Rate Of Invasive Fungal Infections Research Articles

1087. Evaluation of Risk Factors for Infection among Patients Receiving Ibrutinib

BackgroundIbrutinib is a small-molecule inhibitor of Bruton tyrosine kinase (BTK) approved for various B-cell malignancies and cGVHD. Rates of serious infection—defined as requiring hospitalization or parenteral antimicrobials— and invasive fungal infection (IFI) in patients on ibrutinib are as high as 11.4% and 4.2% respectively (Varughese T, et al. Clin Infect Dis 2018;67(5):687-92), which may be related to off-target inhibition of interleukin-2-inducible T-cell kinase or macrophage function.MethodsWe retrospectively reviewed infection complications in patients receiving ibrutinib at our institution between 06/01/2014 and 08/31/2019, including patients who received single-agent or combination ibrutinib. In this study, serious infection was defined as above, or a diagnosis of pneumonia regardless of hospitalization or parenteral antimicrobial therapy. Logistic regression was used to identify risk factors.ResultsBaseline characteristics of 134 included patients are in Table 1. Infection and serious infection occurred in 96 (72%) and 48 (36%) patients, respectively. When pneumonia was not included as a criterion for serious infection, the serious infection rate was 22%. Prior allogeneic stem cell transplant (allo-HSCT) (OR 4.50; 95% CI 1.19 – 17.00) and corticosteroid use (OR 5.42; 95% CI 1.49 – 19.82) were significant risk factors for serious infection without pneumonia (Table 2).Of 37 patients (28%) who received primary HSV/VZV prophylaxis with acyclovir, there was one case of suspected herpes zoster infection (3%). IFI developed in 7 patients (5%): 5 with Pneumocystis jirovecii pneumonia (PJP), 1 with invasive aspergillosis, and 1 with a filamentous fungus, species unknown. Other identified organisms are detailed in Figure 1. Classical risk factors for IFI, including diabetes, allo-HSCT, and concurrent corticosteroid use, were not significant predictors in this group.Table 1. Baseline Characteristics Table 2. Risk Factor Analysis Figure 1. Identified Organisms in Serious Infection ConclusionSerious infections developed at a higher rate than previously reported in the literature, with IFI rates similar to those previously described. Prior allo-HSCT and steroid use were found to be risk factors for serious infection without pneumonia. Treating physicians should have a high index of suspicion for pneumonia, IFI, and PJP in this population.Disclosures All Authors: No reported disclosures

Distribution of invasive fungal infections: Molecular epidemiology, etiology, clinical conditions, diagnosis and risk factors: A 3-year experience with 490 patients under intensive care

Recently, the prevalence of invasive fungal infections (IFIs) is rising. The global mortality rate of IFIs is 10–49%. This study aimed to determine the prevalence, the causative agents, and the risk factors associated with the invasive fungal infections in a tertiary health center to provide valid decision-grounds for healthcare professionals to effectively prevent, control, and treat fungal infections. The current study was conducted on 1477 patients suspected to have systemic fungal infections from different units of the hospital. After screening using routine mycological examination, the patients were confirmed with complementary mycological and molecular methods. Patients were included based on the confirmed diagnosis of IFI and excluded based on lack of a microbiologically and histologically proven diagnosis of IFI. Of the 1477 patients recruited in this study, confirmed cases of fungal infection were 490 (169 proven; 321 cases probable). Among the fungi recovered, Candida species had the highest frequency 337 (68.8%) followed by Aspergillus species 108 (22.1%), Zygomycetes species 21 (4.3%), non-Candida yeast 9 (1.8%). Others were black fungi 5 (1%), mycetoma agents 5 (1%), Fusarium 4 (0.8%), and Trichoderma (0.2%). Hematologic malignancies and diabetes mellitus were the most common underlying diseases among IFI-confirmed patients. This study observed an increased frequency of invasive candidiasis with non-albicans Candida and other invasive saprophytic fungal infections. The increased rate of invasive candidiasis with non-albicans agents highlights a new perspective in the epidemiology and treatment of invasive fungal infections.

CYP3A inhibitors and impact of these agents on outcomes in patients with acute myeloid leukemia treated with venetoclax plus azacitidine on the VIALE-A study

CYP3A inhibitors and impact of these agents on outcomes in patients with acute myeloid leukemia treated with venetoclax plus azacitidine on the VIALE-A study

The Impact of Antifungal Prophylaxis in Lung Transplant Recipients.

