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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.

Candidemia ranks the 4th most prevalence cause of bloodstream infections and stands out as the primary cause of invasive fungal infections among hospitalized patients. Its incidence varies globally from 0.33 to 6.51 episodes per 1000 admissions, representing a major public health burden due to its increasing incidence and high mortality rates. The present research work has been conducted to identify the distribution of Candida species among septicemic patients and to determine the patterns of antifungal susceptibility of Candida species isolates from them in a tertiary care center in South India. Among the 88 Candida isolates, 13 (14.8%) were speciated and identified as C. albicans and 75 (85.2%) were Candida non-albicans. Of them, C. tropicalis (42%) ranks more prevalent. The distribution of virulence factors among 88 Candida isolates revealed that 49 isolates (55.7%) exhibited phospholipase activity, hemolysin production was detected in 68.2% of isolates, biofilm production was demonstrated in 73.9% isolates and coagulase activity was observed in 46.7% isolates. In the present study, Candida species were most sensitive to Amphotericin B (94.3%), which is followed by Caspofungin (93.2%), Voriconazole (92%), Micafungin (90.9%), and the least was observed with Flucytosine (78.4%) and Fluconazole (71.5%). Thus, in order to improve treatment responses, the insights acquired from this research will aid in clinical management and the development of antifungal stewardship recommendations. [ABSTRACT FROM AUTHOR]

Objective In severely burned patients, fungal infections are among the most devastating complications. Candidemia is an important cause of mortality with an increasing incidence despite advances in burn care management. Higher affected body surface area, long intensive care unit (ICU) stay, flame burn, third-degree burn, and previous bacterial infections were associated with the development of candidemia. Candidemia in patients with major burns admitted to an ICU of a tertiary burns center is investigated. Methods Patients hospitalized in the ICU of Adana City Training and Research Hospital from July 1, 2017, to November 10, 2020, were included. The demographic and clinical variables, the Candida species isolated from blood cultures and their antifungal susceptibilities, need for grafting, complications, and rate of mortality are evaluated retrospectively. Patients were grouped as "candidemia" or "noncandidemia" according to whether or not they experienced Candida bloodstream infection. Results A total of 371 patients were included; the mean age was 22.02 ± 20.9 years. Most patients were male (69.5%). The percentage of burned surface area was 25.93 ± 17.6. The mean ICU stay was 16.95 ± 16.3 days. There were 90 candidemia episodes in 69 patients. The most commonly isolated Candida species were C. parapsilosis , C. tropicalis , and C. albicans. The mortality rates in the candidemia and noncandidemia groups were 24.6 and 5.6%, respectively (p < 0.001). Conclusion Adhering to isolation rules, early wound debridement and closure, avoidance of catheters where possible, and avoidance of the early use of broad-spectrum antibiotics are important measures in reducing candidemia in patients with major burns. Candidemia was associated with greater burn surface areas, duration of hospital stay, and larger numbers of interventional procedures. However, previous bacterial infection receiving prolonged antibiotic therapy was the greatest risk factor of candidemia. Culture results are important to select the antifungal agent with high susceptibility, but results are not rapidly available. There is need for early clinical prediction measures to inform early and effective antifungal treatment. [ABSTRACT FROM AUTHOR]

Candidemia leaves a trail of approximately 750,000 cases yearly, with a morbidity rate of up to 30%. While Candida albicans still ranks as the most predominantly isolated Candida species, C. glabrata comes in second, with a death rate of 40–50%. Although infections by Candida spp are commonly treated with azoles, the side effects and rise in resistance against it has significantly limited its clinical usage. The current study aims to address the insolubility of piperine and provide an alternative treatment to Candida infection by formulating a stable piperine-loaded O/W nanoemulsion, comprised of Cremophor RH40, Transcutol HP and Capryol 90 as surfactant, co-surfactant, and oil, respectively. Characterization with zetasizer showed the droplet size, polydispersity (PDI) and zetapotential value of the nanoemulsion to be 24.37 nm, 0.453 and -21.10 mV, respectively, with no observable physical changes such as phase separation from thermostability tests. FTIR peaks confirms presence of piperine within the nanoemulsion and TEM imaging visualized the droplet shape and further confirms the droplet size range of 20–24 nm. The MIC90 value of the piperine-loaded nanoemulsion determined with in vitro broth microdilution assay was approximately 20–50% lower than that of the pure piperine in DMSO, at a range of 0.8–2.0 mg/mL across all Candida spp. tested. Overall, the study showed that piperine can be formulated into a stable nanoemulsion, which significantly enhances its antifungal activity compared to piperine in DMSO. [ABSTRACT FROM AUTHOR]

Purpose: Haematology patients with high-risk neutropenia are prone to mucosal-barrier injury-associated laboratory-confirmed bloodstream infections (MBI-LCBI). We assessed risk factors for MBI-LCBI including candidaemia in neutropenic haematology patients with fever. Methods: This prospective observational study was performed in six dedicated haematology units in the Netherlands. Eligible haematology patients had neutropenia < 500/mL for ≥ 7 days and had fever. MBI-LCBIs were classified according to Centers for Disease Control (CDC) definitions and were followed until the end of neutropenia > 500/mL or discharge. Results: We included 416 patients from December 2014 until August 2019. We observed 63 MBI-LCBIs. Neither clinical mucositis scores nor the blood level of citrulline at fever onset was associated with MBI-LCBI. In the multivariable analysis, MASCC-score (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.05 to 1.29 per point decrease), intensive chemotherapy (OR 3·81, 95% CI 2.10 to 6.90) and Pichia kudriavzevii (formerly Candida krusei) colonisation (OR 5.40, 95% CI 1.75 to 16.7) were retained as risk factors for MBI-LCBI, while quinolone use seemed protective (OR 0.42, 95% CI 0.20 to 0.92). Citrulline level (OR 1.57, 95% CI 1.07 to 2.31 per µmol/L decrease), active chronic obstructive pulmonary disease (OR 15.4, 95% CI 1.61 to 14.7) and colonisation with fluconazole-resistant Candida (OR 8.54, 95% CI 1.51 to 48.4) were associated with candidaemia. Conclusion: In haematology patients with fever during neutropenia, hypocitrullinaemia at fever onset was associated with candidaemia, but not with bacterial MBI-LCBI. Patients with intensive chemotherapy with a low MASCC-score and colonisation with Pichia kudriavzevii had the highest risk of MBI-LCBI. Trial registration: ClinicalTrials.gov (NCT02149329) at 19-NOV-2014. [ABSTRACT FROM AUTHOR]

