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Background: Alteration in the etiology of pediatric bloodstream infections (BSIs) and antimicrobial resistance (AMR) is not well known during the Coronavirus disease 2019 (COVID-19) pandemic. This study aimed to investigate the impact of the COVID-19 pandemic on pediatric BSIs and alteration in antimicrobial resistance phenotypes in Gram-positive bacteria., Methods: The frequency of BSIs among children under 18 years old was retrospectively recorded in a tertiary children's hospital in Tehran, Iran from February 2020 to December 2022. The status of COVID-19 infection using reverse transcription polymerase chain reaction, bacteremia/fungemia according to BACTEC 9120 Culture System results, characterization of bacteria using biochemical tests, and antimicrobial susceptibility patterns for Gram-positive bacterial isolates using disk diffusion method were determined. Statistical analysis was done to measure the correlation of COVID-19 infection with BSIs and AMR., Results: Out of 13,345 COVID-19 tests and 4,194 BACTEC blood culture requests, bacteremia/fungemia were confirmed in 10.37% (435/4,194) of the patients who requested both tests simultaneously. The COVID-19 infection was confirmed in 25.3% (110/435) of the patients with bacteremia/fungemia. The infection with characterized Gram-positive bacteria (GPB) and fungi was detected in 32.3% (140/433) and 8.31% (36/433) of the cases, respectively. Coagulase-negative Staphylococcus (CNS, 72, 16.62%), S. aureus (36, 8.3%), and Enterococcus spp. (22, 5%) were among the common isolates. Candida spp. and non-Candida yeasts were detected in 6.7% and 13.4% of the cases, respectively. A positive correlation was shown between the CNS bacteremia and COVID-19 infection (p-value = 0.019). Antibiotic susceptibility testing results showed the highest frequency of resistance to azithromycin among CNS, azithromycin and tetracycline among S. aureus and tetracycline among Enterococcus spp. Methicillin-resistance phenotype in the S. aureus (MRSA) and coagulase-negative Staphylococcus spp. (MR-CNS) was detected in 40% and 61.5% of the strains, respectively and the Enterococci were resistant to vancomycin in 33.3% of the isolates., Conclusion: A decline in the trend of BSIs by GPB and an increase in AMR was shown in children during the COVID-19 pandemic. Increasing antibiotic resistance is a concern; however, chloramphenicol, linezolid, and vancomycin remain active against common causes of GPB-BSIs., (© 2024. The Author(s).)

Phaeohyphomycosis is caused by dematiaceous (pigmented) fungi. Most phaeohyphomycosis is non-invasive infections, however, they can lead to invasive infections, including fungemia and disseminated disease, particularly in severely immunocompromised patients. Invasive phaeohyphomycosis has recently emerged, however, the treatment strategy was not determined because of the intrinsic resistance to antifungals and the lack of clinical experience. Here, we describe a novel case of echinocandin-breakthrough Coniochaeta hoffmannii (Lecythophora hoffmannii) fungemia after hematopoietic stem cell transplantation, which was identified using matrix-assisted laser desorption ionization time-of-flight mass spectrometry and ribosomal RNA sequencing. The patient was a female in her 40s who had acute myeloid leukemia refractory to chemotherapy before progressing to cord blood transplantation. Before developing fungemia, the patient was administered multiple broad-spectrum antibiotics and micafungin for recurrent infections and prophylaxis. Clinical and microbiological responses to liposomal amphotericin B were poor but improved after replacement to voriconazole and engraftment. A literature review of the previously reported cases with C. hoffmannii human infections imply that disruption of the cutaneous/mucosal barrier and the use of antimicrobial agents, both antibiotics and antifungals, could incite C. hoffmannii invasive infections., Competing Interests: Declaration of Competing interest All authors declare no conflicts of interest associated with this manuscript., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Lomentospora prolificans is an uncommon cause of invasive fungal disease, but it is associated with high mortality because it is difficult to treat. Most of severe cases are produced in immunossupressed patients, especially in those with neutropenia and/or hematological malignancies. Resistance to the majority of antifungal agents can be still observed. Here we report two cases of L. prolificans fungemia with different outcome, since in one of these patients treatment with one of the new antifungals could be applied. Both patients were treated with different antifungal drugs, but only the second one survived due to therapy with fosmanogepix®. The current treatment is still based on a combination of conventional antifungal drugs, although in much cases this strategy is not sufficient. The introduction of new promising antifungal agents such as fosmanogepix® and olorofim® may open new perspectives in the treatment of invasive infections caused by L. prolificans, as in our patient., Competing Interests: Declaration of competing interest The authors declare no competing interest, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Fungal colonization poses a significant risk for neonates, leading to invasive infections such as fungemia. While Candida species are the most commonly identified pathogens, other rare yeasts are increasingly reported, complicating diagnosis and treatment due to limited data on antifungal pharmacokinetics. These emerging yeasts, often opportunistic, underscore the critical need for early diagnosis and targeted therapy in neonates. This systematic review aims to comprehensively analyze all published cases of neonatal fungemia caused by rare opportunistic yeasts, examining geographical distribution, species involved, risk factors, treatment approaches, and outcomes. Searching two databases (PubMed and SCOPUS), 89 relevant studies with a total of 342 cases were identified in the 42-year period; 62% of the cases occurred in Asia. Pichia anomala (31%), Kodamaea ohmeri (16%) and Malassezia furfur (15%) dominated. Low birth weight, the use of central catheters, prematurity, and the use of antibiotics were the main risk factors (98%, 76%, 66%, and 65%, respectively). 22% of the cases had a fatal outcome (80% in Asia). The highest mortality rates were reported in Trichosporon beigelii and Trichosporon asahii cases, followed by Dirkmeia churashimamensis cases (80%, 71%, and 42% respectively). Low birth weight, the use of central catheters, the use of antibiotics, and prematurity were the main risk factors in fatal cases (84%, 74%, 70%, and 67%, respectively). 38% of the neonates received fluconazole for treatment but 46% of them, died. Moreover, the rare yeasts of this review showed high MICs to fluconazole and this should be taken into account when planning prophylactic or therapeutic strategies with this drug. In conclusion, neonatal fungemia by rare yeasts is a life-threatening and difficult-to-treat infection, often underestimated and misdiagnosed.

Saccharomyces cerevisiae is a yeast used mainly as a probiotic for prevention or treatment of diarrhoea. However, the prevalence of S. cerevisiae fungemia has risen over the past years, notably among patients with predisposing factors. This retrospective study presents 21 cases of S. cerevisiae fungemia at the University Hospital of Liege from 2000 to 2022, their clinical relevance and therapeutic management. Each patient presented one or several risk factors prior to fungemia. The isolated strains presented high minimal inhibitory concentration for fluconazole, while MICs for amphotericin B, voriconazole and echinocandins were low. Some patients received antifungal therapy, while for others only central and peripheral lines were removed and probiotics discontinued. The MICs obtained for voriconazole and echinocandins makes them an alternative treatment to fluconazole and amphotericin B as reported in other studies. Since a S. cerevisiae fungemia can induce the same complications as candidemia, follow-up blood cultures should be collected and metastatic foci should be looked for. This study showed an important discrepancy in the clinical management of infections due to S. cerevisiae and highlights the need for guidelines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Competing Interests: Competing interests: CR reports grant funding from the Centers for Disease Control and Prevention and Agency for Healthcare Research and Quality to conduct research related to sepsis and healthcare-associated infections, and royalties from UpToDate, Inc. JS reports grant funding from the Agency for Healthcare Research and Quality unrelated to this work.

