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Background: Isavuconazole (ISA) and voriconazole (VORI) are recommended as the first-line treatment for invasive aspergillosis (IA). Despite theoretical advantages of ISA, both triazole agents have not been compared in solid organ transplant recipients., Methods: We performed a post hoc analysis of 2 retrospective multicenter cohorts of solid organ transplant recipients with invasive fungal disease (the SOTIS [Solid Organ Transplantation and ISavuconazole] and DiasperSOT [DIagnosis of ASPERgillosis in Solid Organ Transplantation] studies). We selected adult patients with proven/probable IA that were treated for ≥48 h with ISA (n = 57) or VORI (n = 77) as first-line therapy, either in monotherapy or combination regimen. The primary outcome was the rate of clinical response at 12 wk from the initiation of therapy. Secondary outcomes comprised 12-wk all-cause and IA-attributable mortality and the rates of treatment-emergent adverse events and premature treatment discontinuation., Results: Both groups were comparable in their demographics and major clinical and treatment-related variables. There were no differences in the rate of 12-wk clinical response between the ISA and VORI groups (59.6% versus 59.7%, respectively; odds ratio [OR], 0.99; 95% confidence interval [CI], 0.49-2.00). This result was confirmed after propensity score adjustment (OR, 0.81; 95% CI, 0.32-2.05) and matching (OR, 0.79; 95% CI, 0.31-2.04). All-cause and IA-attributable mortality were also similar. Patients in the ISA group were less likely to experience treatment-emergent adverse events (17.5% versus 37.7%; P = 0.011) and premature treatment discontinuation (8.8% versus 23.4%; P = 0.027)., Conclusions: Front-line treatment with ISA for posttransplant IA led to similar clinical outcomes than VORI, with better tolerability and higher treatment completion., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Invasive fungal infection (IFI) is an important cause of morbidity and mortality in acute leukemia patients. In the past few decades, the incidence of IFI has dramatically increased. Nevertheless, the management of IFI has become more complicated owing to changes in the epidemiology of fungal diseases and therapeutic regimens. Therefore, it is important to establish an appropriate strategy for centers that provide the diagnosis and treatment of acute leukemia patients based on scientific data and with available resources. In this study we investigated the incidence of IFI, pathogens, the use of diagnostic methods, and risk factors for IFI in acute leukemia patients over a 17-year period. A total of 502 acute leukemia patients (male/female: 57%/43%, mean age: 57.7 ± 15.5 years) hospitalized at adult and oncology hospitals between 2003 and 2020 were reviewed retrospectively. The incidence of proven and probable IFI was 13.2% (33.1%, when possible cases were included). The most common IFI was aspergillosis (49 patients, 9.7%), followed by candidemia, mucormycosis, and Pneumocystis jirovecii pneumonia. The galactomannan antigen test was positive in the serum of 39 (23.5%) patients and in bronchoalveolar lavage (BAL) fluid in 6 (3.6%) patients. Thirteen (7.8%) sputum cultures (11 Aspergillus spp. and 2 Candida spp.) and 4 (2.4%) BAL fluid (1 Aspergillus spp., 2 Candida spp., 1 P jirovecii) were positive for a fungal pathogen. Neutropenia, intensive care unit (ICU) follow-up and mechanical ventilation (MV) increased the risk of IFI by 3.5, 2.5, and 1.8 times, respectively. The median survival was 5 (range: 1.9-8) months. ICU follow-up shortened the survival by 12 months and increased the death risk by 2.49-fold. MV shortened survival by 57 months and increased the death risk by 3.82-fold. IFI remains a significant contributor to the morbidity and mortality in acute leukemia patients. Pulmonary involvement is the most common site. Neutropenia, ICU follow-up and MV are associated with an increased risk for IFI and mortality. We recommend in the IFI approach, to be aware of IFI in patients receiving intensive chemotherapy and/or recipients of hematopoietic stem cell transplantation, and to evaluate with microbiological, serological and radiological tests during the clinical follow-up., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To assess the prevalence and relevance of invasive fungal disease (IFD) during veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO)., Methods: Retrospective analysis from January 2013 to November 2023 of adult V-A ECMO cases at a German University Hospital. Parameters relating to IFD, demographics, length of stay (LoS), days on ECMO and mechanical ventilation, prognostic scores and survival were assessed. Multivariable logistic regression analyses with IFD and death as dependent variables were performed. Outcome was assessed after propensity score matching IFD-patients to non-IFD-controls., Results: 421 patients received V-A ECMO. 392 patients with full electronic datasets were included. The prevalence of IFD, invasive candidiasis and probable invasive pulmonary aspergillosis was 4.6%, 3.8% and 1.0%. Severity of acute disease, pre-existing moderate-to-severe renal disease and continuous kidney replacement therapy were predictive of IFD. In-hospital mortality (94% (17/18) compared to 67% (252/374) in non-IFD patients (p = 0.0156)) was predicted by female sex, SOFA score at admission, SAVE score and IFD (for IFD: OR: 8.31; CI: 1.60-153.18; p: 0.044). There was no difference in outcome after matching IFD-cases to non-IFD-controls., Conclusions: IFD are detected in about one in 20 patients on V-A ECMO, indicating mortality >90%. However, IFD do not contribute to prognosis in this population., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: In burn patients, skin barrier disruption and immune dysfunctions increase susceptibility to invasive fungal diseases (IFDs) like invasive candidiasis (IC) and invasive mold infections (IMI). We provide an in-depth analysis of IFD-related factors and outcomes in a 10-year cohort of severe burn patients., Methods: This retrospective cohort study includes adult patients admitted to the burn intensive care unit (BICU) between April 2014 and May 2023 with total burn surface area (TBSA) ≥15%. Patients were classified as proven IFD according to EORTC/MSGERC criteria applicable for IC. Putative IMIs were defined with: ≥2 positive cultures from a skin biopsy/bronchoalveolar lavage or ≥2 positive blood specific-quantitative polymerase chain reactions (qPCRs) or a combination of both., Results: Among 1381 patients admitted, 276 consecutive patients with TBSA ≥15% were included. Eighty-seven (31.5%; IC n = 30; IMI n = 43; both n = 14) patients fulfilled the criteria for probable/putative IFD. At Day 30 after the burn injury, the estimated cumulative incidence proven/putative (pr/pu) IFD was 26.4% (95% confidence interval [CI], 21.4%-31.8%). Factors independently associated with IFDs were TBSA, severity scores and indoor burn injury (ie, from confined space fire). Overall mortality was 15.3% and 36.8% in the no IFD, pr/pu IFD groups respectively (P < .0001). IFD was independently associated with a risk of death (hazard ratio [HR]: 1.94 for pr/pu IFD; 95% CI, 1.12-3.36; P = .019)., Conclusions: This study describes twenty-first-century characteristics of IFDs in severe burn patients confirming known risk factors with thresholds and identifying the indoor injury as an independent factor associated to IFDs. This suggests a link to contamination caused by fire damage, which is highly susceptible to aerosolizing spores., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest for this study. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: To evaluate surgical outcomes of invasive fungal rhinosinusitis MATERIALS AND METHODS: The National Inpatient Sample Database (2000-2015 Q3) was queried for patients with a diagnosis of aspergillosis and/or mucormycosis and a diagnosis of acute sinusitis using the International Classification of Diseases, Ninth Edition. Factors associated with inpatient mortality were then identified with multivariate logistic regression., Results: 514 adult patients with a median age of 57.0 years were identified, of which 231 (44.9 %) underwent sinus surgery. Surgical patients had a longer length of stay (17.0 vs 9.0 days, p < 0.001) and higher total charges ($139,762.00 vs $57,945.00, p < 0.001). The number of sinus procedures was associated with reduced odds of inpatient mortality (OR 0.69; p < 0.001) in multivariate analysis. Hypertension (OR 0.34, p = 0.002) and chronic kidney disease (OR 0.23, p = 0.034) were associated with reduced odds of inpatient mortality. Total number of procedures (OR 1.24; p = 0.002), mucormycosis (OR 2.75, p = 0.002), age (OR 1.03, p = 0.006) and acid-base disorders (OR 2.85, p = 0.012) were associated with increased odds of inpatient mortality., Conclusion: This represents the first large scale study to evaluate outcomes for invasive fungal rhinosinusitis. These findings suggest the odds of inpatient mortality decrease with greater extent of sinus surgery performed. The potentially protective roles of hypertension and chronic kidney disease should be evaluated in future research., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Invasive fungal disease (IFD) is typically aggressive and related with high mortality in children with a hematological malignancy. The association of medical and surgical treatment may ameliorate the outcome. The aim of this study was to analyze the surgical treatment of fungal infections in pediatric oncological populations., Methods: Retrospective study (2000-2022) of a single-center experience. We reviewed the medical record of all patients with hematologic malignancies and IFD, analyzing the outcome., Results: From the 70 pediatric cases of hematologic malignancies with the diagnosis IFD over 22 years, we included in the present study 44 cases who required surgical approaches for either diagnosis or treatment. Twenty-one patients were males and the mean age was 11 (range 1-23) years. The main indications for surgery were lack of improvement following medical treatment and/or progression of fungal infection (80%) and diagnosis confirmation (20%). Only five patients needed an emergency operation for rapid worsening of symptoms. The most common site of infection was the lung (80%) and the most frequently identified pathogen was Aspergillus (75%). The most common surgical procedures were lobectomy (performed in 17 patients) and atypical lung resection (10). Complications of surgery were mostly treated by medical approach. The mean time of resumption of oncological treatment was 40 (range 0-150) days., Conclusions: Surgery is an important step in the multimodal treatment of invasive fungal infection with excellent resolution rate. Overall mortality depends on the underlying malignancy., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Patients with hematologic malignancies (HM) are at high risk of invasive lung fungal infections (ILFI). To describe the main characteristics, treatment, and outcomes for five years in adult patients with HM and fungal pneumonia., Methods: We conducted a retrospective study at Instituto Nacional de Cancerología (INCan), a referral tertiary care oncology hospital with 135 beds in Mexico City, Mexico. We included all cases of fungal pneumonia in patients with HM from January 1, 2017, to December 31, 2022. Cases were classified as proven, probable, and possible according to EORTC/MSG criteria 2021., Results: Two hundred ten patients were included; the mean age was 40 years. The most frequent HM was acute lymphoblastic leukemia (n = 74) and acute myeloid leukemia (n = 68). One hundred forty patients (66.7%) had severe neutropenia for a median of 16 days. All patients had a CT thorax scan; in 132 (62.9%), multiple nodules were documented. Serum galactomannan (GM) was positive in 21/192 (10.9%) and bronchoalveolar lavage in 9/36 (25%). Fifty-three patients (25.2%) died in the first month. In the multivariate analysis for mortality in the first 30 days, hypoalbuminemia, shock, possible ILFI, and inappropriate antifungal treatment were statistically associated., Conclusions: In high-risk HM patients, CT thorax scan and GM help diagnose ILFI. An appropriate antifungal improves mortality., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Patricia Cornejo-Juarez reports a relationship with Pfizer that includes: speaking and lecture fees. Patricia Cornejo-Juarez reports a relationship with Merck & Co Inc that includes: speaking and lecture fees. If there are other authors, they 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 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Background: The prevalence and outcomes of COVID-19-associated invasive fungal infections (CAIFIs) in solid organ transplant recipients (SOTRs) remain poorly understood., Methods: A retrospective cohort study of SOTRs with COVID-19 admitted to 5 hospitals within Johns Hopkins Medicine was performed between March 2020 and March 2022. Cox regression multilevel mixed-effects ordinal logistic regression was used., Results: In the cohort of 276 SOTRs, 22 (8%) developed IFIs. The prevalence of CAIFIs was highest in lung transplant recipients (20%), followed by recipients of heart (2/28; 7.1%), liver (3/46; 6.5%), and kidney (7/149; 4.7%) transplants. In the overall cohort, only 42 of 276 SOTRs (15.2%) required mechanical ventilation; these included 11 of 22 SOTRs (50%) of the CAIFI group and 31 of 254 SOTRs (12.2%) of the no-CAIFI group. Compared with those without IFIs, SOTs with IFIs had worse outcomes and required more advanced life support (high-flow oxygen, vasopressor, and dialysis). SOTRs with CAIFIs had higher 1-y death-censored allograft failure (hazard ratio 1.6 5.1 16.4 , P  = 0.006) and 1-y mortality adjusting for oxygen requirement (adjusted hazard ratio 1.1 2.4 5.1 , P  < 0.001), compared with SOTRs without CAIFIs., Conclusions: The prevalence of CAIFIs in inpatient SOTRs with COVID-19 is substantial. Clinicians should be alert to the possibility of CAIFIs in SOTRs with COVID-19, particularly those requiring supplemental oxygen, regardless of their intubation status., Competing Interests: N.P. received consulting/advisory board income from Shionogi Inc, Pulmocide Ltd, ClearView HealthCare Partners, and Alcimed; and study grant support from CareDx, IMMY Diagnostics, and Merck. R.A. received grant/research support from Aicuris, Astellas, Chimerix, Merck, Oxford Immunotec, Qiagen, Regeneron, and Takeda/Shire. C.M.D. reported serving on the grant review committee for Gilead Sciences. S.X.Z. received research funds from IMMY Diagnostics and Vela Diagnostics. D.L.S. received honoraria from Sanofi (speaking), Novartis (speaking, consulting), Veloxis (consulting), Mallinckrodt (consulting), Jazz Pharmaceuticals (consulting), CSL Behring (consulting), Thermo Fisher Scientific (consulting), CareDx (speaking, consulting), Transmedics (consulting), Kamada (consulting), MediGO (consulting), Regeneron (consulting), AstraZeneca (speaking, consulting), Takeda (consulting), and Bridge to Life (speaking). K.A.M. received consulting/advisory board income from Cidara and Merck and equity and salary from Sfunga Therapeutics and Pearl Diagnostics. The other authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This systematic review evaluates the current global impact of invasive infections caused by Pneumocystis jirovecii (principally pneumonia: PJP), and was carried out to inform the World Health Organization Fungal Priority Pathogens List. PubMed and Web of Science were used to find studies reporting mortality, inpatient care, complications/sequelae, antifungal susceptibility/resistance, preventability, annual incidence, global distribution, and emergence in the past 10 years, published from January 2011 to February 2021. Reported mortality is highly variable, depending on the patient population: In studies of persons with HIV, mortality was reported at 5%-30%, while in studies of persons without HIV, mortality ranged from 4% to 76%. Risk factors for disease principally include immunosuppression from HIV, but other types of immunosuppression are increasingly recognised, including solid organ and haematopoietic stem cell transplantation, autoimmune and inflammatory disease, and chemotherapy for cancer. Although prophylaxis is available and generally effective, burdensome side effects may lead to discontinuation. After a period of decline associated with improvement in access to HIV treatment, new risk groups of immunosuppressed patients with PJP are increasingly identified, including solid organ transplant patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In this systematic review, we aimed to evaluate the epidemiology and impact of invasive infections caused by Aspergillus fumigatus to inform the first FPPL. The pre-specified criteria of mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence were used to search for relevant articles between 1 January 2016 and 10 June 2021. Overall, 49 studies were eligible for inclusion. Azole antifungal susceptibility varied according to geographical regions. Voriconazole susceptibility rates of 22.2% were reported from the Netherlands, whereas in Brazil, Korea, India, China, and the UK, voriconazole susceptibility rates were 76%, 94.7%, 96.9%, 98.6%, and 99.7%, respectively. Cross-resistance was common with 85%, 92.8%, and 100% of voriconazole-resistant A. fumigatus isolates also resistant to itraconazole, posaconazole, and isavuconazole, respectively. The incidence of invasive aspergillosis (IA) in patients with acute leukemia was estimated at 5.84/100 patients. Six-week mortality rates in IA cases ranged from 31% to 36%. Azole resistance and hematological malignancy were poor prognostic factors. Twelve-week mortality rates were significantly higher in voriconazole-resistant than in voriconazole-susceptible IA cases (12/22 [54.5%] vs. 27/88 [30.7%]; P = .035), and hematology patients with IA had significantly higher mortality rates compared with solid-malignancy cases who had IA (65/217 [30%] vs. 14/78 [18%]; P = .04). Carefully designed surveillance studies linking laboratory and clinical data are required to better inform future FPPL., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Aspergillus species and Mucorales agents are the primary etiologies of invasive fungal disease (IFD). Biomarkers that predict outcomes are needed to improve care. Patients diagnosed with invasive aspergillosis and mucormycosis using plasma cell-free DNA (cfDNA) PCR were retested weekly for 4 weeks. The primary outcome included all-cause mortality at 6 weeks and 6 months based on baseline cycle threshold (CT) values and results of follow-up cfDNA PCR testing. Forty-five patients with Aspergillus and 30 with invasive Mucorales infection were retested weekly for a total of 197 tests. Using the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSG) criteria, 30.7% (23/75), 25.3% (19/75), and 38.7% (29/75) had proven, probable, and possible IFD, respectively. In addition, 97.3% (73/75) were immunocompromised. Baseline CT increased significantly starting at week 1 for Mucorales and week 2 for Aspergillus . Aspergillosis and mucormycosis patients with higher baseline CT (CT >40 and >35, respectively) had a nonsignificantly higher survival rate at 6 weeks, compared with patients with lower baseline CT. Mucormycosis patients with higher baseline CT had a significantly higher survival rate at 6 months. Mucormycosis, but not aspergillosis patients, with repeat positive cfDNA PCR results had a nonsignificantly lower survival rate at 6 weeks and 6 months compared with patients who reverted to negative. Aspergillosis patients with baseline serum Aspergillus galactomannan index <0.5 and <1.0 had significantly higher survival rates at 6 weeks when compared with those with index ≥0.5 and ≥1.0, respectively. Baseline plasma cfDNA PCR CT can potentially be used to prognosticate survival in patients with invasive Aspergillus and Mucorales infections., Importance: We show that Aspergillus and Mucorales plasma cell-free DNA PCR can be used not only to noninvasively diagnose patients with invasive fungal disease but also to correlate the baseline cycle threshold with survival outcomes, thus potentially allowing the identification of patients at risk for poor outcomes, who may benefit from more targeted therapies., Competing Interests: The authors declare no conflict of interest.