The fungus Wickerhamiella pararugosa (Candida pararugosa) has been detected in various human organs but has rarely caused bloodstream infections. This report presents a case of central venous catheter-related bloodstream infection (CRBSI) of W. pararugosa in an adult. A female patient in her 80s was admitted to our facility for intestinal obstruction caused by colorectal cancer. The patient's ability to consume food was hindered, necessitating the insertion of a central venous catheter (CVC) into the internal jugular vein. On day 3 after admission, the patient developed a fever, prompting blood and CVC tip cultures to be performed. On day 5, yeast-like fungi were discovered in the blood cultures, and fosfluconazole (fluconazole [FLCZ] pro-drug) treatment was initiated. On day 8, yeast-like fungi were identified in both the blood and CVC tip cultures, leading to a diagnosis of CRBSI. The fungus was identified as W. pararugosa through biochemical and genetic characterization. This finding justified the use of micafungin (MCFG) for combination therapy. On day 17, the minimum inhibitory concentrations (MIC) for FLCZ and MCFG were 4–8 and 0.06 μg/mL, respectively. Accordingly, the treatment was changed to monotherapy with MCFG. After a 21-day treatment regimen, the patient was discharged on day 31. We present a case of CRBSI caused by W. pararugosa in an adult with intestinal obstruction. The notable increase in the MIC of FLCZ necessitated monotherapy with MCFG, which resulted in successful recovery of the patient. [ABSTRACT FROM AUTHOR]

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Introduction: Blood cultures have low sensitivity for candidemia. Sensitivity can be improved by the culture-independent system T2 Magnetic Resonance (T2). SeptiCyte RAPID is a host response assay quantifying the risk of infection-related inflammation through a scoring system (SeptiScore). We investigate the performance of SeptiScore in detecting persistent candidemia as defined by conventional cultures and T2. Methods: This is a prospective multicentre observational study on patients with candidemia. Blood cultures and blood samples for assessment by T2 and SeptiCyte were collected for 4 consecutive days after the index culture. The performance of SeptiScore was explored to predict persistent candidemia as defined by (1) positive follow-up blood culture (2) either positive follow-up blood culture or T2 sample. Results: 10 patients were enrolled including 34 blood collections assessed with the 3 methods. Overall, 4/34 (12%) follow-up blood cultures and 6/34 (18%) T2 samples were positive. A mixed model showed significantly higher SeptiScores associated with persistent candidemia when this was defined as either a positive follow-up blood culture or T2 sample (0.82, 95%CI 0.06 to 1.58) but not when this was defined as a positive follow-up blood culture only (-0.57, 95%CI -1.28 to 0.14). ROC curve for detection of persistent candidemia by SeptiScore at day 1 follow-up showed an AUC of 0.85 (95%CI 0.52-1.00) when candidemia was defined by positive follow-up blood culture, and an AUC of 1.00 (95%CI 1.00–1.00) when candidemia was defined according to both methods. Conclusion: Integrating transcriptome profiling with culture-independent systems and conventional cultures may increase our ability to diagnose persistent candidemia. [ABSTRACT FROM AUTHOR]

On 22 March 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 end point and 20% noninferiority margin, which demonstrated that rezafungin is noninferior to the comparator echinocandin. Nonclinical studies of rezafungin in nonhuman primates identified a neurotoxicity safety signal; however, rezafungin's safety profile in the completed clinical studies was similar to other Food and Drug Administration-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. Clinical Trials Registration. NCT02734862 and NCT03667690. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion Nakaseomyces glabratus (N. glabratus) formerly known as Candida glabrata (C. glabrata), is an endogenous opportunistic pathogen, which is generally located in the gastrointestinal tract but can spread in immunocompromised patients. N. glabratus is the second most common pathogen that causes candidemia in several countries. N. glabratus virulence factors may increase antifungal resistance and reduce the number of available treatment options. High resistance to azoles and increasing resistance to echinocandins have been previously reported in N. glabratus.To establish the distribution of N. glabratus isolates in Europe and its drug susceptibility/resistance in each country over the last 7 years.The search was performed across three databases: PubMed, Scopus and Scielo, using the MeSH terms: “Candida glabrata”, “Nakaseomyces glabratus”, “Europe”, “resistance” and “Epidemiology” exclusively in English. All available information from January 2002 to December 2022 was included, excluding reviews, meta‐analyses and book chapters.Fifty‐seven articles with information on antifungal susceptibility in Europe were retrieved and analysed with a total of 15,400 reported C. glabrata isolates. Remarkably, nations that presented the maximum number of cases during the study period included the United Kingdom (n = 7241, 47.02%), France (n = 3190, 20.71%), Spain (n = 900, 5.84%), Hungary (n = 745, 4.84%) and Italy (n = 486, 3.16%). C. glabrata isolates presented resistance to azoles [voriconazole (n = 2225, 14.45%), fluconazole (n = 1612, 10.47%), itraconazole (n = 337, 2.19%) and clotrimazole (n = 89, 0.58%)], increased resistance to echinocandins, especially to anidulafungin (n = 138, 0.89%), and high sensitivity to amphotericin B.The number of candidemia cases associated with triazole‐resistant N. glabratus isolates have been increasing in Europe. Therefore, echinocandins and amphotericin B can be considered optional empirical treatments; however, antifungal susceptibility testing is required to determine the best therapeutic options. [ABSTRACT FROM AUTHOR]