Mucormycosis is a rare life-threatening opportunistic infection, with rhinocerebral mucormycosis (ROCM) being the most common presentation. Trichosporon asahii is an emerging pathogen that often causes fatal infections in patients with underlying hematologic malignancies due to its high drug resistance. We report a rare case of concomitant rhinocerebral mucormycosis and T. asahii fungemia secondary to Pseudomonas aeruginosa sepsis in a patient with neutropenia and acute lymphoblastic leukemia. A boy aged one year and two months was diagnosed with B-cell acute lymphoblastic leukemia on January 10 and underwent three courses of regular chemotherapy. He experienced neutropenia for 154 days and was hospitalized for vomiting, diarrhea and fever for 3 days. The day after hospitalization, Pseudomonas aeruginosa was isolated by blood culture and ceftazidime/avibactam was administered. Extracorporeal Membrane Oxygenation (ECMO) was used to provide continuous extracorporeal respiration and circulation for the patient. On day 8, the patient developed T. asahii fungemia. On day 10, he presented with necrotizing skin caused by Rhizopus delemar. He was treated with liposomal amphotericin B for Rhizopus delemar and voriconazole for T. asahii infection. Unfortunately, his health deteriorated and he died on day 11 due to the rapid progression of the infection and multiple organ failure. The management and treatment of such a complex infection requires a multidisciplinary approach and close monitoring of the patient's condition. Therefore, it is imperative to continue to research and report rare cases such as this to further understand the complexities of mucormycosis and trichosporidiosis coinfection and improve patient outcomes.

Severe nephrotoxicity and infusion-related side effects pose significant obstacles to the clinical application of Amphotericin B (AmB) in life-threatening systemic fungal infections. In pursuit of a cost-effective and safe formulation, we have introduced multiple phenylboronic acid (PBA) moieties onto a linear dendritic telodendrimer (TD) scaffold, enabling effective AmB conjugation via boronate chemistry through a rapid, high yield, catalysis-free and dialysis-free "Click" drug loading process. Optimized AmB-TD prodrugs self-assemble into monodispersed micelles characterized by small particle sizes and neutral surface charges. AmB prodrugs sustain drug release in circulation, which is accelerated in response to the acidic pH and Reactive Oxygen Species (ROS) in the infection and inflammation. Prodrugs mitigate the AmB aggregation status, reduce cytotoxicity and hemolytic activity compared to Fungizone®, and demonstrate superior antifungal activity to AmBisome®. AmB-PEG 5k BA 4 has a comparable maximum tolerated dose (MTD) to AmBisome®, while over 20-fold increase than Fungizone®. A single dose of AmB-PEG 5k BA 4 demonstrates superior efficacy to Fungizone® and AmBisome® in treating systemic fungal infections in both immunocompetent and immunocompromised mice., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Scedosporium/Lomentospora is an opportunistic fungal pathogen found worldwide. While Scedosporium apiospermum and Scedosporium boydii are commonly observed globally, Lomentospora prolificans, which mainly affects immunosuppressed individuals, is rarely encountered and is more prevalent in arid climates, particularly in Australia and Spain. L.prolificans is a fungus commonly found in environmental sources such as contaminated water and soil. This species is known as an opportunistic pathogen that can cause deep-seated fungal infections, especially in immunosuppressed individuals. In this case report, a fatal case of L.prolificans fungemia in a patient with T-cell large granular leukemia during profound neutropenia was presented. The patient admitted to the hospital with prolonged fever, neutropenia, and shortness of breath. Antibiotherapy was administered to the patient for febrile neutropenia, but the fever persisted and his clinical status rapidly deteriorated. L.prolificans was isolated from the blood culture, and considering its antifungal resistance, combination therapy of voriconazole and terbinafine was initiated. However, the patient died of septic shock and multiple organ failure. In conclusion, although L.prolificans infections are rare, they can be life-threatening, especially in immunosuppressed individuals. Diagnosis and treatment of such infections may be difficult, therefore rapid diagnostic methods and appropriate treatment protocols should be developed. Consideration of infections caused by rare fungal pathogens in patients with risk factors may be critical for patient care. The literature review revealed that the first case of L.prolificans fungemia from Türkiye was reported in 2023. This case presentation represents the second reported case. However, in our case, L.prolificans fungemia occurred in 2018, it can be considered that L.prolificans may have been an invasive fungal pathogen of significant concern in Türkiye much earlier than previously documented.

Fungemia caused by Geotrichum spp. is rare and highly lethal. The Instituto Nacional de Cancerología in Bogotá reported just two cases: one in the period 2001-2007 and the other in 2012-2018. This type of infection is more common in any kind of immunocompromised patients, so it can occur in those with hematological malignancies. Here we present the case of a 27-year-old man, diagnosed with acute lymphoblastic leukemia in relapse and admitted with polyarthralgia for five days, febrile neutropenia, nonabscessed cellulitis, and bacteremia due to methicillin-sensitive Staphylococcus aureus. The patient received therapy with oxacillin and cefepime, but the febrile neutropenia persisted. A new set of blood cultures was taken, and antifungal treatment was started because of the suspicion of invasive fungal infection. Arthroconidia were identified in blood cultures and Geotrichum spp. was confirmed using matrix-assisted laser desorption-ionization mass spectrometry. The antifungal treatment was adjusted with amphotericin B deoxycholate for 14 days and voriconazole for four weeks, and after a prolonged stay, the patient was discharged. Although the incidence of fungemia caused by Geotrichum spp. is low, it must be considered in patients with hematological malignancies and persistent febrile neutropenia despite the broadspectrum antimicrobial treatment. The confirmation of fungemia causing agents, with proteomic tools such as the mentioned mass spectrometry, allows treatment adjustment and decreases complications, hospital stay, and mortality.

Introduction: Non-Candida yeasts, although rare, are increasingly encountered and recognized as a growing threat., Methods: Cases of bloodstream infections (BSIs) due to non-Candida yeasts (NCYs) during the last four years (2018-2021) are presented., Results: During the study period, 16 cases caused by non-Candida yeasts out of 400 cases of yeast BSIs were recorded, corresponding to an incidence of 4%. Yeasts that were isolated included Cryptococcus spp (4 isolates-25%), Rhodotorula mucilaginosa (2 isolates-12.5%), Trichosporon asahii (7 isolates-43.75%) and Saccharomyces cerevisiae (3 isolates-18.75%). Predisposing factors involved mostly hematological malignancies, long term hospitalization or major surgical interventions. Most isolates, 15 out of 16 were susceptible to amphotericin B. Voriconazole was the most active azole in vitro. All isolates, except Saccharomyces spp., were resistant to echinocandins., Discussion: Early recognition of rare yeasts as causative agents of BSIs and prompt initiation of appropriate treatment based on current guidelines and expertise remain crucial in efficient patient management., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 SFMM. Published by Elsevier Masson SAS. All rights reserved.)

