CGA-N9 is an antifungal peptide that primarily targets Candida spp. with a mild activity. Our preceding research confirmed that the CGA-N9 crosses cell membrane with the assistance of C. tropicalis oligopeptide transporter (CtOPT) -1 and - 9. In this study, CGA-N9-derived peptides were designed following the molecular docking results with CtOPT-1 and -9. Compared with CGAN9, they exhibit higher transmembrane efficiency with the assistance of CtOPT-1 during the early phase of transmembrane processes and CtOPT-9 in the late phase. And they displayed significantly enhanced antifungal activity, with lower minimum inhibitory concentrations (MICs) against C. tropicalis, C. albicans, and C. parapsilosis, as well as improved biosafety. Among them, CGAN93 was the most optimizing, with a therapeutic index of 145.33. Furthermore, in a mouse model of systemic candidiasis, CGAN93 demonstrated a therapeutic effect comparable to fluconazole, significantly improving the survival rate of mice, attenuating organ damage, and enhancing the immune organ index. In conclusion, OPTs-based computer aided design is an effective strategy for enhancing the activities of antimicrobial peptides (AMPs) by improving transmembrane transport efficiency. CGAN93 is a promising drug candidate for treating Candidiasis.

Candida albicans (C. albicans) is the most common cause of invasive Candida infections worldwide. The acquired resistance of C. albicans to fluconazole, a first-line antifungal drug, has been frequently reported, posing significant challenges to treatment. Combination therapy has emerged as an effective strategy to combat drug resistance. In this study, we synthesized a series of sinomenine derivatives and evaluated in vitro synergistic activity against azole-resistant C. albicans. The results demonstrated that compound 3ja exhibited a potent synergistic effect with fluconazole against azole-resistant C. albicans. Mechanism studies revealed that the combination of 3ja and FLC significantly induced reactive oxygen species accumulation, disrupted membrane integrity, altered membrane sterols, and promoted apoptosis in C. albicans.

Antifungal resistance poses a significant challenge to disease management, necessitating the development of novel drugs. Antimicrobial peptides offer potential solutions. This study focused on extraction and characterization of peptides from Adenanthera pavonina seeds with activity against Candida species, Mycobacterium tuberculosis, proteases, and α-amylases. Peptides were extracted in phosphate buffer and heated at 90°C for 10 min to create a peptide rich heated fraction (PRHF). After confirming antimicrobial activity and the presence of peptides, the PRHF underwent ion exchange chromatography, yielding retained and non-retained fractions. These fractions were evaluated for antimicrobial activity and cytotoxicity against murine macrophages. The least toxic and most active fraction underwent reversed-phase chromatography, resulting in ten fractions. These fractions were tested for peptides and antimicrobial activity. The most active fraction was rechromatographed on a reversed-phase column, resulting in two fractions that were assessed for antimicrobial activity. The most active fraction revealed a single band of approximately 6 kDa and was tested for inhibitory effects on proteases and α-amylases. Thermal stability experiments were conducted on the 6 kDa peptide at different temperatures followed by reassessment of antifungal activity and circular dichroism. The 6 kDa peptide inhibited yeasts, M. tuberculosis, human salivary and Tenebrio molitor larvae intestine α-amylases, and proteolytic activity from fungal extracts, and thus named ApPI. Remarkably, ApPI retained antifungal activity and conformation after heating and is primarily composed of α-helices. ApPI is a thermally stable serine protease/α-amylase inhibitor from A. pavonina seeds, offering promise as a foundational molecule for innovative therapeutic agents against fungal infections and tuberculosis.

Candidemia, a common nosocomial bloodstream infection caused by Candida species, is associated with a high mortality rate. This study aimed to analyze the epidemiological characteristics, distribution of Candida species, antifungal susceptibility, and mortality risk factors of adult patients with candidemia in Zunyi, China. These findings are expected to inform treatment and prevention strategies for candidemia in this region.

Clinical data, Candida species, antifungal susceptibility profiles, and prognosis of 92 patients with candidemia at the First People's Hospital of Zunyi (the Third Affiliated Hospital of Zunyi Medical University) from January 2016 to December 2023 were retrospectively analyzed. Univariate and multivariate logistic regression analyses were performed to analyze risk factors for patient death.

Analysis of 92 candidemia cases revealed an average incidence of 0.19% and mortality rate of 35.87%. Candida albicans was responsible for 33.70% of the infections, whereas non-C. albicans accounted for 66.30% of the total. Non-C. albicans was dominated by C. parapsilosis (31.52%), Nakaseomyces glabratus (18.48%), and C. tropicalis (13.04%). The susceptibility of all Candida species to amphotericin B exceeded 96%. C. albicans and C. parapsilosis showed greater than 70% susceptibility to fluconazole, itraconazole, and voriconazole, whereas C. tropicalis showed less than 60% susceptibility to these antifungal agents. Among the 33 dead patients, C. albicans was associated with a higher mortality rate than non-C. albicans (P = 0.007). Logistic multiple regression analysis showed that cardiovascular disease (OR = 8.913, 95% CI: 1.463-54.289, P = 0.018), kidney disease (OR = 13.672, 95% CI: 2.025-92.326, P = 0.007), and antifungal drug treatment duration less than 7 days (OR = 10.694, 95% CI: 1.841-62.112, P = 0.008) were independent risk factors for mortality in adult patients with candidemia.

The mortality rate among patients with candidemia remains high with C. albicans is the predominant pathogen in Zunyi, China. Cardiovascular disease, kidney disease, and antifungal drug treatment duration less than 7 days were independent risk factors for mortality in adult patients with candidemia. Therefore, greater attention should be paid to adult patients with risk factors for mortality to improve the outcomes of adult candidemia.