Background: Burn patients are at high risk of developing secondary invasive fungal infections due to their compromised skin barrier, extensive use of antibiotics, and immunosuppression. Objectives: We investigated demographic characteristics and clinical factors associated with Candida infections in intensive care unit (ICU) burn patients, and the in vitro antifungal susceptibility of species of isolates. Methods: A total of 353 burn patients admitted to three major ICUs of burn centers in Iran were evaluated between 2021 and 2023. Patients were considered as colonisation and candidemia. Demographic characteristics, burn‐related factors, and clinical conditions were compared among the groups. Furthermore, we identified fungi at the species level and performed antifungal susceptibility testing according to CLSI guidelines. Results: Overall, 46.2% of patients were colonised with a Candida species, leading to candidemia in 15.3%. The most frequently isolated species from candidemia and burn wound colonisation were Candida parapsilosis (37.0%) and Candida albicans (31.9%), respectively. Risk factors linked to candidemia included larger total body surface area (TBSA) (>50%), older patients, indwelling catheters, diabetes, and an extended ICU stay. Mortality rate was higher among candidemia patients (82.5%) compared to colonised patients (7.3%). The resistance rate of the strains isolated from candidemia to fluconazole and voriconazole was 28% and 18.2%, respectively. Conclusion: We found that a higher percentage of TBSA burn injuries, longer hospital stays, and catheterization are important predictors of candidemia. The mortality rate was significantly higher in people infected with non‐albicans Candida species. Prevention and treatment strategies for candidemia should be based on updated, regional epidemiological data. [ABSTRACT FROM AUTHOR]

Cryptococcal meningitis (CM) causes significant global morbidity and mortality. Current therapeutic strategies rely on deoxycholated or liposomal forms of the polyene amphotericin B. Nystatin is also a polyene with broad-spectrum antimicrobial activity. Treatment with systemic nystatin has been limited by toxicity, which is a consistent challenge with polyene therapeutics. One mechanism to improve the toxicity is usage of a liposomal form of the active agent. Previous data from a murine candidemia model indicated that liposomal nystatin may be an effective antifungal drug formulation. Since the rabbit model of CM is a highly predictive preclinical system for evaluating antifungal therapeutics, we tested the effectiveness of two doses of daily liposomal nystatin, 3 and 8 mg/kg in the rabbit model of CM. Treatment with liposomal nystatin in this model did not reduce the fungal burden in the cerebrospinal fluid. A subsequent clinical trial also did not find activity in a human population. These data indicate that liposomal nystatin in the current form and at the tested dosages is not an effective therapy for CM. The data provide further evidence for the predictive power of the rabbit model of CM as a vital preclinical system for testing novel antifungal therapeutics for CM. [ABSTRACT FROM AUTHOR]

Introduction: Vascular access devices (VADs), namely peripheral VADs (PVADs) and central venous VADs (CVADs), are crucial in both intensive care unit (ICU) and non-ICU settings. However, VAD placement carries risks, notably catheter-related bloodstream infections (CRBSIs). Candida spp. is a common pathogen in CRBSIs, yet its clinical and microbiological characteristics, especially in non-ICU settings, are underexplored. Methods: We conducted a monocentric, retrospective observational study at Luigi Sacco Hospital from 1 May 2021 to 1 September 2023. We reviewed medical records of non-ICU adult patients with CVADs and PVADs. Data on demographics, clinical and laboratory results, VAD placement, and CRBSI occurrences were collected. Statistical analysis compared Candida spp. CRBSI and bacterial CRBSI groups. Results: Out of 1802 VAD placements in 1518 patients, 54 cases of CRBSI were identified, and Candida spp. was isolated in 30.9% of episodes. The prevalence of CRBSI was 3.05%, with Candida spp. accounting for 0.94%. Incidence rates were 2.35 per 1000 catheter days for CRBSI, with Candida albicans and Candida non-albicans at 0.47 and 0.26 per 1000 catheter days, respectively—patients with Candida spp. CRBSI had more frequent SARS-CoV-2 infection, COVID-19 pneumonia, and hypoalbuminemia. Conclusions: During the COVID-19 pandemic, Candida spp. was a notable cause of CRBSIs in our center, underscoring the importance of considering Candida spp. in suspected CRBSI cases, including those in non-ICU settings and in those with PVADs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Candidemia, a bloodstream infection predominantly affecting critically ill patients, poses a significant global health threat especially with the emergence of non-albicans Candida species, including drug-resistant strains. In Brazil, limited access to advanced diagnostic tools and trained microbiologists hampers accurate identification of Candida species and susceptibility to antifungals testing hindering surveillance efforts. Methods: We conducted a systematic review spanning publications from 2017 to 2023 addressing Candida species distribution and antifungal susceptibility among Brazilian patients with candidemia. Results: Despite initially identifying 7075 records, only 16 met inclusion criteria providing accurate information of 2305 episodes of candidemia. The predominant species were C. albicans, C. parapsilosis, and C. tropicalis, followed by notable proportions of Nakaseomyces glabratus. Limited access to diagnostic tests was evident as only 5 out of 16 studies on candidemia were able to report antifungal susceptibility testing results. In vitro resistance to echinocandins was rare (only 6/396 isolates, 1,5%). In counterpart, fluconazole exhibited resistance rates ranging from 0 to 43%, with great heterogeneity among different studies and species of Candida considered. Conclusion: Our review underscores the critical need for enhanced surveillance and research efforts to address the evolving landscape of candidemia and antifungal resistance in Brazil. Despite some limitations, available data suggest that while resistance to echinocandins and amphotericin B remains rare, there is a growing concern regarding resistance to fluconazole among Candida species. [ABSTRACT FROM AUTHOR]

