Genotypic and phenotypic characteristics of Candida parapsilosis bloodstream isolates: Health Care Associated Infections in a teaching Hospital in Italy.

BACKGROUND: Candidemia is the most common healthcare associated invasive fungal infection. Over the last few decades, candidemia caused by Candida species other than Candida albicans, particularly the Candida parapsilosis complex, has emerged worldwide. The aims of this study were: to analyze the genotypic and phenotypic characteristics of C. parapsilosis strains isolated from blood cultures and the environment in a hospital in southern Italy, to study the possible source of infection and to correlate the isolated strains. METHODS: From April to October 2022, cases of candidemia due to C. parapsilosis in patients admitted to a hospital in the Apulia region were investigated. However, 119 environmental samples from the intensive care unit were collected for identification of the likely environmental reservoir of infection. Routine antifungal (amphotericin B, anidulafungin, fluconazole) susceptibility was performed on all isolates. Whole genome sequencing was performed to study the genotypic correlation of the isolates. Biofilm biomass and metabolic activity were also quantified for all isolates. RESULTS: A total of 43 C. parapsilosis isolates were cultured from the bloodstream of each patient in different departments, and seven surface samples were positive for C. parapsilosis. Most of the isolated yeasts (41/50; 85 %) were resistant to fluconazole and were genetically related to each other, suggesting an ongoing clonal outbreak of this pathogen. The fluconazole-susceptible isolates produced significantly more biofilm than did the resistant isolates. Metabolic activity was also higher for fluconazole-susceptible than resistant isolates. CONCLUSION: Cross-transmission of the microorganisms is suggested by the phenotypic similarity and genetic correlation between clinical and environmental strains observed in our study.

Risk factors and mortality of candidemia in a children's public hospital in Sao Paulo, Brazil.

Candida bloodstream infections in children are of special concern in neonatal and pediatric intensive care and patients with comorbidities. This study aimed to estimate the incidence and risk factors associated with mortality in candidemia cases occurring in a public children's hospital in Ribeirao Preto, Brazil. It is a retrospective transversal study. Every patient under the age of 18 admitted to the study facility from January 1, 2013, to December 31, 2019, was considered potentially eligible to be included if they had candidemia. We collected clinical data from medical records. We included 113 blood cultures yielding positive results for Candida. The incidence rate was 2.12 per 1000 admissions. The most common Candida species was Candida parapsilosis. Septic shock during the candidemia episode was the only clinical outcome associated with a relative risk-adjusted (RRa) of 2.77 with an interval >1 (1.12-6.85). Our findings show that the incidence rate and mortality rates of candidemia are in line with those in other children's services in Brazil. We found a global mortality rate of 28.31% (32/113) from candidemia episodes. We highlight the predominance of non-albicans Candida species including C. parapsilosis. Septic shock was the most important factor showing a significant risk of mortality.

Comparison of fungemia caused by Candida and non-Candida rare yeasts: a retrospective study from a tertiary care hospital.

Although Candida species are the most common cause of fungemia, non-Candida rare yeasts (NCY) have been increasingly reported worldwide. Although the importance of these yeast infections is recognized, current epidemiological information about these pathogens is limited and they have variable antifungal susceptibility profiles. In this study, we aimed to evaluate the clinical characteristics for fungemia caused by NCY by comparing with candidemia. The episodes of NCY fungemia between January 2011 and August 2023 were retrospectively evaluated in terms of clinical characteristics, predisposing factor and outcome. In addition, a candidemia group including the patients in the same period was conducted for comparison. Antifungal susceptibility tests were performed according to reference method. A total of 85 patients with fungemia episodes were included; 25 with NCY fungemia, 60 with candidemia. Fluconazole had high minimal inhibitory concentration (MIC) values against almost all NCY isolates. The MIC values for voriconazole, posaconazole and amphotericin B were ≤ 2 µg/ml and for caspofungin and anidulafungin were ≥ 1 µg/ml against most of isolates. Hematological malignancies, immunosuppressive therapy, neutropenia and prolonged neutropenia, polymicrobial bacteremia/fungemia, preexposure to antifungal drugs and breakthrough fungemia were associated with NCY fungemia, whereas intensive care unit admission, diabetes mellitus, urinary catheters and total parenteral nutrition were associated with candidemia. In conclusion, the majority of fungemia due to NCY species were the problem particularly in hematology units and patients with hematological malignancy. Preexposure to antifungal drugs likely causes a change in the epidemiology of fungemia in favor of non-albicans Candida and/or NCY.