Purpose: We aimed to show the increasing incidence of invasive fungal infections due to Volvariella Volvacea in patients with immunosuppression., Methods: We present a case of an invasive fungal infection caused by Volvariella volvacea, and summarize the clinical and pathological features based on this case and a review of the literature., Results: A total of seven patients with IFIs due to Volvariella Volvacea have been reported in the literature. The majority of cases have been obtained between 2019 and 2022. Including our case, they all had acquired immunosuppression. The lung and brain were the most commonly affected organs. All eight of these patients received antifungal therapy, but five still died one to seven months after occurrences of IFIs., Conclusion: The incidence of invasive fungal infections due to Volvariella Volvacea is increasing in recent years. It mainly occurred in patients with immunosuppression, especially in patients with malignant hematological cancers, and increased mortality., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Invasive Aspergillosis (IA) is a life-threatening fungal disease with significant mortality rates. Timely diagnosis and treatment greatly enhance patient outcomes. This study aimed to explore the association between patient age and the development of IA, as well as the potential implications for risk stratification strategies., Methods: We searched National Center for Biotechnology Information (NCBI) databases for publications until October 2023 containing age characteristics of patients with and without IA. A random-effects model with the application of inverse-variance weighting was used to pool reported estimates from each study, and meta-regression and subgroup analyses were utilized to assess sources of heterogeneity., Results: A systematic review was conducted, resulting in the inclusion of 55 retrospective observational studies with a total of 13,983 patients. Meta-analysis revealed that, on average, patients with IA were approximately two and a half years older (95% Confidence Interval [CI] 1.84-3.31 years; I 2  = 26.1%) than those without the disease (p < 0.0001). No significant moderators could explain the observed heterogeneity in age difference. However, subgroup analysis revealed that age differences were more pronounced within particular patient groups compared to others. For example, patients with and without IA who had primary severe lung infections exhibited a greater difference in mean age than other patient cohorts., Conclusions: Further research, such as individual patient data meta-analysis, is necessary to better understand the potential relationship between increasing age and the likelihood of IA. Improved risk stratification strategies based on patient age could potentially enhance the early detection and treatment of IA, ultimately improving patient outcomes., (© 2024. The Author(s).)