Background: Aspergillus fungemia is encountered infrequently in clinical practice, even in the setting of invasive and disseminated disease. Prolonged Aspergillus fungemia secondary to a central venous catheter is notably rarer., Methods: We describe the case of a 13-year-old boy with Aspergillus fungemia in the setting of a central venous catheter who was found to have pulmonary aspergillosis upon evaluation. We reviewed the literature for published cases of catheter-related Aspergillus fungemia and summarized the findings. We also sought to differentiate true fungemia from pseudofungemia and explored the clinical significance of aspergillemia., Results: We found 6 published cases of catheter-related Aspergillus fungemia in addition to the 1 discussed in this report. Based on the review of case findings, we propose an algorithm for an approach to a patient with a positive blood culture for Aspergillus spp., Conclusions: True aspergillemia is infrequent even in the setting of disseminated aspergillosis among immunocompromised patients and the presence of aspergillemia does not necessarily portend more severe clinical disease course. The management of aspergillemia should involve a determination of the possibility of contamination, and if deemed genuine, a thorough workup to define the extent of the disease process. Treatment durations should be based on tissue sites of involvement and could be shorter in the absence of tissue-invasive disease., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Recent research has suggested that fungemia may demonstrate an epidemiologic shift in etiologic agents. This study focuses on the agents causing fungemia and antifungal resistance in a tertiary hospital., Patients and Methods: We evaluated all-age fungemia cases admitted to Balikesir Ataturk City Hospital in 2017-2021. Blood cultures (BC) were studied using BacT/Alert® 3D (bioMérieux, Marcyl'Etoile, France) and Render BC128 System (Render Biotech Co. Ltd., Shenzhen, China). On the data, we explored only the first fungal positive samples or the first isolates in different episodes of the same patients. Upon The Clinical and Laboratory Standards Institute (CLSI) disk diffusion guidelines, conventional methods and the Phoenix™ 100 System (Becton Dickinson, Franklin Lakes, NJ, USA) were utilized for antifungal susceptibility identifications., Results: The findings showed that 325 (0.84%) of 38,682 BC sets were positive for fungal growth. Except for four cases (1.2%) [Saprochaete capitata (n = 2); Trichosporon asahii (n = 1), and Saccharomyces cerevisiae (n = 1)], all positive cases yielded Candida spp. (98.8%) growth. In these patients, the following Candida spp. were isolated: Candida albicans complex (n = 155; 47.7%), Candida parapsilosis complex (n = 127; 39.1%), Candida glabrata complex (n = 19; 5.85%), Candida tropicalis (n = 12; 3.7%), Candida kefyr (n = 5; 1.54%), Candida krusei (n = 2; 0.62%), and Candida guilliermondii complex (n = 1; 0.31%). We also realized that while none of the Candida spp. had echinocandin resistance, 8 C. parapsilosis complex isolates were resistant to fluconazole, and 17 C. parapsilosis complex and 2 C. tropicalis isolates were susceptible dose-dependent to fluconazole., Conclusions: In brief, antifungal resistance is more likely to restrict therapeutic options, albeit it is, fortunately, not prevalent in Turkey despite a few recent reports. Yet, a robust detection or management of antifungal resistance requires species-level identification and strict compliance with relevant management guidelines. Besides, challenges in research may be compensated with a national data set built with data from local laboratories.

Objectives: We investigated whether patients with cryptococcal meningitis (CM) or fungaemia detected through South Africa's laboratory cryptococcal antigen (CrAg) screening programme had better outcomes than those presenting directly to the hospital., Methods: We compared 14-day in-hospital case-fatality ratios of HIV-seropositive individuals with CD4 counts below 100 cells/μL and laboratory-confirmed CM/fungaemia from 2017-2021, with or without evidence of a positive blood CrAg test within 14 days prior to diagnosis. We evaluated whether the impact of prior CrAg screening on mortality varied according to the study period (pre-COVID-19: before March 2020 vs. COVID-19: after March 2020)., Results: Overall, 24.5% (830/3390) of patients had a prior positive CrAg test within 14 days of diagnosis. CrAg-screened patients were less likely to have an altered mental status at baseline than non-CrAg-screened patients (38.1% [296/776] vs. 42.6% [1010/2372], p = 0.03), and had a lower crude 14-day case-fatality ratio (24.7% [205/830] vs. 28.3% [724/2560]; OR, 0.83 [95% CI, 0.69-0.99]; p = 0.045). Previous CrAg screening was associated with a greater reduction in the crude 14-day mortality during the COVID-19 period (OR, 0.64 [0.47-0.87]; p = 0.005) compared with before (OR, 0.95 [0.76-1.19]; p = 0.68). After adjustment, previous CrAg screening within 14 days was associated with increased survival only during the COVID-19 period (adjusted OR, 0.70 [0.51-0.96]; p = 0.03)., Discussion: Previous CrAg screening was associated with a survival benefit in patients hospitalized with CM/fungaemia during the COVID-19 period, with fewer patients having an altered mental status at baseline, suggesting that these patients may have been diagnosed with cryptococcosis earlier., (Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Lodderomyces elongisporus is a recently emerging yeast pathogen predominantly reported in adult patients who had immunosuppression and/or intravenous access devices. Here, we report a fungemia outbreak caused by L. elongisporus in a neonatal intensive care unit (NICU) in Delhi, India, from September 2021 to February 2022. All 10 neonates had low birthweight, and nine of the patients survived after amphotericin B treatment. Whole-genome sequence analyses of the patient isolates as well as those from other sources in India grouped them into two clusters: one cluster consists of isolates exclusively from stored apples and the other cluster includes isolates from patients, clinical environments, and stored apples. All outbreak strains from patients were closely related to each other and showed highly similar heterozygosity patterns across all 11 major scaffolds. While overall very similar, strains from the inanimate environment of the same neonatal intensive care unit showed loss of heterozygosity at scaffold 2 (NW_001813676) compared to the patient strains. Interestingly, evidence for recombination was found in all samples. All clinical strains were susceptible to 10 tested antifungal drugs, and comparisons with strains with high fluconazole MICs derived from the surface of stored apples revealed significant genome divergence between the clinical and apple surface strains, including 119 nonsynonymous single nucleotide polymorphisms (SNPs) in 24 triazole resistance-related genes previously found in other Candida spp. Together, our results indicate significant diversity, recombination, and persistence in the hospital setting and a high rate of evolution in this emerging yeast pathogen. IMPORTANCE Lodderomyces elongisporus was initially considered a teleomorph of Candida parapsilosis. However, DNA sequence analyses revealed it as a distinctive species. Invasive infections due to L. elongisporus have been reported globally. We report an outbreak of fungemia due to L. elongisporus in a NICU affecting 10 preterm, low-birthweight neonates during a period of 6 months. The outbreak investigation identified two environmental sites, the railing and the temperature panel of the neonate open care warmer, harboring L. elongisporus . Whole-genome sequencing confirmed that the neonate isolates were closely related to each other whereas strains from the inanimate clinical environment were related to clinical strains but showed a marked loss of heterozygosity. Further, L. elongisporus strains recovered previously from the surface of stored apples showed high fluconazole MICs and alterations in triazole resistance-related genes. Genome-wide SNP comparisons revealed recombination as an important source for genomic diversity during adaptation of L. elongisporus to different environments., Competing Interests: The authors declare no conflict of interest.

