Incidence Of Invasive Fungal Infections Research Articles

Exploring European Consensus About the Remaining Treatment Challenges and Subsequent Opportunities to Improve the Management of Invasive Fungal Infection (IFI) in the Intensive Care Unit

BackgroundThe global prevalence of invasive fungal infections (IFI) is increasing, particularly within Intensive Care Units (ICU), where Candida spp. and Aspergillus spp. represent the most important pathogens. Diagnosis and management of IFIs becomes progressively challenging, with increasing antifungal resistance and the emergence of rare fungal species.Through a consensus survey focused on assessing current views on how IFI should be managed, the aim of this project was to identify challenges around diagnosing and managing IFIs in the ICU. The current status in different countries and perceived challenges to date amongst a multidisciplinary cohort of healthcare professionals involved in the care of IFI in the ICU was assessed.MethodsUsing a modified Delphi approach, an expert panel developed 44 Likert-scale statements across 6 key domains concerning patient screening and minimal standards for diagnosis of IFIs in ICU; initiation and termination of antifungal treatments and how to minimise their side effects and insights for future research on this topic. These were used to develop an online survey which was distributed on a convenience sampling basis utilising the subscriber list held by an independent provider (M3 Global). This survey was distributed to intensivists, infectious disease specialists, microbiologists and antimicrobial/ICU pharmacists within the UK, Germany, Spain, France and Italy. The threshold for consensus was set at 75%.ResultsA total of 335 responses were received during the five-month collection period. From these, 29/44 (66%) statements attained very high agreement (≥ 90%), 11/44 (25%) high agreement (< 90% and ≥ 75%), and 4/44 (9%) did not meet threshold for consensus (< 75%). ConclusionThe results outline the need for physicians to be aware of the local incidence of IFI and the associated rate of azole resistance in their ICUs. Where high clinical suspicion exists, treatment should start immediately and prior to receiving the results from any diagnostic test. Beta-D-glucan testing should be available to all ICU centres, with results available within 48 h to inform the cessation of empirical antifungal therapy. These consensus statements and proposed measures may guide future areas for further research to optimise the management of IFIs in the ICU.

Amphotericin B in the Era of New Antifungals: Where Will It Stand?

Amphotericin B (AmB) has long stood as a cornerstone in the treatment of invasive fungal infections (IFIs), especially among immunocompromised patients. However, the landscape of antifungal therapy is evolving. New antifungal agents, boasting novel mechanisms of action and better safety profiles, are entering the scene, presenting alternatives to AmB's traditional dominance. This shift, prompted by an increase in the incidence of IFIs, the growing demographic of immunocompromised individuals, and changing patterns of fungal resistance, underscores the continuous need for effective treatments. Despite these challenges, AmB's broad efficacy and low resistance rates maintain its essential status in antifungal therapy. Innovations in AmB formulations, such as lipid complexes and liposomal delivery systems, have significantly mitigated its notorious nephrotoxicity and infusion-related reactions, thereby enhancing its clinical utility. Moreover, AmB's efficacy in treating severe and rare fungal infections and its pivotal role as prophylaxis in high-risk settings highlight its value and ongoing relevance. This review examines AmB's standing amidst the ever-changing antifungal landscape, focusing on its enduring significance in current clinical practice and exploring its potential future therapeutic adaptations.

Clinical impact of fungal colonization of burn wounds in patients hospitalized in the intensive care unit: a retrospective cohort study

BackgroundInvasive fungal infections in burn victims significantly increase mortality and hospitalization. The effect of fungal burn wound colonization has not been established.MethodsAll adult patients hospitalized in the intensive care unit...

Low incidence of invasive fungal infection and risk factors in a large observational cohort of patients initiating TNF-alpha inhibitors for dermatologic conditions

Low incidence of invasive fungal infection and risk factors in a large observational cohort of patients initiating TNF-alpha inhibitors for dermatologic conditions

Increase in the incidence of invasive fungal infections due to Volvariella Volvacea.

We aimed to show the increasing incidence of invasive fungal infections due to Volvariella Volvacea in patients with immunosuppression. 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. 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. 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.