Scedosporium/Lomentospora species exist as saprophytic moulds that can potentially lead to serious infections in patients who have experienced near-drowning incidents. Scedosporium species are distributed across different regions of the world while Lomentospora prolificans has quite a restricted geographic distribution. We aimed to systematically review scedosporiosis cases after near-drowning, their clinical manifestations, underlying diseases, treatments, outcomes and its impact through disability-adjusted life years (DALYs). Five available sources were searched from 1 January 2007, to 20 April 2022. Thirty-eight studies, including 41 patients, were evaluated. Mean age was 33.6 ± 18.6 years (range 1-68), and 28 were male (68.3%). Central nervous system (CNS) dissemination predominated (36/41; 87.8%), presenting mainly as multiple brain abscesses (26/41; 63.4%), followed by lung involvement (22/41; 56.4%). Scedosporium apiospermum species complex was the most causative agent (38/41; 92.7%). Overall mortality was 51.2%. Half of the patients (18/37) were cured after receiving proper treatment, and in most cases, voriconazole alone or in combination with surgery or other antifungals caused survival. The mean survival time was 123 ± 27 days. Mean DALYs in 1980-2022 were 46.110 ± 3.318 (39.607-52.612). Time to diagnosis was estimated to be 120 days, and there was no association between time to diagnosis and outcome. Voriconazole is a potentially effective therapy, and combination of surgery and antifungal treatment may lead to more favourable outcome. Advances in early diagnosis and appropriate antifungal therapy may have contributed to reducing its mortality., (© 2024 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

Introduction: Invasive fungal infections (IFI) cause significant mortality and morbidity in the Paediatric Intensive Care Unit (PICU). Early recognition and prompt treatment of invasive fungal infections are important. This article reviewed the mortality and morbidity of IFIs in the PICU of Hong Kong Children's Hospital., Methods: A retrospective review of all PICU admissions from April 2019 to May 2021 was performed. The following data were retrieved: age, gender, diagnosis, comorbidity, clinical manifestation, type of fungus, duration of stay at PICU, absolute neutrophil count, use of immunosuppressive therapy, presence of central venous catheter and use of total parental nutrition. The primary outcomes were the incidence and mortality of IFIs among PICU patients. The secondary outcomes were risk factors for developing IFI in PICU and clinical course of IFIs. Numerical variables were compared between groups by Mann-Whitney U test and categorical variables by Fisher's exact test., Results: There were 692 PICU admissions over the study period from April 2019 to May 2021. The crude mortality was 3% (n=24 death cases) in the PICU. Fourteen patients (2%) fulfilling the criteria for IFIs were identified using hospital electronic record system and according to PICU documentation. Eight of these 14 patients (57%) had hematological malignancy, 2 (17%) had solid tumours and 4 had non-oncological conditions. Eight (57%) patients were neutropenic with absolute neutrophil count less than 1x 109 at diagnosis of IFI. Ten (71%) had received immunosuppressive therapy including steroid, cyclosporin A, Mycophenolate mofetil (MMF), Sirolimus or tacrolimus. 12 (86%) had had central venous catheter. Eight (57%) were on parenteral nutrition. IFIs due to Rhizopus or Aspergillus infection (5/14), or in post-haematopoietic stem cell transplant patients (5/14) were associated with non-survival (p = 0.031)., Conclusion: All patients with IFIs managed in the PICU had haemato-oncology diseases or were recipients of stem cell transplantation. IFIs with Rhizopus or Aspergillus as a group were associated with high mortality in the PICU. Awareness of this pathology with prompt diagnosis and treatment may improve the outcome of these infections and reduce the mortality., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: We aimed to describe patients with autoimmune diseases (AID) developing invasive fungal disease (IFD) and identify factors associated with short-term mortality., Methods: We analysed cases of IFD associated with AID from the surveillance network of invasive fungal diseases (Réseau de surveillance des infections fongiques invasives, RESSIF) registry of the French national reference centre for invasive mycoses. We studied association of AID-specific treatments with 30-day mortality. We analysed total lymphocyte and CD4-T cell counts in patients with Pneumocystis jirovecii pneumonia (PCP)., Results: From 2012 to 2018, 549 individuals with IFD and AID were included, mainly with PCP (n=227, 41.3%), fungemia (n=167, 30.4%) and invasive aspergillosis (n=84, 15.5%). Rheumatoid arthritis (RA) and anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) were the most frequent AID in PCP (n=55 and 25, respectively) and invasive aspergillosis (n=15 and 10, respectively), inflammatory bowel diseases (IBDs) were predominant in fungemia (n=36). At IFD diagnosis, 365 (66.5%) patients received glucocorticoids (GCs), 285 (51.9%) immunosuppressants, 42 (7.7%) tumor necrosis factor (TNF)-α blockers, 75 (13.7%) other biologics. Mortality at 30 days was 28.1% (143/508). Fungemia and high-dose GCs were independently associated with higher 30-day mortality. In PCP patients, lymphopenia <1500/mm 3 was frequent (132/179, 73.7%) even if CD4+T cell count exceeded 200/mm 3 in 56/78 patients (71.8%) (median 472.5/mm 3 , IQR 160-858)., Conclusion: IFD associated with AID occurs primarily in RA, AAV and IBD, especially when treated with GCs and immunosuppressants. Mortality is high, especially for patients on high-dose GCs. Lymphopenia may help identify risk of PCP, but normal CD4+T cell count does not rule out the risk. Further studies are needed to assess the individual risk factors for IFD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Invasive fungal infections pose a severe threat in unconventional immunocompromised hosts such as cirrhosis. Herein we review the impact of invasive aspergillosis (IA) on the prognosis of cirrhosis patients. An electronic search for full-text articles describing IA in cirrhosis was conducted and the disease outcomes and mortality (point-estimate and comparative risk) were pooled on random-effects meta-analysis. Of 4127 articles, 11 studies (9 with good/fair and 2 with poor quality) were included. IA was associated with high disease severity and multi-organ failures in cirrhosis. The pooled-mortality of IA was 81.8% (95% CI: 64.3-91.8, I2 = 59%, P < 0.01). Estimate's-heterogeneity (I2) was explored through sub-groups, meta-regression, and influential diagnostics. Mortality estimates were higher among subgroups of acute-on-chronic liver failure (ACLF, 86.4%) and intensive care unit (ICU)-admitted patients (84.0%). The odds of mortality related to IA were 8.9 times higher than controls and much higher in ACLF (OR: 22.5) and ICU-admitted patients (OR: 36.4). The odds of mortality in IA were 4.1, 12.9, and 48.6 times higher than bacterial, no-fungal infections, and no-infection controls. There was no asymmetry in mortality estimates or odds ratios and mortality in IA was high irrespective of country of origin, site of infection, proven or probable category, and quality of study. Thus, IA is associated with very high mortality in cirrhosis patients, especially in ACLF and ICU-admitted patients. Intensive research is needed for the rapid diagnosis and treatment of IA in cirrhosis., Lay Summary: We report a high mortality rate of 81.8% in patients with liver cirrhosis and invasive aspergillosis. Higher odds (8.9 times) of death, especially in patients with ACLF or ICU admission were seen. Mortality was not affected by the country of study, site of infection, proven or probable nature of infection category, and quality of study., (© The Author(s) 2021. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Objectives: To describe the coinfections in invasive aspergillosis (IA), to identify factors associated with coinfections, and to evaluate the impact of coinfection on mortality., Patients and Methods: We conducted a monocentric retrospective study of consecutive putative, probable, or proven IA that occurred between 1997 and 2017. All coinfections, with an onset within 7 days before or after the first sign of aspergillosis, were identified. Factors associated with coinfections and mortality were analysed by multivariable analysis., Results: Among the 690 patients with IA included in the study, the median age was 57 years (range 7 days to 90 years). A coinfection was diagnosed in 272/690 patients (39.4%, 95%CI 35.8-43.2). The location of this coinfection was pulmonary only in 131/272 patients (48%), bloodstream only in 66/272 patients (24%) and other/multiple sites in 75/272 patients (28%). Coinfections were bacterial (110/272 patients, 40%), viral (58/272, 21%), fungal (57/272, 21%), parasitic (5/272, 2%) or due to multiple types of pathogens (42/272, 15%). Factors associated with a coinfection in adjusted analysis were: allogeneic haematopoietic stem-cell transplantation (OR 2.3 (1.2-4.4)), other haematological malignancies (OR 2.1 (1.2-3.8)), other underlying diseases (OR 4.3 (1.4-13.6)), lymphopenia (OR 1.7 (1.1-2.5)), C-reactive protein >180 mg/L (OR 1.9 (1.2-3.0)), fever (OR 2.4 (1.5-4.1)), tracheal intubation (OR 2.6 (1.5-4.7)), isolation of two or more different Aspergillus species (OR 2.7 (1.1-6.3)), and the presence of non-nodular lesions on chest computed tomography (OR 2.2 (1.3-3.7) and OR 2.2 (1.2-4.0)). Coinfections were independently associated with a higher mortality at week 12 (adjusted HR 1.5 (1.1-1.9), p < 0.01)., Conclusions: Coinfections are frequent in IA patients and are associated with higher mortality., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Scedosporiosis/lomentosporiosis is a devastating emerging fungal infection. Our objective was to describe the clinical pattern and to analyze whether taxonomic grouping of the species involved was supported by differences in terms of clinical presentations or outcomes. We retrospectively studied cases of invasive scedosporiosis in France from 2005 through 2017 based on isolates characterized by polyphasic approach. We recorded 90 cases, mainly related to Scedosporium apiospermum (n = 48), S. boydii/S. ellipsoideum (n = 20), and Lomentospora prolificans (n = 14). One-third of infections were disseminated, with unexpectedly high rates of cerebral (41%) and cardiovascular (31%) involvement. In light of recent Scedosporium taxonomic revisions, we aimed to study the clinical significance of Scedosporium species identification and report for the first time contrasting clinical presentations between infections caused S. apiospermum, which were associated with malignancies and cutaneous involvement in disseminated infections, and infections caused by S. boydii, which were associated with solid organ transplantation, cerebral infections, fungemia, and early death. The clinical presentation of L. prolificans also differed from that of other species, involving more neutropenic patients, breakthrough infections, fungemia, and disseminated infections. Neutropenia, dissemination, and lack of antifungal prescription were all associated with 3-month mortality. Our data support the distinction between S. apiospermum and S. boydii and between L. prolificans and Scedosporium sp. Our results also underline the importance of the workup to assess dissemination, including cardiovascular system and brain., (© The Author(s) 2020. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Dermatophyte infections usually present as various types of superficial cutaneous mycoses; on very rare occasions, dermatophytes enter deep into the dermis and cause invasive infections. In this study, we aimed to perform a systematic review of all reported invasive dermatophytosis cases over the past 20 years. We performed systematic searches in PubMed/Medline, EMBASE and Web of Science and identified 123 papers reporting 160 individual cases of invasive dermatophytosis between 2000 and 2020. Our study included 103 (64.4%) males, and the mean age at diagnosis was 43.0 years (range: 3-87 years). The most common predisposing factor was superficial dermatophytosis (56.9%), followed by solid organ transplantation (26.9%), the use of topical immunosuppressants (15.6%), gene mutations (14.4%), diabetes (14.4%) and trauma (6.9%). Trichophyton (T.) rubrum was the most prevalent pathogen (53.1%) responsible for invasive dermatophytosis, followed by T. mentagrophytes (7.5%), Microsporum canis (6.9%), T. tonsurans (5.6%), T. interdigitale (5.0%) and T. violaceum (3.8%). Patients with CARD9 or STAT3 mutations were prone to have mixed infection of two or more dermatophytes, present with eosinophilia and high IgE, and develop disseminated infections. Overall mortality was 7.9%, and the mortality in patients with and without gene mutations was 17.4% and 5.5%, respectively. Most of the normal host patients responded well to oral antifungal agents, while gene-deficient patients usually required lifelong treatment to stabilise their infection status. Our review indicated the importance of preventive treatment of superficial tinea in patients with immunosuppression and gene deficiencies to avoid the development of invasive dermatophytosis., (© 2020 Wiley-VCH GmbH.)