Rationale: Many lung transplant centers prescribe antifungal medications after transplantation to prevent invasive fungal infections (IFIs); however, the effectiveness of antifungal prophylaxis at reducing the risk of all-cause mortality or IFI has not been established.Objectives: We aimed to evaluate the effect of antifungal prophylaxis on all-cause mortality and IFI in lung transplant patients.Methods: Using administrative claims data, we identified adult patients who underwent lung transplantation between January 1, 2005, and December 31, 2018. Propensity score analysis using inverse probability treatment-weighting approach was used to balance the differences in baseline characteristics between those receiving antifungal prophylaxis and those not receiving antifungal prophylaxis. Cox proportional hazards regression was used to compare rates of all-cause mortality and IFI in both groups.Results: We identified 662 lung transplant recipients (LTRs) (387 received prophylaxis and 275 did not). All-cause mortality was significantly lower in those receiving antifungal prophylaxis compared with those not receiving antifungal prophylaxis (event rate per 100 person-years, 8.36 vs. 19.49; hazard ratio, 0.43; 95% confidence interval, 0.26-0.71; P = 0.003). Patients receiving antifungal prophylaxis had a lower rate of IFI compared with those not receiving prophylaxis (event rate per 100 person-years, 14.94 vs. 22.37; hazard ratio, 0.68; 95% confidence interval, 0.44-1.05; P = 0.079), but did not reach statistical significance.Conclusions: In this real-world analysis, antifungal prophylaxis in LTRs was associated with reduced all-cause mortality compared with those not receiving antifungal prophylaxis. Rates of IFI were also lower in those receiving prophylaxis, but this was not statistically significant in our primary analysis.

Incidence of Invasive Fungal Infections in Acute Myeloid Leukemia Without Antifungal Prophylaxis

BackgroundAntifungal prophylaxis during induction for acute myeloid leukemia (AML) varies according to local rates of invasive fungal infections (IFIs). We evaluated fluconazole prophylaxis and no antifungal prophylaxis, as a natural interrupted time-series study to assess survival and infection complications. Patients and MethodsWe identified patients with AML ≥ 18 years old undergoing induction chemotherapy during 2 time periods: period 1, fluconazole prophylaxis from August 1, 2013 to September 30, 2015, and period 2, no prophylaxis from October 1, 2015 to December 31, 2017. The primary outcome was incidence of proven or probable IFI. Secondary outcomes included types of IFIs and 60-day overall survival (OS). IFI was defined by the 2002 European Organization for Research and Treatment of Cancer/Mycoses Study Group Consensus criteria. ResultsOne hundred forty-four patients received induction chemotherapy over the 2 time periods. In the prophylaxis versus no-prophylaxis groups, the rate of proven or probable IFIs was 4 (5%) of 87 versus 12 (21%) of 57 (P = .01). The total number of proven IFIs was 3 (3%) of 87 versus 4 (7%) of 57 (P = .44), whereas probable IFIs were 1 (1%) of 87 versus 8 (14%) of 57 (P < .01). No difference was observed in fungemia. Incidence of IFIs was too low to detect resistance patterns. OS at 60 days was improved in with fluconazole prophylaxis compared with no prophylaxis (hazard ratio, 0.329; 95% confidence interval, 0.12-0.89; P = .028). ConclusionObserved rates of proven or probable IFI were lower in the fluconazole prophylaxis group versus the no-prophylaxis group. Sixty-day OS was higher with fluconazole prophylaxis. Further study is required to evaluate how fluconazole may impart the differences in survival seen in this analysis.

Low Rate of Invasive Fungal Infections During Induction and Consolidation Chemotherapy for Adults with De Novo Acute Myeloid Leukemia Without Anti-mold Prophylaxis: Single-Center 2002-2018 Empirical/Pre-emptive Approach.

