Early Candida colonisation impact on patients and healthcare professionals in an intensive care unit.

OBJECTIVES: Candida spp. is an opportunistic pathogen that causes superficial and invasive infections with nosocomial outbreaks without strict hygiene protocols. Herein, we assessed oral colonisation by Candida spp. in 209 Intensive Care Unit (ICU) patients between July 2021 and April 2022, conducting clinical, epidemiological, and microbiological characterisation of those developing oral or invasive candidiasis. METHODS: Initial oral swabs were collected within 24 h of admission in the ICU, followed by collections on Days 2, 4, 6 and 8. Swabs from denture-wearing patients, abiotic surfaces, healthcare professionals' hands, and retroauricular regions were also obtained. Recovered yeasts and filamentous fungi were identified using MALDI-TOF MS and morphological characteristics, respectively. Genetic similarity of Candida spp. isolates was evaluated using Amplified fragment length polymorphism (AFLP), and the antifungal susceptibility profile was determined by broth microdilution. RESULTS: In the study, 64.11% of patients were orally colonised by Candida spp. Of these, 80.59% were colonised within the first 24 h. Oral colonisation also occurred on subsequent days: 50%/Day 2, 26.92%/Day 4, and 11.53%/Days 6 and 8. Of the patients, 8.61% had oral candidiasis, mainly pseudomembranous. Among orally colonised patients, 2.23% developed invasive candidiasis. Besides, 89.47% of healthcare professionals evaluated were colonised. MALDI-TOF MS identified different yeast species, and C. albicans (45.34%), C. tropicalis (15.7%), and C. parapsilosis sensu stricto (9.88%) were the most prevalent. AFLP analysis indicated a high genetic correlation (≥97%) between C. parapsilosis sensu stricto isolates from patients and professionals. Three resistant C. albicans isolates were also found. CONCLUSION: This study reported a diversity of yeast and filamentous fungi species in ICU patients and highlighted early Candida spp. colonisation risks for invasive candidiasis, as well as the potential horizontal transmission in the nosocomial setting, emphasising the need for effective infection control measures.

Insights from Three Pan-European Multicentre Studies on Invasive Candida Infections and Outlook to ECMM Candida IV.

Invasive candidiasis and candidemia remain a significant public health concern. The European Confederation of Medical Mycology (ECMM) conducted three pan-European multicentre studies from 1997 to 2022 to investigate various aspects of invasive Candida infections. These studies revealed shifting trends in Candida species distribution, with an increase of non-albicans Candida species as causative pathogens, increasing rates of antifungal resistance, and persistently high mortality rates. Despite advancements in antifungal treatment, the persistently high mortality rate and increasing drug resistance, as well as limited drug access in low-income countries, underscore the need for continued research and development in the treatment of Candida infections. This review aims to summarize the findings of the three completed ECMM Candida studies and emphasize the importance of continued research efforts. Additionally, it introduces the upcoming ECMM Candida IV study, which will focus on assessing candidemia caused by non-albicans Candida species, including Candida auris, investigating antifungal resistance and tolerance, and evaluating novel treatment modalities on a global scale.

Expert Panel Recommendations on the Clinical Practice Guidelines for the Diagnosis and Management of Invasive Candidiasis in Indonesia.

Invasive candidiasis (IC) ranks among the primary causes of deadly fungal infections. The frequency of IC rises alongside increasing number of patients with altered immune systems, critically ill, chronic diseases, and various medical procedures. The disease causes high morbidity and mortality, as well as prolonged stay and increases hospital costs. The diagnosis and management of IC in Indonesia is still a challenge. Laboratory facilities in identifying pathogenic fungi and susceptibility tests to antifungals are still limited. Clinical awareness and financial support from health policymakers are also insufficient. Early diagnosis is essential for proper treatment to reduce morbidity and mortality rates. Initiated by the Indonesian Pulmonary Mycoses Centre (IPMC), several expert representatives from six medical professional organizations in Indonesia have agreed to set up a meeting series to prepare a joint draft on the diagnosis and management of IC. The expert panel aimed to achieve a consensus on the clinical practice guidelines for diagnosing and treating IC in Indonesia.

