quantity. We also observed that ethosomes significantly enhanced drug delivery efficacy in vitro and in vivo. These results indicate that farnesol-ethosomes can provide future promising roles in curing cutaneous candidiasis.

Cutaneous candidiasis attributed to Candida infection is a prevalent condition that impacts individuals of all age groups. As a type of microbial community, biofilms confer benefits to host infections and mitigate the clinical effects of antifungal treatments. In C. albicans, the yeast-to-hypha transition and biofilm formation are effectively suppressed by farnesol through its modulation of multiple signaling pathway. However, the characteristics of farnesol such as hydrophobicity, volatility, degradability, and instability in various conditions can impose limitations on its effectiveness. Nanotechnology holds the potential to enhance the efficiency and utilization of this molecule. Treatment of farnesol-ethosomes by transdermal administration demonstrated a very remarkable therapeutic effect against C. albicans in infection model of cutaneous candidiasis in mice. Many patients suffering fungal skin infection will benefit from this study.

With the advancement of modern medicine and the prolonged survival of critically ill patients, unusual organisms are increasingly emerging. Initially found in the environment, these rare organisms started presenting as human pathogens, causing significant morbidity and mortality. Here, we present a rare case of disseminated Lodderomyces elongisporus fungemia and Pantoea dispersa bacteremia in a patient with parapneumonic effusion and ruptured liver abscess. This yeast was identified using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF). Although this organism has no antifungal breakpoint, the isolate shows low minimum inhibitory concentration (MIC) to a wide range of antifungals. The importance of effective communication between microbiologists and clinicians and early referral to the infectious disease team was also highlighted in this case for prompt treatment.

In recent years, non-thermal plasma (NTP) has emerged as a promising tool for decontamination and disinfection within the food industry. Given the increasing resistance of microbial biofilms to conventional disinfectants and their adverse environmental effects, this method has significant potential for eliminating biofilm formation or mitigating the metabolic activity of grown biofilms. A comparative study was conducted evaluating the efficacy of UV radiation and NTP in eradicating mature biofilms of four common foodborne filamentous fungal contaminants: Alternaria alternata, Aspergillus niger, Fusarium culmorum, and Fusarium graminearum. The findings reveal that while UV radiation exhibits variable efficacy depending on the duration of exposure and fungal species, NTP induces substantial morphological alterations in biofilms, disrupting hyphae, and reducing extracellular polymeric substance production, particularly in A. alternata and F. culmorum. Notably, scanning electron microscopy analysis demonstrates significant disruption of the hyphae in NTP-treated biofilms, indicating its ability to penetrate the biofilm matrix, which is a promising outcome for biofilm eradication strategies. The use of NTP could offer a more environmentally friendly and potentially more effective alternative to traditional disinfection methods.

Allogeneic hematopoietic stem cell transplant (HSCT) recipients receiving long-term and high-dose immunosuppressive medications suffer commonly from oral candida infections. This prospective cohort study examined oral fungal carriage in HSCT recipients and screened the susceptibility against commonly used antifungal agents. An increasing oral occurrence of Candida spp. and the development of resistance against clinically administered fluconazole were hypothesized.

Two hundred HSCT recipients were included and followed up for 2 years post-HSCT. Oral microbiological specimens were analyzed with matrix-assisted laser desorption/ionization-time of flight mass spectrometry assays (MALDI-TOF). The colorimetric method was applied for the susceptibility testing by commercially available Sensititre YeastOne (SYO®, TREK Diagnostics Systems, Thermo-Fisher, UK).

The prevalence of oral Candida spp. carriage increased statistically significantly after a year post-HSCT being 30, 26, 35, 44, and 47%, pre-HSCT, 3, 6, 12, and 24 months post-HSCT, respectively. Altogether, 169 clinical oral Candida strains were isolated. Fourteen Candida spp. were identified, and C. albicans was predominant in 74% of the isolates pre-HSCT with a descending prevalence down to 44% 2 years post-HSCT. An increasing relative proportion of non-albicans species post-HSCT was evident. No development of resistance of C. albicans against fluconazole was found. Instead, a shift from C. albicans towards non-albicans species, especially C. dubliensis, C. glabrata, and relatively seldom found C. krusei, was observed.

