Episodes Of Invasive Fungal Infection Research Articles

Usefulness of 18F‐FDG PET‐CT for the management of invasive fungal infections: A retrospective cohort from a tertiary university hospital

AbstractBackground18F‐FDG PET‐CT is a potentially useful technique to help manage invasive fungal infection (IFI), but information on this topic is scarce.ObjectivesTo describe our experience using 18F‐FDG PET‐CT for IFI management.Patients/MethodsRetrospective cohort of IFI episodes in a university hospital from 2018 to 2023 with a18F‐FDG PET‐CT performed during the episode. We analysed its impact on IFI management compared to conventional imaging.ResultsThirty‐five patients diagnosed with 36 episodes of IFI (52.8% moulds, 44.4% yeasts and 2.8% Pneumocystis) underwent 55 18F‐FDG PET‐CT. 74.3% were immunocompromised, including 45.7% solid organ transplant recipients. Indications for 18F‐FDG PET‐CT were diagnostic (10.9%), staging (47.3%) and follow‐up (41.8%). Altogether 18F‐FDG PET‐CT added value to IFI management in 50.9% episodes. In 26 patients who had both staging 18F‐FDG PET‐CT and conventional imaging, sites of IFI dissemination were detected in 53.8% and 19.2%, respectively. Staging 18F‐FDG PET‐CT unveiled occult sites in 34.6%, uncovering unknown dissemination in 19.2%. In the evaluation of endocarditis in patients with fungemia, it contributed in at least 38.5%.Follow‐up 18F‐FDG PET‐CTs had an added value in 47.8% episodes. They were allowed to de‐escalate antifungal therapy in 26.1%. There were discordant findings between 18F‐FDG PET‐CT and CT follow‐up in 40% cases.ConclusionsOverall, 18F‐FDG PET‐CT added value to IFI management in more than 50% of the episodes. It increased the diagnosis of occult sites, unveiled disseminated disease missed out by conventional imaging, and contributed to diagnose or rule out endocarditis in fungemia. Follow‐up 18F‐FDG PET‐CT helped adjust the treatment duration and deserves further study.

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.

Epidemiology and Factors Associated with Treatment Success of Invasive Fungal Infections Among Newly Hematologic Malignancy Patients Receiving Chemotherapy or Hematopoietic Stem Cell Transplant in Thailand.

Invasive fungal infection (IFI) causes disability/death in patients with hematologic malignancy (HM) receiving chemotherapy or hematopoietic stem cell transplant (HSCT). There is limited epidemiological data, treatment outcomes, and factors associated with IFI treatment success in Thailand. This study aimed to identify factors associated with IFI treatment success among new HM patients receiving chemotherapy or HSCT, determine IFI incidence among HM patients receiving chemotherapy or HSCT, and the IFI incidence of a breakthrough in patients receiving primary antifungal prophylaxis, and identify antifungal drugs susceptibility. This study reviewed the charts of patients aged ≥ 15 years with newly HM who received chemotherapy or HSCT between January 2016 and June 2021 at King Chulalongkorn Memorial Hospital, Bangkok, Thailand. The 2020 EORTC/MSG criteria were used to diagnose IFI. IFI treatment success factors were evaluated using logistic regression. Ninety-two patients with 107 episodes of IFI met the inclusion criteria. IFI incidence on proven and probable cases among newly HM patients receiving chemotherapy or HSCT was 7%. Most infections (38.3%) occurred during the induction-phase chemotherapy. Aspergillosis (35.5%) was the commonest IFI, followed by candidiasis (11.2%), Pneumocystis jirovecii pneumonia (8.4%), mucormycosis (3.7%), and others, respectively. The 12-week IFI treatment success rate was 67.3%. It was associated with age < 60 years, absence of coinfection, and the receipt of appropriate empirical therapy on the first day of IFI diagnosis. The incidence of breakthrough IFI from proven and probable cases in patients receiving primary antifungal prophylaxis was 6.1%. Most fungal pathogen isolates were still highly susceptible to antifungal drugs. The IFI treatment success in patients with HM or HSCT in our study was high. Close monitoring of coinfected patients aged ≥ 60 is recommended. Appropriate antifungal drugs are essential for clinical outcomes.

