[Development of Lomentospora prolificans infection during induction therapy with venetoclax and azacitidine for acute myeloid leukemia].

Lomentospora prolificans is a rare filamentous fungus that causes invasive fungal disease (IFD) in immunocompromised patients with hematological malignancies, as well as hematopoietic cell or solid organ transplant recipients. A 75-year-old woman was diagnosed with acute myeloid leukemia, and started induction therapy with azacitidine and adjusted-dose venetoclax along with antifungal prophylaxis with fluconazole. On day 7, she became febrile and chest CT imaging showed multiple nodules in both lung fields, and the serum galactomannan antigen index became positive, indicating probable IFD. Anti-fungal therapy with liposomal amphotericin B was immediately initiated; however, the patient's condition rapidly deteriorated, and she died on day 15. L. prolificans was later identified in blood culture tests that had been repeatedly performed while she had been febrile. L. prolificans is generally resistant to most antifungal agents, which can make it fatal. As early definitive diagnosis is difficult, it may be appropriate to consider combination therapy when conventional anti-IFD therapy seems inadequate.

[Clinical efficacy and safety of liposomal amphotericin B in the salvage treatment of invasive fungal disease in patients with hematological diseases].

Objective: To investigate the efficacy and safety of liposomal amphotericin B (L-AmB) for the salvage treatment of invasive fungal disease (IFD) in patients with hematological diseases. Methods: Data were retrospectively collected from 80 patients with hematological issues treated with L-AmB between June 2023 and December 2023 after failure of previous antifungal therapy. Baseline patient information, clinical efficacy, and factors affecting the efficacy of L-AmB were analyzed by logistic regression. Moreover, adverse effects associated with L-AmB were evaluated. Results: Among the 80 patients, 9 (11.2%) had proven IFD, 43 (53.8%) had probable IFD, and 28 (35.0%) had possible IFD. The efficacy rate of L-AmB salvage therapy for IFD was 77.5%, with a median daily dose of 3 (range: 1-5) mg·kg(-1)·d(-1) and a median dosing course of 14 (range: 8-25) days. Multivariate logistic regression analysis showed that the disease remission status (OR=4.337, 95% CI 1.167-16.122, P=0.029) and duration of medication (OR=1.127, 95% CI 1.029-1.234, P=0.010) were independent factors affecting the efficacy of L-AmB. The incidence of infusion reactions associated with L-AmB, including fever and chills, was 5.0%. The incidence of hypokalemia was 28.8% (predominantly grades 1-2), and the incidence of nephrotoxicity was 11.3% (predominantly grades 1-2) . Conclusion: L-AmB is safe and effective in the treatment of patients with IFD who are intolerant to or who have experienced no effect of previous antifungal therapy, with a low rate of adverse reactions.

Prevalence of fungal DNAemia mediated by putatively non-pathogenic fungi in immunocompromised patients with febrile neutropenia: a prospective cohort study.

Invasive fungal disease (IFD) presents a life-threatening condition in immunocompromised patients, thus often prompting empirical administration of antifungal treatment, without adequate mycological evidence. Over the past years, wide use of antifungal prophylaxis resulted in decreased occurrence of IFD but has contributed to changes in the spectrum of fungal pathogens, revealing the occurrence of previously rare fungal genera causing breakthrough infections. The expanding spectrum of clinically relevant fungal pathogens required the implementation of screening approaches permitting broad rather than targeted fungus detection to support timely onset of pre-emptive antifungal treatment. To address this diagnostically important aspect in a prospective setting, we analyzed 935 serial peripheral blood (PB) samples from 195 pediatric and adult patients at high risk for IFD, involving individuals displaying febrile neutropenia during treatment of hematological malignancies or following allogeneic hematopoietic stem cell transplantation. Two different panfungal-PCR-screening methods combined with ensuing fungal genus identification by Sanger sequencing were employed. In the great majority of PB-specimens displaying fungal DNAemia, the findings were transient and revealed fungi commonly regarded as non-pathogenic or rarely pathogenic even in the highly immunocompromised patient setting. Hence, to adequately exploit the diagnostic potential of panfungal-PCR approaches for detecting IFD, particularly if caused by hitherto rarely observed fungal pathogens, it is necessary to confirm the findings by repeated testing and to identify the fungal genus present by ensuing analysis. If applied appropriately, panfungal-PCR-screening can help prevent unnecessary empirical therapy, and conversely, contribute to timely employment of effective pre-emptive antifungal treatment strategies.

