Outcome Of Invasive Fungal Infections Research Articles

Outcomes of Invasive Fungal Infections Treated with Isavuconazole: A Retrospective Review.

Isavuconazole (ISA) has a favorable side effect profile that makes it attractive for treatment of invasive fungal infections (IFI). It carries FDA approval for invasive aspergillosis and mucormycosis, but there are fewer data for other organisms and non-pulmonary infections. We conducted this review to investigate how ISA performed at treating IFI, with an especial interest in these non-approved indications. We retrospectively identified and reviewed 131 patients who received ISA as treatment for IFI at our institution, some of whom received ISA as their first anti-fungal therapy and others who received ISA as either step-down therapy or salvage therapy. We identified the microbiologic cause of infection as well as the anatomic site involved for each patient. We then classified patients according to their response to ISA: namely cured, partially responded, or stabilized. The majority of patients were immunocompromised (n = 76, 58%). ISA was used primarily as a secondary therapy (n = 116, 89%); either as a step-down/switching from other agents, or as salvage therapy. The most common reasons for switching to ISA were toxicities with prior agents followed by QT prolongation. Although pulmonary aspergillosis and mucormycosis were represented in more than half of the cohort, ISA was also used off-label for treatment of other organisms such as endemic fungi (n = 19, 15%) as well as central nervous system (CNS) infections (n = 15, 11%). We have described the detailed clinical characteristics of these CNS infections cases. The overall clinical response rate varied by type of infection and site involved (57-73% response rate). We demonstrated encouraging clinical responses, particularly outside the FDA-approved indications, as well as good tolerability. This report highlights the critical need for expanded scope of prospective studies to delineate the efficacy of this better-tolerated agent, especially in central nervous system infections.

Rate, Risk Factors, and Outcomes of Invasive Fungal Infections in Patients with Hematologic Malignancies.

Background:Invasive fungal infections (IFIs) are a significant cause of mortality and morbidity in patients with hematological malignancies. Given the considerable prevalence and consequences of IFIs, hence revealing the exact cause of fungal infections, their rate, associated risk factors, and complications could contribute to reducing both financial and life costs, choosing targeted antifungal treatment, and avoiding unnecessary toxic treatments in individuals who are not suffering from mycoses. Materials and Methods:This prospective cross-sectional study was conducted in the first semester of 2019. All patients with hematologic malignancies (HM) admitted to Dr. Shariati Hospital were studied. Only those with probable/proven IFIs defined according to the last update of EORTC/MSG criteria were included in the study. The demographic and clinical data were recorded from the hospital information registration system using a questionnaire. Statistical analysis was performed using SPSS software version 24. Results: Out of 1109 HM patients hospitalized during the study period, 67 (6.04%) IFIs were diagnosed. Of these, 57 (85.04%) were aspergillosis, 7 (10.4%) were mucormycosis, and 3 patients developed other fungal infections. Males constituted 67.2% of the entire IFI population. The mean±SD age of the samples was 43.16 ± 13.8 years. The most common type of malignancy was AML. Lung imaging showed lesions associated with fungal infections in 52 cases (77.6%), with multiple nodules as the most prevalent pattern being observed in 64.2% of cases. Sinus involvement was evidenced in the PNS CT scan of 46 (68.6%) patients. The attributable mortality rate for IFIs was 62.7%. Both the types of IFI and malignancies had no significant relationship with the outcome of patients. Central venous catheter, mucositis, and antibiotic use were the most frequent risk factors. Conclusion:IFI represents a frequent complication for HM patients with high mortality. Aspergillus species are the predominant etiology in these settings. Considering our results, in high-risk patients, manifestations of warning signs in the sinus and lungs, which would not be cleared despite receiving antibiotics, should raise the possibility of IFIs.