Oral Candida carriage increases after HSCT. Instead of the expected development of resistance of C. albicans against fluconazole, the relative proportion of non-albicans strains with innate resistance against azole-group antifungals increased.

Invasive candidiasis (IC), caused by Candida yeasts, particularly Candida albicans, poses a significant threat with high mortality rates. Diagnosis is challenging due to Candida's common presence in human microbiota. To address this, our research group developed an immunofluorescence assay detecting Candida albicans Germ Tube Antibodies (CAGTA) in IC patients. CAGTA, indicative of invasive processes, is associated with a lower mortality rate in ICU patients. Based on this premise, this study aims to provide results regarding the lack of knowledge about the potential activity of CAGTA against invasive infections in humans caused by the fungus Candida albicans. Therefore, in order to characterize the activity of CAGTA produced by patients with IC, we used sera from 29 patients with IC caused by either C. albicans or non-albicans Candida species. Whole serum IgG antibodies were fractionated into anti-blastospores, CAGTA-enriched, and purified CAGTA and the assessments included XTT colorimetric assays for metabolic activity, CFU counts for viability, and microscopy for growth, viability, and morphological analysis. The CAGTA-enriched IgG fraction significantly reduced the metabolic activity and viability of C. albicans compared to anti-blastospores. Purified CAGTA altered germ tube cell wall surfaces, as revealed by electron microscopy, and exhibited fungicidal properties by DiBAC fluorescent staining. In conclusion, antibodies in response to invasive candidiasis have antifungal activity against Candida albicans, influencing metabolic activity, viability, and cell wall structure, leading to cell death. These findings suggest the potential utility of CAGTA as diagnostic markers and support the possibility of developing immunization protocols against Candida infections.

Candida albicans is a common pathogenic fungus that presents a challenge to healthcare facilities. It can switch between a yeast cell form that diffuses through the bloodstream to colonize internal organs and a filamentous form that penetrates host mucosa. Understanding the pathogen's strategies for environmental adaptation and, ultimately, survival, is crucial. As a complementary study, herein, a multi-omics analysis was performed using high-resolution timsTOF MS to compare the proteomes and metabolomes of Wild Type (WT) Candida albicans (strain DK318) grown on agar plates versus liquid media. Proteomic analysis revealed a total of 1793 proteins and 15,013 peptides. Out of the 1403 identified proteins, 313 proteins were significantly differentially abundant with a p-value < 0.05. Of these, 156 and 157 proteins were significantly increased in liquid and solid media, respectively. Metabolomics analysis identified 192 metabolites in total. The majority (42/48) of the significantly altered metabolites (p-value 0.05 FDR, FC 1.5), mainly amino acids, were significantly higher in solid media, while only 2 metabolites were significantly higher in liquid media. The combined multi-omics analysis provides insight into adaptative morphological changes supporting Candida albicans' life cycle and identifies crucial virulence factors during biofilm formation and bloodstream infection.

Candidiasis is a highly pervasive infection posing major health risks, especially for immunocompromised populations. Pathogenic Candida species have evolved intrinsic and acquired resistance to a variety of antifungal medications. The primary goal of this literature review is to summarize the molecular mechanisms associated with antifungal resistance in Candida species. Resistance can be conferred via gain-of-function mutations in target pathway genes or their transcriptional regulators. Therefore, an overview of the known gene mutations is presented for the following antifungals: azoles (fluconazole, voriconazole, posaconazole and itraconazole), echinocandins (caspofungin, anidulafungin and micafungin), polyenes (amphotericin B and nystatin) and 5-fluorocytosine (5-FC). The following mutation hot spots were identified: (1) ergosterol biosynthesis pathway mutations (ERG11 and UPC2), resulting in azole resistance; (2) overexpression of the efflux pumps, promoting azole resistance (transcription factor genes: tac1 and mrr1; transporter genes: CDR1, CDR2, MDR1, PDR16 and SNQ2); (3) cell wall biosynthesis mutations (FKS1, FKS2 and PDR1), conferring resistance to echinocandins; (4) mutations of nucleic acid synthesis/repair genes (FCY1, FCY2 and FUR1), resulting in 5-FC resistance; and (5) biofilm production, promoting general antifungal resistance. This review also provides a summary of standardized inhibitory breakpoints obtained from international guidelines for prominent Candida species. Notably, N. glabrata, P. kudriavzevii and C. auris demonstrate fluconazole resistance.