Background: Saccharomyces cerevisiae is ubiquitous in the gastrointestinal tract and known as brewer's or baker's yeast. We experienced a case of S. cerevisiae and Candida glabrata co-infectious bloodstream infection. It is rare to detect both S. cerevisiae and Candida species in blood cultures together., Case: We treated a 73-year-old man who developed a pancreaticoduodenal fistula infection after pancreaticoduodenectomy. The patient had a fever on postoperative day 59. We took blood cultures and detected C. glabrata. Thus, we started micafungin. On postoperative day 62, we retested blood cultures, and detected S cerevisiae and C. glabrata. We changed micafungin to liposomal amphotericin B. Blood cultures became negative on postoperative day 68. We changed liposomal amphotericin B to fosfluconazole and micafungin because of hypokalemia. He got well, and we terminated antifungal drugs 18 days after the blood cultures became negative., Conclusion: Co-infection with S. cerevisiae and Candida species is rare. In addition, in this case, S. cerevisiae developed from blood cultures during micafungin administration. Thus, micafungin may not be effective enough to treat S. cerevisiae fungemia, although echinocandin is considered one of the alternative therapy for Saccharomyces infections., (© 2023. The Author(s).)

Stenotrophomonas maltophilia is known to be an opportunistic pathogen with intrinsic and acquired resistance mechanisms to multiple antibiotics. Bloodstream infection caused by S. maltophilia is a potentially fatal complication, especially in recipients of umbilical cord blood transplantation (CBT). Infrequent reports of S. maltophilia skin and soft tissue infections (SSTIs), including metastatic cellulitis and ecthyma gangrenosum, have been reported as wound infections. Metastatic cellulitis lesions due to S. maltophilia are typically reported to be tender, erythematous, and to show warm subcutaneous infiltration. There are only a few available reports about the clinical course of metastatic cellulitis due to S. maltophilia. We experienced a case involving the development of metastatic cellulitis with fulminant and extensive exfoliation in a patient who underwent CBT. Despite controlling the bloodstream infection caused by S. maltophilia, the patient succumbed to secondary fungal infection due to the devastation of the skin barrier. Our case highlights that SSTIs due to S. maltophilia can cause the unexpected development of fulminant metastatic cellulitis with systemic epidermal peeling in severely immunocompromised hosts, including CBT recipients undergoing steroid therapy., Competing Interests: DISCLOSURES All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The incidence of invasive candidiasis in pediatric patients is increasing and is associated with significant morbidity and mortality. C. pelliculosa has been rarely reported as a human pathogen, however, it has been associated with serious nosocomial infections and clonal outbreaks with poor clinical outcomes in immunocompromised children were reported. Here, we describe the first case of candidemia due to Candida pelliculosa in a 5-year-old immunocompromised male suffered from Griscelli syndrome with hemophagocytic syndrome hospitalized in the pediatric intensive care unit (PICU), Tehran, Iran. In addition, the history of reported cases or case-series due to C. pelliculosa is reviewed., Competing Interests: Conflicts of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022. Published by Elsevier Masson SAS.)

Fungemia due to Saccharomyces species is reported in considerable numbers, and the increase is attributed to using Saccharomyces boulardii probiotics in clinical settings. The present systematic review addresses the underlying diseases and risk factors in Saccharomyces fungemia patients, along with the treatment and outcome of the disease. The MEDLINE, Scopus, Embase, and Web of Science databases were searched systematically with appropriate keywords from June 2005 to March 2022. This review identified 117 Saccharomyces fungemia cases; 108 cases were included in the analysis. Saccharomyces fungemia is commonly seen in patients treated with S. boulardii probiotics (n = 73, 67.6%), and 35 (32.4%) patients did not receive probiotic therapy. The underlying disease and risk factors significantly associated with S. boulardii probiotic-associated fungemia were intensive care unit stay (n = 34, 31.5%), total parenteral nutrition or enteral feeding (n = 32, 29.6%), patients with gastrointestinal symptoms such as diarrhea (n = 23, 21.3%), and diabetes mellitus (n = 14, 13.0%). In patients without probiotic therapy, immunosuppression (n = 14, 13.0%), gastrointestinal surgery (n = 5, 4.6%), and intravenous drug use (n = 5, 4.6%) were the significant risk factors for Saccharomyces fungemia. The all-cause mortality rate of the total cohort is 36.1%. No significant variation in the mortality rate is observed between S. boulardii probiotic treated patients (n = 29, 26.9%) and patients without probiotic therapy (n = 10, 9.3%). In conclusion, S. boulardii probiotic therapy in debilitated critical care patients may have contributed to increased Saccharomyces fungemia cases. Further, clinicians should be vigilant in preventing S. boulardii fungemia in patients with prophylactic probiotic therapy., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Listeria monocytogenes is a Gram-positive bacteria and etiological agent of listeriosis. It has the ability to colonize the intestinal lumen and cross the intestinal, blood-brain, and placental barriers, leading to invasive listeriosis responsible for septicemia and meningitis in subjects at risk such as patients with diabetes mellitus, the elderly, and immunocompromised individuals and, for maternal-neonatal infection in pregnant women. We report a rare case of L. monocytogenes septicemia and meningitis complicated by Candida glabrata fungemia on a patient with a history of type 2 diabetes mellitus, hypothyroidism, hypertension, chronic kidney failure, chronic ischemic vascular encephalopathy, and atrial fibrillation. Although adequate therapy was rapidly started with an initial partial clinical improvement, the patient suddenly experienced clinical worsening concomitantly with Candida septicemia resulting in a fatal outcome. To our knowledge, this is the first described case of an invasive L. monocytogenes infection complicated by Candida sepsis. We hypothesize that concomitant Candida infection may play a significant role in the pathogenesis and virulence of L. monocytogenes .

Background: Candida auris is an emerging nosocomial pathogen worldwide. However, there has been little published on the management of C. auris in solid organ transplant recipients., Methods: A single-center, retrospective cohort study was conducted to evaluate C. auris bloodstream infections in solid organ transplant recipients between January 2020 and December 2021. Patient-related and outcomes data were extracted from electronic medical records., Results: Of the 42 patients identified with C. auris bloodstream infections, five were in solid organ transplant recipients (1 heart, 3 liver, and 1 combined liver-kidney). The median time to fungemia from hospital admission was 43 days, and the median time to fungemia from transplant was 18 days. All patients received micafungin as initial treatment, at a median of 6 hours from pathogen detection. Four patients achieved blood clearance, two patients had persistent fungemia, and two patients developed secondary complications from hematogenous spread. One patient died, resulting in a mortality rate of 20%., Conclusions: Solid organ transplant recipients are at high risk for developing C. auris bloodstream infections. In order to prevent graft loss and mortality, best practices for the management of C.auris should include rapid screening, diagnosis, and treatment. While echinocandins are considered first-line, antifungal selection should be based on susceptibilities and site of infection. Data to support routine use of combination therapy are lacking, however there may be a role for refractory cases. Prevention efforts against C. auris infection are especially important given the lack of effective decolonization strategies. For transplant recipients, hospitals should seek opportunities to restore patients' gut microbiome by curtailing unnecessary hospital procedures and inappropriate antimicrobial use. Further research and national guidelines are needed to better direct stewardship in this field., (© 2022 Wiley Periodicals LLC.)