Invasive Fungal Infections after CAR T-Cell Therapy for B-Cell Lymphoma: A Study from the French Descart Registry

Introduction: Chimeric antigen receptor (CAR) T cell therapy has emerged as an important treatment option for patients with B-cell malignancies. Despite its major clinical impact, CAR T cell therapy holds a potential risk of increased susceptibility to infections, including invasive fungal infections (IFI). Since data about the prevalence and impact of fungal infections in this population are limited, we aimed to provide a comprehensive overview of IFI using real-world data from the national DESCAR-T registry. Methods: We performed a multi-center retrospective cohort study, quering the French DESCAR-T registry (NCT04328298), to describe type, frequency and outcomes of IFI in adults with refractory or relapsed (R/R) B cell lymphomas. In addition, healthcare providers were contacted to declare any missing cases. Demographic, biological and clinical characteristics were collected retrospectively. Each IFI case was reviewed by an infectious disease specialist and a microbiologist, and classified according to the European Organization for Research and Treatment of Cancer (EORTC) criteria (Donnelly et al. Clinical Infect Dis 2020). Results: Among the 1144 patients included in the registry from 2018 to 2022, we identified 57 suspected IFI cases. After exclusion of 25 patients not adjudicated for IFI, 32 patients (3%) were identified as having presented a proven (n = 14), probable (n = 12), or possible (n = 6) IFI. DLBCL was the primary diagnosis for 30 patients and axi-cel was the most frequent CAR T product (23/32, 72%). Seven patients (22%) had received a previous hematopoietic stem cell transplantation. All patients experienced cytokine release syndrome (including 8 grade ≥ 3) and 21 (66%) experienced immune effector cell-associated syndrome (including 13 grade ≥ 3). Overall, 27 (84%), 21 (66%), and 5 (16%) received tocilizumab (median 960mg, range 120-2880mg), corticosteroids, and anakinra, respectively. Among known risk factors for IFI, grade 4 neutropenia and late neutropenia (< 1g/L) at day 28 after infusion were identified in 25 (78%) and 14 (44%) patients respectively. Overall, 8 (25%) patients received antifungal prophylaxis, posaconazole was used for 4 of them. Over half of the IFI cases occurred between 0 and 30 days after CAR T-cell infusion (18/32, 56%), with a median onset time of 29.5 days (IQR 16.5 - 79.5). The most frequently observed infections were invasive Aspergillosis (n = 13), with pulmonary involvement in 10/13 (77%) of patients, leading to a fatal issue in 3/13 patients (23%). Other mold infections included Mucormycosis (n = 5), with pulmonary involvement in 4/5 patients and a fatal outcome in 1/5, as well as Fusariosis (n = 1). Yeast infections (n = 12) were mostly identified as Candidemia (92%) with a mortality rate of 3/12 (27%). The median overall survival of patients with IFI was 186.5 days (IQR 79-506), 7 deaths being related to IFI and 3 to lymphoma relapse. Median progression-free survival was 94 days (IQR 31 - 252). Conclusions: This study represents one of the largest investigations about IFI in B-cell lymphoma patients treated with CAR T-cells. Even though IFI represent a rare complication after CAR T-cell therapy, the related-mortality is high. Selective antifungal prophylaxis may benefit high-risk patients, while rapid preemptive diagnostic workup, particularly for lung involvement, is mandatory. Analysis to define potential risk factors for IFI are ongoing.

Invasive Fungal Infections in Children With Acute Myeloid Leukemia: A Single-center Experience Over 19 Years.