Systemic Candida infections are routinely treated with amphotericin B (AMB), a highly effective antimycotic drug. However, due to severe toxicities linked to the parenteral administration of conventional micellar formulations (Fungizone®), its clinical utility is limited. Hyperbranched polyglycerols (HPGs) are multi-branched three-dimensional hydrophilic macromolecules that can be used to lessen the toxicity of AMB while also increasing its aqueous solubility. In the current research, to improve the safety and therapeutic efficacy of AMB, we developed new polyhedral oligomeric silsesquioxane - hyperbranched polyglycerol dendrimers with cholesterol termini (POSS-HPG@Chol) using azide-alkyne click reaction. Compared with Fungizone®, the as-synthesized POSS-HPG@Chol/AMB had lower minimum inhibitory and fungicidal concentrations against almost all studied Candida spp., as well as much less hemolysis and cytotoxicity. POSS-HPG@Chol/AMB revealed total protection of Balb/C mice from severe Candida infections in an experimental model of systemic candidiasis and can effectively reduce or eliminate AMB liver and kidney tissue injuries. Thanks to their safety, biocompatibility, and unique therapeutic properties, the developed POSS-polyglycerol dendrimers could be viable nanostructures for the delivery of poorly soluble drugs like AMB.

Candida species are responsible for fungal diseases and the development of nosocomial bloodstream infections. Treatment is resource-intensive and economically challenging for healthcare systems. Cost analyses of drugs against candidiasis, such as rezafungin, are thus of great interest to healthcare payers.

We conducted a cost-of-illness study of patients with Candida infections based on real-word data of the Department I of Internal Medicine, University Hospital Cologne (Germany) between 2016 and 2021. Health-economic parameters were analysed to describe the economic impact of Candida infections. Potential cost savings due to the administration of rezafungin were modelled for patients with invasive candidiasis or candidaemia based on a 5 day reduction of ICU length of stay (LOS) shown by the STRIVE study.

We found 724 cases (652 patients) with Candida infections, of which 61% received ICU treatment (n = 442) and 29% were mechanically ventilated (n = 207). Twenty-six percent died during hospitalization (n = 185). Median LOS was 25 and 15 days, on normal wards and ICU, respectively. Median total treatment costs per case accounted for €22 820. Based on the ICU LOS reduction, the retrospective model showed a median cost-saving potential of €7175 per hospital case with invasive candidiasis or candidaemia. Accumulated cost savings for 37 patients of €283 335 were found.

Treatment of candidiasis is cost intensive due to increased hospital LOS. The ICU LOS reduction rezafungin showed in STRIVE would lead to sustainable cost savings.

Opportunistic fungal infections by Candida species arise among cancer patients due to the weakened immune system following extensive chemotherapy. Prophylaxis with antifungal agents have developed the resistance of Candida spp. to antifungals. Accurate identification of yeasts and susceptibility patterns are main concerns that can directly effect on the treatment of patients.

Over a period of three years, 325 cancer patients suspected to Candida infections were included in the current investigation. The clinical isolates were molecularly identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). All strains, were examined for in vitro susceptibility to the amphotericin B, itraconazole, fluconazole, and anidulafungin according to the CLSI M27 document.

