Definitions Of Invasive Fungal Disease Research Articles

257. Coinfection Characteristics among Children with COVID-19

Abstract Background Coinfection in patients with SARS-CoV-2 has been associated with greater complications. We describe the clinical characteristics and outcomes of 126 pediatric patients with COVID-19 and viral, bacterial, or fungal coinfection. Methods We retrospectively reviewed and analyzed electronic data of all pediatric patients who tested positive for SARS-CoV-2 from April 16, 2020, to April 15, 2022, in our center. Confirmation of COVID-19 was based on positive RT-PCR. Viral coinfections (VC) were identified using a multiplex RT-PCR respiratory viral panel, bacterial coinfection (BC) was determined by positive bacterial culture (blood, bronchoalveolar lavage, sputum, urine) or clinical/radiological manifestations and antimicrobial assessment by a pediatric Infectious Diseases expert and fungal coinfection (FC) diagnosis based on Consensus definitions of invasive fungal disease. Results During the study period, among 400 pediatric patients with COVID-19, 126 children had coinfection. Children >10 years were the most affected age group. Underlying disease was present in 69%, hematological malignancies were the most common (17.5%). BC was detected in 76.9% (n=97), bacterial pneumonia (54.6%) was the main diagnosis, followed by oncologic patients with initial febrile neutropenia and posterior SARS-CoV-2 detection (14,4%). Unusual BC as congenital syphilis w detected; acute appendicitis was the initial presentation of COVID-19 in 8 patients. VC was identified in 15.87% (n=20), prevailing rhinovirus (9.5%) and adenovirus (3.96%), One FC presented as proven pulmonary aspergillosis (0.8%). B-V and B-F coinfection were detected in 2 patients. Fever and cough were the most common symptoms, higher fever >40°C was mostly observed in the BC group (3%). Twenty-seven patients with BC (27.8%) were admitted to intensive care, with the OR 0.7 IR 95% (0.611–1.008), 4.1% died. One ICU admission was observed in the VC group (5%) and all VC cases resolved without complications. Conclusion Pediatric patients with COVID-19 coinfection, especially BC were common in our center representing nearly one-third of the infected children, including unusual coinfections. BC was identified as a risk factor for ICU admission OR 0.7 IR 95% (0.611–1.008). Favorable outcomes were observed in most cases. Disclosures All Authors: No reported disclosures.

Impact of revised EORTC/MSGERC 2020 criteria on diagnosis and prognosis of invasive pulmonary aspergillosis in patients with hematological malignancies undergoing bronchoscopy.

The first consensus definitions for invasive fungal diseases (IFD) were published in 2002. Advances in diagnostic tests and a clear need for improvement in certain areas led to a revision of these definitions in 2008. However, growing data on Aspergillus galactomannan (GM) thresholds and the introduction of new polymerase chain reaction-based diagnostic tests resulted in a further update by EORTC and Mycoses Study Group Education and Research Consortium (MSGERC) in 2020. Compared to the 2008 version, the 2020 EORTC/MSGERC criteria have stricter definitions, especially regarding GM levels, which should lead to improved specificity. Thus, our study aimed to evaluate diagnostic changes, based on GM levels, resulting from these new definitions and ascertain the impact of the new classification on mortality rates. Patients hospitalized in a single tertiary care center with hematologic malignancies and undergoing bronchoscopy for suspected IPA between April 2004 and December 2019 were included in this retrospective study. The study population consisted of 327 patients with 31 patients (nine patients with proven IPA and 22 patients with no IPA) excluded from the study. 194 patients were classified as probable IPA cases according to 2008 EORTC/MSG criteria. However, 53 (27.3%) of these patients were re-classified as possible IPA according to 2020 EORTC/MSGERC criteria, due to novel galactomannan cut-off levels. Compared to re-classified possible IPA patients, those remaining in the probable IPA category experienced a higher incidence of septic shock (34.0% vs 16.9%, p=0.02), and required more non-invasive (12.0% vs 0.0%, p=0.004) and invasive (44.6 vs 24.5%, p=0.01) mechanical ventilation. There was a higher in-hospital mortality rate in probable IPA patients than in the re-classified possible IPA group (42.5% vs 22.6%, p=0.01). Patients reassigned to possible IPA had similar underlying diseases, radiological features and prognosis to patients already classified as possible IPA. Independent risk factors for mortality were classification as probable IPA according to 2020 EORTC/MSGERC criteria, lack of remission from hematologic malignancy, and number of nodules in Thorax CT. The use of 2020 EORTC/MSGERC criteria resulted in a 27.3% significant reduction in probable IPA diagnoses and created a more homogeneous category of patients with respect to treatment response, prognosis and mortality. Therefore, 2020 EORTC/MSGERC criteria afford more reliable mortality prediction than 2008 EORTC/MSG criteria.