Relationships Between Invasive Fungal Infection and Rejection Post Heart Transplantation

<h3>Purpose</h3> Rejection and infections are leading threats in patients undergoing heart transplantation (HTx). While invasive fungal infections (IFI) have decreased due to antifungal prophylaxis and optimised immunosuppressant therapy, IFI remains the most threatening infection after HTx. We performed a single-centre retrospective study on the epidemiology of IFI post HTx. <h3>Methods</h3> All HTx were reviewed from January 2013-December 2020. In accordance with Infectious Disease Society of America (IDSA) guidelines, we looked at IFI seeking histo/cytological, molecular and microbiological findings for aspergillosis; real time PCR for <i>Pneumocystis jirovecii</i> pneumonia (PJP); positive cultures in sterile sites for candidiasis. We compared these findings with the occurrence of ≥ 2R cellular (ACR) and ≥ pAMR1 humoral (AMR) rejections, defined by positive endomyocardial biopsies (EMB), as stated by the International Society for Heart and Lung Transplantation (ISHLT). Appropriate parametric and non-parametric tests were used to analyse the data. <h3>Results</h3> A total of 115 patients underwent HTx from January 2013-December 2020. Median age was 57 years (IQR= 21,50), 75 (65%) male and 34 (29,6% female. Overall, 64 (55%) received a diagnosis of rejection, 57 (89%) ACR, 29 (45%) AMR and 22 (34%) had both types of rejection, occurred a median of 29 days (IQR= 62) after transplant. 15 (23%) of them had at least one episode of IFI, while 4 patients had IFI without rejection (7,8%) (p= 0,04; Fisher), totalling 26 episodes in all. The IFI episodes occurred a median of 45 days (IQR= 214) after the first episode of rejection and a median of 87 days (IQR= 242) after the transplant (p= 0,08). The most common infection was Aspergillosis with 9 episodes (60%); candidiasis was diagnosed 6 times (40%). There were 2 cases of mucormycosis (13%) and 1 case of PJP (7%). <h3>Conclusion</h3> The risk of developing IFI post HTx is considered low. In our single-centre study IFI occurred in almost a quarter of patients following a rejection episode, with aspergillosis being the most common infection. These findings support the consideration of antifungal prophylaxis after treated rejection episodes.

Epidemiology and Antifungal Susceptibility Patterns of Invasive Fungal Infections (IFIs) in India: A Prospective Observational Study.

The epidemiology of invasive fungal infections (IFI) is ever evolving. The aim of the present study was to analyze the clinical, microbiological, susceptibility, and outcome data of IFI in Indian patients to identify determinants of infection and 30-day mortality. Proven and probable/putative IFI (defined according to modified European Organization for Research and Treatment of Cancer/Mycoses Study Group and AspICU criteria) from April 2017 to December 2018 were evaluated in a prospective observational study. All recruited patients were antifungal naïve (n = 3300). There were 253 episodes of IFI (7.6%) with 134 (52.9%) proven and 119 (47%) probable/putative infections. There were four major clusters of infection: invasive candidiasis (IC) (n = 53, 20.9%), cryptococcosis (n = 34, 13.4%), invasive aspergillosis (IA) (n = 103, 40.7%), and mucormycosis (n = 62, 24.5%). The significant risk factors were high particulate efficiency air (HEPA) room admission, ICU admission, prolonged exposure to corticosteroids, diabetes mellitus, chronic liver disease (CLD), acquired immunodeficiency syndrome (AIDS), coronary arterial disease (CAD), trauma, and multiorgan involvement (p < 0.5; odds ratio: >1). The all-cause 30-day mortality was 43.4% (n = 110). It varied by fungal group: 52.8% (28/53) in IC, 58.8% (20/34) in cryptococcosis, 39.8% (41/103) in IA, and 33.9% (21/62) in mucormycosis. HEPA room, ICU admission for IC; HEPA rooms, diabetes mellitus for cryptococcosis; hematological malignancies, chronic kidney disease (CKD), sepsis, galactomannan antigen index value ≥1 for IA and nodules; and ground glass opacities on radiology for mucormycosis were significant predictors of death (odds ratio >1). High minimum inhibitory concentration (MIC) values for azoles were observed in C. albicans, C. parapsilosis, C. glabrata, A. fumigatus, A. flavus, R. arrhizus, R. microsporus, and M. circinelloides. For echinocandin, high MIC values were seen in C. tropicalis, C. guillermondii, C. glabrata, and A. fumigatus. This study highlights the shift in epidemiology and also raises concern of high MICs to azoles among our isolates. It warrants regular surveillance, which can provide the local clinically correlated microbiological data to clinicians and which might aid in guiding patient treatment.