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.

Is the T2 magnetic resonance imaging Candida panel a suitable alternative to the SeptiFast for the rapid diagnosis of candidemia in routine clinical practice?

OBJECTIVES: The diagnosis of invasive Candida infection remains challenging because of tests with slow turnaround times or mediocre performance. T2magnetic resonance imaging is a new diagnostic tool. We investigated the diagnostic accuracy of the T2Candida panel (T2) in comparison with blood culture (BC) and the SeptiFast (SF) for the detection of five different Candida species among high-risk intensive care unit patients with suspected candidemia. METHODS: We analysed blood samples collected from patients with suspected candidemia (177 samples from 138 patients) from August 2018 to April 2020. Blood samples were collected and analysed concurrently by BC, SF, and T2Candida. Subsequently, based on clinical and microbiological findings, patient samples were assigned to specific risk categories (proven, probable, and no candidemia). RESULTS: Twenty-two samples from 17 patients were classified as proven candidemia, and 15 samples from 14 patients were classified as probable candidemia. A sensitivity of 68.2% (95% CI, 45-86%) was observed for the BC and the SF, and a sensitivity of 63.6% (95% CI, 41-83%) was observed for the T2 when only cases with proven candidemia were evaluated. For proven and probable candidemia, the sensitivity was 40.5% (95% CI, 23-58%) for BC, 81.1% (95% CI, 65-92%) for SF, and 73.0% (95% CI, 56-86%) for T2. DISCUSSION: The diagnostic performance of SF and T2 was similar. For samples with proven/probable candidemia, SF and T2 had a higher sensitivity compared to BC. Used in conjunction with other diagnostic methods, T2 can replace the no longer available SF for the diagnosis of candidemia, enabling the timely initiation of targeted antifungal therapy.

COVID-19 associated candidemia: From a shift in fungal epidemiology to a rise in azole drug resistance.

Our understanding of fungal epidemiology and the burden of antifungal drug resistance in COVID-19-associated candidemia (CAC) patients is limited. Therefore, we conducted a retrospective multicenter study in Iran to explore clinical and microbiological profiles of CAC patients. Yeast isolated from blood, were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and subjected to antifungal susceptibility testing (AFST) using the broth microdilution method M27-A3 protocol. A total of 0.6% of the COVID-19 patients acquired CAC (43/6174). Fluconazole was the most widely used antifungal, and 37% of patients were not treated. Contrary to historic candidemia patients, Candida albicans and C. tropicalis were the most common species. In vitro resistance was high and only noted for azoles; 50%, 20%, and 13.6% of patients were infected with azole-non-susceptible (ANS) C. tropicalis, C. parapsilosis, and C. albicans isolates, respectively. ERG11 mutations conferring azole resistance were detected for C. parapsilosis isolates (Y132F), recovered from an azole-naïve patient. Our study revealed an unprecedented rise in ANS Candida isolates, including the first C. parapsilosis isolate carrying Y132F, among CAC patients in Iran, which potentially threatens the efficacy of fluconazole, the most widely used drug in our centers. Considering the high mortality rate and 37% of untreated CAC cases, our study underscores the importance of infection control strategies and antifungal stewardship to minimize the emergence of ANS Candida isolates during COVID-19.

The impact of the fluconazole trailing effect on the persistence of Candida albicans bloodstream infection when treated with fluconazole.