Candida dubliniensis phenotypically mimics Candida albicans in its microbiological features; thus, its clinical characteristics have yet to be fully elucidated. Here we report the case of a 68-year-old Japanese man who developed C. dubliniensis fungemia during treatment for severe coronavirus disease 2019 (COVID-19). The patient was intubated and received a combination of immunosuppressants, including high-dose methylprednisolone and two doses of tocilizumab, as well as remdesivir, intravenous heparin, and ceftriaxone. A blood culture on admission day 11 revealed Candida species, which was confirmed as C. dubliniensis by mass spectrometry. An additional sequencing analysis of the 26S rDNA and ITS regions confirmed that the organism was 100% identical to the reference strain of C. dubliniensis (ATCC MYA-646). Considering the simultaneous isolation of C. dubliniensis from a sputum sample, the lower respiratory tract could be an entry point for candidemia. Although treatment with micafungin successfully eradicated the C. dubliniensis fungemia, the patient died of COVID-19 progression. In this case, aggressive immunosuppressive therapy could have caused the C. dubliniensis fungemia. Due to insufficient clinical reports on C. dubliniensis infection based on definitive diagnosis, the whole picture of the cryptic organism is still unknown. Further accumulation of clinical and microbiological data of the pathogen is needed to elucidate their clinical significance., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

A 66-year-old man was admitted to our hospital for gastrointestinal perforation. He had a history of surgery and chemotherapy for colorectal cancer and had a subcutaneously implanted central venous port catheter. After surgery for gastrointestinal tract perforation, he developed an intra-abdominal abscess, which was treated with broad-spectrum antimicrobial agents and improved. Following this improvement, Rhodotorula spp. was detected in a blood culture and at the catheter tip. He was asymptomatic despite having fungemia. His condition improved after the removal of the catheter and the administration of antifungal drugs. Fungemia due to Rhodotorula spp. is rare, and asymptomatic fungemia is even rarer.

Critically ill patients are at risk for fungal infections, but there is a paucity of data regarding the clinical utility of dedicated fungal blood cultures to detect such infections. A retrospective review was conducted of patients admitted to the surgical and burn intensive care units at Parkland Memorial Hospital between 1 January 2013 and 31 December 2017 for whom blood cultures (aerobic, anaerobic, and/or fungal cultures) were sent. A total of 1,094 aerobic and anaerobic blood culture sets and 523 fungal blood cultures were sent. Of the aerobic and anaerobic culture sets, 42/1,094 (3.8%) were positive for fungal growth. All fungal species cultured were Candida. Of the fungal blood cultures, 4/523 (0.76%) were positive for growth. Fungal species isolated included Candida albicans, Aspergillus fumigatus, and Histoplasma capsulatum. All 4 patients with positive fungal blood cultures were on empirical antifungal therapy prior to results, and the antifungal regimen was changed for 1 patient based on culture data. The average duration to final fungal culture result was 46 days, while the time to preliminary results varied dramatically. Two of the four patients died prior to fungal culture results, thereby rendering the culture data inconsequential in patient care decisions. This study demonstrates that regular aerobic and anaerobic blood cultures sets are sufficient in detecting the most common causes of fungemia and that results from fungal cultures rarely impact treatment management decisions in patients in surgical and burn intensive care units. There is little clinical utility to routine fungal cultures in this patient population. IMPORTANCE This study demonstrates that regular aerobic and anaerobic blood culture sets are sufficient in detecting the most common causes of fungemia, and thus, sending fungal blood cultures for patients in surgical and burn intensive care units is not a good use of resources.

Background: Systemic infections caused by the black yeast-like fungus Exophiala dermatitidis are rare, but are associated with high mortality especially in immunocompromised patients. We report the first case of E. dermatitidis fungemia in a premature extremely low birth weight (ELBW) neonate who succumbed despite antifungal therapy with liposomal amphotericin (AMB) and fluconazole. A systematic review of all fungemia cases due to E. dermatitidis was also conducted aiming for a better understanding of the risk factors, treatment strategies and outcomes., Case Presentation: A male, ELBW premature neonate, soon after his birth, developed bradycardia, apnoea and ultimately necrotizing enterocolitis with intestinal perforation requiring surgical intervention. Meanwhile, he had also multiple risk factors for developing bloodstream infection, such as intubation, mechanical ventilation, central venous catheter (CVC), parenteral nutrition, empirical and prolonged antibiotic use. His blood cultures were positive, firstly for Acinetobacter junii and then for Klebsiella pneumoniae together with E. dermatitidis while on fluconazole prophylaxis and antibiotic empiric therapy. Despite the treatment with broad spectrum antibiotics, liposomal AMB and fluconazole, the newborn succumbed. A literature review identified another 12 E. dermatitidis bloodstream infections, mainly in patients with hematologic malignancies and solid organ transplant recipients (61%), with overall mortality 38% despite CVC removal and antifungal therapy., Conclusions: Due to the rarity of E. dermatitidis infections, little is known about the characteristics of this yeast, the identification methods and the optimal therapy. Identification by common biochemical tests was problematic requiring molecular identification. Resolution of neonatal fungemia is difficult despite proper antifungal therapy especially in cases with multiple and severe risk factors like the present one. Therapeutic intervention may include CVC removal and treatment for at least 3 weeks with an azole (itraconazole or fluconazole after susceptibility testing) or AMB monotherapy but not echinocandins or AMB plus azole combination therapy., (© 2022. The Author(s).)

Background: Cryptococcus spp. infection involving the central nervous system (CNS) is associated with poor outcomes. Current guidelines recommend repeating a cerebrospinal fluid (CSF) fungal culture after 2 weeks of treatment to evaluate for clearance. However, this practice has not clearly been associated with outcomes., Objectives: We sought to assess the relationship between CSF fungal clearance at 2 weeks and 12-month mortality in patients with CNS cryptococcosis., Methods: This is a retrospective cohort study from 2011 to 2020 of patients with CNS cryptococcosis. Factors associated with 12-month mortality were assessed with Fisher's exact test for categorical variables and Mann-Whitney test for continuous variables., Results: Among 51 patients with CNS cryptococcosis, 42 (82.4%) were initially CSF culture positive. Among 27 patients with follow-up CSF culture at 2 weeks, 6 (22.2%) had a positive result. Factors associated with a positive CSF culture at 2 weeks were an initial CSF cryptococcal antigen titre ≥1:2560, fungaemia, and an elevated intracranial pressure requiring therapeutic lumbar punctures. The 12-month mortality rate was 33.3%, and this was significantly associated with baseline fungaemia, extra-CNS cryptococcal involvement and requirement of intensive care unit level of care. Lack of CSF culture clearance by 2 weeks was not associated with 12-month mortality., Conclusions: CNS cryptococcosis has a high mortality rate. A markedly elevated CSF cryptococcal antigen, and opening CSF pressure was associated with lack of CSF culture clearance at 2 weeks of treatment. Severe disseminated disease and cryptococcemia were associated with 12-month mortality., (© 2022 Wiley-VCH GmbH.)