Evolutionary accumulation of FKS1 mutations from clinical echinocandin-resistant Candida auris.

INTRODUCTION: Drug resistance to echinocandins, first-line drugs used to treat Candida auris infection, is rapidly emerging. However, the accumulation of mutations in genes other than FKS1 (before an isolate develops to resistance via FKS1 mutations), remains poorly understood. Methods: Four clinical cases and 29 isolates associated with the incremental process of echinocandin resistance were collected and analyzed using antifungal drug susceptibility testing and genome sequencing to assess the evolution of echinocandin resistance. FINDINGS: Six echinocandin minimum inhibitory concentration (MIC)-elevated C. auris strains and seven resistant strains were isolated from the urinary system of patients receiving echinocandin treatment. Meanwhile, phylogenetic analyses illustrated that the echinocandin-resistant strains were closely related to other strains in the same patient. Genomic data revealed that the echinocandin-resistant strains had FKS1 mutations. Furthermore, three categories (ECN-S/E/R) of non-synonymous mutant SNP genes (such as RBR3, IFF6, MKC1, MPH1, RAD2, and MYO1) in C. auris appeared to be associated with the three-stage-evolutionary model of echinocandin resistance in C. glabrata: cell wall stress, drug adaptation, and genetic escape (FKS mutation). INTERPRETATION: Echinocandin-resistant C. auris undergoes spatial and temporal phase changes closely related to echinocandin exposure, particularly in the urinary system. These findings suggest that FKS1 mutations mediate an evolutionary accumulation of echinocandin resistance followed by modulation of chromosome remodelling and DNA repair processes that ultimately lead to FKS1 hot spot mutations and the development of drug resistance. This study provides an in-depth exploration of the molecular pathways involved in the evolution of Candida auris echinocandin resistance.

Prognostic value of serial (1,3)-ß-D-glucan measurements in ICU patients with invasive candidiasis.

BACKGROUND: To determine whether a decrease in serum (1,3)-ß-D-glucan (BDG) was associated with reduced mortality and to investigate the performance of BDG downslope in predicting clinical outcome in invasive candidiasis. METHODS: Observational cohort study in ICU patients over a ten-year period (2012-2022) in Italy. Proven invasive candidiasis with at least 2 BDG determinations were considered. RESULTS: In the study population of 103 patients (age 47 [35-62] years, SAPS II score 67 [52-77]) 68 bloodstream and 35 intrabdominal infections were recorded. Serial measurements showed that in 54 patients BDG decreased over time (BDG downslope group) while in 49 did not (N-BDG downslope group). Candida albicans was the pathogen most frequently isolated (61%) followed by C. parapsilosis (17%) and C. glabrata (12%), in absence of any inter-group difference. Invasive candidiasis related mortality was lower in BDG downslope than in N-BDG downslope group (17% vs 53%, p < 0.01). The multivariate Cox regression analysis showed the association of septic shock at infection occurrence and chronic liver disease with invasive candidiasis mortality (HR [95% CI] 3.24 [1.25-8.44] p = 0.02 and 7.27 [2.33-22.66] p < 0.01, respectively) while a BDG downslope was the only predictor of survival (HR [95% CI] 0.19 [0.09-0.43] p < 0.01). The area under the receiver operator characteristic curve for the performance of BDG downslope as predictor of good clinical outcome was 0.74 (p = 0.02) and our model showed that a BDG downslope > 70% predicted survival with both specificity and positive predictive value of 100%. CONCLUSIONS: A decrease in serum BDG was associated with reduced mortality and a steep downslope predicted survival with high specificity in invasive candidiasis.

Candida tropicalis-A systematic review to inform the World Health Organization of a fungal priority pathogens list.

