Antifungal susceptibility and virulence determinants profile of candida species isolated from patients with candidemia.

Candida is the most prevalent fungal bloodstream infection (BSI) with a high mortality rate among hospitalized patients. Another concern facing physicians is rising global incidence of drug-resistant Candida. This study aimed to characterize the prevalence, antifungal susceptibility, biofilm formation, and virulence genes (HWP1, ALS1, SAP2) of different Candida spp. isolated from patients with candidemia. 52 isolates of Candida spp. were identified from blood cultures by chromogenic Candida agar and confirmed by the VITEK 2 system. Isolates were tested for antifungal susceptibility by disk diffusion and VITEK 2 system. Biofilm formation and investigated genes were detected by the Congo red method and conventional PCR, respectively. Candida spp. caused 2.3% of detected BSIs, of which 32.7% were caused by Candida albicans (C. albicans) and 67.3% by non-albicans Candida (NAC), with the predominance of C. tropicalis (25%), followed by C. parapsilosis (17.3%), and C. krusei (13.5%). The susceptibility rates to fluconazole, voriconazole, caspofungin, micafungin, amphotericin B, and flucytosine were 64.7%, 76.5%, 100.0%, 100%, 100.0%, and 100.0% in C. albicans, while 53.6%, 71.4%, 91.4%, 91.4%, 94.3%, and 94.3% in NAC, respectively. Biofilm production, HWP1, ALS1, and SAP2 were detected in 70.6%, 82.4%, 76.5%, and 52.9% of C. albicans and 74.3%, 85.7%, 80.0%, and 48.6% of NAC, respectively. There is remarkable shift to NAC BSIs and high azole resistance. Antifungal stewardship and analysis of risk factors associated with this shift are needed.

Analysis of candidemia cases in a city hospital during the COVID-19 pandemic.

OBJECTIVE: The frequency and mortality of candidemia remain important. Non-albicans Candida species such as C. auris are increasing. PATIENTS AND METHODS: A retrospective review of adult patients diagnosed with bloodstream infection due to Candida species in the 17 months between July 1, 2020, and December 1, 2021, was performed. Yeast colonies grown in culture were identified by matrix-assisted laser desorption/ionization time-of-flight. Antifungal susceptibility tests of Candida strains were performed with Sensititre YeastOne (TREK Diagnostic Systems Inc., Westlake, Ohio) kits, and minimum inhibitory concentration values were evaluated according to the Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) clinical breakpoints. RESULTS: In total, 217 patients (mean age 64.9±15.7 years) were included. C. albicans was the most common fungus (detected in 82 patients; 37.8%), followed by C. parapsilosis (17.1%), C. glabrata (15.2%), C. tropicalis (15.2%), and C. auris (9%). Candidemia developed in 175 (81.4%) of the cases during their intensive care unit stay. Fluconazole (41.0%) and caspofungin (36.4%) were the two most frequently used antifungal agents in antifungal therapy. There were 114 (52.3%) deaths in the study group. Mortality rates were found to be lower in patients infected with C. parapsilosis or C. auris. Age and previous COVID-19 infection were other important risk factors. When the 217 Candida spp. were examined, resistance and intermediate susceptibility results were higher when EUCAST criteria were used. While the two methods were found to be fully compatible only for fluconazole, a partial agreement was also observed for voriconazole. CONCLUSIONS: As our study observed, the COVID-19 pandemic brought increasing numbers of immunosuppressed patients, widespread use of antibacterials, and central venous catheters, increasing the frequency and mortality of candidemia cases. All health institutions should be prepared for the diagnosis and treatment of candidemia. In addition, C. auris, the frequency of which has increased in recent years, is a new factor that should be considered in candidemia cases.

Early Prediction of Bloodstream Infection with Complete Blood Count Parameters: an Ex-Vivo Human Whole Blood Model.