An Unexpected Guest in a Patient With Ulcerative Colitis

Question: A 16-year-old girl with a 2-year history of ulcerative colitis was referred to our university hospital because of fever, vomiting, and epigastric pain for 10 days; bloody diarrhea during the last month; and a rapid involuntary weight loss (5 kg). Sixth months earlier, during remission with oral mesalamine (60 mg/kg), she suffered a mild-to-moderate ulcerative colitis flare-up requiring oral prednisolone (1 mg/kg for 2 weeks and then tapered). At admission, physical examination showed pallor, mild signs of dehydration, and diffuse abdominal pain without signs of peritoneal irritation. Written consent for publication was obtained from the patient and her parents. Laboratory investigations revealed anemia, mild eosinophilia, hypoalbuminemia, an increased erythrocyte sedimentation rate, and fecal calprotectin. Specific serologic tests and blood and stool cultures for bacteria and viruses were negative. Colonoscopy showed pancolitis with continuous diffuse granular and friable mucosa (Mayo Score of 2) and upper endoscopy showed antral gastritis and diffuse duodenitis with nonbleeding erosions. The patient was started on steroids (1 mg/kg) followed by the amelioration of diarrhea, but persistence of mild grade fever and vomiting. Histologic examination showed crypt distortions and abscesses associated with goblet cell depletion. An upper endoscopy showed a normal esophageal and gastric mucosa. Duodenal histology (periodic acid–Schiff staining method) is presented in Figure A. What is the diagnosis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Aspergillus fumigatus was identified in duodenal biopsy specimens. Serum galactomannan antigen test (Bio-rad Platelia Aspergillus Ag kit) and specific IgM (DRG IgM ELISA) assays were positive (index 4.1 and 6.5 UI/mL, respectively); chest and brain computed tomography scans were normal.1Donnelly J.P. Chen S.C. Kauffman C.A. et al.Revision and update of the consensus definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium.Clin Infect Dis. 2020; 71: 1367-1376Crossref PubMed Scopus (898) Google Scholar Antifungal treatment with voriconazole (loading dose: 6 mg/kg/12 h on the first day, then 4 mg/kg/12 h) was started and steroids were tapered.2Patterson T.F. Thompson 3rd, G.R. Denning D.W. et al.Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America.Clin Infect Dis. 2016; 63: e1-e60Crossref PubMed Scopus (1405) Google Scholar A comprehensive immune assessment was performed after discontinuing steroid therapy. After 1 week of treatment, the clinical condition and inflammatory markers improved. Aspergillus fumigatus is a ubiquitous saprophytic fungus with low pathogenicity in healthy individuals, but may be the major cause of life-threatening infection in immunocompromised individuals. Enteric aspergillosis is an uncommon presentation of invasive aspergillosis, which can disseminate hematogenously to other organs. Clinical features of invasive aspergillosis include abdominal pain, fever, and hematochezia or peritonitis subsequent to bowel ischemia or perforation; typical endoscopic findings include ulcerations or islands of necrotic tissue. Glucocorticosteroids are critical in the management of inflammatory bowel disease (IBD), but are associated with increased risk of opportunistic infections due to immune suppression. It should also be emphasized that IBD itself predisposes to infective complications3Kucharzik T. Ellul P. Greuter T. et al.ECCO guidelines on the prevention, diagnosis, and management of infections in inflammatory bowel disease.J Crohns Colitis. 2021; 15: 879-913Crossref PubMed Scopus (70) Google Scholar and that gastrointestinal infections can be potential triggers for IBD relapse.