Introduction: A multi-centre study to determine the outcomes and risks for invasive fungal disease (IFD) in myeloma (MM) patients treated with second-generation immunomodulatory drugs, proteasome inhibitors and monoclonal antibodies was conducted., Methods: Clinical and microbiology records were reviewed to capture patient demographics, disease characteristics, treatment, IFD episodes and outcomes. Categorical and continuous variables between patients with IFD and without IFD were compared using chi-square test, Fisher's exact test and Mann-Whitney rank sum test, respectively, with P-value < .05 considered statistically significant., Results: Five out of 148 (3.4%) MM patients were diagnosed with five episodes of IFI: 3 were proven, 1 probable and 1 possible. Median time from commencement of new generation therapy to IFD diagnosis was 4.0 months (Interquartile range [IQR]: 3.4-5.7). In patients with IFD, median cumulative steroid dose over 60 days was 1119 mg (IQR: 1066-1333 mg). None of the patients with IFD had prolonged neutropenia (neutrophil count < 0.5 × 10 9 /L for more than 10 days). Common sites of infection were the respiratory tract (40.0%) and bloodstream (40.0%). Cryptococcus neoformans (n = 2) and Candida krusei (n = 1) were the fungal pathogens isolated in the three proven cases. 30-day mortality rate was 40.0%. Patients with IFD were younger (median 58 versus 68 years, P = .52) and treated with more lines of therapy (median 5 vs 3, P = .04)., Conclusion: IFD rate is low in heavily treated MM patients treated with second-generation therapy including monoclonal antibodies. Patients do not appear to have traditional risk factors such as prolonged neutropenia., (© 2020 Wiley-VCH GmbH.)

Despite the medical advances and interventions to improve the quality of life of those in intensive care, people with cancer or severely immunocompromised or other susceptible hosts, invasive fungal diseases (IFD) remain severe and underappreciated causes of illness and death worldwide. Therefore, IFD continue to be a public health threat and a major hindrance to the success of otherwise life-saving treatments and procedures. Globally, hundreds of thousands of people are affected every year with Candida albicans, Aspergillus fumigatus, Cryptococcus neoformans, Pneumocystis jirovecii, endemic dimorphic fungi and Mucormycetes, the most common fungal species causing invasive diseases in humans. These infections result in morbidity and mortality rates that are unacceptable and represent a considerable socioeconomic burden. Raising the general awareness of the significance and impact of IFD in human health, in both the hospital and the community, is hence critical to understand the scale of the problem and to raise interest to help fighting these devastating diseases.

Objectives: This study aimed to investigate the distinguishing ability of lymphocyte subtyping for diagnosis and prognosis of invasive fungal disease (IFD)., Methods: We assessed lymphocyte subtyping and evaluated the quantitative changes in key immunological parameters at intensive care unit (ICU) admission in critically ill patients at high risk and their potential influence on diagnosis and outcome of IFD. The primary outcome was 28-day mortality., Results: Among the 124 critically ill patients with mean Candida score 3.89 (0.76), 19 (15.3%) were in the IFD group. CD28 + CD8 + T-cell counts (area under the curve [AUC] 0.899, 95% confidence interval [CI], 0.834-0.964, P < .001) had better distinguishing ability than other immune parameters for IFD diagnosis. The cutoff value of CD28 + CD8 + T-cell counts at ICU admission for IFD diagnosis was 59.5 cells/mm 3 , with 83.3% sensitivity and 86.4% specificity. Multivariate logistic regression analysis identified CD28 + CD8 + T-cell count <59.5 cells/mm 3 (odds ratio 59.7, 95% CI, 7.33-486.9, P < .001) as an independent predictor for IFD diagnosis. CD28 + CD8 + T-cell counts could also predict 28-day mortality (AUC 0.656, 95% CI, 0.525-0.788, P = .045). Kaplan-Meier survival analysis provided evidence that natural killer cell count <76.0 cells/mm 3 (log-rank test; P = .001), CD8 + T-cell count <321.5 cells/mm 3 (log-rank test; P = .04), and CD28 + CD8 + T-cell count <129.0 cells/mm 3 (log-rank test; P = .02) at ICU admission were associated with lower survival probabilities., Conclusion: CD28 + CD8 + T-cell counts play an important role in early diagnosis of IFD. Low counts are associated with early mortality in critically ill patients at high risk of IFD. Our findings add evidence to the utility of lymphocyte subtyping in a diagnostic algorithm to better define IFD in critically ill patients at high risk.

Background: Hodgkin (HL) and non-Hodgkin lymphoma (NHL) represent a spectrum of lymphoid malignancies that are often curable with currently applied treatment regimens; however, 15%-30% of lymphoma patients still suffer from relapsed or refractory (rel/ref) disease. Although hematopoietic stem cell transplantation (HSCT) improves outcomes of second-line therapy for lymphoma in childhood, the complication rates in this group of patients, especially infectious complications (IC), remain unclear., Objective: The aim of this population-based cohort study was a retrospective analysis of incidence, epidemiology and profile of bacterial infections (BI), invasive fungal disease (IFD), and viral infections (VI) in primary or rel/ref lymphoma patients, both HL and NHL., Patients and Methods: We subdivided lymphoma patients into three groups: patients with primary conventional chemotherapy/radiotherapy regimens (group A), patients with rel/ref lymphoma treated with second-line chemotherapy (group B), and rel/ref lymphoma patients who underwent HSCT (group C). The medical records of the patients were biannually reported by each pediatric oncology center, and the data were analyzed centrally., Results: Within 637 patients with primary lymphoma, at least one IC was diagnosed in 255 (40.0%), among 52 patients with rel/ref lymphoma 24 (46.2%) ICs were observed, and in transplanted group, 28 (57.1%) out of 49 children were diagnosed with IC (P = .151). The distribution of etiology of IC differed between the patient groups (A, B, C), with a predominance of BI in group A (85.6% vs 72.0% and 47.9%, respectively), VI in group C (9% and 16.0% vs 46.6%, respectively), and IFD in group B (5.4% vs 12.0% vs 5.5%, respectively). Overall, 500 (68.0%) episodes of bacterial IC were diagnosed in the entire group. Apart from HL patients treated with chemotherapy, in all the other subgroups of patients Gram-positives were predominant. The rate of multidrug-resistant bacteria was high, especially for Gram-negatives (41.1% in group A, 62.5% in group B, and 84.6% in group C). The infection-related mortality was comparable for each group., Conclusions: The incidence of IC was comparable during first- and second-line chemotherapy and after HSCT, but their profile was different for primary or re/ref lymphoma and depended on the type of therapy., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Pulmonary mucormycosis (PM) represents a serious burden in terms of morbidity and mortality in immunocompromised patients. Studies of prognostic factors in patients with PM are limited and have involved small numbers of patients., Methods: Adult patients diagnosed with proven and probable PM according to the modified definitions of the EORTC/MSG 2008 in a tertiary hospital in Seoul, South Korea, between 2008 and 2019 were retrospectively enrolled., Results: A total of 49 patients including 31 (63%) with proven PM and 18 (37%) with probable PM were enrolled. The 90-day mortality rate was 49% (24/49). Neutropenia, thrombocytopenia, use of voriconazole at clinical suspicion, positivity of non-sterile culture, use of steroid and treatment without surgery were more common in fatal cases than non-fatal cases. Voriconazole use at clinical suspicion for invasive mould pneumonia (OR 6.91, P = .01) and prolonged neutropenia (OR 4.86, P = .03) were independent risk factors for mortality. Voriconazole use at clinical suspicion was associated with positive galactomannan (GM) assay (OR 5.93, P = .02) and history of invasive pulmonary aspergillosis (OR, 6.88, P = .05)., Conclusion: About half of the patients with PM died within 90 days of diagnosis, and fatal outcomes were common in patients with prolonged neutropenia and empirical voriconazole use. Caution is needed in using voriconazole even in patients with positive GM results and prior histories of invasive pulmonary aspergillosis in whom PM cannot be ruled out by differential diagnosis., (© 2020 Blackwell Verlag GmbH.)