Disseminated paracoccidioidomycosis in a captive western black-handed tamarin (Saguinus niger).

Paracoccidioidomycosis (PCM) is an endemic fungal disease that occurs in Latin America and primarily affects humans. The disease has been rarely documented in non-human primates. This report details a disseminated and fatal case of PCM caused by Paracoccidioides brasiliensis in a western black-handed tamarin (Saguinus niger) under human care. Histopathological examination revealed extensive pyogranulomatous inflammation in the lungs, spleen, liver, lymph nodes, kidneys, epididymis, right testicle, heart, adrenal gland and intestines, associated with characteristic yeast forms consistent with Paracoccidioides spp and confirmed by immunohistochemistry. Molecular analysis indicated a high nucleotide similarity with P. brasiliensis sequences for both the 18S rRNA and gp43 genes. This naturally occurring infection highlights the susceptibility of these animals to PCM and their role in ecoepidemiology warrants further investigation.

Gallic acid loaded self-nano emulsifying hydrogel-based drug delivery system against onychomycosis.

Aim: To developed and investigate gallic acid (GA) loaded self-nanoemulsifying drug delivery systems (SNEDDS) for treating onychomycosis via transungual route. Materials & methods: The SNEDDS were prepared by direct dispersion technique and were evaluated for characteristics parameters using Fourier transform infrared, differential scanning calorimetry, confocal microscopy, transmission electron microscopy and zeta sizer. Furthermore, the safety of prepared formulation was evaluated via Hen's egg test-chorioallantoic membrane study and stability was confirmed using different parameters. Also, its effectiveness was evaluated against fungal strain Trichophyton mentagrophytes. Results: The SNEDDS displayed a particle size of 199.8 ± 4.21 nm and a zeta potential; of -22.75 ± 2.09 mV. Drug release study illustrated a sustained release pattern with a release of 70.34 ± 0.20% over a period of 24 h. The penetration across the nail plate was found to be 1.59 ± 0.002 µg/mg and 0.97 ± 0.001 µg/mg for GA loaded SNEDDS and GA solution respectively. An irritation score of 0.52 ± 0.005 and 3.84 ± 0.001 was reported for GA loaded SNEDDS hydrogel and GA solution, indicating a decrease in the drug's irritation potential from slightly irritating to non irritating due to its entrapment within the SNEDDS. Conclusion: GA loaded SNEDDS has potential to address limitations of conventional treatments, enhancing the drug's efficacy and reducing the likelihood of resistance in the treatment of Onychomycosis.

[Box: see text].

A global perspective of the changing epidemiology of invasive fungal disease and real-world experience with the use of isavuconazole.

Global epidemiological data show that the incidence of invasive fungal disease (IFD) has increased in recent decades, with the rising frequency of infections caused by Aspergillus and Mucorales order species. The number and variety of patients at risk of IFD has also expanded, owing in part to advances in the treatment of hematologic malignancies and other serious diseases, including hematopoietic stem cell transplantation (HCT) and other therapies causing immune suppression. Isavuconazonium sulfate (active moiety: isavuconazole) is an advanced-generation triazole antifungal approved for the treatment of invasive aspergillosis and mucormycosis that has demonstrated activity against a variety of yeasts, moulds, and dimorphic fungi. While real-world clinical experience with isavuconazole is sparse in some geographic regions, it has been shown to be effective and well tolerated in diverse patient populations, including those with multiple comorbidities who may have failed to respond to prior triazole antifungal therapy. Isavuconazole may be suitable for patients with IFD receiving concurrent QTc-prolonging therapy, as well as those on venetoclax or ruxolitinib. Data from clinical trials are not available to support the use of isavuconazole prophylactically for the prevention of IFD or for the treatment of endemic IFD, such as those caused by Histoplasma spp., but real-world evidence from case studies suggests that it has clinical utility in these settings. Isavuconazole is an option for patients at risk of IFD, particularly when the use of alternative antifungal therapies is not possible because of toxicities, pharmacokinetics, or drug interactions.