Broad-spectrum antifungal prophylaxis is currently considered the standard of care for adults with de novo AML for the prevention of invasive fungal infections (IFIs), especially invasive pulmonary aspergillosis (IPA). Because fluconazole has been used in our center as anti-yeast prophylaxis, we sought to analyze in detail the incidence of IFIs over a 17-year period, as well as their impact on outcome. A standardized protocol of patient management, including serum galactomannan screening and thoracic CT-guided diagnostic-driven antifungal therapy, was used in all patients. A total of 214 consecutive adults with de novo AML who were treated in 3 CETLAM (Grupo Cooperativo para el Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias) protocols from 2002 to 2018 were included. The 90-day incidence of any IFI (including possible cases) was 11% (95% CI 4-15%), most cases occurred during induction chemotherapy (8%, 95% CI 4-12%), and most cases were probable/proven IPA (8%, 95% CI 3-13%). Developing an IFI during induction and consolidation had no impact on 1-year survival. A case-control study with 23 cases of IPA and 69 controls identified induction/re-induction chemotherapy, chronic pulmonary disease and age > 60 years/poor baseline performance status as potential pretreatment risk factors. The current study proves that inpatient induction and consolidation chemotherapy for de novo AML can be given in areas with "a priori" high-burden of airborne molds with fluconazole prophylaxis, while the selective use of anti-mold prophylaxis in patients at very high risk may further reduce the incidence of IFI in this specific clinical scenario.

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.

Risk Factors of Invasive Fungal Infections in Heart and Lung Transplantation: Systematic Review and Meta-Analysis

Invasive fungal infection (IFI) remains one of the most common complications after heart and lung transplantation, which relates to high morbidity and mortality rates. However, risk factors associated with this infection have not been well demonstrated. We performed a comprehensive search using Ovid MEDLINE, Ovid Embase, Cochrane database of systematic reviews, and Cochrane central register of a controlled trial. All case-control and cohort studies evaluated the risk factors of IFI in the adult heart, and lung transplantation was screened. Two researchers reviewed, extracted, and assessed all studies independently. We pooled the estimated effect of each independent factor associated with IFI from the multivariate analysis by using the random-effect model. Seventeen studies were included in the systematic review, and nine studies are eligible for meta-analysis. Rates of IFI among all studies range from 8 to 44%. Independent risk factors of IFI in heart and lung transplantation include anti-thymocyte globulin (ATG) therapy (HR 2.87), cytomegalovirus (CMV) infection (HR 2.53), previous fungal colonization (HR 2.43), single lung transplantation (HR 1.79) and rejection (HR 1.54). Antifungal prophylaxis (HR 0.29) and antifungal pre-emptive therapy (HR 0.20) are preventive factors for IFI. CMV infection, previous fungal colonization, rejection, ATG therapy, and single lung transplantation independently increase the risk of IFI in heart and lung transplant recipients. Antifungal prophylaxis and pre-emptive treatment are both practical preventive approaches in this transplant population.

Survival in the First Year of Heart Transplantation in a Center of a Developing Country, Infection versus Rejection as Causes of Mortality

Despite advances in recent years in the surgical technique, immunosuppression and management of complications, infection continues to be a major cause of morbidity and mortality in heart transplantation. Taking into account the allocation of resources by health systems, habits and socio-economic status of patients in Latin America, it is assumed that there is a higher risk of infection in these countries, but the actual effect of the infection on post-transplant survival, and if adapted prophylaxis schemes for opportunistic microorganisms correspond to the reality of the patients. The objective of this study was to determine the survival in the first year of the patients sometimes heart transplant, evaluate the clinical and microbiological characteristics of the infections according to 3 periods of post-transplant follow-up, and compare the mortality associated with the infection versus rejection in a heart transplant center in Colombia. Observational, analytical, retrospective study in a center of IV level in Medellín, Colombia. They included 133 cardiac transplanted patients between 2012 and 2016, the average age was 47.7 years (SD +/- 12 years), 86% were men and 64.7% the cause of the transplant was idiopathic heart disease. The average ischemia time was 218 min (SD 58.22 min). During the first year, 60 infections were considered (45.11%, 60/133), during the first month 21.05%, 29.9% of the month 2-6 and 14.73% in the month 7-12. The majority of infections were 45% viral, 33% bacterial and 6.3% fungal. During the first year after transplant, 18 patients died (13%), due to 9% infection and rejection (4.51%). In a transplant center in Colombia that does not perform universal prophylaxis for CMV, viruses are the first cause of post-transplant infection. The rate of invasive fungal infection is very low. Infections are the leading cause of post-transplant death, doubling the risk associated with rejection, they must establish effective measures for their control.

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.

Evaluation of target attainment of oral posaconazole suspension in immunocompromised children.