Background: Characteristics and outcome of invasive fungal infection (IFI) in critically ill burn patients have been poorly explored., Objectives: We report the factors associated with 90-day mortality in a multicentre retrospective European study., Patients/methods: All burn patients with confirmed IFI admitted between 1 January 2010 to 31 December 2015 in 10 centres in France and Belgium were included., Results: Ninety-four patients were enrolled with 110 cases of IFIs: 79 (71.8%) were yeasts IFI and 31 (28.2%) filamentous IFI. Incidence was 1% among admitted patients. The 90-day mortality was 37.2% for all IFIs combined, 52% for filamentous infection and 31.9% for yeast infection. Patients with more than one IFI had a higher 90-day mortality than patients with only one episode (61.5% vs 33.5% (P = .006)). In multivariate analysis, higher Simplified Acute Physiology Score II (OR = 1.05 (95% CI: 1.02-1.09) P = .003), bacterial co-infection (OR = 3.85 (95% CI: 1.23-12.01), P = .014) and use of skin allografts at the time of IFI diagnosis (OR = 3.87 (95% CI: 1.31-11.42), P = .021) were associated with 90-day mortality., Conclusions: Although rare, invasive fungal infections remain associated with poor outcome in burn patients. Bacterial co-infection and presence of allograft were potentially modifiable factors independently associated with outcome., (© 2020 Blackwell Verlag GmbH.)

Background: Chronic invasive fungal sinusitis (CIFS) is a rare, life-threatening infection of the nose and sinuses. This study aims to identify factors that impact survival in 1 of the largest cohorts to date., Methods: Pathology records were reviewed for biopsy-proven CIFS from 3 tertiary academic institutions from 1995 to 2016. Variables were analyzed using log-rank survival analysis. Univariate Cox regression was performed at 1 and 12 months., Results: Thirty-eight patients were included. Hematologic malignancy and diabetes were the most common underlying diseases (32% each). Aspergillus was the most common fungus (63%). Greater than 75% of the patients had an absolute neutrophil count (ANC) >1000 at the time of diagnosis. Overall survival at 1, 6, and 12 months was 89%, 68%, and 48%, respectively. In univariate analysis, factors associated with worse survival included: ANC <500 at 12 months (hazard ratio [HR] 4.8; p = 0.01), ANC <1000 at 12 months (HR 5.8; p = 0.001), and recent chemotherapy (HR 4; p = 0.01). The following factor was associated with improved survival in univariate analysis: ANC as a linear variable in the entire cohort (HR 0.7; p = 0.005)., Conclusion: We present a multi-institutional case-series of CIFS and long-term follow-up. ANC <1000 at time of diagnosis and recent chemotherapy (within 1 month of diagnosis) are associated with poorer survival, whereas a rising ANC >1000 is associated with improved survival at 12 months. Further prospective studies are needed to further define factors that affect outcomes., (© 2020 ARS-AAOA, LLC.)

Objectives: Invasive fungal infections caused by Lomentospora prolificans are associated with very high mortality rates and can be challenging to treat given pan-drug resistance to available antifungal agents. The objective of this study was to describe the clinical presentation and outcomes in a cohort of patients with invasive L prolificans infections., Methods: We performed a retrospective review of medical records of patients with invasive L prolificans infection in the FungiScope ® registry of rare invasive fungal infections. Patients diagnosed between 01 January 2008 and 09 September 2019 were included in for analysis., Results: The analysis included 41 patients with invasive L prolificans infection from eight different countries. Haematological/oncological malignancies were the most frequent underlying disease (66%), disseminated infection was frequent (61%), and the lung was the most commonly involved organ (44%). Most infections (59%) were breakthrough infections. Progression/deterioration/treatment failure was observed in 23/40 (58%) of patients receiving antifungal therapy. In total, 21/41 (51%) patients, and 77% of patients with underlying haematological/oncological malignancy, had a fatal outcome attributed to invasive fungal infection. Combination antifungal therapy was frequent (24/40) and associated with improved survival. In particular, treatment regimens including terbinafine were significantly associated with higher treatment success at final assessment (P = .012), with a positive trend observed for treatment regimens that included voriconazole (P = .054)., Conclusions: Lomentospora prolificans infections were associated with mortality rates of 77% and above in patients with underlying haematological/oncological malignancies and those with disseminated infections. While combination therapy is the preferred option for now, the hope lies with novel antifungals currently under development., (© 2020 Blackwell Verlag GmbH.)

Mould-active prophylaxis is affecting the epidemiology of invasive mycoses in the form of a shift toward less common entities such as fusariosis. We analyze the characteristics of invasive fusariosis and its association to antifungal prophylaxis in a retrospective cohort (2004-2017) from a tertiary hospital in Madrid, Spain. Epidemiological, clinical, microbiological, and antifungal consumption data were retrieved. Isolates were identified to molecular level, and antifungal susceptibility was tested. Eight cases of invasive fusariosis were diagnosed. Three periods were identified according to incidence: <2008 (three cases), 2008-2013 (zero cases), >2014 (five cases). All except one case involved breakthrough fusariosis. During the earliest period, the episodes occurred while the patient was taking itraconazole (two) or fluconazole (one); more recently, while on micafungin (three) or posaconazole (one). Early cases involved acute leukemia at induction/consolidation, recent cases relapsed/refractory disease (P = .029). Main risk factor for fusariosis (62.5%) was prolonged neutropenia (median 44 days). Galactomannan and beta-D-glucan were positive in 37.5% and 100% of cases, respectively. All isolates except F. proliferatum presented high minimal inhibitory concentrations (MICs) against the azoles and lower MIC to amphotericin B. Most patients received combined therapy. Mortality at 42 days was 62.5%. Resolution of neutropenia was associated with survival (P = .048). Invasive fusariosis occurs as breakthrough infection in patients with hematologic malignancy, prolonged neutropenia, and positive fungal biomarkers. Recent cases were diagnosed in a period of predominant micafungin use in patients who had more advanced disease and protracted neutropenia and for whom mortality was extremely high. Resolution of neutropenia was a favorable prognostic factor., (© The Author(s) 2019. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Objectives: Invasive fungal infection following liver transplant is considered as one of the important factors influencing morbidity and mortality among liver transplant recipients. The aim of the present study was to describe the prevalence of invasive fungal infections and their predisposing factors in a singlecenter cohort of patients who received liver transplant., Materials and Methods: For this study, 250 adult patients undergoing orthotopic liver transplant between March 2010 and March 2015 were enrolled. All patients were followed prospectively for infections., Results: The diagnosis of invasive fungal infection was made in 15 patients (6%). One patient had 2 episodes of fungal infection, and reoperation was performed for 3 patients. Invasive aspergillosis developed in 8 patients (53.3%),followed by Candida species infection in 3 patients (20%) and cryptococcosis in 2 patients (13.3%).The main predisposing factors were renal failure (12/15) and positive history of rejection (11/15). Other risk factors for development of invasive fungal infections were choledochojejunostomy in 3 patients (20%), bile leaks in 3 patients (20%), and pretransplant steroid use in 2 patients (11.8%). Two patients (13.3%) died due to invasive fungal infections., Conclusions: In this single-center series of liver transplant recipients, the incidence of invasive fungal infections was relatively low, probably due to the universal prophylaxis with fluconazole and limited use of the broad-spectrum antibiotics. Early diagnosis and treatment of invasive fungal infections could lead to a better prognosis for liver transplant recipients with invasive fungal infections.