This article summarizes the epidemiology and risk factors for IFD, before focusing on the effectiveness and safety of the antifungal agent isavuconazole for treatment of invasive aspergillosis and mucormycosis, and its potential to prevent IFD in specific patient populations.

The Aspergillus galactomannan Ag VIRCLIA® Monotest and the sõna Aspergillus galactomannan lateral flow assay show comparable performance for the diagnosis of invasive aspergillosis.

BACKGROUND: Rapid galactomannan tests, such as the sõna Aspergillus GM Lateral Flow Assay (GM-LFA) and the Aspergillus Galactomannan Ag VIRCLIA® Monotest (GM-Monotest), which are suitable for the analysis of single samples, have the potential to accelerate diagnosis of invasive aspergillosis (IA). OBJECTIVES: To compare the performance of the GM-Monotest and the GM-LFA for the diagnosis of IA. PATIENTS/METHODS: Two patient cohorts were analysed: adults who had received an allogeneic haematopoietic stem-cell transplant (alloHSCT-cohort) and patients with proven/probable IA from a 5-year period (cross-sectional IA-cohort). In the alloHSCT-cohort, weekly serum samples were tested, whereas in the cross-sectional IA-cohort sera and bronchoalveolar lavage fluids were analysed. The diagnostic performance was calculated using two definitions for positivity: (1) a single positive GM result and (2) at least two positive GM results from consecutive samples. IA classification followed EORTC/MSG 2019. RESULTS: The alloHSCT-cohort included 101 patients. Four had proven/probable IA, 26 possible IA and 71 no IA. The specificity for one positive serum and two consecutively positive sera was 88.7% and 100% (GM-Monotest) and 85.9% and 98.6% (GM-LFA). Comparison of ROC curves in the alloHSCT-cohort showed no significant difference. The cross-sectional IA-cohort included 59 patients with proven/probable IA. The sensitivity for one positive sample and two consecutively positive samples was 83.1% and 55.1% (GM-Monotest) and 86.4% and 71.4% (GM-LFA). CONCLUSIONS: Both assays showed comparable diagnostic performance with a higher sensitivity for the GM-LFA if two consecutive positive samples were required for positivity. However, due to poor reproducibility, positive GM-LFA results should always be confirmed.

Challenges and considerations for antifungal prophylaxis in children with acute myeloid leukemia.

INTRODUCTION: Children receiving treatment for acute myeloid leukemia (AML) are at high risk of invasive fungal disease (IFD). Evidence from pediatric studies support the efficacy of antifungal prophylaxis in reducing the burden of IFD in children receiving therapy for AML, yet existing antifungal agents have specific limitations and comparative data to inform the optimal prophylactic approach are lacking. AREAS COVERED: This review summarizes the epidemiology of invasive fungal disease (IFD) and current antifungal prophylaxis recommendations for children with acute myeloid leukemia (AML). Challenges with currently available antifungal agents and considerations related to the changing landscape of AML therapy are reviewed. A keyword search was conducted to identify pediatric studies regarding IFD and antifungal prophylaxis in children with AML up to December 2023. EXPERT OPINION: Children undergoing treatment for AML are recommended to receive antifungal prophylaxis to reduce risk of IFD, with tolerability, pharmacokinetics, feasibility of administration, and drug interactions all factors that require consideration in this context. With increased use of novel targeted agents for AML therapy, together with the development of new antifungal agents, data from well-designed clinical studies to optimize prophylactic approaches will be essential to limit the burden of IFD in this vulnerable cohort.

Factors Impacting Outcome and Prognosis of Invasive Fungal Sinusitis: How Vital is Iron Metabolism?