Low incidence of invasive fungal infections in a large observational cohort of patients initiating IL-17 or IL-23 inhibitor therapy, United States, 2016-2022

Low incidence of invasive fungal infections in a large observational cohort of patients initiating IL-17 or IL-23 inhibitor therapy, United States, 2016-2022

A chemical screen identifies structurally diverse metal chelators with activity against the fungal pathogen Candida albicans.

Candida albicans, one of the most prevalent human fungal pathogens, causes diverse diseases extending from superficial infections to deadly systemic mycoses. Currently, only three major classes of antifungal drugs are available to treat systemic infections: azoles, polyenes, and echinocandins. Alarmingly, the efficacy of these antifungals against C. albicans is hindered both by basal tolerance toward the drugs and the development of resistance mechanisms such as alterations of the drug's target, modulation of stress responses, and overexpression of efflux pumps. Thus, the need to identify novel antifungal strategies is dire. To address this challenge, we screened 3,049 structurally-diverse compounds from the Boston University Center for Molecular Discovery (BU-CMD) chemical library against a C. albicans clinical isolate and identified 17 molecules that inhibited C. albicans growth by >80% relative to controls. Among the most potent compounds were CMLD013360, CMLD012661, and CMLD012693, molecules representing two distinct chemical scaffolds, including 3-hydroxyquinolinones and a xanthone natural product. Based on structural insights, CMLD013360, CMLD012661, and CMLD012693 were hypothesized to exert antifungal activity through metal chelation. Follow-up investigations revealed all three compounds exerted antifungal activity against non-albicans Candida, including Candida auris and Candida glabrata, with the xanthone natural product CMLD013360 also displaying activity against the pathogenic mould Aspergillus fumigatus. Media supplementation with metallonutrients, namely ferric or ferrous iron, rescued C. albicans growth, confirming these compounds act as metal chelators. Thus, this work identifies and characterizes two chemical scaffolds that chelate iron to inhibit the growth of the clinically relevant fungal pathogen C. albicansIMPORTANCEThe worldwide incidence of invasive fungal infections is increasing at an alarming rate. Systemic candidiasis caused by the opportunistic pathogen Candida albicans is the most common cause of life-threatening fungal infection. However, due to the limited number of antifungal drug classes available and the rise of antifungal resistance, an urgent need exists for the identification of novel treatments. By screening a compound collection from the Boston University Center for Molecular Discovery (BU-CMD), we identified three compounds representing two distinct chemical scaffolds that displayed activity against C. albicans. Follow-up analyses confirmed these molecules were also active against other pathogenic fungal species including Candida auris and Aspergillus fumigatus. Finally, we determined that these compounds inhibit the growth of C. albicans in culture through iron chelation. Overall, this observation describes two novel chemical scaffolds with antifungal activity against diverse fungal pathogens.

Incidence of Invasive Fungal Infections in CAR T-Cell Therapy Recipients: A Single Center Retrospective Analysis.

Incidence of Invasive Fungal Infections in CAR T-Cell Therapy Recipients: A Single Center Retrospective Analysis.

A novel zinc-chelating compound has antifungal activity against a wide range of Candida species, including multidrug-resistant Candida auris.

In recent years, the incidence of invasive fungal infections has increased, resulting in considerable morbidity and mortality, particularly among immunocompromised individuals. Potential challenges in treating these infections with the few existing antifungal agents highlight the urgency of developing new ones. Here, we evaluated six alkyl polyamine compounds (APCs), not previously reported as antifungal drugs to our knowledge, that could deprive fungi of essential transition metals. The APC with confirmed antifungal activity against Candida spp. was analysed by using transcriptomics, followed by metal-addition experiments, mass spectrometric analyses and intracellular zinc quantification with a fluorescent probe. A cyclic APC with three pyridylmethyl groups, APC6, had high antifungal activity against a wide range of Candida species, including MDR Candida auris. We conclusively demonstrated that APC6 was able to capture zinc within fungal cells. APC6 not only exhibited activity against C. auris as a single agent but also enhanced the efficacy of an azole antifungal agent, voriconazole, in vitro and in vivo. APC6 disrupted the biofilms formed by Candida species. This zinc-chelating compound has potential as an antifungal agent, and the control of zinc levels in Candida species could be a powerful approach to treating drug-resistant candidiasis.