In response to the growing global burden of fungal infections with uncertain impact, the World Health Organization (WHO) established an Expert Group to identify priority fungal pathogens and establish the WHO Fungal Priority Pathogens List for future research. This systematic review aimed to evaluate the features and global impact of invasive candidiasis caused by Candida tropicalis. PubMed and Web of Science were searched for studies reporting on criteria of mortality, morbidity (defined as hospitalization and disability), drug resistance, preventability, yearly incidence, diagnostics, treatability, and distribution/emergence from 2011 to 2021. Thirty studies, encompassing 436 patients from 25 countries were included in the analysis. All-cause mortality due to invasive C. tropicalis infections was 55%-60%. Resistance rates to fluconazole, itraconazole, voriconazole and posaconazole up to 40%-80% were observed but C. tropicalis isolates showed low resistance rates to the echinocandins (0%-1%), amphotericin B (0%), and flucytosine (0%-4%). Leukaemia (odds ratio (OR) = 4.77) and chronic lung disease (OR = 2.62) were identified as risk factors for invasive infections. Incidence rates highlight the geographic variability and provide valuable context for understanding the global burden of C. tropicalis infections. C. tropicalis candidiasis is associated with high mortality rates and high rates of resistance to triazoles. To address this emerging threat, concerted efforts are needed to develop novel antifungal agents and therapeutic approaches tailored to C. tropicalis infections. Global surveillance studies could better inform the annual incidence rates, distribution and trends and allow informed evaluation of the global impact of C. tropicalis infections.

Multicenter Candida auris outbreak caused by azole-susceptible clade IV in Pernambuco, Brazil.

BACKGROUND: Candida auris is an emerging multidrug-resistant yeast, frequently causing outbreaks in health care facilities. The pathogen persistently colonises human skin and inanimate surfaces such as catheters, aiding to its spread. Moreover, colonisation is a risk factor to develop invasive infection. OBJECTIVES: We investigated 61 C. auris strains isolated from non-sterile human body sites (n = 53) and the hospital environment (n = 8), originating from four different centres in a single Brazilian state. MATERIALS AND METHODS: Antifungal susceptibility testing (AFST) against common antifungals was performed, and resistance-associated genes were evaluated. Genetic relatedness was investigated with short tandem repeat (STR) genotyping and validated with whole-genome sequencing (WGS) single nucleotide polymorphism (SNP) analysis. RESULTS: Antifungal susceptibility testing demonstrated that all isolates were susceptible to azoles, echinocandins and amphotericin B. No mutations were detected in ERG11 and FKS1 genes. With STR typing, isolates were allocated to clade IV and appeared closely related. This was confirmed by WGS SNP analysis of 6 isolates, which demonstrated a maximal difference of only 41 SNPs between these strains. Furthermore, the Brazilian isolates formed a distinct autochthonous branch within clade IV, excluding recent introductions from outside the country. A molecular clock analysis of clade IV isolates from various countries suggests that early in the previous century there was a unique event causing environmental spread of a C. auris ancestor throughout the Latin-American continent, followed by human introduction during the last decades. CONCLUSION: We report the emergence of C. auris patient colonisation in multiple centres by fluconazole-susceptible clade IV close-related strains in Pernambuco State, Brazil.

Candida albicans-A systematic review to inform the World Health Organization Fungal Priority Pathogens List.

Candida albicans is a common fungal pathogen and amongst the leading causes of invasive candidiasis globally. This systematic review examines the characteristics and global impact of invasive infections caused by C. albicans. We searched on PubMed and Web of Science for studies reporting on criteria such as mortality, morbidity, drug resistance, preventability, yearly incidence, and distribution/emergence during the period from 2016 to 2021. Our findings indicate that C. albicans is the most common Candida species causing invasive disease and that standard infection control measures are the primary means of prevention. However, we found high rates of mortality associated with infections caused by C. albicans. Furthermore, there is a lack of data on complications and sequelae. Resistance to commonly used antifungals remains rare. Although, whilst generally susceptible to azoles, we found some evidence of increasing resistance, particularly in middle-income settings-notably, data from low-income settings were limited. Candida albicans remains susceptible to echinocandins, amphotericin B, and flucytosine. We observed evidence of a decreasing proportion of infections caused by C. albicans relative to other Candida species, although detailed epidemiological studies are needed to confirm this trend. More robust data on attributable mortality, complications, and sequelae are needed to understand the full extent of the impact of invasive C. albicans infections.

Spectrum of infection and outcomes in individuals with Candida auris infection in Qatar.