EORTC/MSGERC Definitions of Invasive Fungal Diseases: Summary of Activities of the Intensive Care Unit Working Group.

The EORTC/MSGERC recently revised and updated the consensus definitions of invasive fungal disease (IFD). These definitions primarily focus on patients with cancer and stem cell or solid-organ transplant patients. They may therefore not be suitable for intensive care unit (ICU) patients. More in detail, while the definition of proven IFD applies to a broad range of hosts, the categories of probable and possible IFD were primarily designed for classical immunocompromised hosts and may therefore not be ideal for other populations. Moreover, the scope of the possible category of IFD has been diminished in the recently revised definitions for classically immunocompromised hosts. Diagnosis of IFD in the ICU presents many challenges, which are different for invasive candidiasis and for invasive aspergillosis. The aim of this article is to review progresses made in recent years and difficulties remaining in the development of definitions applicable in the ICU setting.

Aspergillus Polymerase Chain Reaction-An Update on Technical Recommendations, Clinical Applications, and Justification for Inclusion in the Second Revision of the EORTC/MSGERC Definitions of Invasive Fungal Disease.

Aspergillus polymerase chain reaction testing of blood and respiratory samples has recently been included in the second revision of the EORTC/MSGERC definitions for classifying invasive fungal disease. This is a result of considerable efforts to standardize methodology, the availability of commercial assays and external quality control programs, and additional clinical validation. This supporting article provides both clinical and technical justifications for its inclusion while also summarizing recent advances and likely future developments in the molecular diagnosis of invasive aspergillosis.

Pneumocystis jirovecii Disease: Basis for the Revised EORTC/MSGERC Invasive Fungal Disease Definitions in Individuals Without Human Immunodeficiency Virus.

Pneumocystis jirovecii pneumonia (PCP) causes substantive morbidity in immunocompromised patients. The EORTC/MSGERC convened an expert group to elaborate consensus definitions for Pneumocystis disease for the purpose of interventional clinical trials and epidemiological studies and evaluation of diagnostic tests. Definitions were based on the triad of host factors, clinical-radiologic features, and mycologic tests with categorization into probable and proven Pneumocystis disease, and to be applicable to immunocompromised adults and children without human immunodeficiency virus (HIV). Definitions were formulated and their criteria debated and adjusted after public consultation. The definitions were published within the 2019 update of the EORTC/MSGERC Consensus Definitions of Invasive Fungal Disease. Here we detail the scientific rationale behind the disease definitions. The diagnosis of proven PCP is based on clinical and radiologic criteria plus demonstration of P. jirovecii by microscopy using conventional or immunofluorescence staining in tissue or respiratory tract specimens. Probable PCP is defined by the presence of appropriate host factors and clinical-radiologic criteria, plus amplification of P. jirovecii DNA by quantitative real-time polymerase chain reaction (PCR) in respiratory specimens and/or detection of β-d-glucan in serum provided that another invasive fungal disease and a false-positive result can be ruled out. Extrapulmonary Pneumocystis disease requires demonstration of the organism in affected tissue by microscopy and, preferably, PCR. These updated definitions of Pneumocystis diseases should prove applicable in clinical, diagnostic, and epidemiologic research in a broad range of immunocompromised patients without HIV.

Performance of Existing Definitions and Tests for the Diagnosis of Invasive Fungal Diseases other than Invasive Candidiasis and Invasive Aspergillosis in Critically Ill, Adult Patients: A Systematic Review with Qualitative Evidence Synthesis.