Background: The new Rasamsonia spp. complex can develop invasive infection in immunosuppression or chronic pulmonary disease. It has potential to be misidentified as other genera due to morphological similarities. Nowadays, there is a gap of knowledge on this fungi., Objectives: To provide knowledge base of risk factors and therapeutic decisions in invasive Rasamsonia spp. complex infection., Patients/methods: Cases of invasive infection due to Rasamsonia spp. (formerly Geosmithia/Penicillium spp.) from FungiScope ® registry and all reported cases from a literature were included., Results: We identified 23 invasive infections due to Rasamsonia spp., six (26.1%) in the FungiScope ® registry. Main risk factors were chronic granulomatous disease (n = 12, 52.2%), immunosuppressive treatment (n = 10, 43.5%), haematopoietic stem cell transplantation (n = 7, 30.4%), graft-versus-host disease and major surgery (n = 4, 17.4%, each). Predominantly affected organs were the lungs (n = 21, 91.3%), disease disseminated in seven cases (30.4%). Fungal misidentification occurred in 47.8% (n = 11), and sequencing was used in 69.6% of the patients (n = 16) to diagnose. Breakthrough infection occurred in 13 patients (56.5%). All patients received antifungal treatment, mostly posaconazole (n = 11), caspofungin (n = 10) or voriconazole (n = 9). Combination therapy was administered in 13 patients (56.5%). Susceptibility testing showed high minimum inhibitory concentrations for azoles and amphotericin B, but not for echinocandins. No preferable treatment influencing favourable outcome was identified. Overall mortality was 39% (n = 9)., Conclusion: Rasamsonia spp. are emerging fungi causing life-threatening infections, especially in immunocompromised and critically ill patients. Mortality is high. Treatment is challenging and clinicians dealing with this patient population should become aware of this infection constituting a medical emergency., (© 2019 The Authors. Mycoses published by Blackwell Verlag GmbH.)

Since mould-active azole prophylaxis has become a standard approach for patients with high-risk haematologic diseases, the epidemiology of invasive fungal infections (IFIs) has shifted towards non-Aspergillus moulds. It was aimed to identify the epidemiology and characteristics of non-Aspergillus invasive mould infections (NAIMIs). Proven/probable NAIMIs developed in patients with haematologic diseases were reviewed from January 2011 to August 2018 at Catholic Hematology hospital, Seoul, Korea. There were 689 patients with proven/probable invasive mould infections; of them, 46 (47 isolates) were diagnosed with NAIMIs. Fungi of the Mucorales order (n = 27, 57.4%) were the most common causative fungi, followed by Fusarium (n = 9, 19.1%). Thirty-four patients (73.9%) had neutropenia upon diagnosis of NAIMIs, and 13 (28.3%) were allogeneic stem cell transplantation recipients. The most common site of NAIMIs was the lung (n = 27, 58.7%), followed by disseminated infections (n = 8, 17.4%). There were 23.9% (n = 11) breakthrough IFIs, and 73.9% (n = 34) had co-existing bacterial or viral infections. The overall mortality at 6 and 12 weeks was 30.4% and 39.1%, respectively. Breakthrough IFIs (adjusted hazards ratio [aHR] = 1.99, 95% CI: 1.3-4.41, P = .031) and surgical treatment (aHR = 0.09, 95% CI: 0.02-0.45, P = .003) were independently associated with 6-week overall mortality. NAIMIs were not rare and occur as a complex form of infection often accompanied by breakthrough/mixed/concurrent IFIs and bacterial or viral infections. More active diagnostic efforts for NAIMIs are needed., (© 2019 The Authors. Mycoses Published by Blackwell Verlag GmbH.)

Acute invasive fungal rhinosinusitis (AIFRS) can spread beyond the sinonasal cavity. It is necessary to analyze the association between the specific site involved in the extrasinonasal area and the survival rate to predict patient prognosis. We investigated 50 patients who had extrasinonasal lesions on preoperative gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) scan and underwent wide surgical resection of AIFRS. The specific sites with loss of contrast enhancement (LoCE) on Gd-enhanced MRI were analyzed for AIFRS-specific survival rate. The most common underlying disease was diabetes mellitus followed by hematological malignancy. The most common symptoms were headache and facial pain. Seven patients (14.0%) expired because of AIFRS progression. Poor prognosis was independently associated with LoCE at the skull base on preoperative MRI (HR = 35.846, P = 0.004). In patients with AIFRS extending to the extrasinonasal area, LoCE at the skull base was an independent poor prognostic factor.

There are limited treatment options for immunosuppressed patients with lethal invasive fungal infections due to Fusarium and Scedosporium Manogepix (MGX; APX001A) is a novel antifungal that targets the conserved Gwt1 enzyme required for localization of glycosylphosphatidylinositol-anchored mannoproteins in fungi. We evaluated the in vitro activity of MGX and the efficacy of the prodrug fosmanogepix (APX001) in immunosuppressed murine models of hematogenously disseminated fusariosis and pulmonary scedosporiosis. The MGX minimum effective concentration (MEC) for Scedosporium isolates was 0.03 μg/ml and ranged from 0.015 to 0.03 μg/ml for Fusarium isolates. In the scedosporiosis model, treatment of mice with 78 mg/kg and 104 mg/kg of body weight fosmanogepix, along with 1-aminobenzotriazole (ABT) to enhance the serum half-life of MGX, significantly increased median survival time versus placebo from 7 days to 13 and 11 days, respectively. Furthermore, administration of 104 mg/kg fosmanogepix resulted in an ∼2-log 10 reduction in lung, kidney, or brain conidial equivalents/gram tissue (CE). Similarly, in the fusariosis model, 78 mg/kg and 104 mg/kg fosmanogepix plus ABT enhanced median survival time from 7 days to 12 and 10 days, respectively. A 2- to 3-log 10 reduction in kidney and brain CE was observed. In both models, reduction in tissue fungal burden was corroborated with histopathological data, with target organs showing reduced or no abscesses in fosmanogepix-treated mice. Survival and tissue clearance were comparable to a clinically relevant high dose of liposomal amphotericin B (10 to 15 mg/kg). Our data support the continued development of fosmanogepix as a first-in-class treatment for infections caused by these rare molds., (Copyright © 2020 Alkhazraji et al.)

Objectives: To characterize the clinical presentation and outcomes of invasive mold infections (IMI) in solid organ transplant (SOT) recipients., Methods: Inclusion of all SOT recipients with IMI diagnosed between 2008 and 2016 at a referral center for SOT. Univariable analyses identified factors associated with death at one year, and logistic regression models retained independent predictors., Results: Of the 1739 patients that received a SOT during this period, 68 developed IMI (invasive aspergillosis [IA] in 58). Cumulative incidence of IMI at 1 year ranged from 1.2% to 18.8% (kidney and heart transplantation, respectively). At baseline, compared with other IMI, the need for vasoactive drugs was more frequent in patients with IA. During follow-up, 35 patients (51%) were admitted to the ICU and required mechanical ventilation (n = 27), vasoactive drugs (n = 31), or renal replacement therapy (n = 31). The need for vasoactive drugs (OR 7.34; P = .003) and a positive direct examination (OR 10.1; P = .004) were independently associated with the risk of death at 1 year in patients with IA (n = 33; 57%) CONCLUSIONS: Characteristics of IMI at presentation varied according to the underlying transplanted organ and the mold species. Following IA, one-year mortality may be predicted by the need for hemodynamic support and initial fungal load., (© 2019 Wiley Periodicals, Inc.)

Background: Invasive fungal diseases (IFD) are life-threatening infections most commonly diagnosed in acute leukaemia patients with prolonged neutropenia and are uncommonly diagnosed in patients with lymphoproliferative diseases., Objectives: Following the initial report of aspergillosis diagnosed shortly after beginning ibrutinib for chronic lymphocytic leukaemia, a survey was developed to seek additional cases of IFD during ibrutinib treatment., Methods: Local and international physicians and groups were approached for relevant cases. Patients were included if they met the following criteria: diagnosis of chronic lymphocytic leukaemia/non-Hodgkin lymphoma; proven or probable IFD; and ibrutinib treatment on the date IFD were diagnosed. Clinical and laboratory data were captured using REDCap software., Result: Thirty-five patients with IFD were reported from 22 centres in eight countries: 26 (74%) had chronic lymphocytic leukaemia. The median duration of ibrutinib treatment before the onset of IFD was 45 days (range 1-540). Aspergillus species were identified in 22 (63%) of the patients and Cryptococcus species in 9 (26%). Pulmonary involvement occurred in 69% of patients, cranial in 60% and disseminated disease in 60%. A definite diagnosis was made in 21 patients (69%), and the mortality rate was 69%. Data from Israel regarding ibrutinib treated patients were used to evaluate a prevalence of 2.4% IFD., Conclusions: The prevalence of IFD among chronic lymphocytic leukaemia/non-Hodgkin lymphoma patients treated with ibrutinib appears to be higher than expected. These patients often present with unusual clinical features. Mortality from IFD in this study was high, indicating that additional studies are urgently needed to identify patients at risk for ibrutinib-associated IFD., (© 2019 Blackwell Verlag GmbH.)

Background: The prevention of invasive fungal infections is important in patients with acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) receiving cytoreductive chemotherapy. However, the role of oral voriconazole (VRCZ) in such patients has not been established. This study aimed to investigate the effectiveness of oral VRCZ compared to that of first-generation azoles prescribed within 7 days after the onset of chemotherapy in adult patients with AML/MDS using the Japanese administrative database., Methods: This nationwide retrospective cohort study was conducted using the Diagnosis Procedure Combination/Per-Diem Payment System. The primary outcome was the proportion of patients who switched to intravenous antifungal agents. Analyses using the instrumental variable method were performed to address unmeasured confounding., Results: In total, data on 5517 inpatients from 142 hospitals were analyzed. An oral VRCZ prescription was significantly associated with a reduction in the proportion of patients switching to intravenous antifungal agents compared to first-generation azole prescription (21.0% (95% confidence interval [CI] - 33.4 to - 8.6)). The impact of oral VRCZ in reducing the proportion of patients switching to intravenous antifungal agents was stronger in patients aged < 65 years than in those aged ≥ 65 years (- 40.6%, 95% CI - 63.2 to - 17.9; - 21.9%, 95% CI - 35.8 to - 8.1, respectively) and in patients prescribed oral azole within 3 days from the onset of chemotherapy than in those prescribed the same later (- 32.9%, 95% CI - 46.7 to - 19.2; - 9.0%, 95% CI - 33.7 to 15.7, respectively)., Conclusion: Oral VRCZ administration may benefit adult patients with AML/MDS undergoing chemotherapy.