78. Non-Invasive Prediction of Invasive Fungal Infection by Plasma-Based Microbial Cell-Free DNA Next-Generation Sequencing (mcfDNA NGS) in Pediatric Patients with Relapsed or Refractory Leukemia

BackgroundDiagnosis of invasive fungal infections (IFIs), a life-threatening complication of cancer therapy or hematopoietic cell transplantation (HCT) can be challenging, and IFI has poor outcomes. Prediction or early non-invasive diagnosis of IFI in high-risk hosts before onset of symptoms could reduce morbidity and mortality. Because non-invasive plasma mcfDNA NGS can detect invasive fungal infections, and may predict bloodstream infections in immunocompromised patients, we hypothesized that mcfDNA NGS might also predict invasive fungal infection before clinical presentation.MethodsIn a prospective study, serial remnant plasma samples were collected from pediatric patients undergoing treatment for relapsed or refractory leukemia. IFI events were classified according to EORTC criteria by 2 independent experts, and episodes empirically treated for suspected IFI, but not meeting ‘possible’ criteria were classified as ‘suspected’. All samples collected within 30 days before clinical diagnosis of non-fungemic IFI were tested for fungal DNA by mcfDNA NGS using a research-use only assay by Karius, Inc. optimized for fungi; because of overlapping clinical syndromes, non-fungal DNA was not considered in this study.ResultsThere were 15 episodes of suspected IFI in 14 participants with ≥1 sample available from either diagnostic (within 1 day of diagnosis) or predictive (2 to 30 days prior to diagnosis) periods (5 “suspected”, and 4 probable and 6 proven by EORTC definitions).Of 10 probable or proven IFIs, 6 (60%) had a relevant fungal pathogen identified mcfDNA NGS at diagnosis. In each of these cases the fungal DNA was also detectable prior to clinical onset of IFI (Range 2 to 41 days; Figure 1). In an additional case, manual review of sequence data identified the fungal DNA at diagnosis and during the prior month. Of 5 “suspected” IFI episodes, all were determined by expert review as not representing fungal infection; fungal DNA was identified by mcfDNA NGS in 2/54 (3.7%) of samples from these episodes.Table 1. Characteristics of Invasive Fungal Infections ConclusionmcfDNA NGS can identify fungal pathogen DNA before clinical onset of IFI, so might predict IFI in immunocompromised hosts, and may help differentiate fungal infection from other etiologies of lung nodules or infiltrates.Disclosures Joshua Wolf, MBBS, PhD, FRACP, Karius Inc. (Research Grant or Support) Joshua Wolf, MBBS, PhD, FRACP, Nothing to disclose Radha Duttagupta, PhD, Karius inc (Employee) Lily Blair, PhD, Karius Inc. (Employee) Asim A. Ahmed, MD, Karius, Inc. (Employee)

Invasive Fungal Infections in Children with Leukemia: Clinical Features and Prognosis

Objective:The incidence of invasive fungal infections (IFIs) has increased due to intensive chemotherapy in childhood leukemia. The aim of this study was to evaluate the incidence, risk factors, causative pathogens, and impact on survival of IFIs among pediatric leukemia patients.Materials and Methods:The hospital records of 307 children with acute lymphoblastic leukemia (ALL, n=238), acute myeloid leukemia (AML, n=51), and relapsed leukemia (n=18) between January 2010 and December 2015 were retrospectively evaluated.Results:A total of 1213 febrile neutropenia episodes were recorded and 127 (10.4%) of them were related to an IFI. Of 307 children, 121 (39.4%) developed IFIs. The mean age was significantly older in the IFI group compared to children without IFIs (p<0.001). IFIs were defined as possible, probable, and proven in 73.2%, 11.9%, and 14.9% of the attacks, respectively. Invasive aspergillosis (81.9%) was the most frequent infection, followed by invasive candidiasis (13.4%) and rare fungal diseases (4.8%). The majority of IFI attacks in both ALL and AML occurred during the induction phase. In total, the death rate was 24% and the IFI-related mortality rate was 18%. The mortality rate among children with IFIs was found to be significantly higher than that of children without IFIs (p<0.001). Overall and event-free survival rates at 5 years were also found to be significantly lower in the IFI group (p<0.001). Relapse (odds ratio: 8.49) was the most effective risk factor for mortality, followed by developing an IFI episode (odds ratio: 3.2) and AML (odds ratio: 2.33) according to multivariate regression analysis.Conclusion:Our data showed that IFIs were more common in older children. Although proven and probable IFI episodes were more frequently diagnosed in cases of relapse and AML, children with ALL and AML had similar frequencies of experiencing at least one episode of IFI. Rare fungal diseases were also identified as a major problem. Despite success in treatment, IFIs increased the rate of mortality in children with acute leukemia.