Posaconazole is a broad-spectrum antifungal that is not licensed for use in children <13 years of age. Despite this and by necessity, it is used extensively in paediatric hospitals for prophylaxis of invasive fungal disease. To determine whether initial prophylactic dosing recommendations attain a posaconazole plasma concentration of ≥700 ng/mL in immunocompromised children <13 years of age. We performed a retrospective study of immunocompromised children <13 years of age receiving posaconazole suspension prophylaxis at a starting dose of 5 mg/kg every 8 h for ≥7 days and who had a posaconazole concentration measured after ≥7 days. Posaconazole plasma concentrations and rate of breakthrough infection were recorded. A total of 70 patients were included with a median age of 5 years (range 3 months to 12 years). The mean posaconazole plasma concentration was 783.4 ng/mL (IQR 428.3-980 ng/mL) and the percentage of patients with a posaconazole plasma concentration ≥700ng/mL was 47.9%. Patients who were on a proton pump inhibitor, a histamine H2 antagonist or metoclopramide, had mucositis or were enterally fed had a lower posaconazole plasma concentration compared with patients without these co-administered drugs/mucositis/enteral feeding (542.3 versus 1069.8 ng/mL; P<0.001). The breakthrough invasive fungal infection rate was 4.3% (3/70). The studied 5 mg/kg posaconazole suspension every 8 h resulted in target concentrations in only 47.9% of patients and further studies looking at newer posaconazole formulations are needed.

Single Arm, Single Centre Prospective Study to Assess the Effect of Therapeutic Drug Monitoring (TDM) Based Dosage Adjustment of Posaconazole on the Incidence of Invasive Fungal Infections (IFIs) in AML Patients on Induction Chemotherapy on Posaconazole Prophylaxis

Background: Invasive fungal infections (IFIs) continue to remain a significant cause of morbidity and mortality in AML patients affecting the final outcomes and increasing health care costs. Posaconazole is commonly used as prophylaxis against IFIs due to its broad spectrum of action. The incidence of breakthrough IFIs is particularly high in our setting - one of the several reasons being suboptimal drug levels as we use posaconazole suspension whose absorption is influenced by multiple factors. A breakthrough IFI rate of 51% was seen in a previous study from our centre by Sengar et.al (ASH 2016) and it was seen that sub-optimal drug levels (&lt; 700ng/ml) were associated with a higher rate of breakthrough IFI. This group can benefit from TDM but there are not many studies to guide TDM-based dosing of posaconazole. TDM is expensive and time consuming and the final impact on clinical outcomes has been difficult to estimate. To determine the impact of TDM-based dosing of posaconazole on breakthrough IFI rate, we have undertaken this prospective study. Methods: This prospective, single-arm interventional study included patients 16 years or older undergoing induction chemotherapy for de novo AML with no evidence of IFI at baseline (normal CT chest and normal serum galactomannan ) who have consented for participation (assent and guardian consent were used for those who were &lt; 18 years). Concomitant drugs during induction were recorded everyday. 3 dosing schedules for posaconazole were used based on the drug level : Level 1 - 200mg TDS which was the starting dose in all patients, Level 2 - 200mg QID and Level 3 - 400mg TDS which was the maximum dose. Posaconazole was given with a high fat meal or an aerated drink to improve its absorption. The cut off for day 2 drug level (i.e after atleast 3-4 doses ) was 350ng/ml and the cut-off level at subsequent time points was 700 ng/ml. At any time point, if the patient's drug level was below this cut off, the dose was escalated and a repeat level was sent 5 complete days after the changed dose to allow for re-establishment of the pharmacokinetic equilibrium. A day 2 level was sent for all the patients and the timing of subsequent levels was based on dose escalation. Patients who were continued on the same dose due to adequate drug levels were sampled once in 7 days. QTc interval and liver function tests were monitored for posaconazole toxicity. Posaconazole was continued till the absolute neutrophil count recovered to more than 500 cells/ µl or till the patient was started on an alternative anti-fungal for a proven , possible or probable IFI or empirically at the clinician's discretion for reasons like persistent fever, cough, breathlessness, diarrhoea or vomiting. Relevant imaging and microbiological tests were performed as needed for investigating a suspected IFI. To analyze the primary endpoint chi-square test was used to compare the breakthrough IFI rate with that in a historical cohort from our own centre in which TDM based dosing was not used. Results: A total of 278 samples were collected for drug levels in these 90 patients with a mean of 3.08 (range 1 to 6 samples) per patient . 2 patients were proven to have mixed phenotypic acute leukemia after enrollment and hence were excluded from the analysis. 46 out of 88 patients i.e 52.3% were changed to alternative antifungals. Out of these 46, 13 patients (i.e 28.3%) had proven, probable or possible IFI as per the Revised Definitions of Invasive Fungal Disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) . The change to alternative antifungals in the remaining 33 out of 46 patients (i.e 71.7%) was empirical due to persistent fever spikes, vomiting or diarrhoea. Thus overall 13 out of 88 patients i.e 14.8% had developed a breakthrough IFI. A similar historical cohort from our own institute, without the TDM based dosing of posaconazole, had a breakthrough IFI rate of 52%. The difference between the breakthrough IFI rate of these 2 cohorts was 37.2% which was statistically significant (p &lt; 0.0001, 95% CI 27.9% to 52.4%). 1 patient had developed grade 3 transaminitis and 1 patient had grade 3 rise in total bilirubin while on posaconazole. Conclusion: TDM-based dose escalation of prophylactic posaconazole in AML patients during induction leads to a significant reduction in the breakthrough IFI rates. Disclosures No relevant conflicts of interest to declare.