Invasive candidiasis represents a major global health concern, with incidence and mortality rates expected to rise due to medical advancements and unavoidable risk factors. This retrospective, multicentric study was conducted in eight hospitals in a northeastern Italian region, enrolling adult patients diagnosed with candidemia from 1 January 2018 to 31 December 2022. Epidemiological trends and clinical characteristics were analyzed and compared to those from a prior regional study (2009-2011), allowing a fourteen-year comparative evaluation. A shift in species distribution was observed, with a decline in Candida albicans (from 65.7% to 57.8%) and a rise in non-albicans species, particularly the Candida parapsilosis complex (from 16.1% to 18.2%). Guideline adherence was assessed applying the EQUAL Candida score; scores ≥ than 11.5 were independently associated with improved in-hospital survival (HR 3.51, p < 0.001). Among individual score components, empiric echinocandin therapy and central venous catheter removal correlated with better outcomes. Centers with routine infectious disease (ID) consultations showed higher survival and adherence, reinforcing the value of specialist involvement. These findings support local epidemiological and management practice surveillance program adoption to address context-specific gaps, promote the adoption of best practices in Candida BSI management-as expanded ID specialist consultations and education programs-and, ultimately, reduce candidemia-related mortality rates.

Coinfection is defined as the occurrence of at least two genetically distinct infectious agents within the same host. Historically, fungal infections have been neglected, leading to an underestimation of their impact on public health systems. However, fungal coinfections have become increasingly prevalent, emerging as a significant global health concern. This review explores fungal coinfections commonly associated with HIV, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, Mycobacterium tuberculosis, and Pseudomonas species. These include candidiasis, aspergillosis, paracoccidioidomycosis, cryptococcosis, histoplasmosis, pneumocystosis, sporotrichosis, and mucormycosis. We discuss the key local and systemic mechanisms that contribute to the occurrence of these coinfections. HIV infects CD4+ cells, causing systemic immunosuppression, particularly impairing the adaptive immune response. The inflammatory response to SARS-CoV-2 infection disrupts both pulmonary and systemic homeostasis, rendering individuals more vulnerable to local and disseminated fungal coinfections. Severe influenza promotes fungal coinfections by triggering the production of pro-inflammatory cytokines, which damage the epithelial-endothelial barrier and impair the recognition and phagocytosis of fungal cells. Tuberculosis can replace normal lung parenchyma with collagen tissue, leading to alterations in lung architecture, compromising its function. Interaction between Pseudomonas and Aspergillus during coinfection involves the competition for iron availability and an adaptive response to its deprivation. Therefore, the specific interactions between each underlying disease and fungal coinfections are detailed in this review. In addition, we highlight the risk factors associated with coinfections, pathophysiology, epidemiology, and the challenges of early diagnosis. Recognizing the substantial worldwide public health burden posed by fungal coinfections is crucial to improve survival rates.

Amphotericin B (AmB) is a potent antifungal agent with minimal resistance among clinical isolates, but its use is limited by severe side effects. Reducing its toxicity through combination therapy with synergistic compounds is a promising strategy. This study investigates the antifungal potential of 1,3,4-thiadiazole derivatives, focusing on AT2 and AT10, against Candida species. AT2 demonstrated the highest activity, achieving complete inhibition at 128 µg/mL and notable suppression at lower concentrations. The combination of AT2 and AT10 with amphotericin B exhibited synergistic effects, leading to significant structural alterations in the fungal cell wall, including reduced β-glucan levels and increased synthesis of mannan and phosphomannan. These modifications correlated with enhanced antifungal efficacy without exacerbating cytotoxicity toward human fibroblasts and renal epithelial cells. The spectroscopic analysis suggested that the synergy arose from both cell wall disruptions and amphotericin B disaggregation. These findings highlight the potential of thiadiazole-based combination therapies for combating resistant fungal infections.

Candidemia (Candida bloodstream infection [C-BSI]) in left ventricular assist device (LVAD) recipients is poorly understood. This study aimed to investigate the incidence, risk factors and outcomes of C-BSI in LVAD recipients.

We screened 656 adults who underwent LVAD implantation at our institution from 1 January 2015 to 4 April 2024. Patients with C-BSI (n = 18) were compared with 2 control groups: (1) matched LVAD recipients with no bloodstream infection (N-BSI; matched 1:5; n = 90) to determine risk factors for C-BSI and (2) unmatched LVAD recipients with bacteremia (bacterial BSI [B-BSI]; n = 79) to compare mortality and infectious complication rates. A random forest model identified key predictive factors for C-BSI. Kaplan-Meier survival curves were used for time-to-event analyses.

Median time to C-BSI was 20 days after implantation (interquartile range, 6-42 days). Compared to N-BSI, C-BSI were more likely to require perioperative temporary mechanical circulatory support (9 patients [50%] vs 8 [8.9%], respectively), renal replacement therapy (12 [67%] vs 6 [6.7%]), total parenteral nutrition (6 [33%] vs 2 [2.2%]), and prolonged postoperative mechanical ventilation (for 12 days vs 1 day) (all P < .001). A random forest model identified ventilation duration, renal replacement therapy, and total parenteral nutrition as top predictors of C-BSI. In terms of outcomes, C-BSI was more likely to lead to device endocarditis than B-BSI (in 5 [28%] vs 7 [9.1%], respectively; P = .008) and was associated with shorter median survival after infection (25 [interquartile range, 12 to not estimable due to censoring] vs 490 [54 to not estimable due to censoring] days; P = .04).

C-BSI occurs early in LVAD recipients and is associated with a high mortality rate. Identified risk factors identified may guide antifungal prophylaxis or early empiric antifungal treatment in this susceptible patient population.

Background: Candidiasis remains a chief concern in global healthcare. Drug safety issues and increasing resistance make it urgent to develop alternative antifungal agents, namely antimicrobial peptides. Amidated decoralin (Dec-CONH2) possesses considerable anti-Candida activity, and its association with nanocarriers could help in enhancing efficacy while reducing intrinsic toxicity to the host. Methods: We studied an N-terminal cysteine-modified version of the peptide (Cys-Dec-CONH2) and screened the effects of different nanosystems (polymeric nanoparticles (NPs), liposomes and gold NPs) on its activity against azole-sensitive and azole-resistant Candida species using a clinically relevant in vitro assay. Results: The antifungal activity of Cys-Dec-CONH2 was maintained (minimum inhibitory concentration (MIC) = 16-64 µg/mL), but the presence of poly(d,l-lactic-co-glycolic acid) (PLGA)- and polycaprolactone-based NPs impaired the antifungal effect of the peptide (MIC > 256 µg/mL). This effect was milder for polystyrene-based NPs, liposomes, and gold NPs (MIC ≤ 128 µg/mL). Additionally, the covalent surface functionalization of PLGA-based NPs with Cys-Dec-CONH2 or the presence of relevant biomolecules (albumin and mucin) resulted in complete inhibition of antifungal activity. Conclusions: Our data suggest that Cys-Dec-CONH2 is able to establish strong interfacial interactions with different nanomaterials, which need to be considered when developing nanomedicines based on this peptide for the management of candidiasis.