BACKGROUND: Despite the advanced laboratory technologies available today, blood culture is the gold standard method in the diagnosis of bloodstream infections. Automated blood culture devices give blood culture results for laboratories approximately in 2 - 3 days up to 7 days. Moreover, some microorganisms like nonreproducible bacteria, fungi or viruses cannot be produced in culture. Among all samples taken for blood culture on suspicion of infection approximately 10% are determined as positive whereas the false positive rate due to contamination is 5%. Especially in life-threatening severe conditions such as sepsis early diagnosis and prompt treatment are crucial. Based on this the aim of this study is to investigate complete blood count parameters as potential early markers in Escherichia coli, Staphylococcus aureus and Candida albicans bloodstream infections using an ex vivo whole blood model. METHODS: Blood samples collected from healthy donors (n = 10) were treated with suspensions containing a certain concentration of microorganisms (107 CFU/mL for both E. coli ATCC 25922 and S. aureus ATCC 29213, 106 CFU/mL for C. albicans ATCC 14053). After bacteremia and candidemia were induced, complete blood count parameters were analyzed hourly in the samples until the end of the 4th hour with a Mindray BC-6800 hematology analyzer. Statistical analysis was performed by Tukey-Kramer post-hoc multiple comparison test and statistical significance was accepted as p < 0.05. RESULTS: When platelet derived parameter baseline values were compared to hourly values in E. coli and S. aureus induced whole blood samples, it was found that the decrease in PLT, P-LCC and the increase in IPF% was significant from the first hour whereas the increase in IMG% was found to be significant only from the 3rd hour onward. In the experiments with C. albicans, it was observed that the increase in IPF% and IMG% was significant from the 2nd and 3rd hour onward, respectively. There was no relationship between MPV, P-LCR, and NLR baseline and hourly results in any microorganism induced model. CONCLUSIONS: IPF% can guide clinicians in the early diagnosis and management of treatment of infections caused by S. aureus, E. coli, and C. albicans.

Epidemiological patterns of candidaemia: A comprehensive analysis over a decade.

BACKGROUND: The prevalence of fungal bloodstream infections (BSI), especially candidaemia, has been increasing globally during the last decades. Fungal diagnosis is still challenging due to the slow growth of fungal microorganisms and need for special expertise. Fungal polymicrobial infections further complicate the diagnosis and extend the time required. Epidemiological data are vital to generate effective empirical treatment strategies. OBJECTIVES: The overall aim of this project is to describe the epidemiology of monomicrobial candidaemia and polymicrobial BSI, both with mixed fungaemia and with mixed Candida/bacterial BSIs. METHODS: We conducted a single-centre retrospective epidemiological study that encompasses 950,161 blood cultures during the years 2010 to 2020. The epidemiology of monomicrobial and polymicrobial candidaemia episodes were investigated from the electronic records. RESULTS: We found that 1334 candidaemia episodes were identified belonging to 1144 individual patients during 2010 to 2020. Candida albicans was the most prevalent species detected in candidaemia patients, representing 57.7% of these episodes. Nakaseomyces (Candida) glabrata and Candida parapsilosis complex showed an increasing trend compared to previous studies, whereas Candida albicans demonstrated a decrease. 19.8% of these episodes were polymicrobial and 17% presented with mixed Candida/bacterial BSIs while 2.8% were mixed fungaemia. C. albicans and N. glabrata were the most common combination (51.4%) in mixed fungaemia episodes. Enterococcus and Lactobacillus spp. were the most common bacteria isolated in mixed Candida/bacterial BSIs. CONCLUSIONS: Polymicrobial growth with candidaemia is common, mostly being mixed Candida/bacterial BSIs. C. albicans was detected in more than half of all the candidaemia patients however showed a decreasing trend in time, whereas an increase is noteworthy in C. parapsilosis complex and N. glabrata.

Association of persistent positive blood cultures and infective endocarditis: A cohort study among patients with suspected infective endocarditis.

OBJECTIVES: To ascertain whether infective endocarditis (IE) was associated with persistent bacteraemia/candidaemia among patients with suspected IE. METHODS: This study included bacteraemic/candidaemic adult patients with echocardiography and follow-up blood cultures. Persistent bacteraemia/candidaemia was defined as continued positive blood cultures with the same microorganism for 48 h or more after antibiotic treatment initiation. Each case was classified for IE by the Endocarditis Team. RESULTS: Among 1962 episodes of suspected IE, IE (605; 31%) was the most prevalent infection type. Persistent bacteraemia/candidaemia was observed in 426 (22%) episodes. Persistent bacteraemia was more common among episodes with Staphylococcus aureus bacteraemia compared to episodes with positive blood cultures for other pathogens (32%, 298/933 vs 12%, 128/1029; P < 0.001). Multivariable analysis demonstrated that cardiac predisposing factors (aOR 1.84, 95% CI 1.31-2.60), community or non-nosocomial healthcare-associated (2.85, 2.10-3.88), bacteraemia by high-risk bacteria, such as S. aureus, streptococci, enterococci or HACEK (1.84, 1.31-2.60), two or more positive sets of index blood cultures (6.99, 4.60-10.63), persistent bacteraemia/candidaemia for 48 h from antimicrobial treatment initiation (1.43, 1.05-1.93), embolic events within 48h from antimicrobial treatment initiation (12.81, 9.43-17.41), and immunological phenomena (3.87, 1.09-1.78) were associated with infective endocarditis. CONCLUSIONS: IE was associated with persistent bacteraemia/candidaemia, along with other commonly associated factors.