This article presents a case study of a patient with diabetes who developed a fungal infection in the urinary tract while taking a specific medication. The medication, called an SGLT-2 inhibitor, has been linked to an increased risk of urinary tract infections and genital yeast infections. The article emphasizes the need for more research to understand the connection between fungal infections and the use of SGLT-2 inhibitors in diabetic patients. The text is a correspondence from a researcher at Copenhagen University Hospital and is published by BJU International. [Extracted from the article]

Background: Candidemia is a diverse condition and associated with a broad spectrum of clinical presentation. As mortality is high, timely diagnosis of candidemia and start of correct therapeutic treatment are essential. Objectives: To investigate characteristics and factors influencing outcomes for patients with candidemia in a Swedish setting. Method: All positive blood cultures for any Candida species in Östergötland County from 2012 to 2016 were screened. Medical records of patients fulfilling all inclusion criteria and no exclusion criteria were retrospectively reviewed to obtain data on risk factors, diagnostic and therapeutic procedures and at what wards candidemia was diagnosed. Univariate logistic regression and multivariable regression analysis were used to obtain odds ratio to determine risk factors for 30‐day all‐cause mortality associated with candidemia. A p‐value <.05 was considered statistically significant. Results: Of all analysed risk factors, increasing age, renal failure with haemodialysis, immunosuppressant treatment, and severity of the infection (i.e. if septic shock was present) were significantly associated with 30‐day mortality in univariate analysis (p <.05). Removal of a central venous catheter or an infectious diseases consultant was associated with a significantly lower odds ratio for death at 30 days (p <.05). With multivariable analysis, age, time to start of treatment and infectious disease consultant remained significant (p <.05). Conclusion: In conclusion, this study provides an update of the epidemiology and outcomes of candidemia in a Swedish setting, highlighting that patients with candidemia are present at various departments and indicates the importance of an infectious disease consultant when candidemia is present. [ABSTRACT FROM AUTHOR]

Although advances in the management of pediatric neoplasms have profoundly improved infectious disease outcomes, invasive fungal diseases (IFDs) remain a major cause of morbidity and mortality in children and adolescents with high-risk hematological malignancies. A retrospective study was conducted in the Pediatric Hematology–Oncology Department of the University General Hospital of Heraklion for 2013–2022 to estimate the prevalence and describe the clinical and epidemiological characteristics of IFDs for pediatric and adolescent patients with neoplasia. Demographic, clinical, and laboratory parameters were analyzed to identify risk factors for the development of IFD. The overall prevalence of IFDs was estimated to be 7.8% (12/154 patients) throughout the study. The mean age at IFD diagnosis was 9.8 years (SD 6.4 years). The most common IFD was possible/probable invasive pulmonary aspergillosis (IPA; in ≈50%), followed by candidemia/invasive candidiasis (in 44%). Candida parapsilosis was the most prevalent Candida species (4/6 events). Of interest, the majority (75%) of IFDs were breakthrough infections. Patients with increased risk for IFDs were those who were colonized by fungi in sites other than the oral cavity, hospitalized in the intensive care unit for >7 days, received >7 different antimicrobials in the last 3 months, or had severe neutropenia for >44 days. Two children out of a total of 12 with IFD died due to refractory disease or relapse (16.7%). More detailed and prospective epidemiological studies on fungal infections in pediatric patients with hematological or solid neoplasms can contribute to the optimization of prevention and treatment. [ABSTRACT FROM AUTHOR]

Candidemia is a major cause of morbidity and mortality in health care settings, and its epidemiology is changing. In the last two decades, the proportion of non-albicans Candida (NAC) yeasts in candidemia has increased. These yeasts more often display resistance to common antifungals. In many western countries, candidemia is mainly caused by susceptible C. albicans, while in resource-limited countries, including Iran, the candidemia species distribution is studied less often. Here, we investigated the species distribution, resistance levels, and characteristics of patients with candidemia in five hospitals in Mashhad (northeast Iran) for two years (2019–2021). Yeast isolates from blood were identified with MALDI-TOF MS and subjected to antifungal susceptibility testing (AFST) using the broth microdilution method, while molecular genotyping was applied to Candida parapsilosis isolates. In total, 160 yeast isolates were recovered from 160 patients, of which the majority were adults (60%). Candidemia was almost equally detected in men (48%) and women (52%). Almost half of patients (n = 67, 49%) were from intensive care units (ICUs). C. parapsilosis (n = 58, 36%) was the most common causative agent, surpassing C. albicans (n = 52, 33%). The all-cause mortality rate was 53%, with C. albicans candidemia displaying the lowest mortality with 39%, in contrast to a mortality rate of 59% for NAC candidemia. With microbroth AFST, nearly all tested isolates were found to be susceptible, except for one C. albicans isolate that was resistant to anidulafungin. By applying short tandem repeat (STR) genotyping to C. parapsilosis, multiple clusters were found. To summarize, candidemia in Mashhad, Iran, from 2019 to 2021, is characterized by common yeast species, in particular C. parapsilosis, for which STR typing indicates potential nosocomial transmission. The overall mortality is high, while resistance rates were found to be low, suggesting that the high mortality is linked to limited diagnostic options and insufficient medical care, including the restricted use of echinocandins as the first treatment option. [ABSTRACT FROM AUTHOR]

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. 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%). 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. The current study revealed that heavy trailing in C. albicans isolates is associated with persistent candidemia in patients receiving FLC treatment. [ABSTRACT FROM AUTHOR]