Seventy-four cancer patients had Candida infections (22.7%). Candida albicans was the most common species (83.8%). Antifungal susceptibility results indicated that 100% of the Candida isolates were sensitive to amphotericin B; however, 17.6%, 9.4%, and 5.4% of clinical isolates were resistant to anidulafungin, fluconazole, and itraconazole, respectively.

The findings of the present work shows a warning increase in resistance to echinocandins. Since all fluconazole resistance isolates were obtained from candidemia, we recommend amphotericin B as the first line therapy for this potentially fatal infection.

Recently, antimicrobial resistance has increased globally particularly Candida infections. Most of antifungal drugs used for treating candidiasis became resistant to most of Candida species. In the current study, a nanocomposite based on mycosynthesized copper oxide nanoparticles (CuONPs), nanostarch, nanochitosan was prepared. Results illustrated that twenty-four Candida isolates were isolated from clinical samples. Furthermore, three Candida strains were selected as the most resistant among others toward commercial antifungal drugs; these selected strains were identified genetically as C. glabrata MTMA 19, C. glabrata MTMA 21 and C. tropicalis MTMA 24. Characterization of the prepared nanocomposite was carried out using physiochemical analysis included Ultraviolet-visible spectroscopy (Uv-Vis), Fourier-Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Energy-Dispersive X-ray spectroscopy (EDX) and Transmission Electron Microscopy (TEM). Moreover, the nanocomposite exhibited promising anticandidal activity against C. glabrata MTMA 19, C. glabrata MTMA 21 and C. tropicalis MTMA 24, where the inhibition zones were 15.3, 27 and 28 mm, respectively. Ultrastructure changes observed in nanocomposite-treated C. tropicalis demonstrated disruption of the cell wall which led to cell death. In conclusion, our results confirmed that the novel biosynthesized nanocomposite based on mycosynthesized CuONPs, nanostarch and nanochitosan is a promising anticandidal agent to fight multidrug-resistant Candida.

The yeast Candida glabrata is an emerging, often drug-resistant opportunistic human pathogen that can cause severe systemic infections in immunocompromised individuals. At the same time, it is a valuable biotechnology host that naturally accumulates high levels of pyruvate─a valuable chemical precursor. Tools for the facile engineering of this yeast could greatly accelerate studies on its pathogenicity and its optimization for biotechnology. While a few tools for plasmid-based expression and genome engineering have been developed, there is no well-characterized cloning toolkit that would allow the modular assembly of pathways or genetic circuits. Here, by characterizing the Saccharomyces cerevisiae-based yeast molecular cloning toolkit (YTK) in C. glabrata and by adding missing components, we build a well-characterized CgTK (C. glabrata toolkit). We used the CgTK to build a CRISPR interference system for C. glabrata that can be used to generate selectable phenotypes via single-gRNA targeting such as is required for genome-wide library screens.

One of the problems that most affect hospitals is infections by pathogenic microorganisms. Rapid identification and adequate, timely treatment can avoid fatal consequences and the development of antibiotic resistance, so it is crucial to use fast, reliable, and not too laborious techniques to obtain quick results. Raman spectroscopy has proven to be a powerful tool for molecular analysis, meeting these requirements better than traditional techniques. In this work, we have used Raman spectroscopy combined with machine learning algorithms to explore the automatic identification of eleven species of the genus Candida, the most common cause of fungal infections worldwide. The Raman spectra were obtained from more than 220 different measurements of dried drops from pure cultures of each Candida species using a Raman Confocal Microscope with a 532 nm laser excitation source. After developing a spectral preprocessing methodology, a study of the quality and variability of the measured spectra at the isolate and species level, and the spectral features contributing to inter-class variations, showed the potential to discriminate between those pathogenic yeasts. Several machine learning and deep learning algorithms were trained using hyperparameter optimization techniques to find the best possible classifier for this spectral data, in terms of accuracy and lowest possible overfitting. We found that a one-dimensional Convolutional Neural Network (1-D CNN) could achieve above 80 % overall accuracy for the eleven classes spectral dataset, with good generalization capabilities.