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 patients in the same period was conducted for comparison. Antifungal susceptibility tests were performed according to the reference method. A total of 85 patients with fungemia episodes were included: 25 with NCY fungemia and 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 was 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.

Among all fungemia episodes, hematological malignancies, immunosuppressive therapy, neutropenia, and preexposure to antifungals were risk factors for non-Candida yeast fungemia; diabetes mellitus, urinary catheters, and total parenteral nutrition were risks for candidemia.

Epidemiology, clinical characteristics, outcome and biofilm forming properties in candidaemia: A single-centre retrospective 4-year analysis from Hungary.

BACKGROUND: Candidaemia is a life-threatening disease that is associated with high mortality, especially in intensive care units (ICUs). The number of comprehensive studies dealing with the epidemiologic characteristics of biofilm-related properties is limited. OBJECTIVE: This study evaluated the clinical characteristics of candidaemia, to assess the biofilm-forming properties of isolates, and to identify the risk factors of mortality. PATIENTS AND METHODS: A total of 149 candidaemia episodes from the University of Debrecen, Clinical Centre, between January 2020 and December 2023 were investigated retrospectively. The susceptibility of Candida isolates to fluconazole, amphotericin B, anidulafungin, caspofungin, and micafungin was evaluated and compared to the susceptibility of 1-day-old biofilms. Multivariate logistic regression analysis was applied to identify the independent predictors of 30-day mortality rate. RESULTS: The most common Candida species was Candida albicans (41%), followed by C. parapsilosis (20%), C. glabrata (14%), C. tropicalis (13%), rare Candida species (7%), and C. krusei (5%). Sixty-six percent of Candida isolates were biofilm formers and 44% had high metabolic activity. The 30-day mortality rate was 52%, which was higher in ICUs (65%). The logistic regression analysis revealed several factors significantly influencing mortality including ICU admission (odds ratio [OR] 2.99, 95% confidence interval [CI] 1.17-8.04, p = 0.025), fluconazole treatment (OR 4.12, 95% CI 1.62-11.42, p = .004), and pneumonia (OR 0.261, 95% CI 0.1-0.67, p = .006). CONCLUSIONS: This comprehensive analysis supports the better characterisation of candidaemia in healthcare settings, which ultimately may reduce mortality among patients.

Taxonomy of Candida parapsilosis complex isolated from neonates and the role of Hsp90 inhibitors to enhanced the antifungal activity of micafungin.

Species from Candida parapsilosis complex are frequently found in neonatal candidemia. The antifungal agents to treat this infection are limited and the occurrence of low in vitro susceptibility to echinocandins such as micafungin has been observed. In this context, the chaperone Hsp90 could be a target to reduce resistance. Thus, the objective of this research was to identify isolates from the C. parapsilosis complex and verify the action of Hsp90 inhibitors associated with micafungin. The fungal identification was based on genetic sequencing and mass spectrometry. Minimal inhibitory concentrations were determined by broth microdilution method according to Clinical Laboratory and Standards Institute. The evaluation of the interaction between micafungin with Hsp90 inhibitors was realized using the checkerboard methodology. According to the polyphasic taxonomy, C. parapsilosis sensu stricto was the most frequently identified, followed by C. orthopsilosis and C. metapsilosis, and one isolate of Lodderomyces elongisporus was identified by genetic sequencing. The Hsp90 inhibitor geladanamycin associated with micafungin showed a synergic effect in 31.25% of the isolates, a better result was observed with radicicol, which shows synergic effect in 56.25% tested yeasts. The results obtained demonstrate that blocking Hsp90 could be effective to reduce antifungal resistance to echinocandins.

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.

Determination of amphotericin B antifungal susceptibility in Candida strains using an inverted microscope.