Incidence of invasive fungal infection in acute lymphoblastic and acute myelogenous leukemia in the era of antimold prophylaxis

The incidence of invasive fungal infection (IFI) in patients with acute myeloid leukemia (AML) has decreased with the introduction of antimold prophylaxis. Although acute lymphoblastic leukemia (ALL) has a lower risk of IFI than does AML, the incidences of IFI in both AML and ALL in the era of antimold prophylaxis should be re-evaluated. We analyzed adults with AML or ALL who had undergone induction, re-induction, or consolidation chemotherapy from January 2017 to December 2019 at Seoul National University Hospital. Their clinical characteristics during each chemotherapy episode were reviewed, and cases with proven or probable diagnoses were regarded as positive for IFI. Of 552 episodes (393 in AML and 159 in ALL), 40 (7.2%) were IFI events. Of the IFI episodes, 8.1% (12/148) and 5.9% (13/220) (P = 0.856) occurred in cases of ALL without antimold prophylaxis and AML with antimold prophylaxis, respectively. After adjusting for clinical factors, a lack of antimold prophylaxis (adjusted odds ratio [aOR], 3.52; 95% confidence interval [CI], 1.35–9.22; P = 0.010) and a longer duration of neutropenia (per one day, aOR, 1.02; 95% CI, 1.01–1.04; P = 0.001) were independently associated with IFI. In conclusion, the incidence of IFI in ALL without antimold prophylaxis was not lower than that in AML. A lack of antimold prophylaxis and prolonged neutropenia were independent risk factors for IFI. Clinicians should be on guard for detecting IFI in patients with ALL, especially those with risk factors.

Effectiveness and antimicrobial susceptibility profiles during primary antimicrobial prophylaxis for pediatric acute myeloid leukemia

Limited data are available on antimicrobials exposure and microbiology evolution in pediatric acute myeloid leukemia (AML) patients underwent antimicrobials prophylaxis. To assess the effectiveness of antimicrobials prophylaxis, antibiotic susceptibilities of bacteria, and exposure of antimicrobials during intensive chemotherapy for AML patients, 90 consecutive de novo AML patients aged 0–18 years between January 1, 1997 and March 31, 2018 were enrolled. Vancomycin, ciprofloxacin and voriconazole prophylaxis was administered from January 1, 2010. During the preprophylaxis period, January 1997 to December 2009, 62 patients experienced a total of 87 episodes of bloodstream infection (BSI) and 17 episodes of invasive fungal infection (IFI) among 502 courses of chemotherapy. In contrast, 16 episodes of BSI occurred and no IFIs were reported to occur in 28 patients who received 247 courses of chemotherapy in the prophylaxis period. Patients who received antimicrobial prophylaxis had a significant reduction of BSI, IFI, and febrile neutropenia in comparison with patients without prophylaxis. Exposure to amikacin, carbapenem, amphotericin B was reduced in the prophylaxis period. Imipenem susceptibility of Enterobacter cloacae as well as vancomycin susceptibility of Enterococcus species were reduced in the prophylaxis period. At the time of the last follow up, patients with prophylaxis had a better subsequent 5-year overall survival rate than those without prophylaxis. Prophylactic antimicrobials administration in children with AML who undergo chemotherapy can significantly reduce the rates of life-threatening infection, exposure to antimicrobials, and might result in a better outcome.

Voriconazole Use in Children: Therapeutic Drug Monitoring and Control of Inflammation as Key Points for Optimal Treatment.

Voriconazole plasma concentrations (PC) are highly variable, particularly in children. Dose recommendations in 2–12-year-old patients changed in 2012. Little data on therapeutic drug monitoring (TDM) after these new recommendations are available. We aimed to evaluate voriconazole monitoring in children with invasive fungal infection (IFI) after implementation of new dosages and its relationship with safety and effectiveness. A prospective, observational study, including children aged 2–12 years, was conducted. TDM was performed weekly and doses were changed according to an in-house protocol. Effectiveness, adverse events, and factors influencing PC were analysed. A total of 229 PC from 28 IFI episodes were obtained. New dosing led to a higher rate of adequate PC compared to previous studies; still, 35.8% were outside the therapeutic range. In patients aged < 8 years, doses to achieve therapeutic levels were higher than recommended. Severe hypoalbuminemia and markedly elevated C-reactive protein were related to inadequate PC. Therapeutic PC were associated with drug effectiveness and safety. Higher doses in younger patients and a dose adjustment protocol based on TDM should be considered. Voriconazole PC variability has decreased with current updated recommendations, but it remains high and is influenced by inflammatory status. Additional efforts to control inflammation in children with IFI should be encouraged.