The Fungal Infections Definitions in Intensive Care Unit (ICU) patients (FUNDICU) project aims to provide standard sets of definitions for invasive fungal diseases (IFDs) in critically ill, adult patients, including invasive aspergillosis (IA), invasive candidiasis (IC), Pneumocystis jirovecii pneumonia (PJP), and other non-IA, non-IC IFDs. The first step of the project was the conduction of separated systematic reviews of the characteristics and applicability to critically ill, adult patients outside classical populations at risk (hematology patients, solid organ transplant recipients) of available definitions and diagnostic tests for IFDs. We report here the results of two systematic reviews exploring the performance of available definitions and tests, for PJP and for other non-IA, non-IC IFDs. Starting from 2585 and 4584 records for PJP and other IFDs, respectively, 89 and 61 studies were deemed as eligible for full-text evaluation. However, only two studies for PJP and no studies for other IFDs met the FUNDICU protocol criteria for inclusion in qualitative synthesis. Currently, there is no sufficient solid data for directly evaluating the performance of existing definitions and laboratory tests for the diagnosis of PJP and other non-IA, non-IC IFDs in critically ill adult patients outside classical populations at risk.

Clinical utility of the updated European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and the Mycoses Study Group Education and Research Consortium computed tomography criteria of invasive pulmonary aspergillosis in hematological malignancies

ABSTRACT Introduction: Invasive pulmonary aspergillosis is a life-threatening complication in the cases of patients with hematologic malignancies. In December 2019, the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and the Mycoses Study Group Education and Research Consortium published a revision and an update of the consensus definitions of invasive fungal disease. The aim of this study was to evaluate the signs and radiologic patterns of early-stage invasive pulmonary aspergillosis in computed tomography in patients with hematologic entities according to the latest criteria. Material and methods: This retrospective analysis of a baseline high-resolution computed tomography included neutropenic patients with hematological malignancies and probable invasive pulmonary aspergillosis. The data were collected between the years 2017 and 2019. Computed tomography was performed within 72 h from the beginning of clinical symptoms: fever, dyspnea or nonproductive cough. CT scans were analyzed by two independent radiologists according to the standardized protocol based on predefined criteria. Results: All 35 evaluated patients had typical lesions for early-stage invasive aspergillosis. Wedge-shaped infiltrates were noted in 48.6% of patients. In this group, 40% of patients had coexisting atypical radiological findings. In 11.4% of patients, wedge-shape consolidations were noted as the only type of lesions. Conclusions: Employment of the latest EORTC/MSG criteria increased diagnostic value of the baseline high resolution computed tomography in our study group by 11.4%.

Mucormycosis: Literature review and retrospective report of 15 cases from Portugal.

Background and Purpose: Prevalence of mucormycosis is growing with the increase of the population at risk. Current recommendations for its management are mostly based on retrospective studies. 3 study aimed to present the cumulative experience of an Infectious Diseases Department from a Portuguese hospital in the management of mucormycosis and discuss the potential gaps in the diagnostic and therapeutic approaches of this infection. Materials and Methods: For the purposes of the study, the electronic hospital database was searched for adult patients with mucormycosis from 1996 to 2019 based on the definition provided by the Consensus Definitions of Invasive Fungal Disease. Demographic, clinical, treatment, and outcome data were collected and compared to what had been described in the related literature. Results: In total, 15 cases of mucormycosis were found, including 11 cases with sinus involvement (10 with central nervous system involvement), two pulmonary, and two gastrointestinal infections. Diabetes mellitus (n=7) and corticosteroid therapy (n=7) were frequent risk factors. Median duration of symptoms before the suspicion of diagnosis was 26 days (3-158). The diagnosis was confirmed in 12 patients mostly by histopathology (n=9); the culture was positive only once. Systemic antifungals and surgical debridement were the backbones of treatment; however, side effects, the need for therapeutic drug monitoring, and the anatomical location of lesions added complexity to management. Overall, seven patients died, two of them before the consideration of clinical suspicion. Conclusion: More medications are becoming available for the treatment of mucormycosis. Nevertheless, we believe that its prognosis will only significantly change through the increase of awareness and reduction of the time to diagnosis. An effective multidisciplinary approach among surgeons, infectious diseases specialists, radiologists, microbiologists, and anatomopathologists is critical to the achievement of this goal.

