Neonatal Fungemia by Non-Candida Rare Opportunistic Yeasts: A Systematic Review of Literature.

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.

Recalcitrant Erythrodermic Psoriasis Complicated by Septic Shock and Mycotic Aneurysm: A Call for Treatment Guidelines.

Erythroderma is characterized by diffuse erythema and scale covering over 90% body surface area that can affect individuals with inflammatory dermatoses such as psoriasis. Complications of erythrodermic psoriasis include infection and cardiovascular compromise. Here we present a case of a 68 year-old man who was hospitalized for erythrodermic psoriasis refractory to multiple immunosuppressive and immunomodulatory therapies, ultimately developing sepsis due to bacteremia and fungemia complicated by infective endocarditis and a mycotic aneurysm. Although the widespread loss of epidermal function in erythroderma increases the risk of infection by opportunistic pathogens, water loss, and electrolyte imbalances, there are very few reported cases of psoriatic erythroderma complicated by fungemia and mycotic aneurysm. Given the high mortality associated with widespread epidermal dysfunction, there is a great need for evidence-based treatment guidelines for psoriatic erythroderma. J Drugs Dermatol. 2024;23(8): doi:10.36849/JDD.7751.

Rhinocerebral mucormycosis and Trichosporon asahii fungemia in a pediatric patient with acute lymphoblastic leukemia: a rare coinfection.

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.

Candida lusitaniae Fungemia in Children: A multicenter case series of emerging pathogen.

Candida lusitaniae fungemia is a serious infection that is rarely reported in children. The aim of this study is to describe a case series of C. lusitaniae fungemia and review previous publications regarding this rare pathogen. This is a multicenter case series of children diagnosed with C. lusitaniae fungemia. A total of 18 cases that occurred over a 15-year period in five tertiary hospitals were included. Additionally, a review of the literature regarding C. lusitaniae fungemia in children was performed. A total of 18 cases were enrolled; 11/18 (61%) were males, with a mean age of 2.3 years. All patients had severe underlying diseases and risk factors for opportunistic infection, most commonly prematurity and malignancies. More than one-third of cases occurred during the last 2 years of the study period. All isolates were susceptible to all tested antifungals. The survival rate following the acute infection was 94%, whereas the survival rate of 14 previously published cases was 71%, with the most common underlying diseases being CGD and malignancies. Candida lusitaniae fungemia is not a common event in the pediatric population, occurring exclusively in children with severe underlying diseases and significant risk factors. This cohort revealed better clinical outcomes than previously reported. All tested isolates were susceptible to all antifungal agents; variability in susceptibility as previously reported was not found in this study. The allegedly higher rate of infection in recent years is in need of further investigation in larger prospective studies in order to conclude if a real trend is at play.

Candida lusitaniae fungemia is a serious infection rarely reported in children. This cohort revealed better clinical outcomes than previously reported. All tested isolates were susceptible to all antifungal agents. The higher rate of infection in recent years is in need of further investigation.

Evaluation of hospital-onset bacteraemia and fungaemia in the USA as a potential healthcare quality measure: a cross-sectional study.

BACKGROUND: Hospital-onset bacteraemia and fungaemia (HOB) is being explored as a surveillance and quality metric. The objectives of the current study were to determine sources and preventability of HOB in hospitalised patients in the USA and to identify factors associated with perceived preventability. METHODS: We conducted a cross-sectional study of HOB events at 10 academic and three community hospitals using structured chart review. HOB was defined as a blood culture on or after hospital day 4 with growth of one or more bacterial or fungal organisms. HOB events were stratified by commensal and non-commensal organisms. Medical resident physicians, infectious disease fellows or infection preventionists reviewed charts to determine HOB source, and infectious disease physicians with training in infection prevention/hospital epidemiology rated preventability from 1 to 6 (1=definitely preventable to 6=definitely not preventable) using a structured guide. Ratings of 1-3 were collectively considered 'potentially preventable' and 4-6 'potentially not preventable'. RESULTS: Among 1789 HOB events with non-commensal organisms, gastrointestinal (including neutropenic translocation) (35%) and endovascular (32%) were the most common sources. Overall, 636/1789 (36%) non-commensal and 238/320 (74%) commensal HOB events were rated potentially preventable. In logistic regression analysis among non-commensal HOB events, events attributed to intravascular catheter-related infection, indwelling urinary catheter-related infection and surgical site infection had higher odds of being rated preventable while events with neutropenia, immunosuppression, gastrointestinal sources, polymicrobial cultures and previous positive blood culture in the same admission had lower odds of being rated preventable, compared with events without those attributes. Of 636 potentially preventable non-commensal HOB events, 47% were endovascular in origin, followed by gastrointestinal, respiratory and urinary sources; approximately 40% of those events would not be captured through existing healthcare-associated infection surveillance. DISCUSSION: Factors identified as associated with higher or lower preventability should be used to guide inclusion, exclusion and risk adjustment for an HOB-related quality metric.