Multifocal Candida infections represent a serious threat for cancer patients, often leading to increased mortality. This study investigates the risk factors and outcomes for multifocal Candida infections compared to single-site infections and evaluates species distribution and antifungal susceptibility patterns. Fifty-seven Candida isolates were obtained from 23 cancer patients with multifocal infections. Another 57 isolates were collected from 57 matched patients with single-site infections. Germ tube test and CHROMAgar medium were used for species identification. Antifungal susceptibility of amphotericin B, caspofungin, fluconazole, and voriconazole was determined following the Clinical and Laboratory Standard Institute (CLSI), M60-Ed2. Of the 80 cancer patients, the majority of cases involved solid tumors (85.0 %), with gastrointestinal cancer being the most common in both multifocal and single-focal groups (p = 0.207). Significantly more patients with multifocal infections were admitted to the ICU compared to those with single-site infections (60.9 % versus 34.0 %, p = 0.029). Surgical procedures independently increased the risk for multifocal infections (OR: 10.506, p = 0.047). Multifocal infections had a significantly higher mortality rate than single-site infections (69.6 % versus 42.1 %, OR: 3.143, p = 0.026). Non-albicans Candida (NAC) species constituted 57.9 % (n = 66) of the 114 isolates, with Candida glabrata being the most prevalent (n = 49, 43.0 %). All tested antifungals revealed high resistance rates, particularly amphotericin B (79.8 %) and fluconazole (53.5 %). NAC species demonstrated significantly higher resistance rates than Candida albicans. Multifocal Candida infections in cancer patients showed higher mortality, with surgical procedures and ICU admission as key risk factors. The increasingly prevalent resistant NAC species, particularly C. glabrata, need accurate identification, antifungal stewardship, and new therapeutic strategies.

Candidiasis, caused by Candida spp. is an opportunistic infection with significant healthcare risks, worsened by trends in antifungal resistance. This study aimed to evaluate the antifungal susceptibility profile, investigate resistance mechanisms, assess efflux pump activity, and examine biocide tolerance in clinical Candida isolates.

A total of 100 Candida isolates from hospitalized and outpatient individuals were analyzed for their antifungal susceptibility profile, molecular resistance mechanisms through PCR, efflux pump activity with the Cartwheel method, and biocide tolerance (sodium hypochlorite, hydrogen peroxide, and benzalkonium chloride), which was assessed by disk diffusion.

A high prevalence of resistance (87%) to at least one antifungal was observed, with 47.12% of isolates showing simultaneous multiple resistance to three azole derivatives. The highest antifungal agent resistance was observed for fluconazole (n = 70) and the highest susceptibility for amphotericin B (n = 1). The most common mutation was in the ERG11 gene (n = 38/43.7%). Efflux pump activity was detected in both C. albicans and non-albicans Candida species. Biocide testing revealed a higher tolerance for sodium hypochlorite, with an inhibition zone ranging from 18.25 (4.40) to 34.0 (4.00).

This study highlights significant antifungal resistance in Candida spp. particularly to azoles, stressing the need for improved infection control and novel therapeutic strategies.

Invasive fungal infections in the intensive care unit (ICU) are not uncommon and most cases are caused by Candida species, specifically Candida albicans. However, recently, there has been an increase in non-albicans Candida spp. (C. glabrata; C. parapsilosis) causing invasive fungal infections. This has led to an increasing awareness of this infection due to the increase in documented antifungal resistance in many of these Candida species. In addition, manifestations of invasive candidiasis are often non-specific, and the diagnosis remains extremely challenging. Unfortunately, delays in antifungal therapy continue to hamper the morbidity; length of stay; and the mortality of these infections. Although the echinocandins are the drugs of choice in these infections, antifungal resistance among the non-albicans species (C. glabrata; C. krusei; C. auris; C. parapsilosis) is being observed more frequently. This has led to an increase in morbidity and mortality, specifically in critically ill patients. Overall, the diagnosis and management of invasive candidiasis in the ICU remain challenging. It is imperative that the critical care physician keeps this infection at the forefront of their differential diagnosis in order to decrease the mortality rate of these individuals. In this review, we discuss the current epidemiologic trends, diagnosis, and management of invasive candidiasis in the intensive care unit setting.

The rising prevalence of fungal infections, especially those caused by Candida species, presents a major risk to global health. With approximately 1.5 million deaths annually, the urgency for effective treatment options has never been greater. Candida spp. are the leading cause of invasive infections, significantly impacting immunocompromised patients and those in healthcare settings. C. albicans, C. parapsilosis and the emerging species C. auris are categorized as highly dangerous species because of their pathogenic potential and increasing drug resistance. This review comparatively describes the formation of microbial biofilms of both bacterial and fungal origin, including major pathogens, thereby creating a novel focus. Biofilms can further complicate treatment, as these structures provide enhanced resistance to antifungal therapies. Traditional antifungal agents, including polyenes, azoles and echinocandins, have shown effectiveness, yet resistance development continues to rise, necessitating the exploration of novel therapeutic approaches. Antimicrobial peptides (AMPs) such as the anti-biofilm peptides Pom-1 and Cm-p5 originally isolated from snails represent promising candidates due to their unique mechanisms of action and neglectable cytotoxicity. This review article discusses the challenges posed by Candida infections, the characteristics of important species, the role of biofilms in virulence and the potential of new therapeutic options like AMPs.