BACKGROUND: We investigated the spectrum of infection and risk factors for invasive fungal disease due to Candida auris (CA) in Qatar. METHODS: We performed structured chart reviews on individuals with any positive CA culture between May 2019 and December 2022 at three tertiary care hospitals in Qatar. Invasive CA disease (ICAD) was defined as a positive sterile site culture, or any positive culture for CA with appropriate antifungal prescription. Main outcomes included proportion of individuals who developed ICAD among those with positive cultures, and 30-day/in-hospital mortality. RESULTS: Among 331 eligible individuals, median age was 56 years, 83.1% were male, 70.7% were non-Qataris, and 37.5% had ≥ 3 comorbidities at baseline. Overall, 86.4% were deemed to have colonization and 13.6% developed ICAD. Those with ICAD were more likely to have invasive central venous or urinary catheterization and mechanical ventilation. Individuals with ICAD had longer prior ICU stay (16 vs 26 days, P = 0.002), and longer hospital length of stay (63 vs. 43 days; P = 0.003), and higher 30-day mortality (38% vs. 14%; P<0.001). In multivariable regression analysis, only mechanical ventilation was associated with a higher risk of ICAD (OR 3.33, 95% CI 1.09-10.17). CONCLUSION: Invasive Candida auris Disease is associated with longer hospital stay and higher mortality. Severely ill persons on mechanical ventilation should be especially monitored for development of ICAD.

Antifungal drug penetration in soft tissue abscesses: a comparative analysis.

BACKGROUND: Invasive fungal infections (IFIs) are severe and difficult-to-treat infections affecting immunocompromised patients. Antifungal drug penetration at the site of infection is critical for outcome and may be difficult to achieve. Data about antifungal drug distribution in infected human tissues under real circumstances of IFI are scarce. METHODS: Multiple samples were obtained from soft tissue abscesses of a lung transplant patient with Candida albicans invasive candidiasis who underwent recurrent procedures of drainage, while receiving different consecutive courses of antifungal therapy [itraconazole (ITC), fluconazole, caspofungin]. Antifungal drug concentrations were measured simultaneously at the site of infection (surrounding inflammatory tissue and fluid content of the abscess) and in plasma for calculation of the tissue/plasma ratio (R). The concentration within the infected tissue was interpreted as appropriate if it was equal or superior to the MIC of the causal pathogen. RESULTS: A total of 30 tissue samples were collected for measurements of ITC (n = 12), fluconazole (n = 17) and caspofungin (n = 1). Variable concentrations were observed in the surrounding tissue of the lesions with median R of 2.79 (range 0.51-15.9) for ITC and 0.94 (0.21-1.37) for fluconazole. Concentrations ranges within the fluid content of the abscesses were 0.39-1.83 for ITC, 0.66-1.02 for fluconazole and 0.23 (single value) for caspofungin. The pharmacodynamic target (tissue concentration ≥ MIC) was achieved in all samples for all three antifungal drugs. CONCLUSIONS: This unique dataset of antifungal drug penetration in infected human soft tissue abscesses suggests that ITC, fluconazole and caspofungin could achieve appropriate concentrations in soft tissue abscesses.

Management of invasive candidiasis: A focus on rezafungin, ibrexafungerp, and fosmanogepix.

Management of invasive fungal infections is challenging with growing antifungal resistance. Broad antifungal use has resulted in greater intrinsic and acquired resistance among Candida spp. It is important for clinicians to recognize the relationship between host susceptibility, site of infection, Candida resistance profiles, specific drug pharmacokinetics and pharmacodynamics, and the role of novel antifungal agents. This narrative review covers the role of rezafungin, ibrexafungerp, and fosmanogepix in the management of invasive candidiasis (IC). The PubMed Database, Embase, and ClinicalTrials.gov were searched between January 2006 and January 2024 using the following terms: rezafungin, CD101, ibrexafungerp, SCY-078, fosmanogepix, APX001, candidemia, and invasive candidiasis. Review articles, prospective clinical trials, and observational studies published in the English language were reviewed. Studies evaluating pharmacology, pharmacokinetics, efficacy, and safety in animals and humans were also reviewed. Promising data continues to emerge in support of novel drug therapies for IC and candidemia. Rezafungin possesses a unique pharmacodynamic profile that might be advantageous compared to other echinocandins, with a practical, once-weekly dosing interval. Ibrexafungerp, currently approved for vulvovaginal candidiasis, has been studied off-label for use in IC and candidemia, and initial data is encouraging. Lastly, fosmanogepix, a mechanistically novel, investigational antifungal agent, may be a potential future option in the management of IC and candidemia. Future research is needed to evaluate the potential use of these agents among diverse patient populations.