"Click" amphotericin B in prodrug nanoformulations for enhanced systemic fungemia treatment.

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-PEG5kBA4 has a comparable maximum tolerated dose (MTD) to AmBisome®, while over 20-fold increase than Fungizone®. A single dose of AmB-PEG5kBA4 demonstrates superior efficacy to Fungizone® and AmBisome® in treating systemic fungal infections in both immunocompetent and immunocompromised mice.

Saccharomyces cerevisiae fungemias: how heterogenous is their management?

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.

[Lomentospora prolificans Fungemia in a Patient With T-Cell Large Granular Leukemia: A Rare Pathogen in Türkiye]. / T-hücreli Büyük Granüler Lösemili Bir Hastada Lomentospora prolificans Fungemisi: Türkiye'de Nadir Bir Etken.

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.

An inconspicuous identification: Isolation and identification of a novel Pichia species presenting as fungemia following cardiac surgery.

Fungemia is common in critically ill patient populations, and is associated with a high rate of mortality, especially when caused by nonalbicans Candida species. Herein, we describe a fatal case of fungemia following cardiothoracic surgery in which the organism, initially identified as Candida inconspicua, represents a novel species: Pichia alaskaensis.

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

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

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

Universal antifungal prophylaxis effectively prevents fungal bloodstream infection in pediatric liver transplant recipients: a retrospective real-world study.

OBJECTIVES: Fungal bloodstream infection (fBSI) following pediatric liver transplantation presents a significant challenge; however, there remains a paucity of guidance regarding antifungal prophylaxis in this population. This study aimed to evaluate the effectiveness of universal antifungal prophylaxis and propose a desirable strategy. METHODS: We enrolled 604 pediatric patients who underwent liver transplantation between 2020 and 2023, including 242 patients with empirical prophylaxis and 362 patients with universal prophylaxis. Univariate and multivariate logistic regression analyses were performed to identify independent factors for fBSI. RESULTS: Eight (2.2%) pediatric recipients in the universal prophylaxis group and 13 (5.4%) in the empirical group developed fBSI (P = 0.038). Universal prophylaxis was a protective factor (P = 0.044), while high-volume intraoperative plasma transfusion and deceased donor liver transplantation were independent risk factors for fBSI (P = 0.035 and 0.008, respectively). Universal antifungal strategy showed an increased overall survival trend after liver transplantation although without significant statistical difference (P = 0.217). Patients with fBSI had poorer survival than those without fBSI (P <0.001). CONCLUSIONS: Universal prophylaxis strategy for fBSI in pediatrics after liver transplantation is desirable as it could markedly decrease the occurrence of fBSI. Pediatric patients with deceased donors and high-volume intraoperative transfusion should be paid more attention to preventing fBSI.

Micafungin-breakthrough Coniochaeta hoffmannii (Lecythophora hoffmannii) fungemia following cord blood transplant in a patient with acute myeloid leukemia successfully treated with voriconazole.

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.

Bloodstream infections: trends and evolution of incidence and etiology in a 12-year period (2010-2021).

INTRODUCTION: The epidemiological evolution of bloodstream infections (BSIs) in the last decade is not clearly defined. Our aim was to analyze the changes in the workload in our institution and to describe the evolution of the incidence and etiology of BSIs in a 12-year period, including the COVID-19 pandemic. METHODS: All blood cultures received in the laboratory of a tertiary general hospital between 2010 and 2021 were analyzed. Bloodstream infection episodes refer to each episode of bacteremia or fungemia in each patient. Incidence rates per 1000 admissions and per 100,000 population were calculated. RESULTS: No significant changes in the incidence of BSI episodes/1000 admissions were observed (mean, 31.1), while estimated population-based incidences showed declining trends (mean, 182.8/100,000 inhabitants). There was a slight increase in BSI episodes per 1000 admissions caused by Gram-negatives (mean, 16.6/1000 admissions) and E. coli was the most frequent pathogen (mean, 8.5/1000 admissions). There was no significant rise in episodes caused by ESBL- and carbapenemase-producing E. coli or K. pneumoniae, with a decline in those caused by methicillin-resistant S. aureus. A spike in BSI episodes, fungal BSIs and catheter-related infections was detected in 2020, during the COVID-19 outbreak. CONCLUSIONS: No clear increase in the incidence of BSI episodes was detected in our center over this period. Gram-negatives are the most frequent etiology, with no clear rise in antimicrobial resistance phenotypes. The COVID-19 pandemic accounted for a small increase in BSI episodes in 2020, probably related to the increase of catheter-related infections.

Case report: First case of fungemia caused by Papiliotrema laurentii in a patient with SARS-CoV-2 infection.

Previously considered saprobe and non-pathogenic, the fungus Papiliotrema laurentii (formerly known as Cryptococcus laurentii), is rarely associated with human infection. Nevertheless, there has been an increase in reported infections by non-neoformans cryptococci. After a literature search on the Cochrane Library, LILACS, SciELO, MEDLINE, PubMed, and PMC (PubMed Central) databases, we conclude that this is the first case report of fungemia and probable meningitis caused by Papiliotrema laurentii in a previously immunocompetent host with associated COVID-19.