Fungal pericarditis is a rare disease but its incidence has risen in parallel with the global increase in invasive fungal infections. This systematic review analyzes data from previously reported cases of fungal pericarditis to provide an improved understanding of the etiology, clinical presentation, management, and outcomes of this rare disease. We reviewed Medline and Scopus databases from 1 January 1990 to 29 January 2024 for case reports that documented the isolation of a fungal pathogen from pericardial fluid or tissue. Of the 2330 articles screened, 101 cases met the inclusion criteria. Patients with fungal pericarditis and the involvement of at least one other organ-usually the lungs, brain, or kidney-had worse outcomes than patients with isolated pericardial disease. Immunosuppression was reported in 50% of cases and was associated with worse outcomes in adults. Patients who presented with chest pain, received adequate empiric antifungal therapy, and underwent pericardiocentesis and pericardiectomy had improved survival. The most common isolated pathogens were Candida spp., followed by Aspergillus spp. and Mucor spp., with the latter two linked to worse outcomes. Only 35% of patients received empiric antifungal medications before the causative pathogen was identified, and mortality was associated with a delay in appropriate therapy. Immunosuppression, disseminated disease, and presence of shock/multiorgan failure were additional risk factors associated with death. Fungal pericarditis carries a mortality rate of up to 50%, with nearly half of patients being immunocompromised. Clinicians frequently do not consider fungal pericarditis in the differential diagnoses, which leads to delays in treatment and poorer outcomes. Further prospective multicenter studies are urgently needed to better understand the epidemiology, improve diagnostic testing and management, and decrease unacceptably high mortality in patients with fungal pericarditis.

The Candida Genome Database (CGD; www.candidagenome.org) is unique in being both a model organism database and a fungal pathogen database. As a fungal pathogen database, CGD hosts locus pages for 5 species of the best-studied pathogenic fungi in the Candida group. As a model organism database, the species Candida albicans serves as a model both for other Candida spp. and for non-Candida fungi that form biofilms and undergo routine morphogenic switching from the planktonic form to the filamentous form, which is not done by other model yeasts. As pathogenic Candida species have become increasingly drug resistant, the high lethality of invasive candidiasis in immunocompromised people is increasingly alarming. There is a pressing need for additional research into basic Candida biology, epidemiology and phylogeny, and potential new antifungals. CGD serves the needs of this diverse research community by curating the entire gene-based Candida experimental literature as it is published, extracting, organizing, and standardizing gene annotations. Gene pages were added for the species Candida auris, recent outbreaks of which have been labeled an "urgent" threat. Most recently, we have begun linking clinical data on disease to relevant Literature Topics to improve searchability for clinical researchers. Because CGD curates for multiple species and most research focuses on aspects related to pathogenicity, we focus our curation efforts on assigning Literature Topic tags, collecting detailed mutant phenotype data, and assigning controlled Gene Ontology terms with accompanying evidence codes. Our Summary pages for each feature include the primary name and all aliases for that locus, a description of the gene and/or gene product, detailed ortholog information with links, a JBrowse window with a visual view of the gene on its chromosome, summarized phenotype, Gene Ontology, and sequence information, references cited on the summary page itself, and any locus notes. The database serves as a community hub, where we link to various types of reference material of relevance to Candida researchers, including colleague information, news, and notice of upcoming meetings. We routinely survey the community to learn how the field is evolving and how needs may have changed. For example, we asked our users which species we should next add to CGD, and the clear answer was Candida tropicalis. A key future challenge is management of the flood of high-throughput expression data to make it as useful as possible to as many researchers as possible. The central challenge for any community database is to turn data into knowledge, which the community can access, use, and build upon.

Clinically, timely diagnosis and effective treatment of Candida bloodstream infections rely on rapid and sensitive detection methods. However, the long turn-around time and low detection rate of blood culture (the gold standard) make rapid diagnosis of Candida challenging. This study develops a novel molecular assay (M1-mRAP) designed for the rapid and sensitive detection of three Candida species in blood samples: Candida albicans(CA), Candida tropicalis(CT), and Candida glabrata(CG).

We used the M1-mRAP method aimed at detecting Candida DNA in blood samples, in which we developed a novel multiplex recombinase-aided PCR (mRAP) assay for sensitive amplification of Candida DNA and used a self-developed recombinant human mannan-binding lectin beads (M1 beads)method for enrichment of Candida in blood. The analytical sensitivity of mRAP was evaluated using Candida recombinant plasmids. The analytical sensitivity of the M1-mRAP method for blood sample detection was assessed using quantitative Candida simulated blood samples. The clinical performance of the mRAP and M1-mRAP methods was evaluated in 120 non-blood samples and 9 blood samples and compared with conventional qPCR methods.

The limit of detection(LOD) for CA, CT, and CG by the mRAP method were 4, 4, and 3 copies/μL, respectively. The LOD for CA, CT, and CG simulated blood samples by the M1-mRAP were 2, 2, and 1 CFU/mL, and the overall detection time was about 3.5 h. Clinical assays of mRAP and M1-mRAP showed that these two methods were consistent with qPCR (P<0.05), but had better clinical detection ability than qPCR. Specifically, the mRAP method identified 5 (4.2%) qPCR-negative samples, while M1-mRAP detected 1 (11.1%) classified as the qPCR grey zone sample.

The M1-mRAP method provides rapid and sensitive detection of low concentrations of CA, CT, and CG blood samples and has the potential to emerge as an important tool for the early detection of Candida bloodstream infections in clinical settings.

Various species of fungi can be detected in the environment and within the human body, many of which may become pathogenic under specific conditions, leading to various forms of fungal infections. Antimicrobial peptides (AMPs) are evolutionarily ancient components of the immune response that are quickly induced in response to infections with many pathogens in almost all tissues. There is a wide range of AMP classes in humans, many of which exhibit broad-spectrum antimicrobial function. This review provides a comprehensive overview of the mechanisms of action of AMPs, their distribution in the human body, and their antifungal activity against a range of both common and rare clinical fungal pathogens. It also discusses the current research status of promising novel antifungal strategies, highlighting the challenges that must be overcome in the development of these therapies. The hope is that antimicrobial peptides, as a class of antimicrobial agents, will soon progress through large-scale clinical trials and be implemented in clinical practice, offering new treatment options for patients suffering from infections.

Antimicrobial resistance (AMR) presents a critical challenge in clinical settings, particularly among pediatric patients with life-threatening conditions such as sepsis, meningitis, and neonatal infections. The increasing prevalence of multi- and pan-resistant pathogens is strongly associated with adverse clinical outcomes. Recent technological advances in sequencing methods, including metagenomic next-generation sequencing (mNGS), Oxford Nanopore Technologies (ONT), and targeted sequencing (TS), have significantly enhanced the detection of both pathogens and their associated resistance genes. However, discrepancies between resistance gene detection and antimicrobial susceptibility testing (AST) often hinder the direct clinical application of sequencing results. These inconsistencies may arise from factors such as genetic mutations or variants in resistance genes, differences in the phenotypic expression of resistance, and the influence of environmental conditions on resistance levels, which can lead to variations in the observed resistance patterns. Machine learning (ML) provides a promising solution by integrating large-scale resistance data with sequencing outcomes, enabling more accurate predictions of pathogen drug susceptibility. This review explores the application of sequencing technologies and ML in the context of pediatric infections, with a focus on their potential to track the evolution of resistance genes and predict antibiotic susceptibility. The goal of this review is to promote the incorporation of ML-based predictions into clinical practice, thereby improving the management of AMR in pediatric populations.