Malassezia furfur is a lipophilic, yeast-like fungus that forms part of the normal human skin microflora and is associated with a wide range of infections, such as pityriasis versicolor, folliculitis, and systemic infections in immunocompromised patients. Although matrix-assisted laser desorption/ionization time-of-flight mass spectrometry has enabled rapid identification of Malassezia species, it is still a challenge to diagnose systemic infections because Malassezia fungemia can often be missed by automated blood culture systems. We report a case in which M. furfur in blood was detected by the presence of yeast-like fungi in blood smears. Yeast-like organisms were observed in the blood smears of a 3-year-old boy, taken over 2 weeks without any symptoms. He had undergone several courses of chemotherapy for neuroblastoma via an indwelling central venous catheter (CVC) that was placed in his right anterior chest for 11 months. Although the blood cultures obtained from an automated blood culture system were negative, M. furfur growth was detected in the subcultured blood taken from the CVC. The CVC was removed, and the scheduled chemotherapy was postponed. No systemic M. furfur bloodstream infection occurred; the infection resolved spontaneously without any specific treatment; only prophylactic fluconazole was administered. M. furfur fungemia may not be diagnosable by an automated blood culture system. Further, M. furfur may not cause infections in humans even when administered intravenously. This report may lead to the discovery of factors related to human infectivity of this disease in the future., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The French National Reference Center for Invasive Mycoses and Antifungals leads an active and sustained nationwide surveillance program on probable and proven invasive fungal diseases (IFDs) to determine their epidemiology in France. Between 2012 and 2018, a total of 10,886 IFDs were recorded. The incidence increased slightly over time (2.16 to 2.36/10,000 hospitalization days, P  = 0.0562) in relation with an increase of fungemia incidence (1.03 to 1.19/10,000, P  = 0.0023), while that of other IFDs remained stable. The proportion of ≥65-year-old patients increased from 38.4% to 45.3% ( P  < 0.0001). Yeast fungemia ( n  = 5,444) was due mainly to Candida albicans (55.6%) with stable proportions of species over time. Echinocandins became the main drug prescribed (46.7% to 61.8%), but global mortality rate remained unchanged (36.3% at 1 month). Pneumocystis jirovecii pneumonia ( n  = 2,106) was diagnosed mostly in HIV-negative patients (80.7%) with a significantly higher mortality than in HIV-positive patients (21.9% versus 5.4% at 1 month, P  < 0.0001). Invasive aspergillosis ( n  = 1,661) and mucormycosis ( n  = 314) were diagnosed mostly in hematology (>60% of the cases) with a global mortality rate of 42.5% and 59.3%, respectively, at 3 months and significant changes in diagnosis procedure over time. More concurrent infections were also diagnosed over time (from 5.4% to 9.4% for mold IFDs, P  = 0.0115). In conclusion, we observed an aging of patients with IFD with a significant increase in incidence only for yeast fungemia, a trend toward more concurrent infections, which raises diagnostic and therapeutic issues. Overall, global survival associated with IFDs has not improved despite updated guidelines and new diagnostic tools. IMPORTANCE The epidemiology of invasive fungal diseases (IFDs) is hard to delineate given the difficulties in ascertaining the diagnosis that is often based on the confrontation of clinical and microbiological criteria. The present report underlines the interest of active surveillance involving mycologists and clinicians to describe the global incidence and that of the main IFDs. Globally, although the incidence of Pneumocystis pneumonia, invasive aspergillosis, and mucormycosis remained stable over the study period (2012 to 2018), that of yeast fungemia increased slightly. We also show here that IFDs seem to affect older people more frequently. The most worrisome observation is the lack of improvement in the global survival rate associated with IFDs despite the increasing use of more sensitive diagnostic tools, the availability of new antifungal drugs very active in clinical trials, and a still low/marginal rate of acquired in vitro resistance in France. Therefore, other tracks of improvement should be investigated actively.

Background: Candidemia is rare and has a high mortality rate. This study analyses the impact of bedside antifungal stewardship (AFS) on clinical management and prognosis of patients with candidemia at a university hospital in Germany., Methods: All patients with at least one positive blood culture with Candida species between 2014 and 2016 received bedside AFS with standardized recommendations. Medical records were retrospectively analyzed. Results from the intervention period from 2014-2016 (n=109), with focus on 2016 (n=39), were compared with those from the pre-intervention period in 2013 (n=30)., Results: Bedside AFS was performed in 24/35 (69%) surviving patients in 2016 within the first 3 days after diagnosis of candidemia. All surviving patients (n=35) in 2016 received antifungal treatment compared with 24/28 (86%) in 2013 (p=0.0344). Follow-up blood cultures were performed in 25/35 (71%) in 2016 compared with 10/25 (40%) in 2013 (p=0.0046). Survival in the intervention compared with the pre-intervention group did not differ significantly (p=0.58) one year after the diagnosis of candidemia was made. However, patients with candidemia often have multiple serious comorbidities., Conclusions: Individualized bedside AFS significantly improves adherence to recommendations for patients with Candida fungemia, especially guideline-oriented diagnostics and therapy. Improving the prognosis of patients with candidemia remains a huge challenge for AFS., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Patients hospitalised for COVID-19 may present with or acquire bacterial or fungal infections that can affect the course of the disease. The aim of this study was to describe the microbiological characteristics of laboratory-confirmed infections in hospitalised patients with severe COVID-19., Methods: We reviewed the hospital charts of a sample of patients deceased with COVID-19 from the Italian National COVID-19 Surveillance, who had laboratory-confirmed bacterial or fungal bloodstream infections (BSI) or lower respiratory tract infections (LRTI), evaluating the pathogens responsible for the infections and their antimicrobial susceptibility., Results: Among 157 patients with infections hospitalised from February 2020 to April 2021, 28 (17.8%) had co-infections (≤ 48 h from admission) and 138 (87.9%) had secondary infections (> 48 h). Most infections were bacterial; LRTI were more frequent than BSI. The most common co-infection was pneumococcal LRTI. In secondary infections, Enterococci were the most frequently recovered pathogens in BSI (21.7% of patients), followed by Enterobacterales, mainly K. pneumoniae, while LRTI were mostly associated with Gram-negative bacteria, firstly Enterobacterales (27.4% of patients, K. pneumoniae 15.3%), followed by A. baumannii (19.1%). Fungal infections, both BSI and LRTI, were mostly due to C. albicans. Antibiotic resistance rates were extremely high in Gram-negative bacteria, with almost all A. baumannii isolates resistant to carbapenems (95.5%), and K. pneumoniae and P. aeruginosa showing carbapenem resistance rates of 59.5% and 34.6%, respectively., Conclusions: In hospitalised patients with severe COVID-19, secondary infections are considerably more common than co-infections, and are mostly due to Gram-negative bacterial pathogens showing a very high rate of antibiotic resistance., (© 2022. The Author(s).)