OBJECTIVES: The trailing effect of Candida species is a phenomenon characterized by reduced but persistent growth at antifungal concentrations above the MIC. We assessed the impact of trailing growth on the persistence of Candida albicans candidemia in patients receiving fluconazole (FLC) therapy. METHODS: We retrospectively investigated candidemia isolates at three hospitals in southern Taiwan between 2013 and 2020. Patients treated with FLC for FLC-susceptible C. albicans candidemia were enrolled. The degree of trailing was determined as the average growth above the MIC divided by the measured growth at the lowest drug concentration using the EUCAST method and classified into four categories: residual (0.1-5%), slight (6-10%), moderate (11-15%), and heavy trailers (>15%). RESULTS: Among isolates from 190 patients, the proportions of heavy trailers at 24 hours, 48 hours, and 72 hours were 63.7% (121/190), 63.2% (120/190), and 74.7% (142/190), respectively. Persistent candidemia was observed in 17 (8.9 %) patients. The proportion of persistent C. albicans candidemia in heavy trailing isolates at 48 hours was higher than in isolates without heavy trailing (13.3% [16/120] vs. 1.4% [1/70], p = 0.007). A multivariate analysis showed that immunosuppression (OR = 7.92; 95% CI: 2.38-26.39, p = 0.001), hospitalization days after the index date of C. albicans identification (OR = 1.03; 95% CI: 1.01-1.05, p = 0.011), and heavy trailing isolates at 48 hours (OR = 10.04; 95% CI: 1.27-79.88, p = 0.029) were independent factors for persistent candidemia. DISCUSSION: The current study revealed that heavy trailing in C. albicans isolates is associated with persistent candidemia in patients receiving FLC treatment.

Lower (1,3)-beta-d-glucan sensitivity and in vitro levels in Candida auris and Candida parapsilosis strains.

OBJECTIVES: The serum (1,3)-beta-d-glucan (BDG) assay gives quicker results and has higher sensitivity than blood cultures, therefore it is advised for early diagnosis of invasive candidemia and/or discontinuation of empirical therapy. Its sensitivity may depend on different factors. The aim of our study was to analyse the in vitro and in vivo BDG levels in clinical isolates of three species of Candida responsible for candidemia. METHODS: C. albicans, C. parapsilosis, and C. auris strains were collected from blood cultures of patients who had a concurrent (-1 to +3 days) serum BDG test (Fungitell assay). Supernatants of all strains were tested in quadruplicate for BDG levels. RESULTS: Twenty-two C. auris, 14 C. albicans, and ten C. parapsilosis strains were included. The median BDG levels in supernatants were 463 pg/mL (interquartile range [IQR] 379-648) for C. auris, 1080 pg/mL (IQR 830-1276) for C. albicans, and 755 pg/mL (IQR 511-930) for C. parapsilosis, with the significant difference among the species (p < 0.0001). Median serum BDG levels (IQR) were significantly lower in case C. auris and C. parapsilosis vs. C. albicans (p < 0.0001), respectively, 50 pg/mL (IQR 15-161) and 57 pg/mL (IQR 18-332), vs. 372 pg/mL (IQR 102-520). Sensitivity of serum BDG was 39% (95% confidence interval [CI], 18-64) in case of C. auris, 30% (95% CI, 8-65) C. parapsilosis and 78% (95% CI, 49-94) C. albicans candidemia. DISCUSSION: In our centre C. auris and C. parapsilosis strains have lower BDG content as compared with C. albicans, with a potential impact on serum BDG performance for the diagnosis of candidemia.

Regulatory Considerations in the Approval of Rezafungin (REZZAYO) for the Treatment of Candidemia and Invasive Candidiasis in Adults.

On March 22, 2023, the FDA approved rezafungin (REZZAYO) for the treatment of candidemia and invasive candidiasis in adults with limited or no alternative treatment options. Rezafungin is an echinocandin that supports weekly dosing, enabling outpatient parenteral treatment that potentially avoids the need for a central venous catheter. Approval of rezafungin was based on a single adequate and well-controlled phase 3 study designed with a Day 30 all-cause mortality primary endpoint and 20% noninferiority margin, which demonstrated that rezafungin is noninferior to the comparator echinocandin. Nonclinical studies of rezafungin in non-human primates identified a neurotoxicity safety signal; however, rezafungin's safety profile in the completed clinical studies was similar to other FDA-approved echinocandins. Here we describe the rationale for this approval and important considerations during the review process for a flexible development program intended to expedite the availability of antimicrobial therapies to treat serious infections in patients with limited treatment options.

An evaluation of Rezafungin: the latest treatment option for adults with candidemia and invasive candidiasis.