Invasive fungal infections (IFIs) remain a significant cause of morbidity and mortality in children with acute myeloid leukemia (AML). This study aimed to evaluate the incidence, risk factors, etiology, and outcome of IFIs in children with AML and the effect of mold-active antifungal prophylaxis. We retrospectively reviewed pediatric patients treated for AML between January 2004 and December 2022. Proven, probable, or possible IFIs were defined using standardized definitions of the European Organization for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) classification published at 2008. A total of 298 febrile neutropenia episodes from 78 patients were evaluated. Proven, probable, and possible IFI rates were 3%, 2.6%, and 9.4%, respectively. Profound neutropenia was detected in 18 (58%) and prolonged neutropenia in 20 (64.5%) of the IFI episodes.. Invasive aspergillosis accounted for the majority of IFI episodes; however, non-albicans Candida spp. were the most isolated pathogens in the proven group. Patients with relapsed AML were particularly at risk for the development of IFI ( P =0.02). A significant decrease in IFI episodes was achieved with mold-active antifungal prophylaxis with voriconazole ( P =0.01, odds ratio: 0.288, %95 CI:0.104-0.797). The overall mortality was 35.8%, and the IFI-attributable mortality rate was 25%. In the multivariate analysis, relapsed disease was the most significant risk factor associated with mortality ( P =0.006, odds ratio:4.745; 95% CI: 1.573-14.316). Mold-active prophylaxis reduced the rate of IFIs in this cohort however IFI-related mortality was still high as 25% in pediatric AML patients. Relapsed AML was the most significant risk factor associated with mortality.

Fungal Infections in the ICU during the COVID-19 Pandemic in Mexico.

Background: Invasive Fungal Infections (IFI) are emergent complications of COVID-19. In this study, we aim to describe the prevalence, related factors, and outcomes of IFI in critical COVID-19 patients. Methods: We conducted a nested case-control study of all COVID-19 patients in the intensive care unit (ICU) who developed any IFI and matched age and sex controls for comparison (1:1) to evaluate IFI-related factors. Descriptive and comparative analyses were made, and the risk factors for IFI were compared versus controls. Results: We found an overall IFI prevalence of 9.3% in COVID-19 patients in the ICU, 5.6% in COVID-19-associated pulmonary aspergillosis (CAPA), and 2.5% in invasive candidiasis (IC). IFI patients had higher SOFA scores, increased frequency of vasopressor use, myocardial injury, and more empirical antibiotic use. CAPA was classified as possible in 68% and 32% as probable by ECMM/ISHAM consensus criteria, and 57.5% of mortality was found. Candidemia was more frequent for C. parapsilosis Fluconazole resistant outbreak early in the pandemic, with a mortality of 28%. Factors related to IFI in multivariable analysis were SOFA score > 2 (aOR 5.1, 95% CI 1.5-16.8, p = 0.007) and empiric antibiotics for COVID-19 (aOR 30, 95% CI 10.2-87.6, p = <0.01). Conclusions: We found a 9.3% prevalence of IFIs in critically ill patients with COVID-19 in a single center in Mexico; factors related to IFI were associated with higher SOFA scores and empiric antibiotic use for COVID-19. CAPA is the most frequent type of IFI. We did not find a mortality difference.

The Incidence of Invasive Fungal Infections in Children, Adolescents and Young Adults with Acute Lymphoblastic Leukaemia/Lymphoma Treated with the UKALL2011 Protocol: a Multicentre Retrospective Study