Gallstone disease (GSD) is associated with changes in the gut and gallbladder bacterial composition, but there is limited information on the role of the fungal community (mycobiome) in disease development. This study aimed to characterize the gallbladder mycobiome profiles and their interactions with bacteriome in GSD. A total of 136 bile and gallstone samples (34 paired for bacteriome, and 33 paired and extra 2 bile samples for mycobiome) were obtained from calculi patients with chronic cholecystitis. Bile and gallstone bacteriome and mycobiome were profiled by 16S and internal transcribed spacer (ITS) rRNA gene sequencing, respectively. Gallbladder bacteriome, mycobiome, and interkingdom and intrakingdom interactions were compared between bile and gallstone. In general, microbial diversity was higher in bile than in gallstone, and distinct microbial community structures were observed among them. Deep Sea Euryarchaeotic Group, Rhodobacteraceae, and Rhodobacterales were microbial biomarkers of bile, while Clostridiales and Eubacterium coprostanoligenes were biomarkers of gallstone. Five fungal taxa, including Colletotrichum, Colletotrichum sublineola, and Epicoccum, were enriched in gallstone. Further ecologic analyses revealed that intensive transkingdom correlations between fungi and bacteria and intrakingdom correlations within them observed in gallstone were significantly decreased in bile. Large and complex fungal communities inhabit the gallbladder of patients with GSD. Gallstone, compared with bile, is characterized by significantly altered bacterial taxonomic composition and strengthened bacterial-bacterial, fungal-fungal, and bacterial-fungal correlations in the gallbladder of patients with GSD.

Systemic candidiasis is caused by Candida invading the bloodstream. The efficacy and safety of echinocandins in monotherapy and combination therapy regimes have not been adequately compared in immunocompromised patients with Candidiasis, and thus this systematic review aims to do so.

A protocol was prepared a priori. PubMed, Embase and Cochrane Library databases were searched systematically (from inception of each database to September 2022) to identify randomized controlled trials. Two reviewers performed screening, quality assessment of trials, and extracted data independently. Pairwise meta-analysis was performed using random-effects model to compare echinocandin monotherapy versus other antifungals. The primary outcomes of interest were treatment success and treatment-related adverse events.

547 records (PubMed=310, EMBASE=210 and Cochrane Library=27) were reviewed. Following our screening criteria, six trials involving 177 patients were included. Risk of bias of four included studies had some concerns due to lack of a pre-specified analysis plan. Meta-analysis shows that echinocandin monotherapy does not have significantly higher rates of "treatment success" compared to other classes of antifungals (RR 1.12, 95%CI 0.80-1.56). However, echinocandins appeared to be significantly safer than other forms of antifungal therapy (RR 0.79, 95%CI 0.73-0.86).

Our findings have shown that echinocandin monotherapy (micafungin, caspofungin) given intravenously are just as effective as other antifungals (amphotericin B, itraconazole) in the treatment of systemic candidiasis in immunocompromised patients. There appears to be similar benefits when using echinocandins compared to amphotericin B which has also been used as a broad-spectrum antifungal, while avoiding the severe adverse effects that amphotericin B causes, such as nephrotoxicity.