INTRODUCTION: Invasive fungal infections, especially candidemia and invasive candidiasis, continue to cause substantial morbidity and mortality. In addition, the emergence of drug-resistant Candida species, notably C. glabrata and C. auris, along with limitations in available treatments, highlights the urgent need for novel, effective antifungal agents. AREAS COVERED: This review discusses the results of in vitro studies evaluating the spectrum and highlights the pharmacokinetic/pharmacodynamic properties. It also includes discussions on two key clinical studies that assess safety, tolerability, and efficacy. EXPERT OPINION: Rezafungin has demonstrated comparable efficacy to other echinocandins in two clinical studies and exhibits in vitro activity against a broad range of Candida species and Aspergillus spp. It has a favorable safety profile with minimal side effects, and no drug interactions or effects on QT intervals. In contrast to other echinocandins, it demonstrates dose-dependent killing, a prolonged half-life, and low clearance make it suitable for once-weekly dosing, which is supported by clinical trials confirming its efficacy. Rezafungin offers a promising option for the outpatient management of difficult to treat fungal infections. It has become a valuable addition to the antifungal arsenal, with the potential to reduce hospital length of stay and hospitalization costs and combat drug-resistant Candida species.

Changing Epidemiology of Clinical Isolates of Candida Species during the Coronavirus Disease 2019 Pandemic: Data Analysis from a Korean Tertiary Care Hospital for 6 Years (2017-2022).

This study assessed the changes in Candida species distribution and antifungal susceptibility patterns during the coronavirus disease 2019 (COVID-19) pandemic compared with a pre-pandemic period in Korea. We retrospectively investigated the specimen, species type, and antifungal susceptibility of Candida isolates obtained between 2016 and 2022. Data between two periods were compared: 2016-2019 (pre-pandemic) and 2020-2022 (pandemic). We included 11,396 clinical isolates of Candida species (5137 isolates in the pre-pandemic and 6259 isolates in the pandemic). The most prevalent species was Candida albicans (50.4%), followed by Candida glabrata (22.7%), Candida tropicalis (12.5%), and Candida parapsilosis complex (12.5%). Their ranks were unchanged; however, their relative isolation ratios varied during the pandemic, exhibiting differences ranging from 0.4 to 2.5 across species. The incidence of candidemia increased during the pandemic (average 1.79 episodes per 10,000 patient days) compared with pre-pandemic levels (average 1.45 episodes per 10,000 patient days) in both intensive-care-unit (ICU) and non-ICU patients. Additionally, C. parapsilosis complex candidemia increased by 1.6-fold during the pandemic. During the pandemic, C. albicans and C. tropicalis candidemia significantly increased by 1.5- and 1.4-fold in ICU patients. In contrast, C. parapsilosis complex candidemia surged 2.1-fold in non-ICU patients. These species exhibited reduced resistance to fluconazole, voriconazole, caspofungin, and micafungin in the pandemic compared with the pre-pandemic. This study underscores the heightened incidence of Candida-related infections during the COVID-19 pandemic and emphasizes the importance of ongoing surveillance of Candida species epidemiology beyond the pandemic's scope.

Systemic Candida Infection and Pulmonary Aspergillosis in an Alpaca (Vicugna pacos): A Case Report.

This study reports a peculiar case of systemic candidiasis infection associated with pulmonary aspergillosis in an apparently immunocompetent alpaca. A captive 7-year-old female alpaca exhibited respiratory symptoms, underwent treatment with benzylpenicillin and dexamethasone, and succumbed to the infection 40 days later. During the post-mortem examination, subcutaneous emphysema, widespread pneumonia with multiple suppurative foci, scattered necro-suppurative lesions throughout the renal and hepatic parenchyma were evident. Histopathological analysis of the collected tissues revealed multifocal mild lymphoplasmacytic chronic interstitial nephritis, necro-suppurative pneumonia with the presence of fungal hyphae, multifocal foci of mineralization, and fibrosis in the liver. Fungal cultures confirmed the growth of Aspergillus fumigatus from the lungs, and Candida albicans from the liver, kidney, and heart. The only recognizable risk factor for candidiasis and pulmonary aspergillosis in this case was prior corticosteroid and antibiotic therapy. Nevertheless, it is crucial to consider systemic candidosis and pulmonary aspergillosis as potential differential diagnoses in respiratory infections among camelids. Prolonged treatment with glucocorticoids and antibiotics should be avoided as it could represent a risk factor for the onset of pathologies caused by opportunistic fungi such as Candida spp. and Aspergillus spp.

Outcomes by Candida spp. in the ReSTORE Phase 3 trial of rezafungin versus caspofungin for candidemia and/or invasive candidiasis.