▪Introduction: While it is well-recognised that invasive fungal infections (IFIs) are a major cause of morbidity and mortality in haematological malignancies, epidemiological data in paediatric acute lymphoblastic leukaemia/lymphoma (ALL) is scarce (Groll et al. Lancet Oncology 2014). The incidence of IFI in paediatric ALL is difficult to estimate as differing chemotherapy protocols, patient populations, diagnostic strategies and IFI definitions preclude direct comparisons. Assessment is also limited by major practice variations in the use of prophylactic and empiric systemic antifungals. Despite the lack of published data, there is a concern that IFIs impact on disease outcome and survival, either directly due to infection-related mortality or secondary to chemotherapy omissions, dose reductions and changes to subsequent therapy. To determine the incidence and outcome of IFIs in paediatric, adolescent and young adult patients treated with the UKALL2011 protocol, we conducted a retrospective study in two large London tertiary referral centres over a 4 year period.Methods: All patients diagnosed and treated with ALL at Great Ormond Street Hospital (GOSH) and University College London Hospital (UCLH) between January 1st 2013 and January 1st 2017 were included in the study. Data on IFIs were collected during the following phases of the UKALL2011 protocol: Induction, consolidation, interim maintenance and delayed intensification. Medical records and online databases were used to collate the data. IFIs were classified as proven, probable and possible according to revised EORTC criteria (De Pauw et al. Clinical Infectious Diseases 2008).Results: Between January 1st 2013 and January 1st 2017 296 patients (M=160, F=136) with a median age of 5 years (range 10 months -24 years) were treated for ALL (B-lineage n=249, T lineage n=43, NA n=4) at GOSH (n=233) and UCLH (n=63). Cytogenetic risk profile for B-ALL was classified as good (n=133), intermediate (n=86), poor (n=20) or NA (n=10) (Moorman AV et al. Lancet Oncology 2010).A small cohort of young adult patients aged 20 to 24 years (n=16) received anti-fungal prophylaxis during induction and consolidation in the form of oral itraconazole when the neutrophil count was less than 1.5×109/L. This was substituted with liposomal amphotericin B when vinca alkaloids were scheduled. Routine anti-fungal prophylaxis was not implemented in the remaining cases (n=280)Over a 4 year period the incidence of proven, probable and possible IFI was 2% (n=6), 1.6% (n=5) and 4% (n=12) respectively. Positive mycological results were available in 7 cases: Candida spp in 5, Aspergillus spp in 1 and Scedosporium spp in 1. Disseminated disease (including CNS disease n=2) occurred in 4 cases, all during induction (Table 1).IFIs resulted in a treatment delay of a median of 3 weeks (range 1-15) in 16 cases. Omission of chemotherapy and significant dose reductions occurred in 2 and 4 cases respectively.Follow-up data is available in 22 of the 23 patients diagnosed with a proven, probable or possible IFI during the UKALL2011 protocol (lost to follow-up n=1).With a median follow up of 16 months (range 4-39), 20 patients are alive and in ongoing remission. Three patients proceeded to haematopoietic stem cell transplant (HSCT). Two of these patients died of complications of HSCT. IFI recurrence (candida utilis bacteraemia) was a contributing factor in one case.Conclusions: The incidence of IFIs is low in ALL patients treated with UKALL2011 protocol, with a low risk of mortality but the potential to compromise timely delivery of chemotherapy. The risk appears to be highest in induction. This data does not support the routine administration of prophylactic anti-fungal therapy in children and young people undergoing chemotherapy for ALL. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The application of Voriconazole in 76 patients with cirrhosis at Child-Pugh C stage complicated by invasive fungal infection

Objective: To investigate the safety and efficacy of voriconazole in the patients with cirrhosis at Child-Pugh C stage complicated by invasive fungal infection(IFI). Methods: A retrospective collection of medical records of 76 patients with cirrhosis at Child-Pugh C stage complicated by IFI who were admitted to our hospital, from August 2014 to August 2017 was carried out. All the 76 patients who used voriconazole to treat IFI were divided into recommended dose group for hepatic insufficiency(56 cases) and routine dose group(20cases). The two groups were observed and compared in terms of the voriconazole's plasma concentrations, the outcomes of IFI and the rate of untoward reactions. The liver functional indicators were also compared between before and after treatment each group. We used Student's t test, Z test, chi-square test, or Fisher's exact test, as appropriate, for statistical analysis. Results: Both groups had good performance and low frequencies of side effects in the treatment of IFI, but there were also significant differences in the plasma concentrations of voriconazole and the incidence of untoward reactions between the two groups(P = 0.008 and P = 0.022). There commended dose group for hepatic insufficiency had lower adverse effect rate. The levels of direct bilirubin, alanine aminotransferase and aspartate aminotransferase were significantly lower after treatment of IFI in the recommended dose group for hepatic insufficiency(P < 0.05). Conclusion: In our research, it is relatively safe and effective to use voriconazole to treat IFI in the patients with cirrhosis at Child-Pugh C stage if according to the recommended dose regimen for cirrhosis at Child-Pugh A,B stage.