Incidence of Invasive Fungal Infections in CAR T-Cell Therapy Recipients: A Single-Center Retrospective Analysis

Background: CAR T-cell therapy has transformed the treatment of hematologic malignancies, but challenges persist due to toxicities like cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and infections. Rates of invasive fungal infections (IFI) post CAR T-cell therapy are estimated to range from 1% to 7% (Haidar et al. Clin Infect Dis, 2020). Some centers use positive fungal biomarkers, such as serum (1à3)-β-D-glucan (B-DG) and galactomannan (GM), alongside surveillance radiographic imaging to guide preemptive fungal therapy in this population. The objective of the study was to assess the diagnostic performance of surveillance B-DG and GM for the diagnosis of IFI in recipients of BCMA and CD19-directed CAR T for multiple myeloma (MM) and non-Hodgkin lymphoma (NHL), respectively. Methods: We conducted a retrospective analysis on adult patients who received BCMA-directed CAR T therapy for MM or CD19-directed CAR T for NHL at our institution between 2018-2023. IFI was defined using the Revised European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSG) criteria (Donnelly et al. Clin Infect Dis, 2020). Only patients with proven or probable infection were included in the analysis. The choice of antifungal prophylaxis was determined based on the treating physician's discretion. In the most cases, B-DG and GM monitoring was done prior to apheresis, before CAR T infusion, and subsequently every 14 days for a duration of 6 months. All patients were followed until 7/12/2023, or until their data were censored at the last follow-up. The cumulative incidence was calculated using Kaplan-Meier method, considering the time to IFI, with IFI-free death and disease relapse as competing risks. Statistical analysis was performed using IBM SPSS (version 29.0). Result: Among the 148 subjects in this study, 51 patients (34.5%) received BCMA CAR T, and 97 (65.5%) received CD19 CAR T therapy. The median age at CAR T infusion was 66 years (range 36-78) in the BCMA cohort and 65 years (range 27-83) in the CD19 cohort (p=0.64). The BCMA cohort had a higher number of prior therapies, with a median of 6 (range 2-15) compared to the CD19 cohort, which had a median of 4 (range 2-12) (p&amp;lt;0.001). The median follow-up from CAR T infusion was 9.5 months (range 0-63) in both cohorts, with 12 months (range 0-63) in the BCMA cohort and 8 months (range 0-49) in the CD19 cohort. All patients received prophylactic antifungal agents, including anti-yeast (fluconazole, n=95), and anti-mold (micafungin n=5, isavuconazole n=1, or Posaconazole n=52). Among the BCMA cohort, 92% of the patients received anti-yeast prophylaxis, while 8% were given anti-mold prophylaxis. In the CD19 cohort, 49.5% received anti-yeast prophylaxis, while 50.5% received anti-mold prophylaxis. Out of the 148 patients, 21 individuals (14%) exhibited elevated B-DG levels, while only 2 patients (1%) showed elevated GM levels. However, 20 out of 21 (95%) cases with positive B-DG, and all cases with positive GM were deemed to be false positives. Among these false positives, 60% were attributed to IVIG administration, while the cause for the remaining cases remained unknown (Table 1). Only one patient in this study developed IFI. The patient received anti-yeast prophylaxis (Fluconazole) at CAR-T and had a disseminated Rhizopus infection on day 13 post CD19 CAR T, which ultimately resulted in the patient's death. The 1-year cumulative incidence of IFI, considering competing risks, was 0.7% (95% confidence interval [CI], 0- 2.1). The median progression-free survival (PFS) in the overall cohort was 11.7 months (95% CI, 6.9-16.6), with 8.6 months (95% CI, 3.2-13.97) in the BCMA cohort and 14.6 months (95% CI, NR-NR) in the CD19 cohort (p=0.324). The median overall survival (OS) of the study cohort was 32.4 months (95% CI, 16.3-48.4), with 41.4 months (95% CI, 16.74-66.08) in the BCMA cohort and 23.98 months (95% CI, NR-NR) in the CD19 cohort (p=0.260). Conclusion: The rate of IFI in our cohort was low (0.7%) post-CAR T therapy. The diagnostic performance of serial monitoring of B-DG and GM for the diagnosis of IFI is poor in recipients of BCMA-directed CAR T therapy for MM or CD19-directed CAR T for NHL.