Rezafungin is a long-acting, intravenously administered echinocandin for the treatment of candidemia and invasive candidiasis (IC). Non-inferiority of rezafungin vs caspofungin for the treatment of adults with candidemia and/or IC was demonstrated in the Phase 3 ReSTORE study based on the primary endpoints of day 14 global cure and 30-day all-cause mortality. Here, an analysis of ReSTORE data evaluating efficacy outcomes by baseline Candida species is described. Susceptibility testing was performed for Candida species using the Clinical and Laboratory Standards Institute reference broth microdilution method. There were 93 patients in the modified intent-to-treat population who received rezafungin; 94 received caspofungin. Baseline Candida species distribution was similar in the two treatment groups; C. albicans (occurring in 41.9% and 42.6% of patients in the rezafungin and caspofungin groups, respectively), C. glabrata (25.8% and 26.6%), and C. tropicalis (21.5% and 18.1%) were the most common pathogens. Rates of global cure and mycological eradication at day 14 and day 30 all-cause mortality by Candida species were comparable in the rezafungin and caspofungin treatment groups and did not appear to be impacted by minimal inhibitory concentration (MIC) values for either rezafungin or caspofungin. Two patients had baseline isolates with non-susceptible MIC values (both in the rezafungin group: one non-susceptible to rezafungin and one to caspofungin, classified as intermediate); both were candidemia-only patients in whom rezafungin treatment was successful based on the day 30 all-cause mortality endpoint. This analysis of ReSTORE demonstrated the efficacy of rezafungin for candidemia and IC in patients infected with a variety of Candida species.

Risk factors associated with fluconazole resistance in Candida parapsilosis candidemia: A case-case study.

BACKGROUND: Candida species are among the most important invasive pathogens in intensive care units (ICUs). Non-albicans species including Candida parapsilosis (C. parapsilosis) has increased in recent years. Fluconazole is the leading antifungal agent but resistance is a concern among C. parapsilosis species. OBJECTIVES: The aim of this study was to determine the factors associated with fluconazole resistance in patients with candidemia due to C. parapsilosis in ICUs. METHODS: This case-case study was conducted in a 750-bed, tertiary hospital between 2015 and 2021. Patients with fluconazole-resistant C. parapsilosis candidemia constituted the 'cases of interest' group and patients with fluconazole-susceptible C. parapsilosis candidemia constituted the 'comparison cases' group. Demographic and clinical data of the patients were recorded. Logistic regression analysis was performed using the backward elimination method to determine the independent predictors of fluconazole-resistant C. parapsilosis bloodstream infections. RESULTS: The study included 177 patients. In the cultures of these patients, 76 (43%) fluconazole-resistant, 13 (7.3%) fluconazole-reduced susceptible, and 88 (49.7%) fluconazole-susceptible isolates were found. In the regression analysis the risk factors for fluconazole-resistant C. parapsilosis bloodstream infection, malignancy, immunosuppressive treatment, history of intra-abdominal surgery, hypoalbunemia, previous fluconazole use, and SOFA score were found to be associated in univariate analysis. In multivariate regression analysis, history of intra-abdominal surgery (OR: 2.16; 95% CI: 1.05-4.44), hypoalbuminemia (OR: 2.56; 95% CI: 1.06-6.17) and previous fluconazole use (OR: 3.35; 95% CI: 1.02-11) were found to be independent predictors. CONCLUSIONS: In this study, a significant correlation was found between candidemia due to fluconazole-resistant C. parapsilosis in ICUs and intra-abdominal surgery, hypoalbuminemia, and previous fluconazole use. C. parapsilosis isolates and fluconazole resistance should be continuously monitored, strict infection control measures should be taken and antifungal stewardship programs should be implemented.

Candidemia in critically ill COVID-19 patients: Risk factors and impact on mortality.

Background: Risk factors of candidemia are well-described in intensive care units (ICUs) before the Coronavirus disease 2019 (COVID-19) pandemic. The increased rates of admission to ICUs have appeared during the pandemic. Methods: Patient characteristics and laboratory data of 80 candidemia with COVID-19, 101 candidemia without COVID-19, and 100 non-candidemia with COVID-19 patients were evaluated, in this study. Results: Systemic inflammatory response syndrome (SIRS) ≥ 2, solid malignancy, total parenteral nutrition (TPN), central venous catheterization (CVC), hypotension, fever, urea, alanine aminotransferase (ALT), D-dimer, procalcitonin, ferritin, and delta neutrophil index (DNI) was found to be associated with candidemia in COVID-19 patients. TPN, hypotension, and fever were identified as independent predictors of candidemia in COVID-19, and candidemia in COVID-19 is characterized by significantly high mortality rates. Urea, lactate, and procalcitonin were defined as independent predictors of hospital mortality in candidemia patients with COVID-19. Conclusion: The presence of candidemia increases mortality in COVID-19. TPN, fever, and hypotension werefound to be the most powerful predictors of candidemia in COVID-19. Overall, these data show that candidemia in COVID-19 is characterized by significantly high mortality rates. Determination of distinctive features can prevent candidemia and mortality.