Diagnosis of Invasive Aspergillosis in Intensive Care Unit Patients

Invasive aspergillosis is a frequent opportunistic infection in the intensive care unit. Diagnostic strategies within this setting are not well-defined. In the absence of histopathological proof, estimation of likelihood of disease is required, based on a combination of host factors with clinical, microbiological and radiologic findings. Importantly, the at-risk critically ill population has expanded beyond the classical immunosuppressed patients. Clinical features are non-specific, yet overt organ failure is associated with an increased risk and should raise the suspicion of invasive fungal disease. Validation of serological and molecular diagnostics is complicated by the lack of universal definitions in critically ill patients. Improved awareness of novel risk groups can promote early diagnosis. Development of novel, host immune response driven biomarkers and universal definitions of invasive fungal disease in intensive care units is urgently needed.

Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium.

BackgroundInvasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential.MethodsTo achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups’ findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved.ResultsThere is no change in the classifications of “proven,” “probable,” and “possible” IFD, although the definition of “probable” has been expanded and the scope of the category “possible” has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses.ConclusionsThese updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk.

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 (< 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 < 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 < 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.

1730. Invasive Fusarium Species in Mayo Clinic Patients with Hematologic Malignancies

BackgroundThe epidemiology of fungal infections in hematologic malignancies has changed in the past decade. Triazole prophylaxis has decreased Candida spp infections while infections due to other molds such as Aspergillus and Fusarium species have increased. Fusariosis has very poor prognosis, and after aspergillosis, is the most common invasive fungal infection in this patient population. We sought to describe fusariosis in patients with hematologic malignancy at the Mayo Clinic.MethodsWe performed a retrospective review of patients with culture-positive Fusarium infection from January 2003 to October 2016 at the Mayo Clinic, Rochester, MN. The records of patients were reviewed for demographics, diagnosis, treatment, and outcomes including mortality. Patients without a diagnosis of hematologic malignancy were excluded. Patients were classified with proven or probable Fusariosis based on the Revised Definitions of Invasive Fungal Disease from the EORTC/MSG Consensus Group.ResultsWe identified 14 patients with hematologic malignancies (age range 17–76 years; median 60 years) with a confirmed culture diagnosis of Fusarium infection classified as proven (9 patients) or probable (5 patients). Two cases were isolated pulmonary infections, 3 extra-pulmonary, and 9 disseminated cases. Two patients had previously undergone stem cell transplantation. Eight patients (57%) were receiving antifungal prophylaxis at the time of diagnosis: 2 on voriconazole, 1 on posaconazole, 1 on fluconazole, 3 on echinocandins, and 1 on Amphotericin B. Nine patients (64%) were neutropenic at the time of diagnosis. Amphotericin was the initial treatment in 7 (50%) patients, with voriconazole added for 4 patients for combination therapy the first week. Voriconazole monotherapy was given initially in 5 patients. Seven patients (50%) were deceased at 6 weeks after culture positivity, with an additional 2 patients deceased by 12 weeks.Conclusion Fusarium infection outcomes in patients with hematologic malignancies are poor. Neutropenia was common in those diagnosed, and infections were more likely to be disseminated, with high mortality rates. Amphotericin was commonly used as initial treatment, with many physicians recommending combination therapy with two agents, commonly voriconazole.Disclosures All authors: No reported disclosures.

Developing definitions for invasive fungal diseases in critically ill adult patients in intensive care units. Protocol of the FUNgal infections Definitions in ICU patients (FUNDICU) project

The reliability of diagnostic criteria for invasive fungal diseases (IFD) developed for severely immunocompromised patients is questionable in critically ill adult patients in intensive care units (ICU). To develop a standard set of definitions for IFD in critically ill adult patients in ICU. Based on a systematic literature review, a list of potential definitions to be applied to ICU patients will be developed by the ESCMID Study Group for Infections in Critically Ill Patients (ESGCIP) and the ESCMID Fungal Infection Study Group (EFISG) chairpersons. The proposed definitions will be evaluated by a panel of 30 experts using the RAND/UCLA appropriateness methods. The panel will rank each of the proposed definitions on a 1-9 scale trough a dedicated questionnaire, in two rounds: one remote and one face-to-face. Based on their median rank and the level of agreement across panel members, selected definitions will be organised in a main consensus document and in an executive summary. The executive summary will be made available online for public comments. The present consensus project will seek to provide standard definitions for IFD in critically ill adult patients in ICU, with the ultimate aims of improving their clinical outcome and facilitating the comparison and generalizability of research findings.