Antifungal Prophylaxis in Newly Diagnosed Acute Myeloid Leukemia Treated with a Hypomethylating Agent and Venetoclax: A Real-World Experience in Pharmacovigilance

Background: The oral BCL2 inhibitor venetoclax, in combination with hypomethylating agents (HMA/Ven) improves overall survival in patients with acute myeloid leukemia (AML) either ≥ 75 years or medically unfit for intensive chemotherapy with a tolerable safety profile. It requires significant dose modification when used concomitantly with moderate-strong CYP3A inhibitors, typically azole antifungal agents. In the VIALE-A trial, over 60% of patients in the HMA/Ven arm received antifungal prophylaxis. However, there is no consensus of antifungal prophylaxis in AML patients treated with HMA/Ven given the incidence of invasive fungal infection is overall low and its impact on long-term outcomes remains not well-defined. Method: In the current study, we retrospectively reviewed the upfront treatment with HMA/Ven in newly diagnosed AML patients who were seen at Moffitt Cancer Center with detailed information of venetoclax dosing and concurrent antifungal use between 2018 and 2021, representing our first three years of real-world experience following accelerated approval of venetoclax by the FDA. Results: We identified 120 patients who received at least one cycle of HMA/Ven treatment. The median age at diagnosis was 76 years, and 62.5% being male. The baseline disease-related features are shown in Table. A prior history of myeloid malignancy was reported in 42 patients (35%), and 16 of them received HMA based therapy (13.3%). TP53 mutations were identified in 29 patients (24.8%), and 92 patients (76.7%) were classified as adverse risk based on ELN 2022 risk stratification. In terms of the HMA choice, 79 (65.8%) received azacitidine and rest were given decitabine. The median cycle of HMA/Ven treatment was 4, and HMA dose adjustment was rarely needed in the first 3 cycles (2.0-3.3%). In the first cycle, venetoclax dose was ramped up in 26.9%, and 34.4% received a target dose of 400 mg daily. Its dose required adjustment in about two-thirds of patients during the first three cycles (65.6-72.9%), with the primary reason being concurrent antifungal use (90.2-92.2%). Delays in treatment were found in nearly one fourth of patients (25.5%) during cycle 2 and 3, mainly attributed to poor count recovery and/or bacterial infections. In contrast, invasive fungal infection was uncommon during the first 3 cycles (cycle 1, 3.3%; cycle 2, 2.0%; cycle 3, 3.3%) with a cumulative incidence of 5% (6 patients with 5 possible and 1 proven fungal infections) despite most of them (83.3%) receiving antifungal prophylaxis before the development of invasive fungal infection. Eighty patients (66.7%) achieved complete remission or complete remission with incomplete hematologic recovery (CR/CRi) as the best response. In total, 19 patients (15.8%) ultimately underwent allogeneic stem cell transplant. The median overall survival was 10.8 months, and antifungal prophylaxis during the first three cycles was associated with a consistent trend of inferior overall survival (yes vs. no of antifungal use: cycle 1, 8.9 vs. 12.5 months, p = 0.296; cycle 2, 11.5 vs. 15.6 months, p = 0.206; cycle 3, 14.1 months vs. not reached, p = 0.063). In patients who were able to complete ≥ 3 cycles of HMA/Ven treatment, antifungal prophylaxis at any time was still associated with a trend of inferior overall survival (hazard ratio 1.79, 95% confidence interval 0.76-4.20, p = 0.183), after adjusting ELN 2022 risk status. Conclusion: The observed trend of inferior outcomes in newly diagnosed AML patients receiving HMA/Ven with concomitant antifungal prophylaxis might reflect poor count recovery due to underlying disease and/or treatment-related toxicity, which requires further prospective studies.