748. Epidemiology and Outcomes of Invasive Fungal Infections Following Civilian Trauma

BackgroundInvasive fungal infections (IFI) following traumatic injury are devastating complications that threaten life and limb. In military combat wounds, post-traumatic IFI patients have up to 6 times higher mortality rates and 2.6-5.1 times higher rate of high-level amputations compared to non-IFI patients, though no such data exists for the civilian population. This study is the first cohort to analyze a post-traumatic civilian population for IFI, its epidemiology and outcomes.MethodsWe conducted a single-center retrospective cohort study of all trauma patients over the age of 18 years admitted to a large tertiary referral hospital between 2004 to 2015 who required surgery for their injury and had operative cultures submitted from their wounds. Patient demographics, comorbid conditions, mechanisms of trauma, environmental exposures, and laboratory data were included for analysis. Patients with positive culture for fungus from a site compatible with IFI were considered IFI patients. Data was analyzed using descriptive statistics with p≤0.05 considered significant.ResultsOur cohort includes 1,107 patients that met inclusion criteria. Of these, 120 patients had a positive culture for fungus, 454 patients had a positive culture for bacteria and 533 patients had no positive culture from a site of interest. Basic patient demographics, geographical setting of the trauma, and anatomical site of injury were not significantly associated with having a positive fungal culture. Necrosis was present in 19 (15.8%) IFI vs. 74 (7.5%) non-IFI patients (p=0.002). Soil contamination of a wound was present in 6 (5.0%) IFI vs. 11 (1.1%) non-IFI patients (p=0.001). 55.8% of 120 IFI wounds penetrated below fascial layers compared to 26.7% of 987 non-IFI wounds (p< 0.001).Presence of IFI increased likelihood of requiring amputation (6.7% vs. 2.7%, p=0.02) and prolonged hospitalization >14 days (77.5% vs. 57.4%, p< 0.001) compared to those without.ConclusionIFI significantly increased patient risk for amputation and prolonged hospital length of stay following traumatic injury in a civilian population. Presence of IFI was associated with wounds penetrating below the fascial layer, presence of wound necrosis, and soil contamination of a wound.Disclosures Andrej Spec, MD, MSCI, Astellas (Grant/Research Support)Mayne (Consultant)Scynexis (Consultant)

908P Impact of serum galactomannan assay on diagnosis and outcome of invasive fungal infections in high risk febrile neutropenia: A prospective cohort study

908P Impact of serum galactomannan assay on diagnosis and outcome of invasive fungal infections in high risk febrile neutropenia: A prospective cohort study

Invasive fungal infections in a pediatric hematology-oncology department: A 16-year retrospective study

Background and Purpose: Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in immunocompromised children. The purpose of our study was to evaluate the incidence of IFIs in pediatric patients with underlying hematologic malignancies and determine the patient characteristics, predisposing factors, diagnosis, treatment efficacy, and outcome of IFIs.Materials and Methods: For the purpose of the study, a retrospective analysis was performed on cases with proven and probable fungal infections from January 2001 to December 2016 (16 years)Results: During this period, 297 children with hematologic malignancies were admitted to the 2nd Pediatric Department of Aristotle University of Thessaloniki, Greece, and 24 cases of IFIs were registered. The most common underlying diseases were acute lymphoblastic leukemia (ALL; n=19,79%), followed by acute myeloid leukemia (AML; n=4, 17%) and non-Hodgkin lymphoma (NHL; n=1,4%). The crude incidence rates of IFIs in ALL, AML, and NHL were 10.5%, 18.2%, and 2.8% respectively. Based on the results, 25% (n=6) and 75% (n=18) of the patients were diagnosed as proven and probable IFI cases, respectively. The lung was the most common site of involvement in 16 (66.7%) cases. Furthermore, Aspergillus and Candida species represented 58.3% and 29.1% of the identified species, respectively. Regarding antifungal treatment, liposomal amphotericin B was the most commonly prescribed therapeutic agent (n=21), followed by voriconazole (n=9), caspofungin (n=3), posaconazole (n=3), micafungin (n=1), and fluconazole (n=1). In addition, 12 children received combined antifungal treatment. The crude mortality rate was obtained as 33.3%.Conclusion: As the findings of the present study indicated, despite the progress in the diagnosis and treatment of IFIs with the use of new antifungal agents, the mortality rate of these infections still remains high.