Invasive infections due to filamentous fungi other than Aspergillus: epidemiology and determinants of mortality

The epidemiology of invasive fungal disease (IFD) due to filamentous fungi other than Aspergillus may be changing. We analysed clinical, microbiological and outcome data in Australian patients to determine the predisposing factors and identify determinants of mortality. Proven and probable non-Aspergillus mould infections (defined according to modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria) from 2004 to 2012 were evaluated in a multicentre study. Variables associated with infection and mortality were determined. Of 162 episodes of non-Aspergillus IFD, 145 (89.5%) were proven infections and 17 (10.5%) were probable infections. The pathogens included 29 fungal species/species complexes; mucormycetes (45.7%) and Scedosporium species (33.3%) were most common. The commonest comorbidities were haematological malignancies (HMs) (46.3%) diabetes mellitus (23.5%), and chronic pulmonary disease (16%); antecedent trauma was present in 21% of cases. Twenty-five (15.4%) patients had no immunocompromised status or comorbidity, and were more likely to have acquired infection following major trauma (p <0.01); 61 (37.7%) of cases affected patients without HMs or transplantation. Antifungal therapy was administered to 93.2% of patients (median 68 days, interquartile range 19–275), and adjunctive surgery was performed in 58.6%. The all-cause 90-day mortality was 44.4%; HMs and intensive-care admission were the strongest predictors of death (both p <0.001). Survival varied by fungal group, with the risk of death being significantly lower in patients with dematiaceous mould infections than in patients with other non-Aspergillus mould infections. Non-Aspergillus IFD affected diverse patient groups, including non-immunocompromised hosts and those outside traditional risk groups; therefore, definitions of IFD in these patients are required. Given the high mortality, increased recognition of infections and accurate identification of the causative agent are required.

Micafungin compared with caspofungin for the treatment of febrile episodes in neutropenic patients with hematological malignancies: A retrospective study.

Invasive fungal infections are associated with morbidity and mortality in neutropenia secondary to hematological malignancies. Empirical antifungal agents are used to reduce their consequences. Caspofungin is the only echinocandin approved for this indication. Micafungin was compared with caspofungin for the treatment of patients with hematological malignancies and prolonged neutropenia. A retrospective cohort study was conducted involving patients who had hematological malignancies with profound neutropenia for a minimum of 10 days, and received empirical micafungin or caspofungin for a minimum of five days, between April 2005 and November 2009. Successful outcome was based on a composite end point: survival for a minimum of seven days following antifungal cessation, successful treatment of baseline fungal infection, absence of adverse events and absence of breakthrough fungal infection. Fungal infections were defined according to 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) criteria, with modification of the diagnostic imaging criteria. Micafungin had similar overall success to caspofungin (60.4% [29 of 48] versus 57.3% [47 of 82], respectively; P=0.729). Survival was higher in the micafungin group compared with the caspofungin group (100% [48 of 48] versus 89% [73 of 82]; P=0.02). No baseline invasive fungal infections were identified in the micafungin group, compared with three proven infections treated successfully with caspofungin (3.7%; P=0.18). Three proven breakthrough infections were observed in the micafungin group (three of 48 [27.3%]) compared with none in the caspofungin group (zero of 82; P=0.02). Micafungin has similar efficacy to caspofungin as empirical antifungal therapy in febrile neutropenic patients with hematological malignancies. Verification of these results in a prospective trial is warranted.

FRI0327 Invasive aspergillosis: A severe infection in juvenile systemic lupus erythematosus patients

BackgroundInfections are an important cause of morbidity and mortality in juvenile systemic lupus erythematosus (JSLE). Invasive aspergillosis (IA) is a fungal infection caused by Aspergillus spp., usually affects the pulmonary...