2716. Epidemiology of invasive fungal infection in pediatric liver transplant recipients: A retrospective, single-center study, 2012-2022

Abstract Background Studies on liver transplant (LT) recipients have reported an incidence of invasive fungal infection (IFI) ranging from 2.5 to 5%; however, antifungal prophylaxis has not yet been approved by the Ministry of Food and Drug Safety in Korea. We investigated the incidence of early-onset IFI and its characteristics in pediatric LT recipients in Korea, and also explored the risk factors for IFIs. Methods This is a retrospective, single-center study on children (&amp;lt; 19 years of age) who have undergone LT from 2012 to 2022 at Severance Hospital, Korea. IFI was defined as the detection of fungus in sterile fluid, tissue, and/or blood with symptoms of a fungal infection. Superficial fungal infection and colonization on the skin or urine were excluded. The primary outcome is the occurrence of IFI within 90 days of LT. The logistic regression method was used to analyze the risk factors for IFI. Results A total of 104 LT children were included, among whom 6 received multiple transplantations, resulting in 111 LT cases. 42% (n = 44) were male, and the median age at LT was 4.0 years of age (IQR 1.0–11.0). Two thirds of the patients received LT due to biliary atresia (n = 69, 66%), and the remaining were diagnosed with acute liver failure (n = 17, 16%), miscellaneous causes (n = 11, 11%), and so on (n = 7, 7%). Antifungal prophylaxis, except nystatin gargle, was done in 12.8% of recipients. IFI was identified in 19 patients (18%), and due to five multiple IFI events per patient, a total of 23 IFI events were noted at a median time of 16.5 days after LT (IQR 10-38). 87% of the pathogens detected were Candida species (C. albicans 40%, C. parapsilosis 35%, C. auris 15%), and Aspergillus fumigatus (13%). Antifungal susceptibility patterns are described in Table 1. The risk of IFI was significantly increased in those who underwent acute re-transplantation, postoperative intervention, or surgery due to bleeding, vascular, and bile duct complications (OR = 4.6; 95% CI, 1.5–13.6; P = 0.006) 8) and renal replacement therapy (OR=3.2; 95% CI, 1.1-8.8; P=0.028).Table.Antifungal susceptibility patterns of identified pathogens according to Clinical and Laboratory Standards Institute (CLSI). a Number of cases identified with the fungal pathogen b Antifungal susceptibility testing has to be additionally requested, so it was not performed in all cases. c 1 case had a fluconazole-resistant C.parapsilosis strain with intermediate resistance to other antifungal agents (MIC: fluconazole 32, micafungin 2, caspofungin 2, voriconazole 0.12, amphotericin B 0.5). d CLSI does not provide a tentative MIC breakpoint for voriconazole and other second generation azoles, but that of fluconazole may be considered as a surrogate. Conclusion The incidence of early IFI after LT in Korean children is considerable; therefore, universal antifungal prophylaxis is necessary. High-risk IFI patients, such as those undergoing reoperation, intervention, or renal replacement therapy, require attention and close monitoring. Disclosures All Authors: No reported disclosures

2446. Effect of the Implementation of a Fluconazole Prophylaxis Protocol on the Incidence of Invasive Fungal Infection in High-Risk Neonates