Iron is an important micronutrient involved in cell biology through vital reactions. We examined the correlations between iron metabolism parameters and the course of invasive fungal sinusitis. Patients with invasive fungal sinusitis were enrolled. Serum iron and ferritin levels, total iron-binding capacity, and transferrin saturation were measured at the initiation of treatment. Patients were followed for 6 months, and the clinical course was categorised as improvement or worsening/death. A total of 35 patients were enrolled. The average ferritin levels in mucormycosis patients was 944.9 ng/ml, versus 110.7 ng/ml for aspergillosis patients. Iron levels were significantly lower in mucormycosis than in aspergillosis (29.14 µg/dl vs. 68.55 µg/dl). Total iron-binding capacity was significantly different between the two groups (16.76 µg/dl vs. 330.36 µg/dl). After 6 months, improvement, worsening, and death were noted for 18, 8, and 9 patients, respectively. Higher iron levels and lower ferritin levels were linked with improvement. Total iron-binding capacity was significantly higher in improved patients (2314 vs. 151). Iron metabolism parameters play significant roles in the preemptive judgment of the course of fungal sinusitis. Based on these findings, studies on drugs affecting iron metabolism should be conducted.

Retrospective Detection of Ophidiomyces ophidiicola from Snake Moults Collected in Bieszczady Mountains, Poland.

Ophidiomyces ophidiicola, the causative agent of ophidiomycosis, poses a potential threat to wild snakes worldwide. This study aimed to retrospectively investigate the prevalence of O. ophidiicola in archived snake moults collected from the San River Valley in the Bieszczady Mountains, Poland, from 2010 to 2012. Using qPCR for O. ophidiicola detection and conventional PCR for clade characterisation, we analysed 58 moults and one road-killed specimen of Zamenis longissimus and Natrix natrix. A novel combination of primers (ITS2L) was used to simultaneously confirm SYBR Green-based qPCR results and perform genotyping. O. ophidiicola has been detected from two Z. longissimus and one N. natrix specimens. The identified clade (I-B) is consistent with those found in wild snakes of eastern Europe and San River Valley, indicating that O. ophidiicola has been present in this region for at least a decade. This study underscores the value of historical samples in understanding the long-term presence of pathogens and highlights the potential role of environmental reservoirs in the persistence of O. ophidiicola. Our findings are crucial for informing conservation strategies for the endangered Aesculapian snake populations in Poland, emphasising the need for ongoing monitoring and habitat management to mitigate the potential impact of ophidiomycosis.

Characterization and Fungicide Sensitivity of Phaeosphaeriopsis obtusispora That Causes Marginal Leaf Blight in Agave hybrid H.11648.

Sisal is an important tropical cash crop in southern China. Unfortunately, it is threatened by various diseases. In 2022, a new disease tentatively named marginal leaf blight disease (MLBD) was first observed in sisal fields across Guangxi and Guangdong provinces, with an incidence rate ranging from 13% to 30%. In this work, to isolate and identify the pathogens causing MLBD, sisal leaves exhibiting the typical MLBD symptoms were collected, and nine strains were obtained. Pathogenicity tests, morphological observations, and phylogenetic analyses confirmed that two strains, namely 22GX1-3 and 22GD1-4, identified as Phaeosphaeriopsis obtusispora, were the causative pathogens of MLBD. Further investigations into the biological characteristics of P. obtusispora showed that its mycelia exhibited optimal growth on PDA medium, with the most favourable temperature and pH being 25 °C and 7.0, respectively. The mycelia could grow in temperatures ranging from 10 °C to 32 °C but ceased at 35 °C. Lactose and yeast extract powder were also identified as the optimal carbon and nitrogen sources, respectively. Additionally, the effectiveness of various control agents was assessed on a single strain, 22GX1-3. Among the twelve fungicides tested, difenoconazole was proven the most effective, with an EC50 value of 0.5045 µg/mL. To our knowledge, this is the first report for sisal MLBD caused by P. obtusispora. Our results provide crucial pieces of information for the development of effective management strategies to control sisal MLBD caused by P. obtusispora.

Cold atmospheric plasma inactivates Aspergillus flavus and Fusarium keratoplasticum biofilms and conidia in vitro.