Epidemiology and risk of invasive fungal infections in systemic lupus erythematosus: a nationwide population-based cohort study.

Introduction:Infections are a leading cause of mortality in patients with systemic lupus erythematosus (SLE). Among various infections, invasive fungal infections (IFIs) have a particularly high mortality rate; however, studies examining IFIs in patients with SLE are limited.Methods:Patients diagnosed as having SLE between 1997 and 2012 were enrolled from Taiwan’s National Health Insurance Research Database along with age- and sex-matched non-SLE controls at a ratio of 1:10. IFIs were identified based on International Classification of Diseases, Ninth Revision, Clinical Modification codes and validated by the prescriptions of systemic antifungal agents. The incidence rate (IR), incidence rate ratio (IRR), and all-cause mortality rate of IFIs and its subtypes were analyzed. A Cox multivariate regression model with time-dependent covariates was applied to analyze independent risk factors for IFIs.Results:A total of 24,541 patients with SLE and 245,410 non-SLE controls were included. We observed 445 IFI episodes in the SLE cohort, with an all-cause mortality rate of 26.7%. Candida spp. (52.8%) was the most common pathogen, followed by Cryptococcus spp. (18.2%) and Aspergillus spp. (18.2%). The IR of IFIs in the SLE cohort was 20.83 per 10,000 person-years, with an IRR of 11.1 [95% confidence interval (CI): 9.8–12.6] relative to the non-SLE controls. Juvenile patients with SLE aged ⩽18 years had the highest IRR of 47.2 (95% CI: 26.9–86.8). Intravenous steroid therapy administered within 60 days (hazard ratio: 29.11, 95% CI: 23.30–36.37) was the most critical risk factor for overall IFIs and each of the three major fungal pathogens. Distinct risk factors were found among different IFI subtypes.Conclusion:Patients with SLE had a higher risk of IFIs, especially juvenile patients. Intravenous steroid therapy is the most critical risk factor for IFIs. This study provides crucial information for the risk stratification of IFIs in SLE.Plain Language SummariesPatients with systemic lupus erythematosus and physicians treating this patient group should be aware of the risk of invasive fungal infections.Invasive fungal infections (IFIs) are a severe complication with a high mortality rate among patients with systemic lupus erythematosus (SLE); however, studies on this topic are scant. We performed a nationwide population-based study in Taiwan to estimate the incidence and mortality of and risk factors for IFIs. We found an incidence rate of 20.83 per 10,000 person-years for IFIs, with a mortality rate of 26.7%. Juvenile patients aged ⩽18 years had the highest relative risk of IFIs. Although candidiasis was the most common IFI, cryptococcosis and aspergillosis should be concerned in juvenile patients as well. Intravenous steroid therapy was the most critical risk factor for all IFIs, and different immunosuppressive agents posed different risks in patients for acquiring certain fungal pathogens.Our findings provide pivotal epidemiological information and indicate risk factors for IFIs in patients with SLE. Age and exposure to specific immunosuppressants and steroids might help predict the risk of IFIs. Because the manifestation of these infections is sometimes indistinguishable from a lupus flare, physicians should be aware of this fatal complication, especially when patients are not responsive to immunosuppressive therapy. Early recognition, implication of diagnostic tools, and empirical antimicrobial agents can be the key to treating patients with IFIs. Additional studies are required to develop a risk management program for patients with SLE.

Safety and Efficacy of Intermittent High-Dose Liposomal Amphotericin B Antifungal Prophylaxis in Haemato-Oncology: An Eight-Year Single-Centre Experience and Review of the Literature.

Triazoles remain first-line agents for antifungal prophylaxis in high-risk haemato-oncology patients, but their use is increasingly contraindicated due to drug–drug interactions and additive toxicities with novel treatments. In this retrospective, single-centre, observational study, we present our eight-year experience of antifungal prophylaxis using intermittent high-dose liposomal Amphotericin B (L-AmB). All adults identified through our Antifungal Stewardship Programme as receiving L-AmB prophylaxis at 7.5 mg/kg once-weekly between February 2012 and January 2020 were included. Adverse reactions, including infusion reactions, electrolyte loss, and nephrotoxicity, were recorded. ‘Breakthrough’ invasive fungal infection (IFI) occurring within four weeks of L-AmB was classified using 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) criteria. Moreover, 114 courses of intermittent high-dose L-AmB prophylaxis administered to 92 unique patients were analysed. Hypokalaemia was the most common grade 3–4 adverse event, with 26 (23%) courses. Grade 3 nephrotoxicity occurred in 8 (7%) and reversed in all six patients surviving to 90 days. There were two (1.8%) episodes of breakthrough IFI, one ‘probable’ and one ‘possible’. In this study, the largest evaluation of intermittent high-dose L-AmB prophylaxis conducted to date, toxicity was manageable and reversible and breakthrough IFI was rare. L-AmB prophylaxis represents a viable alternative for patients with a contraindication to triazoles.