Outcome and characteristics of invasive fungal infections in critically ill burn patients: A multicenter retrospective study.

Characteristics and outcome of invasive fungal infection (IFI) in critically ill burn patients have been poorly explored. We report the factors associated with 90-day mortality in a multicentre retrospective European study. All burn patients with confirmed IFI admitted between 1 January 2010 to 31 December 2015 in 10 centres in France and Belgium were included. 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. 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.

Incidence &amp; outcome of invasive fungal infections in patients with febrile neutropenia

Abstract Background Invasive fungal infection (IFI) is a major cause morbidity and mortality among patients with hematological malignancies who receive chemotherapy or hematopoietic stem cell transplantation (HSCT). Thus, early diagnosis and treatment of these infections are of crucial importance. Certain factors have been identified as risk factors for IFI. Objectives Assessment of incidence and outcome of IFI in Egyptian patients with febrile neutropenia. Patients and Methods 50 febrile neutropenia episodes were studied. Patients were all subjected to history taking, clinical examination and further investigations including imaging studies, Galactomannan and Mannan antigen assays, and patients were followed up for observing the outcome. Results Our study found that hypertensive patients had significantly reduced LA function as measured by speckle tracking when compared to normotensive controls (P-value &amp;lt; 0.001). Also, many factors were associated with worse LA function in hypertensive patients as old age, high BMI, DM, LV diastolic dysfunction, high LV mass index, larger LA size, lower LA expansion index and higher systolic BP. Conclusion IFI incidence is affected by age, gender, primary diagnosis and severity of neutropenia, and IFI has a worse outcome compared to other causes of febrile neutropenia.

Incidence and outcomes of invasive fungal infection among solid organ transplant recipients: A population-based cohort study.

Invasive fungal infection (IFI) in solid organ transplant (SOT) recipients is associated with significant morbidity and mortality. The long-term probability of post-transplant IFI is poorly understood. We conducted a population-based cohort study using linked administrative healthcare databases from Ontario, Canada, to determine the incidence rate; 1-, 5-, and 10-year cumulative probabilities of IFI; and post-IFI all-cause mortality in SOT recipients from 2002 to 2016. We also determined post-IFI, death-censored renal allograft failure. We included 9326 SOT recipients (median follow-up: 5.35years). Overall, the incidence of IFI was 8.3 per 1000 person-years. The 1-year cumulative probability of IFI was 7.4% for lung, 5.4% for heart, 1.8% for liver, 1.2% for kidney-pancreas, and 1.1% for kidney-only allograft recipients. Lung transplant recipients had the highest incidence rate and 10-year probability of IFI: 43.0 per 1000 person-years and 26.4%, respectively. The 1-year all-cause mortality rate after IFI was 34.3%. IFI significantly increased the risk of mortality in SOT recipients over the entire follow-up period (hazard ratio: 6.50, 95% CI: 5.69-7.42). The 1-year probability of death-censored renal allograft failure after IFI was 9.8%. Long-term cumulative probability of IFI varies widely among SOT recipients. Lung transplantation was associated with the highest incidence of IFI with considerable 1-year all-cause mortality.

Breakthrough Invasive Fungal Infections in Patients with Acute Myeloid Leukemia.