Introduction. Aspergillus flavus and Fusarium keratoplasticum are common causative pathogens of fungal keratitis (FK), a severe corneal disease associated with significant morbidity and vision loss. Escalating incidence of antifungal resistance to available antifungal drugs poses a major challenge to FK treatment. Cold atmospheric plasma (CAP) is a pioneering nonpharmacologic antimicrobial intervention that has demonstrated potential as a broad-spectrum antifungal treatment.Gap statement. Previous research highlights biofilm-associated resistance as a critical barrier to effective FK treatment. Although CAP has shown promise against various fungal infections, its efficacy against biofilm and conidial forms of FK pathogens remains inadequately explored.Aim. This study aims to investigate the antifungal efficacy of CAP against clinical fungal keratitis isolates of A. flavus and F. keratoplasticum in vitro.Methodology. Power parameters (22-27 kVpp, 300-400 Hz and 20-80 mA) of a dielectric barrier discharge CAP device were optimized for inactivation of A. flavus biofilms. Optimal applied voltage and total current were applied to F. keratoplasticum biofilms and conidial suspensions of A. flavus and F. keratoplasticum. The antifungal effect of CAP treatment was investigated by evaluating fungal viability through means of metabolic activity, c.f.u. enumeration (c.f.u. ml-1) and biofilm formation.Results. For both fungal species, CAP exhibited strong time-dependent inactivation, achieving greater than 80 % reduction in metabolic activity and c.f.u. ml-1 within 300 s or less, and complete inhibition after 600 s of treatment.Conclusion. Our findings indicate that CAP is a promising broad-spectrum antifungal intervention. CAP treatment effectively reduces fungal viability in both biofilm and conidial suspension cultures of A. flavus and F. keratoplasticum, suggesting its potential as an alternative treatment strategy for fungal keratitis.

How can we optimize antifungal use and stewardship in the treatment of acute leukemia?

INTRODUCTION: The global need for antifungal stewardship is driven by spreading antimicrobial and antifungal resistance. Triazoles are the only oral and relatively well-tolerated class of antifungal medications, and usage is associated with acquired resistance and species replacement with intrinsically resistant organisms. On a per-patient basis, hematology patients are the largest inpatient consumers of antifungal drugs, but are also the most vulnerable to invasive fungal disease. AREAS COVERED: In this review we discuss available and forthcoming antifungal drugs, antifungal prophylaxis and empiric antifungal therapy, and how a screening based and diagnostic-driven approach may be used to reduce antifungal consumption. Finally, we discuss components of an antifungal stewardship program, interventions that can be employed, and how impact can be measured. The search methodology consisted of searching PubMed for journal articles using the term antifungal stewardship plus program, intervention, performance measure or outcome before 1 January 2024. EXPERT OPINION: Initial focus should be on implementing effective antifungal stewardship programs by developing and implementing local guidelines and using interventions, such as post-prescription review and feedback, which are known to be effective. Technologies such as microbiome analysis and machine learning may allow the development of truly individualized risk-factor-based approaches to antifungal stewardship in the future.

Consensus for antifungal stewardship in China (2024 edition).

Background: Invasive fungal disease (IFD) has become a serious threat to human health in China and around the world, with high mortality and morbidity. Currently, the misdiagnosis rate of IFD is extremely high, compounded with the low quality of prescription antifungals and the high incidence of adverse events associated with IFD treatment, resulting in lengthy hospitalization, low clinical response, and high disease burden, which have become serious challenges in clinical practice. Antifungal stewardship (AFS) can not only significantly increase the early diagnosis rate of IFD, reduce inappropriate utilization of antifungal drugs, improve patient prognosis, but can also improve therapeutic safety and reduce healthcare expenses. Thus, it is urgent to identify key AFS metrics suitable for China's current situation. Methods: Based on metrics recommended by international AFS consensuses, combined with the current situation of China and the clinical experience of authoritative experts in various fields, several metrics were selected, and experts in the fields of respiratory diseases, hematology, intensive care units (ICUs), dermatology, infectious diseases, microbiology laboratory and pharmacy were invited to assess AFS metrics by the Delphi method. Consensus was considered to be reached with an agreement level of ≥80% for the metric. Results: Consensus was reached for 24 metrics, including right patient metrics (n=4), right time metrics (n=3), and right use metrics (n=17). Right use metrics were further subdivided into drug choice (n=8), drug dosage (n=4), drug de-escalation (n=1), drug duration (n=2), and drug consumption (n=2) metrics. Forty-six authoritative experts assessed and reviewed the above metrics, and a consensus was reached with a final agreement level of ≥80% for 22 metrics. Conclusions: This consensus is the first to propose a set of AFS metrics suitable for China, which helps to establish AFS standards in China and is also the first AFS consensus in Asia, and may improve the standard of clinical diagnosis and treatment of IFD, and guide hospitals to implement AFS, ultimately promoting the rational use of antifungal drugs and improving patient prognosis.