1741. Invasive Fungal Infections in Patients with Multiple Myeloma in the Era of Novel Therapies

BackgroundRapid advances in multiple myeloma (MM) therapy have led to improved survival, yet the impact of novel agents on the risk of invasive fungal infection (IFI) is largely unknown. We aim to describe the epidemiology of IFIs in MM patients in the current era of chemotherapy.MethodsWe performed a retrospective chart review of MM patients at Mount Sinai Hospital in New York, NY who entered care between December 2009 and October 2016 and had proven or probable IFI between January 2011 and October 2017. Probable and proven IFIs were defined by revised EORTC/MSG criteria. Descriptive statistics are reported as median (range). We evaluated factors associated with mortality by univariate analysis using Fisher’s exact and Mann–Whitney U tests.Results2,960 MM patients entered care during the study period. We identified 30 episodes of IFI among 29 patients. Median age was 59 (42–80) years and 21 (70%) were men. IFI occurred at a median of 3.7 (0.3–18) years from MM diagnosis. At the time of IFI diagnosis, patients had received a median of 4 (1–12) lines of chemotherapy, 18 (60%) had undergone autologous stem cell transplant (ASCT), and 21 (70%) had progressive disease status. Agents received immediately prior to IFI were immunomodulators (n = 14), proteasome inhibitors (n = 14), conventional chemotherapy (n = 11), monoclonal antibodies (n = 6), checkpoint inhibitors (n = 3) and other (n = 3). Twenty-two (73%) patients received corticosteroids in the prior 30 days. Neutropenia and lymphopenia were present in 12 (40%) and 13 (43%) patients, respectively. There were 9 proven and 21 probable IFIs: invasive aspergillosis (n = 19), candidemia (n = 5), cryptococcosis (n = 3), talaromycosis (n = 1), mucormycosis (n = 1) and other (n = 2). Bacterial and viral respiratory co-infections occurred in 7 and 4 patients, respectively. Eight (27%) patients required ICU admission and 9 (30%) died within 30 days of IFI diagnosis. In univariate analysis, number of lines of chemotherapy (P = 0.05), progressive disease status (P = 0.03), and prior ASCT (P = 0.004) were associated with 30-day mortality.ConclusionIFIs are uncommon in MM patients receiving newer agents but are associated with significant morbidity and mortality. Further study is needed to identify high-risk subgroups that may benefit from antifungal prophylaxis or increased surveillance.Disclosures All authors: No reported disclosures.

1739. Epidemiology of Invasive Fungal Infections in Allogenic Hematopoietic Stem Cell Transplant Recipients in Utah

BackgroundInvasive fungal infections are a leading cause of death in allo-HSCT (allogenic hematopoietic stem cell transplant) recipients. We describe the epidemiology of IFIs (invasive fungal infections) in allo-HSCT recipients at a single institution in Salt Lake City, Utah between 2006 and 2015.MethodsWe searched all encounters in the Intermountain Healthcare electronic medical record from 2006 to 2015 for clinical data associated with IFIs in allo-HSCT recipients. EORTC-MSG definitions were applied to categorize IFI as proven, probable, or possible. Linear regression was used to model the variation in incidence over time.Results326 unique allo-HSCT were performed; of these 114 episodes of IFI occurred in 105 patients. Mean incidence was 35.9 IFI per 100 transplants, and increased by 2.3 IFI cases/100 transplants per year. 25.4% of cases were classified as proven; 47.4% as probable and 19.3% as possible. Invasive Aspergillus represented the majority of cases (62.3%), followed by non-specified (in most cases positive imaging and a positive β-d-glucan, 18%), Candidiasis (10%), and Mucorales (3.5%). The median age was 50 years, range 22 to 73, with males representing 52.6% of cases. The most common non-hematologic comorbidities were chronic pulmonary disease (42.9%), chronic heart failure (32.4%), and hepatic disease (31.4%). 48.6% of patients received matched unrelated allo-HSCT, 34.3% received matched sibling donor allo-HSCT, 14.3% received haploidentical allo-HSCT, and 3% received cord allo-HSCT. 79% of transplants were myeloablative. Median time from transplant to onset of IFI was 145 days (95% CI 39–259). The median time to onset of Aspergillosis was 120 days (95% CI 34–241 days), Candidiasis was 130 days (95% CI 12–283 days), and Mucorales was 246 days (95% CI 126–338 days). Active GVHD was present in 60% of IFI cases. 63% of cases were on antifungal prophylaxis, most commonly an echinocandin. All-cause mortality was 30.5% at 42 days and 65.7% at 1 year. The median time to death from the onset of IFI was 68.5 days.ConclusionIFIs are common in allo-HSCT recipients and appear to be increasing in frequency. Further work is needed to risk-stratify patients, determine optimal prophylaxis and empiric treatment, and define resistance trends. Disclosures All authors: No reported disclosures.