We sought to determine the occurrence, risk factors, effect of antifungal prophylaxis, and outcomes of invasive fungal infections (IFIs) in patients with acute myeloid leukemia (AML). We performed a retrospective analysis of all adult patients admitted to the University of Michigan Health System for AML over a 3-year period from 2010 to 2013. We determined comorbidities, hematopoietic cell transplant (HCT) status, antifungal prophylaxis, proven and probable IFI, and outcomes at 12weeks after initiation of appropriate antifungal therapy. Of 333 patients in our cohort, 116 of whom had received a HCT, 98 (29%) developed an IFI. Of the 30 (9%) patients who had a proven or probable IFI, 18 had breakthrough infection while on micafungin (n = 5), voriconazole (n = 4), posaconazole (n = 5), or fluconazole (n = 4). Breakthrough IFIs were due to Aspergillus species (n = 11), other molds (n = 4), and Candida species (n = 3). Factors associated with breakthrough IFI were prolonged severe neutropenia (p = .05) and having received tacrolimus (p = .04). Antifungal therapy was successful in 7 of the 18 (39%) patients with breakthrough IFI and 8 of the 12 (67%) patients with non-breakthrough IFI, p = .13. Mortality at 12weeks was 27%, 5 with breakthrough IFI and 3 with non-breakthrough IFI and was associated with prolonged severe neutropenia, p = .04. Patients with AML remain at risk for IFI despite the use of several different antifungal agents for prophylaxis. Mortality remains high in patients with AML who develop IFI.

Clinical Outcomes of Invasive Fungal Infections in Hospitalized Patients

Clinical Outcomes of Invasive Fungal Infections in Hospitalized Patients

Invasive fungal infections in children with acute lymphoblastic leukaemia: Results from four Australian centres, 2003-2013.

Invasive fungal infections (IFI) are an important complication of acute lymphoblastic leukaemia (ALL) treatment. Our study describes the prevalence and outcomes of IFI in children with ALL. IFI episodes in children with primary or relapsed ALL, identified for The Epidemiology and Risk Factors for Invasive Fungal Infections in Immunocompromised Children study, were analysed. IFI were classified according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group criteria with a 'modified-possible' category included. A total of 123 IFI episodes in 119 patients with ALL were included. A proven, probable, possible and modified-possible IFI was diagnosed in 56 (45.5%), 22 (17.9%), 39 (31.7%) and six (4.9%) episodes, respectively. The prevalence was 9.7% (95% confidence interval [CI] 8-11.4%) overall and 23.5% (95% CI 14.5-32.5%) for relapsed/refractory ALL. For non-relapsed ALL, the IFI prevalence was significantly higher for children with high-risk compared to standard-risk ALL (14.5% vs 7.3%, P=.009), and IFI were more common during induction, consolidation and delayed intensification phases. Mould infections occurred more frequently than non-mould infections. Thirteen children (10.9%) died within 6 months of IFI diagnosis with five deaths (4.2%) attributable to an IFI. IFI is more common in children with high-risk ALL and in relapsed disease. Overall survival was encouraging, with IFI contributing to very few deaths.

Invasive fungal infection in liver transplant recipients in a prophylactic era: A multicenter retrospective cohort study in Korea.

The epidemiology of invasive fungal infections (IFIs) after liver transplantation (LT) is continuing to evolve in the current era of antifungal prophylactic therapy. This multicenter retrospective cohort study aimed to evaluate the epidemiology, risk factors, and outcomes of IFIs among LT recipients in the current era.We analyzed a total of 482 LT recipients aged 18 years and older who were admitted to 3 tertiary hospitals in Korea between January 2009 and February 2012.Twenty-four episodes of IFIs occurred in 23 patients (4.77%; 23/482). Of these episodes, 20 were proven cases and 4 were probable cases according to EORTC/MSG criteria. Among these cases, IFI developed within 30 days of transplantation in 47.8% of recipients, from 31 to 180 days in 34.8% of recipients, and from 181 to 365 days in 17.4% of recipients. The most common isolates were Candida species (n = 12, 52.2%; Candida albicans, 6 cases; Candida tropicalis, 1 case; Candida glabrata, 1 case; Candida parapsilosis, 1 case; and unspecified Candida species, 1 case) and Aspergillus species (n = 7, 30.4%). The mortality in patients with IFIs was significantly higher than that in patients without IFIs (47.83% [11/23] vs 7.18% [33/459], P < .001). The incidence of late-onset IFIs is increasing in the antifungal prophylactic era, and fluconazole-resistant non-albicans Candida species have not yet emerged in Korea.