Prevention and management of invasive fungal infections is challenging due to the complexity of at-risk patient population, high morbidity and mortality of these infections, and pharmacologic aspects of available antifungal agents. While there has been substantial investment in antifungal drug development over past 20 years, the ideal antifungal remains elusive. Clinicians must be aware of differences in spectrum of activity, pharmacokinetic/dynamic dosing, toxicity, resistance, and drug interaction profiles of antifungals to use them most effectively. This article will review key features of U.S. Food and Drug Administration-approved and pipeline antifungals to facilitate an understanding of their role in treatment and/or prevention of invasive fungal infections.

Candidiasis poses a significant threat to human health, especially in immunocompromised patients. However, there is a paucity of epidemiological data concerning the prevalence of candidiasis in developing regions of China. We conducted a retrospective study on patients positive for Candida infections in a tertiary care hospital in Shantou, China, to identify the clinical characteristics and risk factors for candidiasis. Of 5,095 cases of candidiasis, 489 (9.59%) were candidemia infections. Candida albicans (n = 230, 47.0%) was the predominant species identified among all patients. Non-albicans Candida (NAC) was more prevalent in adult patients, while Candida glabrata was slightly more frequent in pediatric patients (n = 10, 14.7%). Pulmonary diseases (n = 200, 47.8%) were the most common underlying comorbidities in adult patients (n = 25, 35.2%). Thrombocytopenia was the only laboratory finding higher in adult patients than in pediatric patients. Respiratory dysfunction, the presence of a central venous catheter, septic shock, and thrombocytopenia were independent risk factors for candidemia-related 30-day mortality. Amphotericin B exhibited high efficacy (100%), and itraconazole exhibited the lowest efficacy against all tested Candida isolates. C. glabrata had a lower susceptibility to azole, although this was not statistically significant. The epidemiological data on candidiasis, specifically candidemia in pediatric and adult patients, varied regarding the prevalence of Candida species and associated risk factors. This study provides guidance for prescribing the appropriate therapy and yields insights into the susceptibility patterns of different Candida isolates to antifungal drugs.

Many risk factors, including COVID-19 infection, lead to the development of invasive Candida infection in intensive care unit patients. The aim of this study was to evaluate the risk factors affecting mortality along with the clinical characteristics of candidemia patients.

This retrospective study was conducted among patients hospitalized at the Anesthesiology and Reanimation Clinic between June 2020 and December 2021. The clinical and laboratory characteristics of 165 patients with candidemia were recorded. The difference between patients with and without COVID-19 infection was evaluated statistically. Multivariate analysis was performed to determine factors affecting mortality.

A total of 165 patients were included in the study, 52.1% of whom were male. The mean age of the patients was 66.5 (median 18-97) years. The percentage of patients with COVID-19 infection was 70.9%. The mean leukocyte count and aspartate transaminase, alanine transaminase, C-reactive protein, lactate dehydrogenase, ferritin, and D-dimer levels were significantly greater in COVID-19 patients than non COVID-19 patients (p < 0.05). The mortality rate in patients with candidemia was 80.2%. The presence of comorbidities, corticosteroid use, advanced age, and high ferritin and D-dimer levels negatively affected mortality, according to the multivariate analysis results. C. albicans was the most frequently isolated Candida species.

We detected higher mortality rates in patients with candidemia who were elderly, had comorbidities, received corticosteroid treatment and had elevated ferritin and D-dimer levels. When steroids are used, it is necessary to remember that this drug is a double-edged sword and to be careful of fungal infections.

We evaluated the diagnostic performance of the newly developed MoiM Dx Candida 9-plex (MoiM) assay for the detection of Candida species from positive blood cultures and compared the results with those obtained from the BIOFIRE Blood Culture Identification 2 (BCID2) Panel. This study included 39 candidaemia cases and 40 cases of non-Candida bloodstream infections as negative controls. Routine culture results, which were identified via matrix-assisted laser desorption/ionization time‒of‒flight mass spectrometry (MALDI‒TOF MS), were used as the reference standard for analysis. The performance of the MoiM assay was evaluated using positive percent agreement (PPA) and negative percent agreement (NPA). The MoiM assay demonstrated a PPA of 97.1% and an NPA of 100% for detecting the five most common Candida species (C. albicans, C. glabrata, C. tropicalis, C. parapsilosis, and C. krusei) in candidaemia cases. In comparison, the BCID2 panel yielded a PPA of 67.6% and an NPA of 100.0% (P = 0.001). Additionally, the MoiM assay correctly identified C. guilliermondii and C. lusitaniae, not covered by the BCID2 panel. Among the 10 discrepant results between the two assays, all 10 cases were incompletely identified by the BCID2 panel, but the results from the MoiM assay were identical to the culture results. The MoiM assay was designed as an automated sample-to-answer molecular assay for the detection of Candida species from positive blood cultures. Our study revealed that this assay shows good overall agreement with routine culture and is comparable to the BCID2 panel.

Since Candida albicans, a type of fungus, causes severe infections that pose a significant threat to human health, its rapid detection is critical in clinical antifungal therapy. Traditional fungal diagnostic approaches are largely based on the culture method. This method is time-consuming and laborious, taking about 48-72 h, and cannot identify emerging species, making it unsuitable for critically ill patients with bloodstream infections, sepsis, and so on. Other antigen or nucleic acid amplification-based methods were also found to be unsuitable for Point-of-Care Testing (POCT) diagnosis due to various limitations. Therefore, establishing a new approach for the rapid diagnosis of Candida spp is imperative. Herein, we proposed a novel diagnostic method for invasive fungi detection. Specifically, we created a new CRISPR diagnostic platform for Candida albicans-specific Internal Transcriptional Spacer 2 (ITS2) gene by combining the DNase cleavage activity of Cas12a with Recombinase Polymerase Amplification (RPA). Furthermore, to achieve rapid on-site detection under low-resource conditions, we used a transverse lateral flow strip with a single target to visualize the Cas12a single enzyme digestion product. We designated the platform as a rapid molecular detection tool that integrates RPA and the CRISPR-Cas12a technology. The entire platform can accurately identify Candida albicans within 50 minwhile remaining unaffected by other fungi or bacteria. Furthermore, the detection limit of the platform could reach 102 CFU/ml. Moreover, this approach offers additional benefits, including easy operation, low set-up cost, and broad applicability for Candida albicans detection across medical institutions at all levels, especially in township health centers in resource-poor regions.