1127. Utilization of Combination Anti-fungal Therapy in Hospitalized Children and Adverse Events

BackgroundCombination antifungal therapy (CAF) is often prescribed to treat invasive fungal infections, despite equivocal data showing benefit. We evaluated number of CAF for treatment of proven, probable and possible invasive fungal infection (IFI) in hospitalized children, associated adverse effects (AE), and use of therapeutic drug monitoring (TDM).MethodsMedical charts of patients ≤ 18 years old that received CAF for ≥72 hours with normal liver function test between 1/1/13 through December 31/18 were reviewed. Patients could be included for multiple episodes of CAF. Data included primary site of IFI, host risk factors, demonstration of fungal elements in tissue/sterile sites, clinical and mycological criteria for IFI (defined by European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group), CAF regimen, incidence of TDM, and AE.ResultsOverall, 73 episodes of IFI were reviewed [unique patients (n) =60]. The median age was 10 years. Majority (61.6%) of patients were diagnosed with a hematological malignancy (n = 20 acute lymphoblastic leukemia, n = 12 acute myeloid leukemia, n = 5 aplastic anemia). A number of proven, possible, probable IFI were 36, 27 and 20, respectively (Table 1). Most frequent organism isolated in proven IFI was Aspergillus fumigatus (episodes=5, n = 4). Most common primary site of IFI was pulmonary (episodes=32, n = 27). Median days of CAF was 6.8 (range: 3–170). Sixty-six episodes included treatment with a triazole-containing regimen (90%). TDM was conducted in 51 (77%) episodes of triazole-containing regimens. AE were reported in 14 episodes (n = 10) (infusion-related reactions and nephrotoxicity reported in 4 episodes each, electrolyte abnormalities and skin reaction reported in 2 episodes each, and liver dysfunction and hypersensitivity reported in 1 episode each).ConclusionPatients diagnosed with proven or probable IFI received a longer duration of CAF in comparison to possible IFI. Voriconazole was frequently prescribed in combination with either micafungin or liposomal amphotericin B for IFI. Antifungal stewardship opportunities exist to improve TDM and reduce the incidence of AE when prescribing CAF. Disclosures All authors: No reported disclosures

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.

High incidence of invasive fungal infection during acute myeloid leukemia treatment in a resource-limited country: clinical risk factors and treatment outcomes.

Invasive fungal infection (IFI) causes high morbidity and mortality during acute myeloid leukemia (AML) treatment. Interventions to prevent fungal infection, including air filtration systems and antifungal prophylaxis, may improve outcomes in this group of patients. However, they are expensive and therefore inapplicable in resource-limited countries. The benefit of antifungal therapy is also dependent on the local epidemiology. That led us to conduct the study to evaluate the characteristics and impact of IFI in AML patients without prophylaxis in our setting. Clinical data from patients with AML who have been treated with chemotherapy without antifungal prophylaxis were retrieved during a 5-year period at Thailand's hematology referral center. Incidence and risk factors of IFI and outcomes of patients were evaluated. Among 292 chemotherapy courses, there were 65 (22.3%) episodes of IFI. Of those, 10 (15.4%) were proven, 19 (29.2%) were probable, and 36 (55.4%) were categorized as being possible IFI. Molds were the most commonly observed causative pathogens (93.1%). The incidence of probable/proven IFI was highest during first induction (20.5%), followed by second induction (6.1%), and consolidation (2.7%). A long duration of neutropenia, old age, and low serum albumin were the strongest predictors of IFI. Compared with patients who had no IFI, patients with probable/proven IFI had a longer length of hospital stay and higher in-hospital mortality. Patients with proven IFI had a significantly worse outcome at 1 year. These results suggest the change in health policy to implement IFI preventive measures to improve outcomes of AML treatment.