Objective Health care-associated infections (HAIs) are important causes of morbidity and mortality in neonatal intensive care units (NICUs). This study aimed to evaluate the frequency of HAIs and related factors in the NICU. Methods HAIs detected and monitored by daily active surveillance by the Infection Control Team at Necmettin Erbakan University Faculty of Medicine NICU between January 1, 2017 and December 31, 2022 were evaluated retrospectively. There were a total of 43 incubators in our hospital's NICU (19 secondary level units and 24 tertiary level). Between 2017 and 2022, there was an average of 982 admissions to the NICU per year. Results A total of 5,895 newborns and 74,726 patient days were monitored in the study. The average HAIs rate for all study years was 3.4% and the incidence density was 2.68 per thousand patient days. The highest HAI rate was in newborns with birth weights < 750 g. A total of 201 HAIs were detected in 172 patients. Bloodstream infection (BSI) was the most frequent HAI. The most frequent pathogens were Klebsiella spp. (44.8%), methicillin-resistant coagulase-negative staphylococci (CoNS) (24.4%), and Acinetobacter spp. (11.6%). Note that 88.5% of Enterobacterales were extended-spectrum beta-lactamase producers, and 26% of Klebsiella spp. were carbapenem-resistant. No colistin resistance was detected in Pseudomonas aeruginosa and Acinetobacter spp. Methicillin resistance was detected in 86.5% of CoNS and 50% of Staphylococcus aureus. The vancomycin resistance rate in Enterococcus spp. was 40%. Note that 16.7% of Candida spp. were fluconazole-resistant; no resistance to caspofungin was found. The most common risk factors for development of HAI were prematurity, umbilical catheter use, total parenteral nutrition, and mechanical ventilation. The mortality rate in patients with HAIs was 20.9%. Conclusion HAIs, including those caused by multidrug-resistant Gram-negative bacteria, are an important problem in our hospital, and also globally. Active surveillance should be continued, and changes over the years evaluated. Infection control programs should be executed by determining the risk and mortality factors attributed to infection and their implementation should be closely monitored. These practices will increase success in the fight against HAIs and antimicrobial resistance. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, an increase in the incidence of bloodstream infections caused by fungi of the Candida genus, also known as candidemia, was observed in patients with SARS-CoV-2 infection. This study aimed to assess the incidence of candidemia, the factors related to COVID-19-associated candidemia (CAC), and prognostic factors. A non-concurrent cohort of 87 cases of patients aged over 18 years with candidemia between March 2020 and February 2022 was evaluated. Incidence density (ID) was calculated by the number of patient-days during the period. All causes of mortality within 30 days of observation were considered. Logistic regression and Cox proportional hazards regression were used, respectively, to determine factors associated with CAC and prognostic factors. Values <0.05 were considered significant. The ID of CAC was eight times higher than candidemia in patients without COVID-19 [2.40 per 1000 person-days vs. 0.27 per 1000 person-days; P  < .01]. The corticosteroid therapy was as an independent factor associated with CAC [OR = 15.98 (3.64–70.03), P  < .01], while abdominal surgery was associated with candidemia in patients without COVID-19 [OR = 0.09 (0.01–0.88), P  = .04]. Both patients with and without COVID-19 had a high 30 days-mortality rate (80.8% vs. 73.8%, respectively; P  = .59). Liver disease [HR = 3.36 (1.22–9.27); P  = .02] and the Charlson score [HR = 1.17 (1.01–1.34); P  = .03] were independent factors of death, while the use of antifungals [HR = 0.15 (0.07–0.33); P  < .01] and removal of the central venous catheter [HR = 0.26 (0.12–0.56); P  < .01] independently reduced the risk of death. These findings highlight the high incidence of candidemia in COVID-19 patients and its elevated mortality. [ABSTRACT FROM AUTHOR]

Candida species, typically part of the human skin and mucous membrane flora, can cause opportunistic fungal infections, notably urinary tract infections (UTIs), which are on the rise among hospitalized COVID-19 patients. The lack of understanding of UTIs in this population, coupled with the emergence of multidrug-resistant strains, poses significant challenges for effective treatment and further investigations. In this study, urine samples were collected from 70 COVID-19 patients with UTIs in sterile containers for microbiology examination. After microscopic observation, the isolates were identified both by phenotypic and molecular techniques such as multiplex PCR. Antifungal susceptibility testing (AFST) against fluconazole (Flu), itraconazole (Itr), and amphotericin B (AMB) was performed according to CLSI M27/S4 standard methods, with the frequency of isolates including Candida albicans (n = 20, 51.3%), Candida tropicalis (n = 15, 38.4%), Nakaseomyces glabrata (previously Candida glabrata) (n = 2, 5.1%), Pichia kudriavzevii (previously Candida krusei), and Candida parapsilosis (n = 1, 2.5%). All isolates of C. albicans, C. tropicalis, C. glabrata, and C. parapsilosis were sensitive to amphotericin B, while C. kruzei was resistant to AMB. Around 70% of C. albicans isolates were sensitive to Flu; 20% of C. tropicalis were resistant to itraconazole, while 33% were resistant to fluconazole. C. albicans and C. tropicalis were the main causes of candiduria in infected cases and both Flu and AMB showed good results in AFST in these species. Performing drug susceptibility testing for clinical isolates of Candida spp. provided guidance for appropriate management and control, and timely antifungal treatment. [ABSTRACT FROM AUTHOR]