Purpose: Invasive fungal sinusitis is a rare but potentially lethal disease that primarily affects immunocompromised patients. The purpose of this study was to review an academic medical center's experience in the presentation, diagnosis, and treatment of invasive fungal sinusitis., Methods: A retrospective chart review was performed at a single institution over a 17-year period. Medical records, radiographic imaging, and operative reports were analyzed. Bivariate and multivariable analyses were performed to determine factors that affected visual acuity outcomes and mortality., Results: Fifty-five patients with histopathologically confirmed invasive fungal sinusitis were included. The average duration of follow up was 1.8 ± 2.6 years (range: 1 week to 10 years). The most common causes of immunosuppression were hematologic malignancy (45%), diabetes (31%), and organ transplantation (9%). At presentation, 35% of individuals were neutropenic (absolute neutrophil count < 500/μl). All patients received systemic antifungal treatment. A surgical intervention was performed on 50 patients (91%), and all but one had functional endoscopic sinus surgery. Nine (16%) patients underwent orbital exenteration. Multivariable analysis of visual acuity outcomes demonstrated that individuals infected with Zygomycota had 6-7 lines worse vision than those infected with Ascomycota (mean difference in logMAR 0.66, 95% confidence interval 0.27 to 1.06, p = 0.001). Patients who had functional endoscopic sinus surgery had 7-8 lines better visual acuity than those without functional endoscopic sinus surgery (mean difference in logMAR -0.76, 95% confidence interval -1.13 to -0.38, p < 0.001). The overall death rate due to infection was 24%. Bivariate models demonstrated no difference in mortality in patients receiving exenteration versus those who did not (p = 0.14). Multivariable analysis of mortality demonstrated that neutropenia increased mortality (adjusted odds ratio 10.05, 95% confidence interval 1.49 to 67.67, p = 0.02). Having a greater number of surgeries was associated with an increased rate of survival (adjusted odds ratio 0.39, 95% confidence interval 0.15 to 0.96, p = 0.04)., Conclusions: Invasive fungal sinusitis is an aggressive disease with significant mortality. Patients with neutropenia had a lower rate of survival, and infection with Zygomycota was associated with worse visual acuity outcomes. Those having functional endoscopic sinus surgery had better final visual acuity, and an increased number of surgeries was associated with a decreased chance of death. Exenteration yielded no observed survival benefit.Endoscopic sinus debridement portends better visual acuity outcomes in patients with invasive fungal sinusitis, whereas exenteration yields no difference in survival benefit.

Background: Autologous hematopoietic stem cell transplantation (HSCT) carries risks of infectious morbidity. We analysed epidemiology and management burden associated with invasive fungal diseases (IFDs) in children and adolescents undergoing autologous HSCT., Methods: In a retrospective, single-centre observational study, epidemiology and management burden associated with IFDs were analysed in all paediatric cancer patients who underwent autologous HSCT between 2005 and 2014. Clinical, radiographic and microbiological data were assessed up to 100 days post-transplant. The primary endpoint was the incidence of proven, probable and possible IFDs. Further endpoints included the use of systemic antifungal agents for prevention and management of IFDs; infectious and non-infectious comorbidities; and survival until day + 100., Results: Of 95 patients (median age: 8 years; r, 0.75-20) underwent 103 HSCT procedures for solid tumours (92) or lymphoma (11). Primary antifungal prophylaxis was administered in 49 procedures (47.5%). No single case of proven/probable IFD was diagnosed. Nine cases (8.7%) fulfilled criteria of possible pulmonary mould infection and received treatment for a median of 14 days (r, 7-35). In an additional 12 procedures, empiric antifungal therapy with mould active agents was given for a median of 8 days (r, 3-105). Microbiologically documented non-fungal infections were observed in 17 procedures, and five patients were transferred to the ICU. There was one death from biopsy documented toxic endothelial damage at day 83 post-transplant., Conclusions: Autologous HSCT for solid tumours or lymphoma was associated with low morbidity from IFDs. However, utilisation of systemic antifungal agents for prevention and management of suspected IFDs was considerable., (© 2019 The Authors. Mycoses published by Blackwell Verlag GmbH.)

Fungal infections are an important cause of morbidity and mortality in renal transplant recipients. These infections account for 5% of all infections in renal transplant recipients. The symptoms of systemic fungal infections are nonspecific, particularly in their early stages, and this can lead to delay in diagnosis. Retrospective analysis was conducted on all renal transplants that were performed at our center over a 20-year period from 1996-2016. Cases of invasive fungal infections (IFIs) that occurred among renal transplant recipients were identified to describe the epidmeiology of these infections. A total of 67 (9.2%) IFI cases were identified among 725 renal transplant recipients. Of the 67 patients (9.24%) with IFI, 31 (46.2%) cases were seen in deceased donor transplant recipients. Of 67 cases with IFI, 42 (62.7%) had received induction therapy. The incidence of fungal infections according to the induction agent used was, 14.3% with basiliximab, 12.3% each with daclizumab and rabbit antithymocyte globulin, and 6.3% among patients not given any induction. Invasive candidiasis was the most common IFI overall, followed by mucormycosis, invasive aspergillosis, and cryptococcosis. Median time to onset of IFI was 117.9 days. Majority of infections occurred within 180 days after transplantation. Late posttransplant (>180 days after transplantation) IFI's were predominantly caused by Candida, followed by Cryptococcus. The longest time to infection was a case of histoplasma, occurring seven years posttransplant. The overall 12-month cumulative incidence (CI) for any IFI was 9.1%. The 12-month CI of the first IFI increased from 7.3% between 1996 and 2001 to 10.5% between 2010 and 2016. The overall mortality rate was 38.8%. The use of newer and more-effective immunosuppressive agents in recent years are associated with increased rates of fungal infections in renal transplant recipients. Therefore, early detection of fungal infections and proper therapy are important in improving survival and reducing mortality.

Background: Increasing resistance of Aspergillus fumigatus to triazoles in high-risk populations is a concern. Its impact on mortality is not well understood, but rates from 50% to 100% have been reported., Objectives: To determine the prevalence of voriconazole-resistant A. fumigatus invasive aspergillosis (IA) and its associated mortality in a large multicentre cohort of haematology patients with culture-positive IA., Methods: We performed a multicentre retrospective study, in which outcomes of culture-positive haematology patients with proven/probable IA were analysed. Patients were stratified based on the voriconazole susceptibility of their isolates (EUCAST broth microdilution test). Mycological and clinical data were compared, along with survival at 6 and 12 weeks., Results: We identified 129 A. fumigatus culture-positive proven or probable IA cases; 103 were voriconazole susceptible (79.8%) and 26 were voriconazole resistant (20.2%). All but one resistant case harboured environment-associated resistance mutations in the cyp51A gene: TR34/L98H (13 cases) and TR46/Y121F/T289A (12 cases). Triazole monotherapy was started in 75.0% (97/129) of patients. Mortality at 6 and 12 weeks was higher in voriconazole-resistant cases in all patients (42.3% versus 28.2%, P = 0.20; and 57.7% versus 36.9%, P = 0.064) and in non-ICU patients (36.4% versus 21.6%, P = 0.16; and 54.4% versus 30.7%; P = 0.035), compared with susceptible ones. ICU patient mortality at 6 and 12 weeks was very high regardless of triazole susceptibility (75.0% versus 66.7%, P = 0.99; and 75.0% versus 73.3%, P = 0.99)., Conclusions: A very high prevalence of voriconazole resistance among culture-positive IA haematology patients was observed. The overall mortality at 12 weeks was significantly higher in non-ICU patients with voriconazole-resistant IA compared with voriconazole-susceptible IA., (© The Author(s) 2019. 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.)

Patients who develop severe graft-versus-host disease (GvHD) after allogeneic stem cell transplantation (alloSCT) have a higher risk for invasive fungal infection (IFI). At our center, fluconazole prophylaxis is standard and upfront mold-effective prophylaxis performed only in patients with specific risk constellations. A total of 290 patients undergoing alloSCT between May 2002 and August 2011 were analyzed. Patients were regarded as high-risk if they suffered from acute GvHD II-IV° or extensive chronic GvHD. The 2-year incidence of an IFI after alloSCT was 8.97% (26/290) in the entire cohort and 7.78% (7/90) in the high-risk group. Mortality due to IFI was 3.85% (1/26) without including a high-risk patient. In the multivariate analysis a pre-transplant fungal infection was the only significant risk factor for developing an IFI after alloSCT (HR = 5.298; p  = .001). A fluconazole prophylaxis in patients with GvHD after alloSCT is feasible in facilities with HEPA filtration and high awareness of clinical signs for IFI.

Background: There is limited information concerning the overall epidemiology of invasive fungal disease (IFD) in children. The aim of this study was to clarify the clinical features of IFD in a tertiary pediatric care hospital., Methods: Patients diagnosed with proven or probable IFD at our hospital between 2011 and 2015 were retrospectively reviewed. Proven and probable IFD were defined according to the European Organization for Research and Treatment of Cancer/Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group consensus. Patients with possible IFD were excluded., Results: The incidence of proven or probable IFD was 26 of 20,079 hospitalized patients (0.13%). The predominant underlying disease was malignancy (54%) and congenital anomaly (27%). The most common diagnosis was candidemia among the patients with proven IFD (8 of 13, 62%). All the isolated pathogens in the candidemia patients were non-albicans Candida spp. The most common site of infection was the lungs in patients with probable IFD (11 of 13 patients, 85%). In probable IFD episodes, positive β-D-glucan and galactomannan were found in 12 of 13 (92%) and 5 of 13 (38%) patients, respectively. All but one patient (96%) received empirical antifungal therapy. No patients underwent surgical resection of residual lesions. The overall mortality was 23% and the attributable mortality of IFD was 12%., Conclusion: Our results suggest the emergence of non-albicans Candida species as important pathogens in childhood IFD.