Abstract Background Invasive fungal infection (IFI) is one of the most important causes of morbidity and mortality in the neonatal intensive care unit. International societies have supported the use of fluconazole prophylaxis for neonates weighing &amp;lt; 1000 grams, but administration to other high-risk patients remains controversial. An institutional fluconazole prophylaxis guideline was implemented in December 2020 to include two other groups of neonates. Methods One hundred thirty infants who were admitted at the NICU from January 2020 to January 2022 and fulfilled one of the following criteria: weight of &amp;lt; 1000 grams (Group A), weight of ≤1500 grams and on broad-spectrum antibiotics (Group B), or weight of &amp;gt;1500 grams and on prolonged nil per os (NPO) (Group C) were included in the study. They were divided into two groups: those who were born prior to the implementation of the protocol (January to December 2020) and not given fluconazole prophylaxis, and those born after (January 2021 to January 2022) and given prophylaxis. The primary outcome was the development of IFI. Results A total of 130 infants were included in this study with 21 (5 control, 16 prophylaxis), 69 (28 control, 41 prophylaxis), and 40 (16 control, 24 prophylaxis) patients in Groups A, B, and C, respectively. There were no significant differences in the development of IFI among the groups (Group A: control - 40%, prophylaxis - 62%; Group B: control - 21.4%, prophylaxis - 22%; Group C: control - 29.2%, prophylaxis 31.5%) with a p-value of &amp;gt; 0.05. The presence of a central vascular access line, endotracheal tube, placement on NPO, histamine H2-blockers, and necrotizing enterocolitis were associated with the development of IFI. Candida parapsilosis comprised 60% of isolates. All isolates had 100% susceptibility to fluconazole. Jaundice developed in 3.7% of patients given fluconazole, with elevations in AST, ALT, and TB. Incidence of fungal infection in high-risk neonates There were no significant differences in the development of IFI among the three high-risk groups, with p-value of &amp;gt; 0.05. Conclusion Invasive fungal infection remains a heavy burden to high-risk neonates. The protocol at present does not significantly prevent the occurrence of IFI. There is a need to revise the protocol to include the presence of a combination of multiple risk factors (central line, endotracheal tube, prolonged NPO, H2-blockers, and necrotizing enterocolitis) before initiating fluconazole prophylaxis. Disclosures All Authors: No reported disclosures

2884. Incidence of Invasive Fungal Infections After Pancreas Transplantation

Abstract Background There is scarce data surrounding the epidemiology of invasive fungal infections (IFI) after pancreas transplantation (PT). Our centers’ PT protocols recommend universal fluconazole prophylaxis for at least 1 month, which is extended to 1 year for recipients who live in Coccidioides endemic areas. The purpose of our study was to evaluate the epidemiology of IFIs after PT while on our antifungal prophylaxis protocol. Methods A retrospective cohort study was performed among adult patients who underwent PT at Mayo Clinic sites in Arizona, Florida, or Minnesota between January 1, 2010 and December 31, 2020. IFI was defined based on EORTC/MSGERC criteria. The primary aim was to describe epidemiology and timing of IFI after PT, particularly in the context of the universal antifungal prophylaxis protocol. Results Among 482 pancreas transplant recipients, 35 developed IFIs (7.3%). All patients received antifungal prophylaxis per protocol for a median duration of 33 days (Figure 1). Median duration from time of transplant to IFI was 16 (IQR 10.5-28.2) days for Candida IFIs versus 529 (IQR 192.5-1195.0) days for non-Candida IFI. 20 IFIs (57.1%) were secondary to Candida species with 45% of these cases caused by either C. glabrata or C. krusei (Figure 2). 90% were on antifungal prophylaxis (85% fluconazole) at time of diagnosis of invasive candidiasis. All the Candida IFIs were intra-abdominal infections. Amongst the 15 non-Candida IFIs (42.9%), 9 were secondary to endemic mycoses and 4 were secondary to invasive molds. Conclusion Our study shows a high incidence of IFIs secondary to Candida, with few patients diagnosed with non-Candida IFIs (Figure 3). Non-Candida IFIs, mostly secondary to endemic mycoses, occurred more than a year after transplant. Patients are at highest risk for Candida IFIs within the first 30 days after PT, likely secondary to organ space surgical site infections, despite receipt of antifungal prophylaxis. Breakthrough invasive candidiasis occurred in 90% of cases. Though our study lacked a comparator group without prophylaxis, these data question the effectiveness of fluconazole prophylaxis after PT. Disclosures All Authors: No reported disclosures

2607. The impact of portable high efficiency Hepa Filters on the incidence of invasive fungal infection in Covid 19 inpatients in a tertiary care hospital: a retrospective analysis from Pakistan