Unresolved issues in the diagnosis of catheter related candidemia: A position paper / Cuestiones no resueltas en el diagnóstico de la candidemia relacionada con el catéter: un documento de opinión

The incidence and recent trends of candidemia and the contribution of the COVID-19 pandemic to its evolution are not well documented. The catheter is a major focus of Candida spp. infections, but the methods used to confirm the origin of candidemia are still based on the data generated for bacterial infection. The presence of Candida spp. on the tip of a removed catheter is the gold standard for confirmation but it is not always possible to remove it. Conservative methods, without catheter removal, have not been specifically studied for microorganisms whose times of growth are different from those of bacteria and therefore these results are not applicable to candidemia. The different Candida species do not have a particular tropism for catheter colonization and fungal biomarkers have not yet been able to contribute to the determination of the origin of candidemia. Techniques such Candida T2 Magnetic Resonance (T2MR) has not yet been applied for this purpose. Finally, there is not yet a consensus of how to proceed when Candida spp. is isolated from an extracted catheter and blood cultures obtained from simultaneous peripheral veins are negative. In this lack of firm data, a group of experts has formulated a series of questions trying to answer them based on the literature, indicating the current deficiencies and offering their own opinion. All authors agree with the conclusions of the manuscript and offer it as a position and discussion paper. (AU)

La incidencia y las tendencias recientes de la candidemia y la contribución de la pandemia de COVID-19 a su evolución no están bien documentadas. El catéter es uno de los principales focos de infecciones por Candida spp., pero los métodos empleados para confirmar el origen de la candidemia siguen basándose en los datos generados para la infección bacteriana. La presencia de Candida spp. en la punta de un catéter retirado es el método de referencia para la confirmación, pero no siempre es posible proceder a dicha retirada. Los métodos conservadores, sin retirada del catéter, no han sido estudiados específicamente para microorganismos cuyos tiempos de crecimiento son diferentes a los de las bacterias y, por tanto, estos resultados no son aplicables a la candidemia. Las diferentes especies de Candida spp. no tienen un tropismo particular para la colonización del catéter y los biomarcadores fúngicos, aún no han podido contribuir a la determinación del origen de la candidemia. Técnicas como la resonancia magnética T2MR todavía no se ha empleado para este fin. Por último, todavía no existe un consenso sobre cómo proceder cuando se aísla Candida spp. en un catéter extraído y los hemocultivos obtenidos por venas periféricas simultáneas son negativos. Ante esta falta de datos firmes, un grupo de expertos ha formulado una serie de preguntas y ha tratado de responderlas en base a la literatura, indicando las carencias presentes y ofreciendo su propia opinión. Todos los autores están de acuerdo con las conclusiones del manuscrito y lo ofrecen como documento de posición y discusión. (AU)

First report of Candida auris in Guangdong, China: clinical and microbiological characteristics of 7 episodes of candidemia.

Candida auris is an emerging multidrug-resistant fungal pathogen worldwide. To date, it has not been reported in Guangdong, China. For the first time, we reported 7 cases of C. auris candidemia from two hospitals in Guangdong. The clinical and microbiological characteristics of these cases were investigated carefully. Two geographic clades, i.e. III and I, were found popular in different hospitals by whole genome sequencing analyses. All C. auris isolates from bloodstream were resistant to fluconazole, 5 of which belonged to Clade III harbouring VF125AL mutation in the ERG11 gene. The isolates with Clade I presented Y132F mutation in the ERG11 gene as well as resistance to amphotericin B. All isolates exhibited strong biofilm-forming capacity and non-aggregative phenotype. The mean time from admission to onset of C. auris candidemia was 39.4 days (range: 12 - 80 days). Despite performing appropriate therapeutic regimen, 42.9% (3/7) of patients experienced occurrences of C. auris candidemia and colonization after the first positive bloodstream. C. auris colonization was still observed after the first C. auris candidemia for 81 days in some patient. Microbiologic eradication from bloodstream was achieved in 85.7% (6/7) of patients at discharge. In conclusion, this study offers a crucial insight into unravelling the multiple origins of C. auris in Guangdong, highlighting great challenges in clinical prevention and control.