The D-index is not correlated with invasive fungal infection during the early-post engraftment phase among allogeneic hematopoietic stem cell transplant recipients.

The D-index assesses neutropenia dynamics. Prolonged neutropenia is a major risk for invasive fungal infection (IFI); we hypothesized that D-index is predictive of IFI risk. We retrospectively reviewed 789 adults who underwent allogeneic hematopoietic transplant (HSCT) from 1/1/2005 to 9/30/2015. Medical records were reviewed from transplant (D0) through Day 100. The D-index was calculated as area over the neutrophil curve until engraftment. 714 patients were included for analysis. Sixteen (2%) developed probable (11) or proven (5) IFI. Median time to IFI was 40days (range 8-98) after HSCT. Groups with and without IFI did not differ significantly in duration of mild or profound neutropenia. Median D-index of those with IFI was 4293daysneutrophil/µl compared to 3590daysneutrophil/µl for those without IFI (P = 0.17). Patients who were neutropenic on D0 showed higher rates of IFI than those who were not (10/123 [8%] vs 6/591 [1%]; P < 0.001). Only 2% developed IFI, likely due to mold-active antifungal prophylaxis. The D-index was not significantly higher in those with IFI. Duration of profound neutropenia and neutropenia at D0 may be better markers for IFI among HSCT recipients during the first 30 and 100days after transplant.

1709. Epidemiology of Invasive Fungal Infection (IFI) after Severe Influenza Requiring Intensive Care Unit (ICU) Admission: 10-Year Experience at a Tertiary Care Center in the United States

BackgroundDespite increasing recognition of aspergillosis complicating severe influenza and its associated high fatality in Europe, incidence and features of the disease in the United States are unknown.MethodsWe reviewed all influenza cases requiring ICU admission from 2009 to 2019 at our center.Results262 patients with influenza required ICU admission. 4% (10) developed IFI at median 2d after influenza diagnosis. 80% (8/10) of patients with IFI were infected with influenza A vs. 88% (221/252) without IFI. 20% were on steroids at the time of IFI diagnosis. 70% of IFI required mechanical ventilation. Types of IFI were pneumonia (70%, 6 Aspergillus and 1 Wangiella), endobronchial IFI (20%, 1 each with Aspergillus and Lictheimia), and Coccidioides fungemia (10%). 4% (10) of patients were fungal colonized, but did not have IFI (5 A. fumigatus, 1 A. terreus, 4 Penicillium). CT findings of IFI included nodules (4), cavitation (3), and ground-glass opacities (2). Serum galactomannan (GM) was positive in 3 (43%). Median time to antifungal therapy (AF) was 2 days. Triazoles were prescribed to all 7 patients with aspergillosis. Posaconazole and amphotericin B were AF for patients with Wangiellaand Lichteimia, respectively. Patients with C. immitis fungemia died before AF. Median duration of AF was 60 days among survivors. Patients with IFI required acute hemodialysis more frequently than colonized patients (60% vs. 0%, P = 0.01). 30-day mortality was 60% (6/10) and 20% 92/10) in patients with IFI and colonization, respectively (P = 0.2). Patients with IFI had significantly higher in-hospital and 60-day mortality than those without IFI (Fig 1, P = 0.009).ConclusionOur rate of post-influenza IFI (4%) was lower than reported in Europe (~15%), which might stem from a lack of systematic BAL GM testing at our center, over-reliance on GM to make diagnoses in Europe, and/or differences in pt populations and clinical practices in treating severe influenza. IFI and fungal colonization rates were similar at our center, highlighting the importance of using well-defined criteria to define disease. Given the high mortality of post-influenza IFI, priority should be given to defining risk factors that might identify patients for targeted AF prophylaxis. In using AF, it is important to recognize that Aspergillus is not the only cause of IFI. Disclosures All authors: No reported disclosures.