Nakaseomyces glabratus (N. glabratus) formerly known as Candida glabrata (C. glabrata), is an endogenous opportunistic pathogen, which is generally located in the gastrointestinal tract but can spread in immunocompromised patients. N. glabratus is the second most common pathogen that causes candidemia in several countries. N. glabratus virulence factors may increase antifungal resistance and reduce the number of available treatment options. High resistance to azoles and increasing resistance to echinocandins have been previously reported in N. glabratus.

To establish the distribution of N. glabratus isolates in Europe and its drug susceptibility/resistance in each country over the last 7 years.

The search was performed across three databases: PubMed, Scopus and Scielo, using the MeSH terms: "Candida glabrata", "Nakaseomyces glabratus", "Europe", "resistance" and "Epidemiology" exclusively in English. All available information from January 2002 to December 2022 was included, excluding reviews, meta-analyses and book chapters.

Fifty-seven articles with information on antifungal susceptibility in Europe were retrieved and analysed with a total of 15,400 reported C. glabrata isolates. Remarkably, nations that presented the maximum number of cases during the study period included the United Kingdom (n = 7241, 47.02%), France (n = 3190, 20.71%), Spain (n = 900, 5.84%), Hungary (n = 745, 4.84%) and Italy (n = 486, 3.16%). C. glabrata isolates presented resistance to azoles [voriconazole (n = 2225, 14.45%), fluconazole (n = 1612, 10.47%), itraconazole (n = 337, 2.19%) and clotrimazole (n = 89, 0.58%)], increased resistance to echinocandins, especially to anidulafungin (n = 138, 0.89%), and high sensitivity to amphotericin B.

The number of candidemia cases associated with triazole-resistant N. glabratus isolates have been increasing in Europe. Therefore, echinocandins and amphotericin B can be considered optional empirical treatments; however, antifungal susceptibility testing is required to determine the best therapeutic options.

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.

The increasing detection rate of C. tropicalis and its azole resistance have made clinical treatment difficult. The presence of candiduria seems to correlate with invasive candida infection, especially for patients admitted to ICUs. However, the prevalence and antifungal resistance of C. tropicalis isolates in urine samples has not been well studied.

To retrospectively investigate the clinical features, antifungal resistance, and genetic relatedness of C. tropicalis isolates from urine samples.

A total of 107 clinical C. tropicalis isolates were retrospectively studied, including phenotypes of isolates and characteristics of patients. The genetic profiles of 107 isolates were genotyped using multi-locus sequence typing (MLST). Phylogenetic analysis was inferred using unweighted pair group method with arithmetic averages. MLST clonal clusters (CCs) were analysed by goeBURST.

Of the 107 isolates, 27.1% were resistant to fluconazole, and there was a notable increasing trend of fluconazole resistance from 16.1% in 2019 to 40.0% in 2021. Forty-seven diploid sequence types (DSTs) were assigned to ten major CCs. CC1 was the predominant fluconazole-susceptible group; 24 isolates from CC1 belonged to DST333, an outbreak clone in NICU ward. The azole-resistant CC4 contained 19 isolates, accounting for 65.5% of the azole-resistant isolates in this study. CC4 belongs to a prevalent FNS CC1 globally, of which the putative founder genotype was DST225.

This study revealed an outbreak of azole-susceptible C. tropicalis isolates in urine specimens and a high azole resistance rate of C. tropicalis in candiduria, and the MLST type showed clonal aggregation in azole-resistant isolates from urine samples.

Candidemia and invasive candidiasis persist as significant causes of morbidity and mortality. As fluconazole resistance rates rise, alternative means of treatment are necessary, either via mold-active azoles or extended durations of echinocandins. These come with the potential for undesirable side effects for triazoles or choosing between prolonged hospitalization or outpatient parenteral antimicrobial therapy in the case of echinocandins. Rezafungin offers an opportunity to manage extended treatment durations with shorter hospital stays and no extended parenteral access. Herein, we review the most recent published data pertaining to rezafungin including anti-fungal activity, pharmacokinetics, and clinical data relating to the treatment of invasive candidiasis. Given its prolonged half-life allowing for once-weekly dosing, rezafungin has the potential as an anti-fungal prophylactic agent in high-risk patients, and studies to examine this potential role are ongoing.

This study evaluated the relationship between total plasma and free kidney concentrations of amphotericin B (AmB) in healthy and C. albicans-infected Wistar rats using microdialysis and has the potential to significantly impact future research in this field and promote the development of antifungal drugs. The findings of this study, which show that plasma levels are a good predictor for AmB kidney concentrations and can be used to optimize its dosing regimen, underscore the importance of this research.

Microdialysis probe recovery rates were determined by dialysis and retrodialysis in vitro, as well as by retrodialysis in vivo. The intravenous (i.v.) administration of 2.5 × 106 CFU/mL of C. albicans ATCC induced the infection. A 2.5 mg/kg i.v. bolus was used in healthy and C. albicans-infected rats (n = 6/group). Plasma and microdialysate samples were analyzed using HPLC-diode-array detection. AmB tissue penetration was analyzed using the ratio between the total plasma and kidney concentrations and population pharmacokinetics (PopPK) to assess the impact of the infection on the pharmacokinetic parameters. The chosen flow rate was set to 1.5 μL/min, and there was no statistical difference between the relative recovery values when changing AmB concentrations.

The in vivo relative recovery was determined to be 10.9% ± 3.7%. The antifungal tissue penetration was 0.77 and 0.71 for the healthy and infected animals, respectively. The structural PK model with two compartments and linear elimination describes the concentration versus time profile of AmB simultaneously in the plasma and tissue. Infection by C. albicans does not interfere with AmB kidney penetration. AmB protein binding is demonstrated to be nonlinear and dependent on the AmB concentration in the plasma of healthy and infected animals.