INTRODUCTION: Invasive Candida infections have recently shown a significant increase in prevalence and are associated with high mortality rates. Initiating early antifungal treatment in patients with candidemia is vital. The aim of our study was to compare the antifungal susceptibility results of a new method called Flat Plate Method modified from reference "Clinical and Laboratory Standards Institute (CLSI) microdilution method by us with Sensitititre Yeast One colorimetric method and the reference CLSI method. METHODOLOGY: We tested 100 Candida isolates from blood cultures. We followed the CLSI M27-A3 (reference method for broth dilution antifungal susceptibility testing of yeasts; third edition) guidelines for testing in vitro susceptibility to amphotericin B. In the Flat Plate method, 96-well plates were used for evaluation with an inverted microscope. Minimum inhibitory concentration (MIC) values in the SYO method were measured following the manufacturer's instructions. The MIC values obtained by all three methods were considered compatible if they were within ± 2 dilution limits. RESULTS: The SYO method detected C. albicans and C. glabrata with 100% essential agreement, whereas there was 96.29% essential agreement in the case of C. parapsilosis. In the Flat Plate method, the essential agreement with amphotericin B was 91.42%, for C. albicans isolates and 89.47%.for C. glabrata strains. CONCLUSIONS: When determining early antifungal susceptibility using the Flat Plate method, the results are obtained quickly, with high accuracy, and without incurring additional costs. However, there is a need for comprehensive studies comparing different antifungals.

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.

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.

Rapid identification,fluconazole and micafungin susceptibility testing of Candida species from blood culture by a short incubation method.

This study aimed to develop and validate a rapid method for identification by MALDI-TOF system and determination of the susceptibility to Fluconazole and Micafungin by broth microdilution among Candidaspecies causing bloodstream infections. Subcultures from blood culture bottles were incubated for 5 hours (+/- 1h) and used to perform the tests, so that the turnaround time of rapid identification and susceptibility profile was about 5 and 24 hours, respectively. The rapid identification showed agreement of 92.05 %. Regarding the rapid broth microdilution for Fluconazole and Micafungin, the agreement was 97.06 % (p<0.001) and 100 % (p<0.001), and the Kappa coefficient was 0.91 (p<0.001) and 1.0 (p<0.001), respectively. To conclude, both rapid methods showed to be reproducible, inexpensive, easy to perform and time-saving. Thus, these methodologies could be useful to guide and adjust empirical antifungal therapy.

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.

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)

Evaluation of Candidemia in Solid-Organ Transplant Recipients.

OBJECTIVES: Solid-organ transplant recipients have high rates of invasive fungal infections. Candida species are the most commonly isolated fungi. Our aim was to identify risk factors, clinical presentations, and outcomes of candidemia in solid-organ transplant recipients. MATERIALS AND METHODS: We evaluated adult (≥18 years old) transplant recipients seen from May 2011 to December 2022 at Baskent University Ankara Hospital. From medical records, we retrospectively reviewed age, sex, transplant type, candidemia agent, risk factors, concomitant infections, and mortality of patients with Candida detected in blood culture. We used SPSS statistics software (version 25) to analyze data. RESULTS: There were 1080 organ transplants performed during the study period (717 kidney, 279 liver, 84 heart). There were 855 who were ≥18 years (655 kidney, 127 liver, 73 heart), of whom candidemia was detected in 26 (16 male; 11 kidney, 11 liver, 4 heart) with a median age of 47.5 years. The most common agents were Candida albicans and Candida glabrata. The most common chronic diseases were hypertension, cirrhosis, and cardiomyopathy. Eighteen patients had a concomitant focus of infection. Ten patients had pneumonia accompanying candidemia. The 30-day mortality rate was as high as 53.8%. The mean duration of candidemia after transplant was 23 months. Catheter-related candidemia was observed in 65% of patients. The 30-day mortality was found to be significantly higher in patients followed in the intensive care unit (P = .014), receiving total parenteral nutrition (P = .001), using broad-spectrum antibiotics (P = .001), and having pneumonia (P = .042) accompanying candidemia. CONCLUSIONS: For adult solid-organ transplant recipients with candidemia, careful monitoring is essential for successful management of total parenteral nutrition, central catheter, use of broadspectrum antibiotics, and invasive interventions.

Estimated burden of fungal infections in Panama.