Posaconazole gastro-resistant tablets for preventing invasive fungal disease after haematopoietic stem cell transplantation: a propensity-matched cohort study.

OBJECTIVES: To evaluate posaconazole (POS) gastro-resistant tablets for preventing invasive fungal disease (IFD) in haematopoietic stem cell transplantation (HSCT) patients and analyse POS plasma concentrations. METHODS: A single-arm trial was designed with a historical cohort as a control. Patients aged 13 years and older undergoing HSCT at the HSCT Center of Blood Diseases Hospital, Chinese Academy of Medical Sciences between December 2020 and May 2022 were enrolled, prospectively taking POS gastro-resistant tablets orally from day 1 to day 90 post-transplant and monitoring plasma concentrations. We also identified a retrospective cohort treated with alternative antifungal prophylaxis between January 2018 and December 2020, matched using propensity score methods. The primary outcome was the cumulative incidence of IFD at day 90 post-transplant. RESULTS: The prospective study involved 144 patients receiving POS gastro-resistant tablets for IFD prevention, contrasting with 287 patients receiving non-POS tablets. By day 90 post-transplant, the POS tablet group exhibited a significantly lower cumulative incidence of IFD (2.81%; 95% CI, 0.09-5.50% vs. 7.69%; 95% CI, 4.60-10.78%; p 0.044). Adverse events were comparable between the groups with liver changes in 33/144 (22.92%) vs. 84/287 (29.27%) (p 0.162), and renal injuries in 15/144 (10.41%) vs. 37/287 (12.89%) (p 0.457). Mean POS plasma concentrations on days 4, 8, 15, and 22 post-administration were 930.97 ng/mL, 1143.97 ng/mL, 1569.8 ng/mL, and 1652.57 ng/mL, respectively. DISCUSSION: Patients administered POS gastro-resistant tablets for antifungal prophylaxis experienced a lower cumulative incidence of IFD. POS plasma concentrations in HSCT patients stabilized by day 15 of medication.

Mucorales: A systematic review to inform the World Health Organization priority list of fungal pathogens.

The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list (FPPL). This systematic review aimed to evaluate the epidemiology and impact of invasive fungal disease due to Mucorales. PubMed and Web of Science were searched to identify studies published between January 1, 2011 and February 23, 2021. Studies reporting on mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence during the study time frames were selected. Overall, 24 studies were included. Mortality rates of up to 80% were reported. Antifungal susceptibility varied across agents and species, with the minimum inhibitory concentrations lowest for amphotericin B and posaconazole. Diabetes mellitus was a common risk factor, detected in 65%-85% of patients with mucormycosis, particularly in those with rhino-orbital disease (86.9%). Break-through infection was detected in 13.6%-100% on azole or echinocandin antifungal prophylaxis. The reported prevalence rates were variable, with some studies reporting stable rates in the USA of 0.094-0.117/10 000 discharges between 2011 and 2014, whereas others reported an increase in Iran from 16.8% to 24% between 2011 and 2015. Carefully designed global surveillance studies, linking laboratory and clinical data, are required to develop clinical breakpoints to guide antifungal therapy and determine accurate estimates of complications and sequelae, annual incidence, trends, and global distribution. These data will provide robust estimates of disease burden to refine interventions and better inform future FPPL.

Aspergillus fumigatus-a systematic review to inform the World Health Organization priority list of fungal pathogens.

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.

Talaromyces marneffei, Coccidioides species, and Paracoccidioides species-a systematic review to inform the World Health Organization priority list of fungal pathogens.