This is a timely and important review that focuses on the appropriateness of established cleaning, disinfection, and sterilization methods to safely and effectively address infectious fungal drug-resistant pathogens that can potentially contaminate reusable medical devices used in healthcare environment in order to mitigate the risk of patient infection. The release of the World Health Organization (WHO) fungal priority pathogen list (FPPL) in 2022 highlighted the public health crisis of antimicrobial resistance (AMR) in clinically relevant fungal species. Contamination of medical devices with drug-resistant fungal pathogens (including those on the FPPL) in healthcare is a rare event that is more likely to occur due to cross-transmission arising from lapses in hand hygiene practices. Established disinfection and sterilization methods decontaminate fungal pathogens on single-use and reusable medical devices; however, there are assumptions that reusable devices destined for semi-critical use are appropriately cleaned and do not harbour biofilms that may undermine the ability to effectively decontamination these type devices in healthcare. International standards dictate that manufacturer's instructions for use must provide appropriate guidance to healthcare facilities to meet safe reprocessing expectations that include addressing drug-resistant fungal pathogens. Increased environmental monitoring and vigilance surrounding fungal pathogens in healthcare is advised, including adherence to hand hygiene/aseptic practices and appropriate cleaning encompassing the simplification of reusable device features for 'ease-of-reach'. There are emereging opportunities to promote a more integrated multiactor hub approach to addressing these sophisticated challenges, including future use of artificial intelligence and machine learning for improved diagnostics, monitoring/surveillance (such as healthcare and wastewater-based epidemiology), sterility assurance, and device design. There is a knowledge gap surrounding the occurrence and potential persistence of drug-resistant fungal pathogens harboured in biofilms, particularly for ascertaining efficacy of high-level disinfection for semi-critical use devices.

Candida species produce a wide array of infections ranging from mucocutaneous to systemic infections. Candida albicans remains the most common species identified; however, the non-albicans Candida species have continued to increase as the diagnosis and therapeutic regimens have progressed.

This review with discussion of the various Candida species, especially the non-albicans species, some of the important mechanisms of resistance, and newer in vitro and clinical studies describing the recent and novel antifungal options such as rezafungin, ibrexafungerp, and oteseconazole, along with a novel antifungal, fosmanogepix.

Initial antifungal therapy is frequently obsolete due to the expansion of antifungal resistance. This is especially true with C. glabrata, C. krusei, and most recently with C. auris. The newer and novel antifungals discussed here will add valuable tools to our antifungal armamentarium to be able to appropriately and adequately treat and manage these difficult infections. Each of the antifungals has unique and novel properties that will expand the arsenal useful to treat these fungal infections in the years to come.

Some pro-inflammatory and anti-inflammatory cytokines were significantly elevated in patients with candidemia patients, but no studies have included these cytokines in the analysis of risk factors for mortality of candidemia. This study aims to analyze the risk factors of short-term mortality of candidemia and the predictive value of serum cytokines.

We retrospectively analyzed and compared the clinical features, risk factors and cytokine interleukin (IL)-6, interferon-γ (IFN-γ), IL-10 and IL-17 between survival group and death group in 53 patients with candidemia. Receiver operating of the characteristic curve (ROC) analysis was performed and figured up area under the curve (AUC), sensitivity and specificity values to assess the predictive power of independent factors associated with mortality.

The overall in-hospital mortality rate of candidemia was 62.3 % (33/53), and the 30-day mortality rate was 52.8 % (28/53). The C. albicans accounting for 17.0 % (9/53), and the non-albicans Candida was 83.0 % (44/53). Serum IL-6 (p = 0.041, HR = 1.009), IFN-γ (p = 0.013, HR = 1.007, 95 %), procalcitonin (PCT) (p = 0.010, HR = 0.899) and Candida score (p = 0.033, HR = 1.659) were independent risk factors, while Initiation of targeted antifungal therapy within 48 h of positive blood cultures (BC) (P = 0.015, HR = 0.266) was a protective factor. The AUC of ROC for Candida score, serum IL-6, PCT, IFN-γ, and Initiation of targeted antifungal therapy within 48 h of positive BC showed 0.933, 0.841, 0.801, 0.732, 0.714, respectively. IL-6 and IFN-γ comprised good performing model for predicting 30-day and 90-day mortality, while IL-6 and IL-10 were the best combinations for predicting 90-day mortality.

Serum IL-6, IFN-γ, PCT, and Candida score can predict short-term mortality risk in patients with candidemia, while prompt and targeted antifungal treatment may reduce mortality. IL-6 could serve as a possible biomarker for predicting short-term mortality of candidemia and its combination with IL-10 or IFN-γ may further improve the predictive value.

Candidemia is the predominant form of invasive candidiasis and the most frequently occurring serious fungal infection in critically ill patients in Intensive Care Units (ICU). Studies carried out in Latin America reveal a higher incidence of candidemia and higher mortality rates when compared to North America or Europe. This highlights the need to develop guidelines for correctly diagnosing and treating candidemia in critically ill patients in the ICU. These guidelines are part of the efforts to implement antifungal optimization programs in the region to obtain better clinical outcomes and promote rational antifungal use. This evidence-based clinical standard, established through expert consensus for the Latin American context, contains recommendations and algorithms for diagnosing and treating candidemia in critically ill ICU patients.

This study aimed to investigate changes in candidemia incidence, species distribution, antifungal susceptibility, initial antifungal use, and mortality trends in Korea before and during the COVID-19 pandemic. A retrospective analysis was conducted on candidemia cases from two tertiary care hospitals in Korea between 2017 and 2022. Data were compared between the pre-pandemic (2017-2019) and pandemic (2020-2022) periods. Statistical methods included incidence rate ratios (IRRs) and multivariate Cox regression to assess 30-day mortality risk factors. A total of 470 candidemia cases were identified, with 48.7% occurring pre-pandemic and 51.3% during the pandemic. While the overall incidence of candidemia remained similar across the two periods (IRR 1.15; p=0.13), the incidence in intensive care units (ICUs) significantly increased during the pandemic (IRR 1.50; p<0.01). The distribution of Candida species did not differ significantly between the two periods. Fluconazole non-susceptibility in C. albicans markedly decreased (10.0% vs. 0.9%, p<0.01), whereas C. glabrata exhibited a significant rise in caspofungin non-susceptibility during the pandemic (0% vs. 22.4%, p<0.01). Echinocandin use increased (21.8% vs. 34.4%; p<0.01), while fluconazole use declined (48.0% vs. 32.8%; p<0.01). Although the 30-day mortality rate was higher during the pandemic (60.2% vs. 57.2%), the difference was not statistically significant (p=0.57). The findings highlight the need for region-specific surveillance and tailored management strategies to improve candidemia outcomes, especially during healthcare disruptions like the COVID-19 pandemic.