Data published on Panamanian fungal disease are scarce, mostly case reports. To date, there is no paper that compiles the burden of fungal disease Here we estimate for the first time the incidence and prevalence of fungal diseases in Panama. Data on fungal disease were obtained from different search engines: PubMed, Google Scholar, Scielo and Lilacs. For population and at risk diseases, we used statistics from worldometer, UNAIDS, and WHO. Incidence, prevalence, and absolute numbers were calculated based on the population at risk. Panamanian population in 2022 was 4,429,739. We estimated that 85,530 (1.93 %) people suffer from fungal diseases. The most frequent fungal infection was recurrent Candida vaginitis (3285/100,000). There are 31,000 HIV-infected people in Panama and based on the number of cases not receiving anti-retroviral therapy (14,570), and previous reports of prevalence of opportunistic infections, we estimated annual incidences of 4.0/100,000 for cryptococcal meningitis, 29.5/100,000 for oral candidiasis, 23.1/100,000 for esophageal candidiasis, 29.5/100,000 for Pneumocystis pneumonia, 15.1/100,000, and for histoplasmosis. For chronic pulmonary aspergillosis (CPA) and fungal asthma we used data from Guatemala and Colombia to estimate COPD and asthma prevalence and WHO report for tuberculosis. We estimated annual incidences of 6.1/100,000 for invasive aspergillosis and prevalence of 31.5/100,000 for CPA, 60.2/100,000 for allergic bronchopulmonary aspergillosis, and 79.5/100,000 for severe asthma with fungal sensitisation. Other incidence estimates were 5.0/100,000 for candidaemia, 0.20/100,000 for mucormycosis, and 4.97/100,000 for fungal keratitis. Even though this report on burden of fungal disease is a forward step, more epidemiological studies to validate these estimates are needed.

Comparative assessment of Sensititre YeastOne and Micronaut-AM EUCAST for antifungal susceptibility testing in candidaemia isolates.

PURPOSE: Antifungal susceptibility testing (AFST) is essential to ensure appropriate antifungal therapy in candidaemia. This study compared two commercial colorimetric broth microdilution tests: Sensititre YeastOne (SYO; Thermo Scientific) and Micronaut-AM EUCAST AFST (M-AM; Bruker) for the AFST of Candida spp. MATERIAL AND METHODS: A total of 74 yeast strains, including C. albicans (n = 40) and non-albicans Candida species (NACS) (n = 34), were obtained from blood cultures of patients admitted to a tertiary care hospital in Belgium from 2017 to 2022. AFST by SYO and by M-AM were performed according to the manufacturers' protocols and interpreted using CLSI and EUCAST guidelines, respectively. Essential and categorical agreements (EA and CA), very major, major and minor discrepancies were calculated for amphotericin B, echinocandins and azoles considering SYO as the reference method. RESULTS: In total, 441 and 392 isolate-antifungal results were evaluable for EA and CA, respectively. SYO and M-AM, showed a high level of concordance for C. albicans strains, with an EA and CA ≥90 % for all tested antifungals. However, we noted significant discordances for NACS, the lowest EA were observed with micafungin (50 %) and voriconazole (58.8 %). These discrepancies were likely due to differences in the raw MIC values obtained by the two methods and the different interpretation breakpoints used by CLSI and EUCAST. CONCLUSION: Our study showed excellent agreement between SYO and M-AM for AFST of C. albicans, while the equivalency was lower for NACS. AFST method should be carefully selected, considering the results might impact the choice of antifungals for non-albicans candidaemia.

Understanding clinical outcomes and factors influencing mortality in intensive care unit patients with COVID-19-associated candidemia.

BACKGROUND: During the COVID pandemic, research has shown an increase in candidemia cases following severe COVID infection and the identification of risk factors associated with candidemia. However, there is a lack of studies that specifically explore clinical outcomes and mortality rates related to candidemia after COVID infection. OBJECTIVES: The aim of this international study was to evaluate the clinical outcomes and identify factors influencing mortality in patients who developed candidemia during their COVID infection. PATIENTS/METHODS: This study included adult patients (18 years of age or older) admitted to the intensive care unit (ICU) and diagnosed with COVID-associated candidemia (CAC). The research was conducted through ID-IRI network and in collaboration with 34 medical centres across 18 countries retrospectively, spanning from the beginning of the COVID pandemic until December 2021. RESULTS: A total of 293 patients diagnosed with CAC were included. The median age of the patients was 67, and 63% of them were male. The most common Candida species detected was C. albicans. The crude 30-day mortality rate was recorded at 62.4%. The logistic regression analysis identified several factors significantly impacting mortality, including age (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.02-1.07, p < .0005), SOFA score (OR 1.307, 95% CI 1.17-1.45, p < .0005), invasive mechanical ventilation (OR 7.95, 95% CI 1.44-43.83, p < .017) and duration of mechanical ventilation (OR 0.98, 95% CI 0.96-0.99, p < .020). CONCLUSIONS: By recognising these prognostic factors, medical professionals can customise their treatment approaches to offer more targeted care, leading to improved patient outcomes and higher survival rates for individuals with COVID-associated candidemia.