PB2362 GRANULOCYTE TRANSFUSIONS IN SEVERELY NEUTROPENIC CHILDREN: A SINGLE CENTRE EXPERIENCE

Background:Severe neutropenia occurs in majority of children undergoing intensive chemotherapy and during hematopoietic stem cell transplant(HSCT). During these episodes, bacterial and fungal infections are frequently observed. Recently, there has been an increase in the incidence of multi‐drug resistant(MDR) bacterial infections. Antibiotics alone, may not be enough in combatting these MDR organisms and thus there was a felt need for using granulocyte infusions, at least until marrow recovery. Despite numerous clinical trials, efficacy of granulocyte transfusions yet remains controversial. However, we hereby collate a tertiary pediatric centre's experience on the use of granulocytes.Aims:To determine whether early Granulocyte transfusions makes a difference in outcomes of septic neutropenic childrenMethods:A retrospective analysis on all those children in the pediatric oncology or HSCT unit who received granulocyte infusions from November 2017‐July 2018 was conducted for this study. Collated data included age, sex, hospital number, primary diagnosis, indication for granulocyte infusion, blood culture and/or histopathology results, number of granulocyte infusions, dose of granulocytes infused and outcome. Granulocyte transfusion was considered in the setting of a documented GNB in blood culture or a definite invasive fungal infection(IFI) and severe neutropenia. A universal protocol of performing hemapheresis on a voluntary granulocyte donor 6‐8 hours after administering 8 mg oral dexamethasone along with subcutaneous GCSF (10mcg/kg, to a maximum of 600 mcg) was used.Results:Total of six episodes of gram negative bacilli(GNB) bacteremia and one episode of definite IFI in children with severe neutropenia were treated with granulocyte infusions and other supportive care measures from November 2017‐July 2018. Five boys and one girl with a median age of 8 years (range 7‐13 years) underwent 30 granulocyte infusions from 17 voluntary donors. The commonest primary diagnosis in this cohort was acute leukemia(3 = ALL,2 = AML,1 = very severe aplastic anemia). Notably, in all but one, GNB blood cultures were carbapenem resistant. Median dose of granulocytes infused was 1 × 1010/infusion(range 0.6‐1.65 × 1010). In four of these episodes, granulocytes were initiated before hemodynamic compromise(defined as transfer of the child to the pediatric intensive care unit and/or initiating ionotropic support and/or need for mechanical ventilation). Outcome of three of these four(75%) children was favourable i.e. the infection was controlled and these children survived the crisis. Of the entire cohort, three of the seven infection episodes(42%) had a favourable outcome.Summary/Conclusion:Granulocyte transfusions before hemodynamic compromise in cases of severe neutropenia after myelosuppressive chemotherapy or while awaiting engraftment following HSCT, in the setting of proven MDR‐GNB bacteremia or disseminated fungal infections is safe and can be considered as a life‐saving measure, in reducing morbidity and mortality.

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 Infection After Lung Transplantation: Epidemiology in the Setting of Antifungal Prophylaxis.

Lung transplant recipients commonly develop invasive fungal infections (IFIs), but the most effective strategies to prevent IFIs following lung transplantation are not known. We prospectively collected clinical data on all patients who underwent lung transplantation at a tertiary care academic hospital from January 2007-October 2014. Standard antifungal prophylaxis consisted of aerosolized amphotericin B lipid complex during the transplant hospitalization. For the first 180 days after transplant, we analyzed prevalence rates and timing of IFIs, risk factors for IFIs, and data from IFIs that broke through prophylaxis. In total, 156 of 815 lung transplant recipients developed IFIs (prevalence rate, 19.1 IFIs per 100 surgeries, 95% confidence interval [CI] 16.4-21.8%). The prevalence rate of invasive candidiasis (IC) was 11.4% (95% CI 9.2-13.6%), and the rate of non-Candida IFIs was 8.8% (95% CI 6.9-10.8%). First episodes of IC occurred a median of 31 days (interquartile range [IQR] 16-56 days) after transplant, while non-Candida IFIs occurred later, at a median of 86 days (IQR 40-121 days) after transplant. Of 169 IFI episodes, 121 (72%) occurred in the absence of recent antifungal prophylaxis; however, IC and non-Candida breakthrough IFIs were observed, most often representing failures of micafungin (n = 16) and aerosolized amphotericin B (n = 24) prophylaxis, respectively. Lung transplant recipients at our hospital had high rates of IFIs, despite receiving prophylaxis with aerosolized amphotericin B lipid complex during the transplant hospitalization. These data suggest benefit in providing systemic antifungal prophylaxis targeting Candida for up to 90 days after transplant and extending mold-active prophylaxis for up to 180 days after surgery.