Cryptococcus laurentii fungemia in a patient with chronic kidney disease on hemodialysis / Fungemia por cryptococcus laurentii em paciente com doença renal crônica em hemodiálise

Introduction: Chronic Kidney Disease (CKD) is a relevant comorbidity from clinical and public health perspectives. Infections are an important cause of death in those patients. Although rare, fungal infections are increasing in incidence. Case report: a 45-year-old female patient with CKD due to systemic lupus erythematosus (SLE) was admitted to a tertiary hospital due to a bloodstream infection (BSI) caused by Cryptococcus laurentii. She received treatment with anidulafungin with good initial response but presented clinical and laboratory worsening after a few days, and the treatment was switched to amphotericin B. The hemodialysis access was changed. Chest tomography, echocardiogram, eye fundus examination, and cerebrospinal fluid study did not show changes. After 32 days of amphotericin B, the patient presented clinical improvement and was discharged to take oral fluconazole for three (3) months. Conclusion: BSI due to Cryptococcus laurentii is rare in patients on chronic hemodialysis with a high potential for complications. Physicians should have clinical suspicion for those infrequent infections infractions, and culture evaluation should always be performed. The diagnosis is still a challenge, as well as the therapeutic regimen.

Introdução: a doença renal crônica (DRC) é uma comorbidade relevante do ponto de vista clínico e de saúde pública. As infecções configuram importante causa de morte nesses pacientes. Embora raras, as infecções por fungos têm incidência crescente. Relato de caso: uma paciente do sexo feminino, 45 anos, com DRC por lúpus eritematoso sistêmico (LES) foi internada em hospital terciário devido à infecção de corrente sanguínea (ICS) por Cryptococcus laurentii. Recebeu tratamento com anidulafungina com boa resposta inicial, porém, devido à piora clínica e laboratorial, o tratamento foi modificado para anfotericina B, assim como foi realizada a troca do acesso para hemodiálise. A tomografia de tórax, o ecocardiograma, o exame de fundo de olho e o estudo do líquido cefalorraquidiano não evidenciaram alterações. Após 32 dias de anfotericina B, a paciente apresentou melhora clínica e recebeu alta hospitalar com fluconazol via oral por 3 meses. Conclusão: a ICS por Cryptococcus Laurentii é rara nos pacientes em hemodiálise crônica, porém com alto potencial de complicações. Há a necessidade de suspeição clínica e avaliação por culturas, sendo o diagnóstico ainda um desafio, bem como o esquema terapêutico.

Severe hypercalcemia as a result of disseminated Candida krusei infection.

Candida krusei disseminated infection is a rare complication of protracted neutropenia. Herein, we report a case of a 31-year-old male with relapsed acute myeloid leukemia who developed Candida krusei fungemia with cutaneous, ocular, splenic, renal, bone marrow and osseous involvement leading to severe hypercalcemia, treated with parenteral antifungals followed by oral ibrexafungerp.

Epidemiology and preventability of hospital-onset bacteremia and fungemia in 2 hospitals in India.

OBJECTIVE: Studies evaluating the incidence, source, and preventability of hospital-onset bacteremia and fungemia (HOB), defined as any positive blood culture obtained after 3 calendar days of hospital admission, are lacking in low- and middle-income countries (LMICs). DESIGN, SETTING, AND PARTICIPANTS: All consecutive blood cultures performed for 6 months during 2020-2021 in 2 hospitals in India were reviewed to assess HOB and National Healthcare Safety Network (NHSN) reportable central-line-associated bloodstream infection (CLABSI) events. Medical records of a convenience sample of 300 consecutive HOB events were retrospectively reviewed to determine source and preventability. Univariate and multivariable logistic regression analyses were performed to identify factors associated with HOB preventability. RESULTS: Among 6,733 blood cultures obtained from 3,558 hospitalized patients, there were 409 and 59 unique HOB and NHSN-reportable CLABSI events, respectively. CLABSIs accounted for 59 (14%) of 409 HOB events. There was a moderate but non-significant correlation (r = 0.51; P = .070) between HOB and CLABSI rates. Among 300 reviewed HOB cases, CLABSIs were identified as source in only 38 (13%). Although 157 (52%) of all 300 HOB cases were potentially preventable, CLABSIs accounted for only 22 (14%) of these 157 preventable HOB events. In multivariable analysis, neutropenia, and sepsis as an indication for blood culture were associated with decreased odds of HOB preventability, whereas hospital stay ≥7 days and presence of a urinary catheter were associated with increased likelihood of preventability. CONCLUSIONS: HOB may have utility as a healthcare-associated infection metric in LMIC settings because it captures preventable bloodstream infections beyond NHSN-reportable CLABSIs.