Abstract Background Objective: To identify impact of air filtration on incidence of Invasive fungal infections in COVID-19 patients after restructuring of COVID-19 wards. Introduction Most COVID-19 patients present with mild or moderate disease; but patients with comorbidities may be predisposed to secondary and opportunistic infections. Aspergillus infections resulting from failure in air filtration systems have been reported. Our study aims to determine the impact of installation of such preventative measures in covid units on the frequency of invasive fungal disease as a complication of covid 19 illness Methods All COVID-19 patients &amp;gt;18 years (non-severe, severe and/or critical) admitted at the tertiary care center were included. Even COVID-19 patients with suspected IPA, based on isolation of fungal species from one or more respiratory samples were included. Two time frames were used for inclusion of patients, one three months prior to and second three months after installation of HEPA filters in COVID wards. Patients with underlying respiratory disease, previous history of invasive pulmonary aspergillosis, on chronic steroid use ( &amp;gt;3 months), on broad-spectrum antibiotics and with hematological malignancies were excluded. SPSS version 23.0 was used for data analysis. Results From 187 patients, 97 enrolled before installation of HEPA filters while 90 after installation of HEPA filters. Overall the mean age of patients was 62.7 ± 14.6 years. A significant difference of p-0.04 was observed in terms of length of stay in-between before installation of HEPA filter group (13.1 ± 11.2 days) and in after installation of HEPA filter group (10.2 ± 8.2 days). Beta-D-Glucan test with HEPA filter was positive in 17 (17.5%) of patients while in 28 (31.1%) of patients without HEPA filter (p-0.03). Treatment with Azoles was found to have significant difference in-between both groups (p-0.002). Overall, treatment was successful in 16 (16.5%) patients in without HEPA filter group while in 38 (42.2%) of patients with HEPA filter (p&amp;lt; 0.001) Conclusion Substantial decrease in incidence of invasive fungal infections among COVID-19 patients was reported in terms of age, length of stay, Beta-D-Glucan, treatment with azoles and overall treatment in favor of HEPA filters. Disclosures All Authors: No reported disclosures

Invasive fungal infection incidence and risk factors in patients receiving ibrutinib in real-life settings: A nationwide population-based cohort study.

Data on the risk of invasive fungal infections (IFI) with ibrutinib treatment are scarce. This study aimed to determine IFI incidence and risk factors in ibrutinib-treated patients in real-life settings. We constituted a cohort of ibrutinib incident users in the French National Healthcare Database. All patients ≥18 years with a first dispensing of ibrutinib between 21 November 2014 and 31 December 2019 were included. Patients were followed from the cohort entry date until IFI, ibrutinib discontinuation, death, or 31 December 2020, whichever came first. The cumulative incidence function method was used to estimate the probability of IFI accounting for competing risk of death. A multivariate cause-specific Cox proportional hazards model was used to assess independent IFI risk factors. Among 6937 ibrutinib-treated patients, 1-year IFI cumulative incidence was 1.3%, with invasive aspergillosis being the most frequent. Allogenic or autologous stem cell transplantation (ASCT) (hazard ratio [HR] 3.59, 95% confidence interval [1.74; 7.41]), previous anticancer treatment (HR 2.12, CI 95% [1.34; 3.35]) and chronic respiratory disease (HR 1.66, [1.03; 2.67]) were associated with higher risk of IFI. Besides neutropenia and corticosteroids, use of anti-CD20 agents was significantly more frequent in patients having experienced IFI (HR 3.68, [1.82; 7.45]). In addition to patients with ASCT history, severe neutropenia or treated with corticosteroids, our findings support active surveillance of IFIs in those with chronic respiratory disease, previously treated, or treated with anti-CD20 agents in combination with ibrutinib. Further studies are needed to optimise IFI prophylaxis in these patient subgroups.

Assessing the impact of prophylactic anidulafungin during remission induction of acute myeloid leukemia - A propensity-score matching analysis.

Invasive fungal infection (IFI) accounts for substantial morbidity during the treatment of acute myeloid leukemia (AML) in adults. Antifungal prophylaxis (AP) is needed during intensive chemotherapy, and posaconazole is not widely available. In this study, we aimed to examine the impact of prophylactic anidulafungin during intensive AML remission induction. This is a retrospective cohort encompassing newly diagnosed AML adult patients. All subjects received intensive chemotherapy and were divided into three groups: patients who did not receive any AP and patients who received fluconazole (150-400mg/day) or anidulafungin (100mg/day). During AML induction, 82 patients did not receive AP, 108 and 14 patients received anidulafungin and fluconazole, respectively. IFI incidence was 27%, classified as possible, probable, and proven in 65, 2 and 33%, respectively. Multivariable analysis showed that lower neutrophil counts are associated with IFI (OR=2.8), whereas age, genetic classification, and lymphocyte counts were not. To examine the impact of anidulafungin in comparison with 'no AP', a propensity score matching analysis was performed. Use of anidulafungin was not related to less IFI during induction, while neutrophil counts remained significant. Patients under prophylactic anidulafungin received less amphotericin B (p<0.001) but not voriconazole (p=0.49). To our knowledge, this is the first study addressing the role of anidulafungin during AML induction. Here, the incidence of mold infections did not decrease with AP, suggesting that in a setting with a high incidence of IFI, broad spectrum AP might be more suitable.