Limited data are available on breakthrough fungemia, defined as fungemia that develops on administration of antifungal agents, in patients with hematological disorders. We reviewed the medical and microbiological records of adult patients with hematological diseases who had breakthrough fungemia between January 2008 and July 2019 at Toranomon Hospital and Toranomon Hospital Kajigaya in Japan. A total of 121 cases of breakthrough fungemia were identified. Of the 121 involved patients, 83, 11, 5, and 22 were receiving micafungin, voriconazole, itraconazole, and liposomal amphotericin B, respectively, when the breakthrough occurred. Of the 121 causative breakthrough fungal strains, 96 were Candida species, and the rest were 13 cases of Trichosporon species, 7 of Fusarium species, 2 of Rhodotorula mucilaginosa, and 1 each of Cryptococcus neoformans, Exophiala dermatitidis, and Magnusiomyces capitatus. The crude 14-day mortality rate of breakthrough fungemia was 36%. Significant independent factors associated with the crude 14-day mortality rate were age of ≥60 years ( P =  0.011), chronic renal failure ( P =  0.0087), septic shock ( P <  0.0001), steroid administration ( P =  0.0085), and liposomal amphotericin B breakthrough fungemia ( P =  0.0011). An absolute neutrophil count of >500/μL was significantly more common in candidemia in the multivariate analysis ( P = 0.0065), neutropenia and nonallogeneic hematopoietic stem cell transplants were significantly more common in Trichosporon fungemia ( P =  0.036 and P =  0.033, respectively), and voriconazole breakthrough fungemia and neutropenia were significantly more common in Fusarium fungemia ( P =  0.016 and P =  0.016, respectively). The epidemiological and clinical characteristics of breakthrough fungemia of patients with hematological disorders were demonstrated. Some useful factors to predict candidemia, Trichosporon fungemia, and Fusarium fungemia were identified.

Trichosporon species are emerging as opportunistic pathogens that mainly affect immunocompromised patients. Patients with onco-hematological diseases usually present with fungemia by Trichosporon species, especially by T. asahii . Reports of this infection by other species of the genus are uncommon. Thus, in this paper, we present a case of T. inkin fungemia in a 39-year-old female patient with intestinal obstruction and absence of malignant hematological diseases. The late mycological diagnosis, the ineffective control of her pre-existing conditions and consequent failure to start antifungal therapy were the contributing factors for the patient's death.

Objective: This study intends to analyze the data of fungemia in a large tertiary hospital from 2010 to 2019, and is aimed at understanding its epidemic characteristics and drug resistance., Methods: The "Hospital Infection Real-Time Monitoring System" was used to retrieve the case information of patients who were hospitalized for more than 48 hours from 2010 to 2019. The questionnaire was designed to collect patients' basic information, infection situation, drug resistance, and other related information. Statistical software was used for analysis., Results: The fungi detection rate was in the range of 0.19%~0.75% in ten years, the average rate was 0.29%, and the rate 0.2%~0.3% since 2013, which was lower than that from 2010 to 2012. Non- Candida albicans was the main fungus, accounting for 62.50%. The drug resistance of non- C. albicans was higher than that of C. albicans , among which C. glabrata had the highest resistance rate. Data analysis showed that the patients with more serious basic diseases, combined with infection of other sites, surgery, long hospital stay, combination of antibiotics, and invasive catheterization, were more likely to occur fungemia., Conclusion: We should pay more attention to the patients with high-risk factors of fungemia and focus on the drug resistance of non- C. albicans , choose the right antifungal drugs, so as to improve the level of diagnosis and treatment., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2021 Yanling Bai et al.)

The aim of this study was to evaluate diagnostic means, host factors, delay of occurrence, and outcome of patients with COVID-19 pneumonia and fungal coinfections in the intensive care unit (ICU). From 1 February to 31 May 2020, we anonymously recorded COVID-19-associated pulmonary aspergillosis (CAPA), fungemia (CA-fungemia), and pneumocystosis (CA-PCP) from 36 centers, including results on fungal biomarkers in respiratory specimens and serum. We collected data from 154 episodes of CAPA, 81 of CA-fungemia, 17 of CA-PCP, and 5 of other mold infections from 244 patients (male/female [M/F] ratio = 3.5; mean age, 64.7 ± 10.8 years). CA-PCP occurred first after ICU admission (median, 1 day; interquartile range [IQR], 0 to 3 days), followed by CAPA (9 days; IQR, 5 to 13 days), and then CA-fungemia (16 days; IQR, 12 to 23 days) ( P < 10 -4 ). For CAPA, the presence of several mycological criteria was associated with death ( P < 10 -4 ). Serum galactomannan was rarely positive (<20%). The mortality rates were 76.7% (23/30) in patients with host factors for invasive fungal disease, 45.2% (14/31) in those with a preexisting pulmonary condition, and 36.6% (34/93) in the remaining patients ( P = 0.001). Antimold treatment did not alter prognosis ( P = 0.370). Candida albicans was responsible for 59.3% of CA-fungemias, with a global mortality of 45.7%. For CA-PCP, 58.8% of the episodes occurred in patients with known host factors of PCP, and the mortality rate was 29.5%. CAPA may be in part hospital acquired and could benefit from antifungal prescription at the first positive biomarker result. CA-fungemia appeared linked to ICU stay without COVID-19 specificity, while CA-PCP may not really be a concern in the ICU. Improved diagnostic strategy for fungal markers in ICU patients with COVID-19 should support these hypotheses. IMPORTANCE To diagnose fungal coinfections in patients with COVID-19 in the intensive care unit, it is necessary to implement the correct treatment and to prevent them if possible. For COVID-19-associated pulmonary aspergillosis (CAPA), respiratory specimens remain the best approach since serum biomarkers are rarely positive. Timing of occurrence suggests that CAPA could be hospital acquired. The associated mortality varies from 36.6% to 76.7% when no host factors or host factors of invasive fungal diseases are present, respectively. Fungemias occurred after 2 weeks in ICUs and are associated with a mortality rate of 45.7%. Candida albicans is the first yeast species recovered, with no specificity linked to COVID-19. Pneumocystosis was mainly found in patients with known immunodepression. The diagnosis occurred at the entry in ICUs and not afterwards, suggesting that if Pneumocystis jirovecii plays a role, it is upstream of the hospitalization in the ICU.