Recent studies revealed a significant role of the gut fungal community in human health. Here, we investigated the content and variation of gut mycobiota among subjects from the European population. We explored the interplay between gut fungi and various host-related sociodemographic, lifestyle, health, and dietary factors. The study included 923 participants. Fecal DNA samples were analyzed by whole-metagenome high-throughput sequencing. Subsequently, fungi taxonomic profiles were determined and accompanied by computational and statistical analyses of the association with 53 host-related factors. Fungal communities were characterized by a high prevalence of Saccharomyces, Candida, and Sporisorium. Ten factors were found to correlate significantly with the overall mycobiota variation. Most were diet related, including the consumption of chips, meat, sodas, sweetening, processed food, and alcohol, followed by age and marital status. Differences in α- and/or β-diversity were also reported for other factors such as body mass index (BMI), job type, autoimmunological diseases, and probiotics. Differential abundance analysis revealed fungal species that exhibited different patterns of changes under specific conditions. The human gut mycobiota is dominated by yeast, including Saccharomyces, Malassezia, and Candida. Although intervolunteer variability was high, several fungal species persisted across most samples, which may be evidence that a core gut mycobiota exists. Moreover, we showed that host-related factors such as diet, age, and marital status influence the variability of gut mycobiota. To our knowledge, this is the first large and comprehensive study of the European cohort in terms of gut mycobiota associations with such an extensive and differentiated host-related set of factors. IMPORTANCE The human gut is inhabited by many organisms, including bacteria and fungi, that may affect human health. However, research on human gut mycobiome is still rare. Moreover, the large European-based cohort study is missing. Here, we analyzed the first large European cohort in terms of gut mycobiota associations with a differentiated host-related set of factors. Our results showed that chips, meat, sodas, sweetening, processed food, beer, alcohol consumption, age, and marital status were associated with the variability of gut mycobiota. Moreover, our analysis revealed changes in abundances at the fungal species level for many investigated factors. Our results can suggest potentially valuable paths for further, narrowly focused research on gut mycobiome and its impact on human health. In the coming era of gut microbiome-based precision medicine, further research into the relationship between different mycobial structures and host-related factors may result in new preventive approaches or therapeutic procedures.

Candidemia is one of the significant causes of mortality amongst critically ill patients in Intensive Care Units (ICUs). This study aimed to assess the incidence, risk factors and antifungal susceptibility pattern in candidemia cases admitted in ICU in a tertiary care hospital in Jaipur, Rajasthan from June 2021 to November 2021. Candida species isolated from blood culture of clinically suspected patients of sepsis were defined as candidemia cases. Blood culture and antifungal susceptibility testing were performed as per standard laboratory protocol. Analyses of risk factors was done between candidemia cases and matched controls in a ratio of 1 : 3. Forty-six candidemic cases and 150 matched controls were included in the study. C. tropicalis was the most prevalent species (22/46; 48%) followed by C. auris (8/46; 17%) and C. albicans (7/46; 15%). Candida species showed good sensitivity to echinocandins (97%) followed by amphotericin B (87%) and voriconazole (80%). In multivariate analysis, longer stay in ICU, presence of an indwelling device, use of immunosuppressive drugs and positive SARS-CoV-2 infection were associated with increased risk of candidemia. The constant evaluation of risk factors is required as prediction of risks associated with candidemia may help to guide targeted preventive measures with reduced morbidity and mortality.

The main objective was to assess the clinical characteristics, associated factors, and outcomes of patients admitted to the ICU for candidemia. The secondary objective was to examine the relationship of candidemia with the length of stay and mortality.

The analysis was a retrospective single-center cohort study addressing the effect of invasive candidemia on outcomes. This study was performed in a medical-surgical ICU located in a tertiary private hospital in São Paulo, Brazil. Data was collected through the review of the hospital database.

In total, 18,442 patients were included in our study, including 22 patients with candidemia. The median age was similar in patients with and without candidemia [67 (56-84) vs. 67 (51-80)]. Most patients were male, and the proportion of men was higher among patients with candidemia (77% vs. 55.3%). The rates of renal replacement therapy (40.9% vs. 3.3%), mechanical ventilation (63.6% vs. 29.6%), and parenteral nutrition (40.9% vs. 4.8%) were higher in patients with candidemia than in those without candidemia. The mortality rate (77.3% vs. 11.9%) and length of hospital stay [42 days (23.0-78.8) vs. 8 days (5.0-17.0)] were significantly higher in patients with candidemia.

Patients with candidemia are prone to longer hospital stay and mortality. In addition, we found associations of candidemia with the use of invasive mechanical ventilation, renal replacement therapy, and parenteral nutrition.