1701. Differences in Diagnostic Performance of β-d-Glucan Testing in Patients with Varying Degrees of Susceptibility to Invasive Fungal Infections

BackgroundUsefulness of β-d-glucan (BDG) testing in high-risk patients for invasive fungal infection (IFI) diagnosis has been well demonstrated. However, data on its usefulness in patients without risk factors are limited. We evaluated differences in the diagnostic performance of BDG testing in patients with varying degrees of susceptibility to IFI.MethodsFrom April 2017 to May 2018, all consecutive patients (≥18year-old) who were performed BDG testing (Beijing Gold Mountainriver Tech) were enrolled. Patients were classified into three groups: Group A for patients with host factors defined by 2008 European Organization for Research and Treatment of Cancer-Mycoses Study Group diagnostic (EORTC-MSG) criteria, Group B for patients with malignancy receiving recent chemotherapy within 1 month without host factors, and Group C for others. Cases of proven and probable IFI defined by EORTC-MSG criteria, Pneumocystis pneumonia and all fungemia were considered as true IFIs. Sensitivity, specificity, positive and negative predictive value (PPV and NPV) were calculated with a cut-off value for positivity ≥80 pg/mL.ResultsAmong 473 eligible patients, 190, 142, and 141 patients were classified into group A, B, and C, respectively. Rates of true IFI were significantly different in each group (57/190, 19/142, and 10/141 in each group, P < 0.001). Sensitivities were 0.83, 0.68, and 0.70 and specificities were 0.62, 0.59, and 0.63 in group A, B, and C, respectively. PPVs were considerably different among three groups (PPV for 0.48, 0.20, and 0.12; NPV for 0.89, 0.92 and 0.97 in each group, respectively).ConclusionThe BDG test is a useful assay for IFI diagnosis; however, the clinical interpretation should be different by patient risks. Whereas BDG testing could be considered as a tool for predicting IFI in high-risk patients, it only could be a tool for excluding IFI in patient without risk factors.Disclosures All authors: No reported disclosures.

Clinical experience with new formulation SUBA®-itraconazole for prophylaxis in patients undergoing stem cell transplantation or treatment for haematological malignancies.

SUper BioAvailability-itraconazole (SUBA®-itraconazole) was introduced into Australia in April 2014 as a substitute for standard itraconazole on the basis of improved bioavailability, tolerance and interpatient variability. Shortly after its introduction, our centre converted to the novel formulation for mould prophylaxis in patients undergoing allogeneic HSCT, autologous HSCT or treatment for haematological malignancies with an intermediate/high risk of invasive fungal infection (IFI). A single-institution, investigator-initiated retrospective cohort study was conducted between June 2016 and April 2018 to assess therapeutic drug concentrations, safety and tolerability of a standard prophylactic dose of SUBA®-itraconazole. A total of 74 patients were assessed across 98 admissions with 178 measured itraconazole trough concentrations. The median duration of prophylaxis was 15.5 (1-59) days. No significant correlation was identified between trough concentrations and patient demographics including gender and weight. Drug concentrations were reduced by gastric acid suppression and diarrhoea. Therapeutic itraconazole trough concentrations (≥0.5 mg/L) were achieved at a median of 7 (95% CI = 6-8) days, with 87% of patients achieving therapeutic concentrations at day 14 (expected steady-state). One (1%) proven/probable IFI and 5 (5%) possible breakthrough IFIs were identified. Although adverse events were experienced by 42% of the cohort, only a single event was directly attributable to SUBA®-itraconazole, resulting in change of prophylactic agent. SUBA®-itraconazole achieved rapid therapeutic trough concentrations, was associated with low rates of IFI and was well tolerated in the study population. This formulation should be considered a realistic and safe first-line agent for the prevention of IFIs in those undergoing HSCT and intermediate/high-risk therapy for haematological malignancies.