The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal pathogen priority list. This systematic review aimed to evaluate the epidemiology and impact of infections caused by Talaromyces marneffei, Coccidioides species, and Paracoccidioides species. PubMed and Web of Sciences databases were searched to identify studies published between 1 January 2011 and 23 February 2021 reporting on mortality, complications and sequelae, antifungal susceptibility, preventability, annual incidence, and trends. Overall, 25, 17, and 6 articles were included for T. marneffei, Coccidioides spp. and Paracoccidioides spp., respectively. Mortality rates were high in those with invasive talaromycosis and paracoccidioidomycosis (up to 21% and 22.7%, respectively). Hospitalization was frequent in those with coccidioidomycosis (up to 84%), and while the duration was short (mean/median 3-7 days), readmission was common (38%). Reduced susceptibility to fluconazole and echinocandins was observed for T. marneffei and Coccidioides spp., whereas >88% of T. marneffei isolates had minimum inhibitory concentration values ≤0.015 µg/ml for itraconazole, posaconazole, and voriconazole. Risk factors for mortality in those with talaromycosis included low CD4 counts (odds ratio 2.90 when CD4 count <200 cells/µl compared with 24.26 when CD4 count <50 cells/µl). Outbreaks of coccidioidomycosis and paracoccidioidomycosis were associated with construction work (relative risk 4.4-210.6 and 5.7-times increase, respectively). In the United States of America, cases of coccidioidomycosis increased between 2014 and 2017 (from 8232 to 14 364/year). National and global surveillance as well as more detailed studies to better define sequelae, risk factors, outcomes, global distribution, and trends are required.

Fusarium species,Scedosporium species, and Lomentospora prolificans: A systematic review to inform the World Health Organization priority list of fungal pathogens.

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 infections caused by Fusarium spp., Scedosporium spp., and Lomentospora prolificans to inform the first FPPL. PubMed and Web of Sciences databases were searched to identify studies published between January 1, 2011 and February 23, 2021, reporting on mortality, complications and sequelae, antifungal susceptibility, preventability, annual incidence, and trends. Overall, 20, 11, and 9 articles were included for Fusarium spp., Scedosporium spp., and L. prolificans, respectively. Mortality rates were high in those with invasive fusariosis, scedosporiosis, and lomentosporiosis (42.9%-66.7%, 42.4%-46.9%, and 50.0%-71.4%, respectively). Antifungal susceptibility data, based on small isolate numbers, showed high minimum inhibitory concentrations (MIC)/minimum effective concentrations for most currently available antifungal agents. The median/mode MIC for itraconazole and isavuconazole were ≥16 mg/l for all three pathogens. Based on limited data, these fungi are emerging. Invasive fusariosis increased from 0.08 cases/100 000 admissions to 0.22 cases/100 000 admissions over the time periods of 2000-2009 and 2010-2015, respectively, and in lung transplant recipients, Scedosporium spp. and L. prolificans were only detected from 2014 onwards. Global surveillance to better delineate antifungal susceptibility, risk factors, sequelae, and outcomes is required.

Shared Vision for Improving Outcomes for Serious Fungal Diseases: Report of a Patient, Caregiver, and Clinician Summit.

Background: Recently, increasing focus on patient input into research and healthcare improvements has fostered expanded patient-centered advocacy efforts. This first pan-fungal disease summit, part of the MYCology Advocacy, Research, & Education effort, brought together patients, caregivers, and mycology experts to better document patient experiences with invasive fungal disease (IFD) and establish priorities for mycology education, advocacy, and research. Methods: Patients who had suffered from IFD, their caregivers, clinicians, industry representatives, government officials, and patient advocacy professionals were invited. Patients and caregivers shared their stories and struggles with IFD. Breakout sessions separated mycology experts from patients and caregivers for further discussions to identify commonalities and perceived gaps and to formulate recommendations. The 2 groups then reconvened to develop consensus recommendations. Results: IFD patients and their caregivers shared experiences reflecting the typically lengthy prediagnosis, acute treatment, long-term treatment, and posttreatment recovery stages of IFD. They reported substantial physical, psychological, and financial burdens associated with the IFD experience, particularly related to delayed diagnoses. They reaffirmed a need for coordinated patient-centered education, peer support, and advocacy to document the burden of serious fungal infections. Mycology experts discussed strategies to address gaps in the mycology field, such as insufficient training, inadequate workforce support, and a need to partner more with patient groups. Conclusions: A summit involving patients with IFD, family caregivers, and mycology experts identified a substantial nonclinical burden of disease associated with IFD. Patients and mycology experts prioritized several goals for education, advocacy, and research to raise awareness of IFD and improve outcomes.