Delays in the treatment of proven invasive fungal disease have been shown to be harmful. However, empiric treatment for all patients at risk of infection has not demonstrated benefit. This study evaluates the effects of a micafungin stewardship initiative on the duration of therapy and clinical outcomes at the University of Mississippi Medical Center in Jackson, Mississippi. This single-center quasi-experiment evaluated patients who received micafungin. Adult inpatients who received at least one treatment dose of micafungin in the pre-intervention (1 October 2020 to 30 September 2021) or post-intervention (1 October 2021 to 30 April 2022) groups were included. Patients were placed on micafungin for prophylaxis and those who required definitive micafungin therapy were excluded. An algorithm was used to provide real-time recommendations in order to assess change in the treatment days of micafungin therapy. A total of 282 patients were included (141 pre-group versus 141 post-group). Over 80% of the patients included in the study were in an intensive care unit, and other baseline characteristics were similar. The median number of treatment days with micafungin was 4 [IQR 3-6] in the pre-group and 3 [IQR 2-6] in the post-group (p = 0.005). Other endpoints, such as time to discontinuation or de-escalation, hospital mortality, and hospital length of stay, were not significantly different between the groups. An antifungal stewardship initiative can be an effective way to decrease unnecessary empiric antifungal therapy for patients who are at risk of invasive fugal disease.

A common defense challenge when antemortem blood ethanol results are presented at trial is the assertion that ethanol was formed in the blood tube after the blood draw through fermentation of the blood glucose by Candida albicans (C. Albicans). In contrast, decades of research into the stability of ethanol in antemortem blood collected for forensic purposes have consistently shown that any analytically significant change in ethanol concentration is a decrease and initially, ethanol-negative blood remains ethanol-negative with storage. For there to be any possibility of fermentation to occur by C. Albicans in an antemortem blood sample there must be a plausible mechanism for introduction of C. Albicans into the blood. One mechanism proffered at trial is environmental contamination resulting from ambient air drawn into the evacuated blood collection tube. Blood was drawn from ethanol-free individuals into 6 and 10-ml gray-top Vacutainer® tubes containing sodium fluoride and 6-ml Vacutainer® tubes without a preservative. Following the blood draws, the tubes were stored unstoppered at room temperature for 24 or 48 h in various locations. Following unstoppered storage, the tubes were stoppered and stored refrigerated (~4°C), left at room temperature (~22°C), or placed in an oven (37°C). The refrigerated blood was analyzed for ethanol using headspace gas chromatography after both 5 days and 32 months. Unrefrigerated blood samples were analyzed after being stored at room temperature or in an oven for up to 30 days. Ethanol was not detected in any of the blood tubes after storage regardless of storage time, storage temperature, or preservative concentration.

Almonertinib was included in the first-line treatment of non-small cell lung cancer with EGFR T790M mutations by the Chinese Society of Clinical Oncology in 2021. Considering that immunocompromised lung cancer patients are prone to opportunistic fungal infections, and most triazole antifungal drugs are moderate or strong inhibitors of CYP3A4, this study was conducted to develop and validate an accurate and rapid ultra-performance liquid chromatography tandem mass spectrometry method for quantifying almonertinib in plasma and for investigating the pharmacokinetic changes of almonertinib caused by voriconazole and fluconazole in rats. After liquid-liquid extraction with tert-butyl methyl ether, an XSelect HSS T3 column (2.1 × 100 mm, 2.5 μm, Waters) was used for the chromatographic separation of almonertinib and sorafenib-D₃ (internal standard). The analytes were detected using an AB Sciex Triple Quad 5,500 mass spectrometer in the positive ionization mode. The method exhibited great linearity (0.5-200 ng/ml, r > 0.997) and stability under the established experimental conditions. All validation experiments were in accordance with the guidelines, and the results were all within the acceptable limits. This method was successfully applied to the researches of pharmacokinetics and drug interactions for almonertinib in rats. Voriconazole and fluconazole significantly altered the pharmacokinetic profiles of almonertinib and increased the systemic exposure of almonertinib in rats to different degrees, but further human trials should be conducted to validate the results.