Neonatal innate immunity response in invasive candidiasis.

Infections caused by Candida spp. are frequent in critically hospitalized patients, especially among premature neonates, representing one of the most common healthcare-related infections. Although there is considerable production of current knowledge about the mechanisms of immune response, aspects involved in the newborn's innate defense are not fully understood. The aim of this study was to describe the innate immune mechanisms involved in the defense of neonates against invasive candidiasis. This is an integrative literature review from the Scopus, Scifinder, Medline, Web of Science databases and the electronic libraries ScienceDirect and Scielo, in the period between 2002 and 2020, with rescue based on primary descriptor Immunity Innate plus secondary descriptors Candidiasis Invasive AND Infant Newborn. We have observed the involvement of various mechanisms in the neonatal response against invasive candidiasis, including the recognition, signaling, recruitment, and initiation of an effective immune response. These mechanisms encompass the presence of antimicrobial peptides, phagocytosis, synthesis of reactive oxygen species, inflammatory mediators, and complex cell signaling systems mediated by Pattern Recognition Receptors (PRRs). With this study, it is expected to contribute to the expansion of knowledge about the immunological mechanisms involved in the innate immune response of the newborn against disseminated infections caused by Candida species, and in the same sense, highlight the importance of this knowledge as a reflex in the decrease in mortality in the neonatal period.

Enhancing prognostic prediction of invasive candidiasis among cancer patients with a serum C5a-based scoring model.

PURPOSE: Invasive candidiasis poses a life-threatening risk, and early prognosis assessment is vital for timely interventions to reduce mortality. Serum C5a levels have recently been linked to prognosis, but confirmation in cancer patients is pending. METHODS: We detected the concentrations of serum C5a in hospitalized cancer patients with invasive candidiasis from 2020 to 2023, and retrospectively analyzed the clinical data. RESULTS: 372 cases were included in this study, with a 90-day mortality rate of 21.8%. Candida albicans (48.7%) remained the predominant pathogen, followed by Candida glabrata (25.5%), Candida tropicalis (12.4%), and Candida parapsilosis (8.3%). Gastrointestinal cancer was the most diagnosed pathology type (37.6%). Serum C5a demonstrated a noteworthy correlation with 90-day mortality, and employing a cutoff value of 36.7 ng/ml revealed significantly higher 90-day mortality in low-C5a patients (41.2%) compared to high-C5a patients (6.3%) (p < 0.001). We also identified no source control, no surgery, metastasis, or chronic renal failure independently correlated with the 90-day mortality. Based on this, a prognostic model combining C5a and clinical parameters was constructed, which performed better than models built solely on C5a or clinical parameters. Furthermore, we weighted scores to each parameter in the model and presented diagnostic sensitivity and specificity corresponding to different score points calculated by the model. CONCLUSION: We constructed a prognostic scoring model including serum C5a and clinical parameters, which would contribute to precise prognosis assessment and benefit the outcome among cancer patients.

Candida albicans cDNA library screening reveals novel potential diagnostic targets for invasive candidiasis.

The detection of patterns associated with the invasive form of Candida albicans, such as Candida albicans germ tube antibodies (CAGTA), is a useful complement to blood culture for Invasive Candidiasis (IC) diagnosis. As CAGTA are detected by a non-standardisable and non-automatable technique, a Candida albicans cDNA expression library was screened with CAGTA isolated from serum of an animal model of invasive candidiasis, and five protein targets were identified: hyphally regulated cell wall protein 1 (Hyr1), enolase 1 (Eno1), coatomer subunit gamma (Sec21), a metallo-aminopeptidase (Ape2) and cystathionine gamma-lyase (Cys3). Homology with proteins from other organisms rules out Cys3 as a good biomarker while Sec21 results suggest that it is not in the germ tubes surface but secreted to the external environment. Our analysis propose Ape2, Sec21 and a region of Hyr1 different from the one currently being studied for immunoprotection as potential biomarker candidates for the diagnosis of IC.