Rethinking the definition of 'less intensive' for venetoclax-combining regimens in acute myeloid leukaemia patients.

Invasive fungal infections (IFIs), mainly due to pulmonary aspergillosis, are considered a serious complication in acute leukaemia, with an unfavourable impact on patient. In this well-conducted retrospective study, Reynolds et al. suggest that the use of posaconazole prophylaxis in association with venetoclax plus hypomethylating agents or chemotherapy leads to a reduction of IFI incidence. Therapeutic drug monitoring of posaconazole levels is suggested, even if no correlation with IFI risk has been demonstrated. Commentary on: Reynolds et al. Invasive fungal infection following venetoclax and posaconazole co-administration. Br J Haematol 2023;203:593-598.

Drug Utilization Evaluation of Systemic Antifungals in a Tertiary Care Hospital

Introduction: The incidence of Invasive Fungal Infection has increased, and it constitutes a serious threat to human health and life, especially in immunocompromised and critically ill patients. We aimed to evaluate the appropriateness of antifungal agents along with their risk factors and sensitivity pattern. Methods: It is a retrospective, cross-sectional study, which includes details of patients prescribed with systemic antifungal agents during a period of five years (01-06-2016 to 31-05-2021). Collected details were compared with Infectious Diseases Society of America (IDSA) guidelines and mycological results to determine the overall appropriateness. Results: A total of 102 patients prescribed with systemic antifungals were selected for the study. The majority of the drugs were prescribed as Definitive (59.19%) and T Fluconazole (39.4%) was the most common drug given. The most common indication for antifungal prescriptions was found to be Respiratory tract infection. Appropriateness of antifungal use was assessed on indication, dosage, contraindication, and drug-drug interaction. Overall assessment of antifungal agents and treatment strategy demonstrated that antifungal treatment was appropriate in 41.6% cases, debatable in 36% cases and inappropriate in 22.4% of cases. The most common culture specimen collected was urine and Candida tropicalis (42.86%) was the frequently separated organism from it. Sepsis (21.4%) was the most common risk factor associated with invasive fungal infection. Conclusion: By implementing an effective antifungal stewardship program, we could improve the rational use of systemic antifungals and thereby prevent the future resistance and improve clinical outcome.

The Austrian landscape of diagnostic capacity and access to treatment for invasive fungal infections.

Immunosuppression after chemotherapy, stem cell transplantation or solid organ transplantation are the main risk factors for invasive fungal infections in Austria. Here, we aim to describe the status of laboratory mycology and the access to antifungal treatment in Austria. Between October and November 2021, hospitals were contacted to participate in our online survey: www.clinicalsurveys.net/uc/IFI_management_capacity/. Centres were required to provide information on their institutional profile; self-assessment of burden of invasive fungal infections; access to microscopy, culture, serology, antigen detection and molecular testing; and availability of antifungal agents and therapeutic drug monitoring. Responses were collected from university hospitals and laboratories in Graz, Innsbruck, Linz and Vienna. The four hospitals can provide tertiary care and were highly specialised, including management of patients with severe immunosuppression. All sites consider the incidence of invasive fungal infections to be moderate. Access to microscopy, culture, serology, antigen detection and molecular testing is provided regardless of laboratory. The maximum capacity to identify fungi varies from institution to institution. All currently marketed antifungal agents are available at the four sites. Austria is currently well equipped to deal with the emerging threat of invasive fungal infections. However, hospitals may consider preparing for the potential endemicity of certain infections in the near future.