Epidemiology and treatment approaches in management of invasive fungal infections in hematological malignancies: Results from a single-centre study.

Invasive fungal infections (IFIs) are a leading cause of morbidity and attributable mortality in oncohematologic patients. Timely diagnosis is essential but challenging. Herein we retrospectively describe 221 cases of antifungal treatments (AFT) administered in a monocentric real-life cohort of hematological malignancies. Between January 2010 and July 2017, 196 oncohematologic patients were treated with AFT at our Hematology Department. Diagnosis of IFIs was carried out according to EORTC/MSG-2008 guidelines.The most represented disease was acute myeloid leukemia (104 patients). Median age was 61 years; at fever onset 177 (80%) patients had a neutrophil count<0.5x109/L. Twenty-nine (13%) patients were receiving antifungal prophylaxis (26 posaconazole, 2 fluconazole, 1 itraconazole). The incidence of AFT was 13%. Serum galactomannan antigen (GM) was positive in 20% of the tested cases, while 85% of the patients had a CT scan suggestive for IFI. Twenty-one percent of these cases had a GM positive. Sixty-five out of 196 patients (33%) showed positive culture results, in particular Candida spp. were identified in 45 isolates, while Aspergillus spp. in 16 cases. Fourteen patients presented multiple positivity. Twenty-two (10%) cases were classified as proven IFIs, 61 (28%) as probable and 81 (37%) as possible, but 57 (26%) cases could not be classified. Fifty-nine percent of the patients received single agent AFT, 37% sequential AFT, 8% a combination regimen. Liposomal-amphotericin-B was the most used AFT. IFIs attributable mortality was 20%. This epidemiologic survey underlined a persistent significant use of AFT and a high mortality rate of IFIs. We suggest that further powerful diagnostic approaches should be investigated to improve the diagnostic accuracy and potential therapeutic implication.

Invasive Fungal Infections While on Voriconazole, Liposomal Amphotericin B, or Micafungin for Antifungal Prophylaxis in Pediatric Stem Cell Transplant Patients.

This study aimed to report the incidence of invasive fungal infections (IFIs) in pediatric hematopoietic stem cell transplant (HSCT) patients who received voriconazole, liposomal amphotericin B (L-AMB), or micafungin for primary antifungal prophylaxis (PAP). Using data retrospectively collected from institution's electronic records, this study analyzed the incidence of IFIs in pediatric HSCT patients between November 2012 and November 2016. A total of 103 patients were screened. Of the 84 patients who met inclusion criteria, 76.2%, 29.8%, and 19% patients received voriconazole, L-AMB, and micafungin, respectively. The incidence of overall IFIs was 2.08 per 1000 prophylaxis days. There were 2 mold infections identified in 2 patients. Among 3 antifungal agents, the rates of IFIs were 2.67 per 1000 prophylaxis days in L-AMB group, 2.08 per 1000 prophylaxis days in micafungin group, and 1.17 per 1000 prophylaxis days in voriconazole group. Patients who received L-AMB or micafungin had higher rates of IFIs than those who received voriconazole for PAP.

Epidemiology of invasive fungal infections in lung transplant recipients in Western Australia.

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

Antifungal Prophylaxis in Lung Transplant Recipients: A Network Meta-Analysis

Purpose Invasive fungal infections (IFIs), in particular invasive aspergillosis cause significant morbidity and mortality in lung transplant recipients (LTRs). Various antifungal agents are used either for universal or pre-emptive/ targeted prophylaxis. However, as there is a lack of randomized control studies, the best agent for prophylaxis/ pre-emptive treatment remains unknown. Methods We identified studies comparing regimens for antifungal prophylaxis in LTRs. We ran a frequentist network (Figure 1). We checked for inconsistency in the network. We could not reject the null hypothesis that the model was consistent between the direct and indirect estimates. Therefore, the model was run under the consistency assumption. Results Ten observational studies were included, which reported comparisons of liposomal amphotericin B (L-AmB), itraconazole, voriconazole, isavuconazole and no treatment. Amphotericin B was the best agent for reducing the rate of IFI in the network meta-analysis, followed by isavuconazole and voriconazole respectively (Table 1). Conclusion Our network analysis suggests that L-AmB and isavuconazole are the preferred antifungal agents for reducing IFI in LTRs.