Non-albicans Candida (NAC) species are increasingly recognized as significant contributors to candidemia infections; however, relatively less is known about the immune responses induced by these species. In this study, we compared the cytokine production ability of human peripheral blood mononuclear cells (PBMCs) upon stimulation with different Candida species (Candida spp.). We measured secreted cytokines using ELISA and checked the functional profiles of T-cell responses using multicolor flow cytometry. Although there was a differential expression of cytokines against Candida spp., significant difference were observed in the levels of IFN-γ, TNF-α, IL-10, IL-12p40, and IL-23 (p < 0.05) between Candida spp. A significant difference was observed between C. albicans and C. glabrata (p = 0.026) in the levels of TNF-α. C. glabrata showed significant differences compared to C. albicans, C. parapsilosis, and C. krusei in the levels of IL-10 (p values of 0.02, 0.04, and 0.01, respectively). Despite the percentages of CD4+ and CD8+ expressing Th1, Th2, and Th17 cytokines being higher in stimulated PBMCs, none of the Candida spp. showed significant differences. The levels of secreted IL-17A and IL-23 were consistently lower in Candida spp. regardless of the stimulus used. Here, we showed the differential regulation of Th1, Th2, and Th17 during Candida spp. stimulation of the immune system ex vivo. Additionally, our findings suggest that C. albicans elicits an IFN-γ response, whereas C. glabrata promotes IL-10 cellular responses, but this warrants additional studies to conclude this association. This investigation holds the potential to advance our comprehension of the distinct immune responses induced by Candida spp., with probable implications in designing antifungal immunotherapeutics. [ABSTRACT FROM AUTHOR]

Racially and ethnically minoritized (REM) patients are disproportionately affected by infectious diseases, including candidemia. REM patients with candidemia were significantly younger, with trends toward more risk factors for candidemia and longer lengths of stay. Although Candida parapsilosis was more common in REM patients, there were no differences in mortality rates.

BACKGROUND: Fosmanogepix is a first-in-class antifungal targeting the fungal enzyme Gwt1, with broad-spectrum activity against yeasts and moulds, including multidrug-resistant fungi, formulated for intravenous (IV) and oral administration. METHODS: This global, multicenter, non-comparative study evaluated the safety and efficacy of fosmanogepix for first-line treatment of candidaemia in non-neutropenic adults. Participants with candidaemia, defined as a positive blood culture for Candida spp. within 96 h prior to study entry, with ≤2 days of prior systemic antifungals, were eligible. Participants received fosmanogepix for 14 days: 1000 mg IV twice daily on Day 1, followed by maintenance 600 mg IV once daily, and optional switch to 700 mg orally once daily from Day 4. Eligible participants who received at least one dose of fosmanogepix and had confirmed diagnosis of candidaemia (

Introducción. Los datos sobre la prevalencia de coinfecciones o sobreinfecciones fúngicas en pacientes con COVID-19 son limitados. Objetivo. Describir la prevalencia de coinfecciones o sobreinfecciones fúngicas en pacientes con COVID-19, así como los factores de riesgo y las características demográficas, clínicas y microbiológicas. Material y métodos. Se incluyeron pacientes con diagnóstico confirmado de COVID-19, hospitalizados en la unidad de cuidados intensivos y con infección fúngica confirmada entre marzo del 2020 y diciembre del 2021. Del expediente clínico se obtuvieron datos sobre edad, sexo, comorbilidades, días de estancia hospitalaria, resultados de laboratorio (ferritina) y microbiológicos, tratamiento contra COVID-19, terapia antifúngica y desenlace. Resultados. Once de 740 pacientes cumplieron con los criterios de inclusión. La tasa de coinfección fue del 0,3 % y la de sobreinfección fue del 1,2 %. La población más afectada fue la de hombres adultos. Las coinfecciones o sobreinfecciones diagnosticadas fueron candiduria y candidemia, causadas por Candida albicans, C. tropicalis, C. glabrata, C. lusitaniae y Kluyveromyces marxianus (C. kefyr). Además, se encontró una traqueobronquitis por Aspergillus fumigatus. Los antifúngicos más administrados fueron fluconazol y caspofungina. La letalidad en pacientes con coinfecciones fue del 50 % y con sobreinfecciones fúngicas, del 22 %. El tiempo de estancia intrahospitalaria fue de 11 a 65 días. Ocho de los pacientes requirieron asistencia respiratoria mecánica y seis recibieron corticoides. La principal comorbilidad fue diabetes mellitus (81,8 %). Conclusiones. La tasa de coinfecciones o sobreinfecciones por hongos en pacientes con COVID-19 fue baja, pero la letalidad de estas requiere, con urgencia, la realización de pruebas de rutina para detectar hongos en pacientes con COVID-19 grave para diagnosticar oportunamente infecciones fúngicas que puedan comprometer aún más la vida del paciente

Abstract Introduction Blood cultures have low sensitivity for candidemia. Sensitivity can be improved by the culture-independent system T2 Magnetic Resonance (T2). SeptiCyte RAPID is a host response assay quantifying the risk of infection-related inflammation through a scoring system (SeptiScore). We investigate the performance of SeptiScore in detecting persistent candidemia as defined by conventional cultures and T2. Methods This is a prospective multicentre observational study on patients with candidemia. Blood cultures and blood samples for assessment by T2 and SeptiCyte were collected for 4 consecutive days after the index culture. The performance of SeptiScore was explored to predict persistent candidemia as defined by (1) positive follow-up blood culture (2) either positive follow-up blood culture or T2 sample. Results 10 patients were enrolled including 34 blood collections assessed with the 3 methods. Overall, 4/34 (12%) follow-up blood cultures and 6/34 (18%) T2 samples were positive. A mixed model showed significantly higher SeptiScores associated with persistent candidemia when this was defined as either a positive follow-up blood culture or T2 sample (0.82, 95%CI 0.06 to 1.58) but not when this was defined as a positive follow-up blood culture only (-0.57, 95%CI -1.28 to 0.14). ROC curve for detection of persistent candidemia by SeptiScore at day 1 follow-up showed an AUC of 0.85 (95%CI 0.52-1.00) when candidemia was defined by positive follow-up blood culture, and an AUC of 1.00 (95%CI 1.00–1.00) when candidemia was defined according to both methods. Conclusion Integrating transcriptome profiling with culture-independent systems and conventional cultures may increase our ability to diagnose persistent candidemia.