Pore-forming peptide C14R exhibits potent antifungal activity against clinical isolates of Candida albicans and Candida auris.

Introduction: Invasive candidiasis is a global public health problem as it poses a significant threat in hospital-settings. The aim of this study was to evaluate C14R, an analog derived from peptide BP100, as a potential antimicrobial peptide against the prevalent opportunistic yeast Candida albicans and the emergent multidrug-resistant yeast Candida auris. Methods: Antifungal susceptibility testing of C14R against 99 C. albicans and 105 C. auris clinical isolates from Colombia, was determined by broth microdilution. Fluconazole was used as a control antifungal. The synergy between C14R and fluconazole was assessed in resistant isolates. Assays against fungal biofilm and growth curves were also carried out. Morphological alterations of yeast cell surface were evaluated by scanning electron microscopy. A permeability assay verified the pore-forming ability of C14R. Results: C. albicans and C. auris isolates had a geometric mean MIC against C14R of 4.42 µg/ml and 5.34 µg/ml, respectively. Notably, none of the isolates of any species exhibited growth at the highest evaluated peptide concentration (200 µg/ml). Synergistic effects were observed when combining the peptide and fluconazole. C14R affects biofilm and growth of C. albicans and C. auris. Cell membrane disruptions were observed in both species after treatment with the peptide. It was confirmed that C14R form pores in C. albicans' membrane. Discussion: C14R has a potent antifungal activity against a large set of clinical isolates of both C. albicans and C. auris, showing its capacity to disrupt Candida membranes. This antifungal activity remains consistent across isolates regardless of their clinical source. Furthermore, the absence of correlation between MICs to C14R and resistance to fluconazole indicates the peptide's potential effectiveness against fluconazole-resistant strains. Our results suggest the potential of C14R, a pore-forming peptide, as a treatment option for fungal infections, such as invasive candidiasis, including fluconazole and amphotericin B -resistant strains.

Risk Factors for Invasive Candidiasis in Critically Ill Patients Who Underwent Emergency Gastrointestinal Surgery for Complicated Intra-Abdominal Infection.

Background: Candida species account for approximately 15% of hospital-associated infections, causing fatal consequences, especially in critically ill patients. This study aimed to evaluate invasive candidiasis (IC) risk factors in critically ill patients undergoing surgery. Patients and Methods: We retrospectively reviewed the medical records of 583 patients who underwent emergency surgery for complicated intra-abdominal infections between January 2016 and December 2021. Patients were divided into two groups according to the presence or absence of IC during their hospital stay. IC was defined as culture-proven candidemia and intra-abdominal candidiasis. Results: This study included 373 patients for the final analysis, of whom 320 were discharged without IC (IC absent group) and 53 presented with IC (IC present group) during their hospital stay. The IC present group showed a higher in-hospital mortality rate (35.8 vs. 8.8%; p < 0.001), with 66.0% of the patients diagnosed within 10 days, whereas only 6.5% were diagnosed beyond 20 days after admission. Stomach (odds ratio [OR], 4.188; 95% confidence interval [CI], 1.204-14.561; p = 0.024) and duodenum (OR, 7.595; 95% CI, 1.934-29.832; p = 0.004) as infection origin, higher Acute Physiology and Chronic Health Evaluation II (APACHE II) score (OR, 1.097; 95% CI, 1.044-1.152; p < 0.001), and lower initial systolic blood pressure (OR, 0.983; 95% CI, 0.968-0.997; p = 0.018) were risk factors of IC after emergency gastrointestinal surgery. Conclusions: Patients who had stomach and duodenum as infection origin, higher APACHE II scores, and lower initial systolic blood pressure had a higher risk of developing IC during their hospital stay after emergency gastrointestinal surgery. Prophylactic antifungal agents can be carefully considered for critically ill patients with these features.