Background: Invasive fungal infections (IFI) are common after lung transplantation with reported incidence of 8.1% to 16% at 12 months post-transplant, and 3-month all-cause mortality after IFI of 21.7%., Methods: We performed a retrospective study of IFI and fungal colonization in lung transplants (LTs) from November 2004 to February 2017., Results: 137 LTs were followed for a median 4.1 years (IQR 2.1-6.2 years). In addition to nebulized amphotericin for the transplant admission to all LTs, systemic mold-active azole was given to 80/130 (61.5%) LTs in the first 6 months post-transplant, 57/121 (47.1%) in the period 6-12 months after transplant, and 93/124 (75%) in the period more than 12 months post-transplant. Mold airways colonization was found in 81 (59.1%) LTs before and 110 (80.3%) LTs after transplantation. There were 13 IFIs for an overall incidence of 2.1 per 100 person-years, occurring at a median 583 days (IQR 182-1110 days) post-transplant, a cumulative incidence of 3.8% at 1 year, 7.6% at 3 years and 10.1% at 5 years post-transplant. All-cause 3-month mortality after IFI was 7.7%. Aspergillus species followed by Scedosporium apiospermum and Cryptococcus species were the commonest fungi causing IFI., Conclusions: In our cohort the rate of IFI was comparatively low, likely because of comprehensive early antifungal use and preemptive therapy at any time after transplant. Prospective studies of fungal colonization late after LT are required to determine the risks and benefits of watchful waiting compared to preemptive therapy., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Patients with invasive fungal diseases (IFDs) generally have a high mortality rate, and resistance to antifungal drugs and the high costs associated with it have led to recent problems, necessitating the appropriate use of antifungals. To this end, we launched Antifungal Stewardship Programs (AFSPs) in our hospital. Patients who were systemically administered antifungals from January 2011 to December 2016 were enrolled this study and divided into pre-intervention and intervention groups. No significant difference was observed in defined daily doses per 1000 patient-days (23.3 ± 8.0 vs 20.4 ± 10.8, p = 0.251) between the groups. The monthly average for the days of therapy per 1000 patient-days was significantly lower in the intervention group (15.1 ± 3.1 vs 12.7 ± 4.3, p = 0.009). The cost of the antifungals reduced over the 3-year period by $260,520 (13.5%). Furthermore, a decreasing trend was observed in both the 30-day mortality (40.9% vs 30.0%, p = 0.414) and in-hospital mortality (63.6% vs 36.7%, p = 0.054) in patients with candidemia. Our results indicate that AFSPs are efficacious and cost-effective approaches., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: Novel formulations (gastro-resistant tablet and intravenous solution) of posaconazole (POS) have been approved in prophylaxis and therapy of invasive fungal diseases (IFDs). Study aim was to analyze treatment strategies and clinical effectiveness., Methods: We set up a web-based registry on www.ClinicalSurveys.net for documentation of comprehensive data of patients who received novel POS formulations. Data analysis was split into two groups of patients who received novel POS formulations for antifungal prophylaxis (posaconazole prophylaxis group) and antifungal therapy (posaconazole therapy group), respectively., Results: Overall, 180 patients (151 in the posaconazole prophylaxis group and 29 in the posaconazole therapy group) from six German tertiary care centers and hospitalized between 05/2014 - 03/2016 were observed. Median age was 58 years (range: 19 - 77 years) and the most common risk factor for IFD was chemotherapy (n = 136; 76%). In the posaconazole prophylaxis group and posaconazole therapy group, median POS serum levels at steady-state were 1,068 μg/L (IQR 573-1,498 μg/L) and 904 μg/L (IQR 728-1,550 μg/L), respectively (P = 0.776). During antifungal prophylaxis with POS, nine (6%) probable/proven fungal breakthroughs were reported and overall survival rate of hospitalization was 86%. The median overall duration of POS therapy was 18 days (IQR: 7 - 23 days). Fourteen patients (48%) had progressive IFD under POS therapy, of these five patients (36%) died related to or likely related to IFD., Conclusions: Our study demonstrates clinical effectiveness of antifungal prophylaxis with novel POS formulations. In patients treated for possible/probable/proven IFD, we observed considerable mortality in patients receiving salvage treatment and with infections due to rare fungal species., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Early diagnosis of acute invasive fungal rhinosinusitis (AIFRS) is vital to improving outcomes in immunocompromised patients. This study evaluated the impact of a systematic protocol with nasal endoscopy and biopsies to early detect AIFRS in immunocompromised patients. Additionally, we compared the accuracy of frozen-section biopsy and culture with formalin-fixed paraffin-embedded (FFPE) biopsy., Methods: Retrospective cohort in a Tertiary Referral Hospital. Patients with the suspected diagnosis of AIFRS were evaluated following a standardized protocol, including serial nasal endoscopies and biopsies when necessary. The sensitivity and specificity of frozen-section biopsy and culture were also compared with FFPE., Results: The mortality rate related to AIFRS of this standardized cohort (13/43) was 30.2%. Better outcomes were observed in patients with disease limited to the turbinates and in those with higher peripheral neutrophils count. Frozen-section biopsy positivity correlated with FFPE findings for fungi detection (p-value < 0.0001), with a sensitivity of 90.6%, specificity of 72.7%, and accuracy of 86.0%., Conclusion: Implementation of this standardized protocol was related to a considerably low mortality rate among patients with suspected AIFRS at our Institution. Frozen-section biopsy revealed high accuracy to diagnose AIFRS. The current protocol including frozen-tissue biopsy improved the evaluation and survival rates of immunocompromised patients with presumed AIFRS.

Invasive fungal infections constitute an important cause of morbidity and mortality in solid organ transplantation recipients. Since solid organ transplantation is an effective therapy for many patients with end-stage organ failure, prevention and treatment of fungal infections are of vital importance. Diagnosis and management of these infections, however, remain difficult due to the variety of clinical symptoms in addition to the lack of accurate diagnostic methods. The use of fungal biomarkers can lead to an increased diagnostic accuracy, resulting in improved clinical outcomes. The evidence for optimal prophylactic approaches remains inconclusive, which results in considerable variation in the administration of prophylaxis. The implementation of a standard protocol for prophylaxis remains difficult as previous treatment regimens, which can alter the distribution of different pathogens, affect the outcome of antifungal susceptibility testing. Furthermore, the increasing use of antifungals also contributes to incremental costs and the risk of development of drug resistance. This review will highlight risk factors, clinical manifestations and timing of fungal infections and will focus predominately on the current evidence for diagnosis and management of fungal infections., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: A thorough understanding of local and contemporary invasive fungal infection (IFI) epidemiology in immunocompromised children is required to provide a rationale for targeted prevention and treatment strategies., Methods: Retrospective data over 10 years from four tertiary pediatric oncology and hematopoietic stem cell transplant (HSCT) units across Australia were analyzed to report demographic, clinical, and mycological characteristics of IFI episodes, and crude IFI prevalence in select oncology/HSCT groups. Kaplan-Meier survival analyses were used to calculate 180-day overall survival., Results: A total of 337 IFI episodes occurred in 320 children, of which 149 (44.2%), 51 (15.1%), and 110 (32.6%) met a modified European Organization for Research and Treatment of Cancer (mEORTC) criteria for proven, probable, and possible IFI, respectively. There were a further 27 (8.0%) that met a "modified possible IFI" criteria. Median age at IFI diagnosis was 8.4 years. Crude mEORTC IFI prevalence in acute lymphoblastic leukemia, acute myeloid leukemia, solid tumor, and allogeneic HSCT cohorts was 10.6%, 28.2%, 4.4%, and 11.7%, respectively. Non-Aspergillus species represented 48/102 (47.1%) molds identified, and non-albicans Candida represented 66/93 (71.0%) yeasts identified. There were 56 deaths among 297 children who met mEORTC criteria, with 180-day overall survival for proven, probable, and possible IFIs of 79.7%, 76.2%, and 84.4%, respectively., Conclusion: Non-Aspergillus molds and non-albicans Candida contributed substantially to pediatric IFI in our study, with high IFI prevalence in leukemia and allogeneic HSCT cohorts. Inclusion of IFIs outside of European Organization for Research and Treatment of Cancer criteria revealed an IFI burden that would go otherwise unrecognized in published reports., (© 2018 Wiley Periodicals, Inc.)

Background: Invasive fungal disease (IFD) and graft-versus-host disease (GVHD) are major causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the impacts of IFD on chronic GVHD remain unknown., Methods: We conducted a retrospective study of 510 patients with hematologic malignancy undergoing allo-HSCT to explore the effects of IFD on chronic GVHD., Results: The 2-year cumulative incidences of overall (limited and extensive) and extensive chronic GVHD post-transplantation were higher in patients with IFD compared with those without IFD (69.5% ± 4.2% versus 32.9% ± 2.4%, P < .001; 43.0% ± 5.2% versus 6.6% ± 1.4%, P < .001, respectively). Moreover, the patients with IFD had higher 5-year transplant-related mortality, lower 5-year overall survival and lower 5-year disease-free survival (29.8% ± 4.3% versus 9.8% ± 1.6%, P < .001; 50.5% ± 4.9% versus 71.3% ± 2.4%, P < .001 and 48.8% ± 4.7% versus 71.8% ± 2.3%, P < .001, respectively). Multivariable analyses demonstrated that IFD increased the risk of chronic GVHD., Conclusion: Our results suggest that IFD significantly contributes to the development of chronic GVHD after allo-HSCT.