Liang Chen,1,2 Zeqiang Xie,1,2 Jiyong Jian1,2 1Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing, People’s Republic of ChinaCorrespondence: Jiyong Jian, Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, NO. 10, Tie Yi Road, Yang Fang Dian, Beijing, Haidian District, People’s Republic of China, Email jianjiyong3137@bjsjth.cnPurpose: We investigated the Epidemiology, risk factors and outcomes of Candida bloodstream infection.Methods: The electronic laboratory records data of patients with candidemia (2015– 2022) were collected. We used univariate and multivariate logistic regression to determine the risk factors of candidemia.Results: Of the 134 patients with candidemia, the most prevalent species were Candida albicans (37.2%), followed by Candida glabrata (27.7%), Candida parapsilosis (18.9%), and others. The mean annual incidence was 0.33/1000 admissions. The overall resistance rate of Candida spp. against fluconazole and voriconazole were 4.9% (7/142) and 5.9% (6/101), while Candida tropicalis showed high resistance to fluconazole (38.8%) and voriconazole (27.8%). The 30-day mortality rate was 32.8%. On multivariate analysis, age ≥ 65 (odds ratio [OR] = 3.874, 95% confidence interval [CI]: 1.146, 13.092; P = 0.029), high Acute Physiology and Chronic Health Evaluation II (APACHE II) score (OR = 12.384, 95% CI: 2.963, 51.762; P = 0.001), shock (OR = 3.428, 95% CI: 1.097, 10.719; P = 0.034), initial antifungal therapy (OR = 0.057, 95% CI: 0.011, 0.306; P = 0.001) and White blood cells (OR = 1.129, 95% CI: 1.016, 1.255; P = 0.024) were the independent risk factors with mortality within 30 day in patients with candidemia.Conclusion: The incidence rate and the mortality rate of candidemia are high, and lower azole susceptibility was found in Candida tropicalis. Age≥ 65 years, Shock, high APACHE II score, Antifungal therapy and White blood cells count were independently associated with 30-day mortality.Keywords: Candidemia, Epidemiology, Antifungal susceptibility, Mortality, Risk factors

Abstract Federated learning (FL) has emerged as a significant method for developing machine learning models across multiple devices without centralized data collection. Candidemia, a critical but rare disease in ICUs, poses challenges in early detection and treatment. The goal of this study is to develop a privacy-preserving federated learning framework for predicting candidemia in ICU patients. This approach aims to enhance the accuracy of antifungal drug prescriptions and patient outcomes. This study involved the creation of four predictive FL models for candidemia using data from ICU patients across three hospitals in China. The models were designed to prioritize patient privacy while aggregating learnings across different sites. A unique ensemble feature selection strategy was implemented, combining the strengths of XGBoost’s feature importance and statistical test p values. This strategy aimed to optimize the selection of relevant features for accurate predictions. The federated learning models demonstrated significant improvements over locally trained models, with a 9% increase in the area under the curve (AUC) and a 24% rise in true positive ratio (TPR). Notably, the FL models excelled in the combined TPR + TNR metric, which is critical for feature selection in candidemia prediction. The ensemble feature selection method proved more efficient than previous approaches, achieving comparable performance. The study successfully developed a set of federated learning models that significantly enhance the prediction of candidemia in ICU patients. By leveraging a novel feature selection method and maintaining patient privacy, the models provide a robust framework for improved clinical decision-making in the treatment of candidemia.

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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.

Abstract 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.

Candidemia, linked to high mortality rates, requires prompt antifungal therapy for better outcomes. Treatment is structured as an action bundle, which is beneficial when followed closely. However, the Japanese action bundle lacks detailed guidance on severe complications like endocarditis or ocular issues. To address this, we adjusted the action bundle and assessed outcomes with and without AFT intervention. We strengthened protocols for blood cultures and organ assessments, and the AFT contacted the primary physician when yeast-like fungi were detected in the patient’s blood culture bottles. Analyzing 204 candidemia cases from 2008–2021, we observed increased adherence and reduced mortality post-AFT intervention. Ophthalmology consultations rose significantly, but many patients had only one visit, suggesting inadequate follow-up. If endophthalmitis is diagnosed, a change in the treatment approach may be necessary. There is a possibility that abnormal ocular findings will be detected during subsequent visits, which highlights the need for improvement in ophthalmology follow-up rates as a future challenge for our AFT activities.

In recent years, an evident rise in the frequency of candidaemia caused by non-albicans Candida species has been reported. Candida utilis is a low-virulence fungus that is commonly used in the food processing industry. Only a few studies have reported invasive infection due to C. utilis. In this paper, we present two cases of clinically manifested candidaemia and sepsis caused by C. utilis. This was a retrospective study carried out at a tertiary intensive care center in Turkey. Two C. utilis were isolated from blood culture over a 6-month period. C. utilis fungemia has mainly been reported in immunocompromised patients, neonates, and following surgical intervention. The two cases discussed here did not have a defined immunodeficiency. Both patients had common risk factors such as prolonged stay in the pediatric intensive care unit and the presence of a central venous catheter. Our aim in reporting these cases is to highlight C. utilis as a probable cause of candidemia in hospitalized pediatric patients and can be mortal.