Correlation between antifungal clinical practices and a new clinical decision support system ANTIFON-CLIC® for the treatment of invasive candidiasis: a retrospective multicentre study.

BACKGROUND: Invasive candidiasis is still recognized as a major cause of morbidity and mortality. To support clinicians in the optimal use of antifungals for the treatment of invasive candidiasis, a computerized decision support system (CDSS) was developed based on institutional guidelines. OBJECTIVES: To evaluate the correlation of this newly developed CDSS with clinical practices, we set-up a retrospective multicentre cohort study with the aim of providing the concordance rate between the CDSS recommendation and the medical prescription (NCT05656157). PATIENTS AND METHODS: Adult patients who received caspofungin or fluconazole for the treatment of an invasive candidiasis were included. The analysis of factors associated with concordance was performed using mixed logistic regression models with department as a random effect. RESULTS: From March to November 2022, 190 patients were included from three centres and eight departments: 70 patients from centre A, 84 from centre B and 36 from centre C. Overall, 100 patients received caspofungin and 90 received fluconazole, mostly (59%; 112/190) for empirical/pre-emptive treatment. The overall percentage of concordance between the CDSS and medical prescriptions was 91% (173/190) (confidence interval 95%: 82%-96%). No significant difference in concordance was observed considering the centres (P > 0.99), the department of inclusion (P = 0.968), the antifungal treatment (P = 0.656) or the indication of treatment (P = 0.997). In most cases of discordance (n = 13/17, 76%), the CDSS recommended fluconazole whereas caspofungin was prescribed. The clinical usability evaluated by five clinicians was satisfactory. CONCLUSIONS: Our results demonstrated the high correlation between current antifungal clinical practice and this user-friendly and institutional guidelines-based CDSS.

First imported case of Candida auris infection in Milan, Italy: genomic characterisation.

PURPOSE: Candida auris, an emerging multidrug-resistant yeast, has been reported worldwide. In Italy, the first case was reported in 2019. We describe the first case of C. auris, imported from Greece, in Milan, using whole genome sequencing to characterise mutations associated with antifungal resistance. CASE PRESENTATION: On October 2022 an 80-year-old Italian man was hospitalised in Greece. In the absence of clinical improvement, the patient was transferred to our hospital, in Italy, where blood culture resulted positive for C. auris. Despite therapy, the patient died of septic shock. In a phylogenetic analysis the genome was assigned to Clade I with strains from Kenya, United Arab Emirates and India. D1/D2 region resulted identical to a Greek strain, as for many other strains from different World regions, highlighting the diffusion of this strain. CONCLUSION: Importation of C. auris from abroad has been previously described. We report the first case of C. auris imported into Italy from Greece, according to phylogenetic analysis. This case reinforces the need for monitoring critically ill hospitalised patients also for fungi and addresses the need for the standardisation of susceptibility testing and strategies for diagnosis and therapy.

Invasive candidiasis.

Invasive candidiasis is an important fungal disease caused by Candida albicans and, increasingly, non-albicans Candida pathogens. Invasive Candida infections originate most frequently from endogenous human reservoirs and are triggered by impaired host defences. Signs and symptoms of invasive candidiasis are non-specific; candidaemia is the most diagnosed manifestation, with disseminated candidiasis affecting single or multiple organs. Diagnosis poses many challenges, and conventional culture techniques are frequently supplemented by non-culture-based assays. The attributable mortality from candidaemia and disseminated infections is ~30%. Fluconazole resistance is a concern for Nakaseomyces glabratus, Candida parapsilosis, and Candida auris and less so in Candida tropicalis infection; acquired echinocandin resistance remains uncommon. The epidemiology of invasive candidiasis varies in different geographical areas and within various patient populations. Risk factors include intensive care unit stay, central venous catheter use, broad-spectrum antibiotics use, abdominal surgery and immune suppression. Early antifungal treatment and central venous catheter removal form the cornerstones to decrease mortality. The landscape of novel therapeutics is growing; however, the application of new drugs requires careful selection of eligible patients as the spectrum of activity is limited to a few fungal species. Unanswered questions and knowledge gaps define future research priorities and a personalized approach to diagnosis and treatment of invasive candidiasis is of paramount importance.