Healthcare Resource Utilization and Discharge Readiness in Adult Hospitalized Patients With Candidemia or Invasive Candidiasis Who Received an Echinocandin: An Analysis of United States Hospitals.

Background: Scant real-world outcomes data are available among hospitalized patients with candidemia (C) or invasive candidiasis without candidemia (IC) who were treated with an echinocandin and few have assessed if there is an opportunity to accelerate the transition of their care to the outpatient setting. This study described the outcomes associated with echinocandin therapy for C/IC and determined the proportion of patients on an echinocandin at hospital discharge (HD) who were potentially eligible for an earlier HD. Methods: A retrospective, multicenter observational study was performed using the PINC AI Healthcare Database (January 2016-April 2019) of hospitalized adult patients with C/IC who received ≥3 days of an echinocandin. Outcomes included post-index culture hospital costs and discharge location. Patients were considered potentially dischargeable earlier than actual HD day if they met the following 3 criteria prior to their actual HD day: resided on a non-intensive care unit hospital ward until HD, received any oral medications, and had no diagnostic/therapeutic interventions. Results: A total of 1865 patients met study criteria. Mean (standard deviation) post-index culture hospital costs for patients with C and IC were 50 196 (64 630) US dollars and 61 551 (73 080) US dollars, respectively. Of the 1008 patients on an echinocandin near HD and discharged alive, 432 (42.9%) were potentially dischargeable prior to their actual hospital day. Most patients (35.8%) were discharged to a long-term care facility. Conclusions: The findings suggest that a high proportion of hospitalized C/IC patients receiving an echinocandin near the time of HD were potentially dischargeable earlier. Like all studies of this nature, the findings need to be prospectively validated.

Molecular typing and antifungal susceptibility profile of Candida krusei bloodstream isolates from Türkiye.

Candida krusei also known as Pichia kudriavzevii is a potentially multidrug-resistant yeast because it is intrinsically resistant to fluconazole and develops acquired resistance to echinocandins and polyenes. Here, we aim to provide a better understanding of the epidemiology and transmission modes of C. krusei infections by comparing invasive bloodstream (n = 35) and non-invasive vaginal (n = 20) C. krusei isolates. The genetic relatedness of the isolates was assessed using a newly described short tandem repeat (STR) analysis and their sensitivity to eight antifungal compounds was evaluated by antifungal susceptibility testing using the CLSI microbroth dilution method. All C. krusei isolates revealed unique STR genotypes, indicating the absence of clonal transmission in the study group. Furthermore, no drug-resistant or non-wild-type isolates were identified. Our findings demonstrated high resolution of STR genotyping for the detection and simultaneous genetic analysis of multiple C. krusei strains in clinical samples and excellent in vitro activity of common antifungal agents against invasive strains.

Elevated serum level of progranulin is associated with increased mortality in critically ill patients with candidemia.

Candidemia is a severe disease with high mortality in both intensive care unit (ICU) and non-ICU settings. Considering that progranulin (PGRN) is a potential therapeutic target for the candidemia caused by Candida albicans, we determined the serum level of PGRN after candidemia and evaluated its association with mortality. A retrospective discovery cohort (62 patients) and a validation cohort (70 patients) were enrolled. Blood was collected on day of first blood culture positivity for C. albicans, and serum PGRN levels were then measured. In the discovery cohort, all serum PGRN studied were expressed at higher levels in candidemia patients than in bacteremia patients and healthy volunteers, non-survivors presented with significantly higher serum PGRN concentrations when compared with survivors. Serum PGRN concentration was associated with 30-day mortality and patients at a higher risk of death showed higher serum PGRN levels. These results were confirmed in the independent validation cohort. Interestingly, in vitro study demonstrated that macrophages, neutrophils and lymphocytes may be the major source of PGRN production after C. albicans infection instead of epithelial cells. Our findings highlight that serum PGRN appears as a biomarker in candidemia patients and as a promising tool for mortality risk stratification in managing candidemia.