Background: The aim of this study was to investigate the usefulness of serum procalcitonin (PCT), C-reactive protein (CRP), neutrophil to lymphocyte count ratio (NLR), and their combination, in distinguishing candidemia from bacteremia in intensive care unit (ICU) patients. Methods: This is a retrospective study in ICU patients with documented bloodstream infections (BSIs) and with both serum PCT and CRP measurements on the day of the positive blood sample. Illness severity was assessed by sequential organ failure assessment (SOFA) score on both admission and BSI day. Demographic, clinical, and laboratory data, including PCT and CRP levels and NLR on the day of the BSI, were recorded. Results: A total of 63 patients were included in the analysis, of whom 32 had bacteremia and 31 had candidemia. PCT, CRP, and NLR values were all significantly lower in candidemia compared with bacteremia (0.29 (0.14–0.69) vs. 1.73 (0.5–6.9) ng/mL, p < 0.001, 6.3 (2.4–11.8) vs. 19 (10.7–24.8) mg/dl, p < 0.001 and 6 (3.7–8.6) vs. 9.8 (5.3–16.3), p = 0.001, respectively). PCT was an independent risk factor for candidemia diagnosis (OR 0.153, 95%CI: 0.04–0.58, p = 0.006). A multivariable model consisting of the above three variables had better predictive ability (AUC-ROC = 0.88, p < 0.001), for candidemia diagnosis, as compared to that of PCT, CRP, and NLR, whose AUC-ROCs were all lower (0.81, p < 0.001, 0.78, p < 0.001, and 0.68, p = 0.015, respectively). Conclusions: A combination of routinely available laboratory tests, such as PCT, CRP, and NLR, could prove useful for the early identification of ICU patients with candidemia. [ABSTRACT FROM AUTHOR]

No guidelines currently exist for the management of Candida auris bloodstream infection in patients with left ventricular assist devices (LVADs). We aim to share our management experience through this retrospective case series outlining 15 episodes of C auris candidemia identified in 7 patients over 18 months. The initial source of candidemia was central venous catheter in 5 patients, driveline exit site infection in 1 patient, and possible pump infection in 1 patient. All patients were initially treated with micafungin. Despite susceptibility to micafungin, 4 patients experienced recurrent C auris candidemia. All patients died within 1 year of their first episode of C auris candidemia. Source control is challenging in patients with LVADs, and strict infection prevention measures should be practiced. More studies are needed to evaluate the role of newer antifungal agents, use of combination antifungal regimens, and impact on morbidity in patients with LVADs. [ABSTRACT FROM AUTHOR]

Background Reports of fluconazole-resistant Candida parapsilosis bloodstream infections are increasing. We describe a cluster of fluconazole-resistant C parapsilosis bloodstream infections identified in 2021 on routine surveillance by the Georgia Emerging Infections Program in conjunction with the Centers for Disease Control and Prevention. Methods Whole-genome sequencing was used to analyze C parapsilosis bloodstream infections isolates. Epidemiological data were obtained from medical records. A social network analysis was conducted using Georgia Hospital Discharge Data. Results Twenty fluconazole-resistant isolates were identified in 2021, representing the largest proportion (34%) of fluconazole-resistant C parapsilosis bloodstream infections identified in Georgia since surveillance began in 2008. All resistant isolates were closely genetically related and contained the Y132F mutation in the ERG11 gene. Patients with fluconazole-resistant isolates were more likely to have resided at long-term acute care hospitals compared with patients with susceptible isolates (P =.01). There was a trend toward increased mechanical ventilation and prior azole use in patients with fluconazole-resistant isolates. Social network analysis revealed that patients with fluconazole-resistant isolates interfaced with a distinct set of healthcare facilities centered around 2 long-term acute care hospitals compared with patients with susceptible isolates. Conclusions Whole-genome sequencing results showing that fluconazole-resistant C parapsilosis isolates from Georgia surveillance demonstrated low genetic diversity compared with susceptible isolates and their association with a facility network centered around 2 long-term acute care hospitals suggests clonal spread of fluconazole-resistant C parapsilosis. Further studies are needed to better understand the sudden emergence and transmission of fluconazole-resistant C parapsilosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are available online to subscribers. Monographs can be customized to meet the needs of a facility. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, contact Wolters Kluwer customer service at 866-397-3433. [ABSTRACT FROM AUTHOR]

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. 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). 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. 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. [ABSTRACT FROM AUTHOR]

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. 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. 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. albican s, 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. 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. [ABSTRACT FROM AUTHOR]

Background: The intensive care unit (ICU) is a treatment room exposed to nosocomial infections. Mechanical ventilation support is often required by 10%-20% of patients admitted to the ICU, where there is a risk of candidemia occurrence. Candidemia is a disease that occurs in any patient at a health care facility, where Candida species are found in blood culture specimens processed at laboratories. Candida species are some of the most common species causing bloodstream infections in nonneutropenic patients treated in the ICU and are responsible for 8%-12% of cases. Antifungal prophylaxis is often used in ICU for patients prone to candidemia using the Candida score, which includes parameters such as Candida colonization, history of surgery, severe sepsis, and total parenteral nutrition. Nystatin is considered a prophylactic antifungal in the ICU to reduce the incidence of candidemia and the morbidity and mortality of patients in the ICU. Methods: This was a randomized clinical trial conducted using a double-blind method. After approval by the Faculty of Medicine Ethics Committee, Universitas Sumatera Utara, Medan, 40 research samples were collected, which were randomly divided into two groups after verifying the inclusion criteria. Groups A and B received 100,000 IU nystatin and 0.9% NaCl, respectively. The obtained research data were tested using a Statistical Package for the Social Sciences (SPSS). Results: Positive blood culture results were fewer in the nystatin group than in the 0.9% NaCl group (3 vs. 4). Additionally, positive tracheal aspirate culture results were fewer in the nystatin group than in the 0.9% NaCl group (0 vs. 1). The largest distribution of Candida in blood culture was Candida tropicalis, whereas only one species of Candida glabrata was found in tracheal aspirate culture. The 7th-day mortality in the nystatin group was lower than that in the 0.9% NaCl group (11 vs. 14). Conclusion: Nystatin effectively reduced the incidence of candidemia, which was lower in the nystatin group than in the 0.9% NaCl group. Moreover, tracheal aspirate culture results in the nystatin group were better than those in the 0.9% NaCl group. Furthermore, the 7th-day mortality rate in the nystatin group was lower than that of the 0.9% NaCl group. The most distributed Candida species in the blood culture was Candida tropicalis, whereas only one species, Candida glabrata, was found in the tracheal aspirate culture. [ABSTRACT FROM AUTHOR]