This study aimed to develop and validate a nomogram based on lymphocyte subtyping and clinical factors for the early and rapid prediction of Intra-abdominal candidiasis (IAC) in septic patients. A prospective cohort study of 633 consecutive patients diagnosed with sepsis and intra-abdominal infection (IAI) was performed. We assessed the clinical characteristics and lymphocyte subsets at the onset of IAI. A machine-learning random forest model was used to select important variables, and multivariate logistic regression was used to analyze the factors influencing IAC. A nomogram model was constructed, and the discrimination, calibration, and clinical effectiveness of the model were verified. High-dose corticosteroids receipt, the CD4+T/CD8+ T ratio, total parenteral nutrition, gastrointestinal perforation, (1,3)-β-D-glucan (BDG) positivity and broad-spectrum antibiotics receipt were independent predictors of IAC. Using the above parameters to establish a nomogram, the area under the curve (AUC) values of the nomogram in the derivation and validation cohorts were 0.822 (95% CI 0.777-0.868) and 0.808 (95% CI 0.739-0.876), respectively. The AUC in the derivation cohort was greater than the Candida score [0.822 (95% CI 0.777-0.868) vs. 0.521 (95% CI 0.478-0.563), p < 0.001]. The calibration curve showed good predictive values and observed values of the nomogram; the Decision Curve Analysis (DCA) results showed that the nomogram had high clinical value. In conclusion, we established a nomogram based on the CD4+/CD8+ T-cell ratio and clinical risk factors that can help clinical physicians quickly rule out IAC or identify patients at greater risk for IAC at the onset of infection.

Invasive fungal infections, particularly candidemia, pose significant clinical challenges globally. Understanding local epidemiology, species distribution, and antifungal susceptibility patterns is crucial for effective management despite regional variations.

To investigate the epidemiology, species distribution, antifungal susceptibility patterns, and associated risk factors of candidemia among patients in Bahrain from 2021 to 2023.

This retrospective study analyzed demographic data, Candida species distribution, antifungal susceptibility profiles, and risk factors among candidemia patients treated at a tertiary care hospital in Bahrain over three years. Data was collected from medical records and analyzed using descriptive statistics.

A total of 430 candidemia cases were identified. The mean age of patients was 65.7 years, with a mortality rate of 85.5%. Candida albicans (C. albicans) was the most common species, followed by Candida parapsilosis, Candida tropicalis (C. tropicalis), and emerging multidrug-resistant Candida auris (C. auris). Antifungal susceptibility varied across species, with declining susceptibility to azoles observed, particularly among C. albicans and C. tropicalis. Major risk factors included central venous catheters, broad-spectrum antibiotics, and surgical procedures.

This study highlights the substantial burden of candidemia among older adults in Bahrain, characterized by diverse Candida species. It also concerns levels of antifungal resistance, notably in C. auris. The findings underscore the importance of local epidemiological surveillance and tailored treatment strategies to improve outcomes and mitigate the spread of multidrug-resistant Candida species. Future research should focus on molecular resistance mechanisms and optimizing therapeutic approaches to address this growing public health concern.

Covering: 2013 to 2023In an era where antimicrobial resistance severely threatens our ability to treat infections, the discovery of new drugs that belong to different chemical classes and/or bear original modes of action is urgently needed. In this case, diterpenoids comprise a productive field with a proven track record in providing new anti-infectives to tackle bacterial infections and malaria. This review highlights the potential of both naturally occurring and semi-synthetic bi- and tricyclic diterpenoids to become leads in search of new drugs to treat infections caused by bacteria, fungi, viruses and protozoan parasites. The literature from the last decade (2013-2023) is covered, focusing on naturally occurring and semi-synthetic bicyclic (labdanes and labdane-type) and tricyclic (all classes) diterpenoids, detailing their relevant biological activities in the context of infection, which are explained through structure-activity relationships.

Candida species resistant to fluconazole have raised concern in the scientific medical community due to high mortality in patients with invasive disease. In developing countries, such as Brazil, fluconazole is the most commonly used antifungal, and alternative treatments are expensive or not readily available. Furthermore, the occurrence of biofilms is common, coupled with their inherent resistance to antifungal therapies and the host's immune system, these microbial communities have contributed to making infections caused by these yeasts an enormous clinical challenge. Therefore, there is an urgent need to develop alternative medicines, which surpass the effectiveness of already used therapies, but which are also effective against biofilms. Therefore, the present study aimed to describe for the first time the antifungal and antibiofilm action of the derivative 2-amino-5,6,7,8-tetrahydro-4 H-cyclohepta[b]thiophene-3-isopropyl carboxylate (2AT) against clinical strains of Candida spp. resistant to fluconazole (FLZ). When determining the minimum inhibitory concentrations (MIC), it was found that the compound has antifungal action at concentrations of 100 to 200 µg/mL, resulting in 100% inhibition of yeast cells. Its synergistic effect with the drug FLZ was also observed. The antibiofilm action of the compound in subinhibitory concentrations was detected, alone and in association with FLZ. Moreover, using scanning electron microscopy, it was observed that the compound 2AT in isolation was capable of causing significant ultrastructural changes in Candida. Additionally, it was also demonstrated that the compound 2AT acts by inducing characteristics compatible with apoptosis in these yeasts, such as chromatin condensation, when visualized by transmission electron microscopy, indicating the possible mechanism of action of this molecule. Furthermore, the compound did not exhibit toxicity in J774 macrophage cells up to a concentration of 4000 µg/mL. In this study, we identify the 2AT derivative as a future alternative for invasive candidiasis therapy, in addition, we highlighted the promise of a strategy combined with fluconazole in combating Candida infections, especially in cases of resistant isolates.