Invasive fungal infections in critically ill patients: A prospective study from a tertiary care hospital in India

Invasive fungal infections (IFI) are commonly seen in immunosuppressed individuals but their epidemiology in critically ill patients has not been well described. The aim of this study was to determine the frequency, risk factors and outcome of invasive fungal infections in a medical intensive care unit. A prospective observational study was carried out between August 2016 and March 2018 in the medical intensive care unit. Patients above the age of 14 years with endotracheal intubation and/or central venous catheter for at-least three days and sepsis (not responding to 48 hours of intravenous antibiotic therapy) were included in the study. Suitable samples were collected and were subjected to fungal diagnostics. Invasive fungal disease was defined according to standard guidelines. Of the 100 recruited patients, a total of 11 patients had invasive aspergillosis, three patients had invasive candidiasis and one patient had both invasive aspergillosis and mucormycosis. IFI was more commonly seen in patients with auto-immune diseases (p = 0.002, odds ratio-10.13 (95% CI: 2.3-44)). A mortality of 73% was observed in patients with IFI. In conclusion, IFI, especially aspergillosis is grossly under-reported in critical settings. Early suspicion, thorough investigation and timely diagnosis may alleviate patients of significant mortality and morbidity.

Isavuconazole in Hematological Patients: Results of a Real-Life Multicenter Seifem Study

Isavuconazole in Hematological Patients: Results of a Real-Life Multicenter Seifem Study

1129. Targeted Voriconazole Prophylaxis in Heart Transplantation Recipients

BackgroundThe use of antifungal prophylaxis, targeted or universal, remains controversial and unstudied. The goal of this study is to determine the role of targeted voriconazole prophylaxis (VORI) in prevention of invasive fungal infections (IFI) after heart transplantation (HT).MethodsWe conducted a single-center, prospective, observational cohort study of 276 HT recipients from June 2005 to April 2017 to characterize the incidence and outcome of IFI following targeted VORI. Starting in June 2013, HT recipients with thymoglobulin (ATG) treatment received VORI for 3 months. Probable/proven IFI were defined by EORTC/MSG criteria. Descriptive frequencies and univariate analyses were performed.ResultsMean duration of follow-up post-HT was 1,165 days (0–3,152 days). 149 (54%) and 70 (25%) received basiliximab and thymoglobulin induction, respectively. Thirty-one (11%) received VORI, following use of ATG in the setting of induction (68%) or rejection (32%). VORI was started at median of 6 days (0–1,008 days) post-HT for a mean duration of 97 days (5–251 days). Overall, 23 IFIs occurred in 23 recipients (8%) at mean 283 days post-HT (range 2–1,579 days), including seven Aspergillus (one occurring after VORI completion), seven invasive Candida (five with candidemia), two Rhizopus, one Cunninghamella, two histoplasma, two blastomyces, one Cryptococcus, and one multifocal cutaneous Alternaria. ConclusionTargeted VORI resulted in reduced incidences of both early and overall IFI after HT although this did not reach statistical significance. Since instituting this strategy, we have observed a single case of aspergillosis following VORI discontinuation. Overall and 1-year mortality were not impacted. The use of antifungal prophylaxis following HT requires continued investigation both to determine efficacy and toxicity in this patient population.Disclosures All authors: No reported disclosures.