Candida auris is a species of fungus that has gained importance in recent years owing to its ability to cause hospital infections and epidemics, resistant to antifungal agents and disinfection processes and frequently misidentified by commercial systems. Hospital outbreaks caused by C.auris have been reported from some countries. It has been determined that C.auris has lower virulence than Candida albicans; however, it is associated with high mortality rates in immunocompromised individuals. An increase in the incidence of invasive fungal infections which can lead to serious complications and death, has been identified in severe coronavirus-2019 (COVID-19) patients or immunocompromised individuals with underlying disease. Studies demonstrated an increase in the frequency of C.auris isolation in COVID-19 patients with candidemia. In this report, the first case of COVID-19 positive C.auris fungemia detected in Turkey was presented. A 71-year-old male patient with a history of myocardial infarction, diabetes mellitus, donation of a single kidney and lobectomy surgery due to lung cancer was hospitalized in the pandemic thoracic surgery service due to the findings consistent with viral pneumonia on thoracic computed tomography. Favipiravir 2 x 600 mg and intravenous dexamethasone 1 x 6 mg therapy was administered. The patient tested positive for SARS-CoV-2 polymerase chain reaction, and severe involvement of the left lung was detected in the following days. Antibiotics were administered, followed by insertion of a right jugular vein catheter and initation of tocilizumab. The patient was transferred to the intensive care unit due to increased respiratory distress. Yeast growth was detected in the patient's hemoculture. The yeast strain could not be identified using API ID 32C (bioMerieux, France) (Sacchromyces kluyveri, Candida sake, unacceptable profile), but was identified as C.auris using the VITEK MALDI TOF MS (bioMerieux, France) (99.9%) system and confirmed by sequencing. The minimum inhibitor concentration values were detected as 3 µg/ml for amphotericin B; > 256 µg/ml for fluconazole; 0.19 µg/ml for voriconazole; 0.19 µg/ml for itraconazole; 0.016 µg/ml for posaconazole; 1 µg/ml for caspofungin and 0.094 µg/ml for anidulafungin by using the antibiotic gradient method. The patient's initial treatment comprised meropenem 3 x 1 g, vancomycin 2 x 1 g, caspofungin 1 x 70 mg, and continued as caspofungine 1 x 50 mg after the loading dose, and vancomycin 1 x 1 g/48 hours from the third day of treatment. The patient died on the ninth day after developing candidemia. The present case is the first case of fungemia caused by C.auris in a COVID-19 positive patient in Turkey, and it emphasizes the need of caution for fungemia due to C.auris in intensive care units in our country which has a high COVID-19 incidence.

Background/purpose: Invasive Trichosporon infections are emerging, but association of different therapeutic management of Trichosporon fungemia and clinical outcomes were rarely reported. This study investigates the epidemiology, species distribution and genotypes of trichosporonosis in Taiwan, and identified the predictors of clinical outcomes in patients with Trichosporon fungemia., Methods: Strains collected from four medical centers in Taiwan, during 2010-2018. Species identification was confirmed by sequencing of IGS1 region, and antifungal susceptibility was performed using Sensititre YeastOne panel., Results: Among 115 isolates, Trichosporon asahii was the leading species (73.0%), followed by Trichosporon dermatis (11.3%), Trichosporon faecales (6.1%), and Trichosporon montevideense (5.2%). Of the 84 T. asahii isolates, genotype 1 was the predominant (41.7%). High fluconazole minimal inhibitory concentration (MICs,≧8 μg/mL) were observed for 70.2% T. asahii isolates and 16.1% non-asahii Trichosporon isolates. Posaconazole and voriconazole possess the most potent antifungal activity against all Trichosporon isolates, with geometric mean values of 0.251 μg/mL and 0.111 μg/mL, respectively. Fifty-three isolates collected from blood cultures, and 42 patients with fungemia enrolled for the Kaplan-Meier plot which revealed that voriconazole treatment had a significantly better survival rate compared with those without (p = 0.042). In multivariate analysis, source control (odds ratio [OR]: 0.13 95%CI [confidence interval]: 0.02-0.83, p = 0.031) and voriconazole use (OR: 0.11 95%CI: 0.02-0.74, p = 0.023) are independent predictors of 14-day mortality., Conclusion: This is the largest series of Trichosporon fungemia up till the present moment. Voriconazole therapy and source control play important roles in 14-day mortality., Competing Interests: Declaration of competing interest None declared., (Copyright © 2020. Published by Elsevier B.V.)

Renal transplant recipients are at risk for opportunistic infections due to their immunosuppressed state. We describe the case of a 59-year-old renal transplant recipient who presented with sepsis and bilateral pulmonary emboli due to Candida parapsilosis She was treated with intravenous caspofungin and had a transoesophageal echocardiogram, which revealed vegetations on her pacemaker leads. She then underwent surgery to replace her pacemaker; however, her blood cultures remained positive for C. parapsilosis postoperatively. Her antifungal was switched to liposomal amphotericin B and flucytosine for 6 weeks, which yielded sterile blood cultures, and she was then initiated on lifelong fluconazole. Her recovery was complicated by tacrolimus toxicity 1 month after discharge due to fluconazole-induced CYP3A inhibition., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Trichosporon fungaemia (TF) episodes have increased in recent years and mortality rates remain high despite the advances in the management of sepsis. New concepts about its clinical course, treatment and microbiology need to be investigated for the better management of this infection., Objectives: To describe the aetiology, natural history, clinical management and prognostic factors of TF., Methods: TF episodes documented between 2005 and 2018 in 23 South American centres were retrospectively investigated by using a standard clinical form. Molecular identification, antifungal susceptibility testing and biofilm production were also performed., Results: Eighty-eight TF episodes were studied. Patients had several underlying conditions, including haematological diseases (47.7%), post-operative status (34%), solid organ transplants (n = 7, 7.9%), among others. Seventy-three (82.9%) patients had a central venous catheter (CVC) at TF diagnosis. The 30 day mortality rate was 51.1%. Voriconazole-based therapy was given to 34 patients (38.6%), with a 30 day mortality rate of 38.2%. Multivariate predictors of 30 day mortality were age (OR 1.036), mechanical ventilation (OR 8.25) and persistent neutropenia (OR 9.299). CVC removal was associated with over 75% decreased risk of 30 day mortality (OR 0.241). Microbiological analyses revealed that 77.7% of the strains were identified as Trichosporon asahii, and voriconazole showed the strongest in vitro activity against Trichosporon spp. Most of the strains (63%) were considered medium or high biofilm producers., Conclusions: Older age, mechanical ventilation and persistent neutropenia were associated with poor prognosis. CVC may play a role in the pathogenicity of TF and its removal was associated with a better prognosis., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Bacterial and fungal bloodstream infections (BSI) are common after pediatric liver and kidney transplantations and associated with morbidity and mortality. However, knowledge about incidence rates, pathogen composition, and resistance patterns is limited. We aimed to describe the pattern of bacterial and fungal BSI in a cohort of pediatric liver and kidney transplant recipients., Methods: A prospective study of 85 pediatric liver and kidney transplant recipients transplanted from 2010 to 2017 with a total of 390 person-years of follow-up. Clinical characteristics and BSI were retrieved from national registries assuring nationwide follow-up for at least 1 year. BSI incidence rates and pathogen composition were investigated and stratified by the time post-transplantation and type of transplanted organ., Results: A total of 29 BSI were observed within the first 5 years post-transplantation with 16 different pathogens. The overall incidence rate of first BSI was 1.91 per 100 recipients per month (95% CI, 1.1-3.1) in the first year post-transplantation. The most common pathogens were Enterococcus faecium, Candida albicans, Escherichia coli, and Klebsiella pneumoniae. The pathogen composition depended on the transplanted organ with a higher proportion of BSI with Enterobacterales in kidney transplant recipients than in liver transplant recipients (67% vs. 20%, p = 0.03), while multiple pathogens were detected in the liver transplant recipients., Conclusions: BSI were common in pediatric liver and kidney transplant recipients and the pathogen composition differed between liver and kidney transplant recipients. Guidelines for empiric antibiotic therapy should consider the type of transplanted organ as well as the local resistance patterns.