Aspergillosis in Solid Organ Transplantation

Invasive aspergillosis (IA) occurs in 1–15% of the solid organ transplant (SOT) recipients. Mortality rate in transplant recipients with IA historically has ranged from 65% to 92% (1–4). However, currently reported mortality rate in IA among SOT recipients is 22% (5). An estimated 9.3– 16.9% of all deaths in transplant recipients in the first year have been considered attributable to IA (6). Although the outcomes have improved in the current era, IA remains a significant posttransplant complication in SOT recipients. The review herein discusses the epidemiologic characteristics, risk factors, diagnostic laboratory assays and the approach to antifungal prophylaxis and treatment of IA in SOT recipients.

Editorial Commentary: Galactomannan Antigen Testing for Diagnosis of Invasive Aspergillosis in Pediatric Hematology Patients

Invasive fungal diseases, in particular those due to Aspergillus spp., are increasing in incidence and constitute an important cause for morbidity and mortality in children and adolescents with hematologic malignancies and those undergoing allogeneic hematopoietic stem cell transplantation (HSCT) [1]. A contemporary retrospective analysis demonstrated that corticosteroid therapy, neutropenia, immunosuppressive therapy, malignancy, and allogeneic HSCT are the most common risk factors for invasive aspergillosis in pediatric age groups [2]. The overall case fatality rate of invasive aspergillosis in this study was 53%, which is similar to that seen in adult patients. Invasive aspergillosis significantly contributes to the in-house mortality of children with acute lymphoblastic and myeloid leukemia, lymphoma, allogeneic HSCT, and solid organ transplantation. In a retrospective cohort study using a national database of hospital inpatient stays during 2000, 18% (122 of 666) of children with invasive aspergillosis died in the hospital, compared with 1% (1736 of 151 537) of similarly immunocompromised children without invasive aspergillosis [3]. Despite substantial achievements over the past 2 decades, diagnosis and treatment of invasive fungal diseases in children and adolescents are still limited by a number of factors. As a matter of fact, not all antifungal agents are approved in the pediatric population, the appropriate dosage of several drugs has not been established for all age groups, and postmarketing data providing information on safety and efficacy of approved agents under real-life circumstances are scant. Similarly, the value of newer diagnostic tools is not defined in the pediatric population, although they are of major impact for establishing preventive and treatment strategies of invasive aspergillosis [4]. Whereas both the halo sign and the air-crescent sign revealed by pulmonary computed tomography scan are common and highly suggestive for invasive mold infection in adult patients and are included as clinical criteria in the revised definitions of invasive fungal disease set forth by the European Organization for Research and Treatment of Cancer and the Mycosis Study Group (EORTC/MSG) [5], radiographic findings in immunocompromised children with proven pulmonary invasive fungal disease are often nonspecific. In younger children (aged <5 years) in particular, typical signs of pulmonary invasive fungal disease are not seen in the majority of patients. In contrast, multiple nodules or fluffy masses and infiltrates that look like mass lesions are frequently reported [2]. Testing galactomannan (GM), a polysaccharide cell-wall component that is released by all Aspergillus spp. during cell growth, has been evaluated in multiple studies in adults and is included as a microbiological criterion in the revised definitions of invasive fungal disease by the EORTC/MSG consensus group and in a number of Editorial Commentary

Utility of galactomannan enzyme immunoassay and (1,3)beta-D-glucan assay in invasive fungal infection

To evaluate the performance of the galactomannan enzyme immunoassay (GM test) and (1,3)beta-D-glucan assay (G test) for the diagnosis of invasive fungal infection (IFI). A retrospective study was performed in 115 hospitalized patients at Peking University First Hospital who were at risk of IFI. Patients were diagnosed as IFI according to 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) Consensus Group. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated at different cutoff values for two assays respectively. Two tests were combined to evaluate the changes of sensitivity, specificity, PPV and NPV. The best sensitivity (54.5%, 63.6%) and specificity (77.9%, 69.2%) were obtained with the cutoff values of 0.5 and 20 x 10(3) pg/L in GM test and G test respectively. The PPV were 20.7% and 17.9%, and the NPV were 94.2% and 94.7% respectively. The sensitivity increased to 90.9% and the specificity was 52.9% after a combined utility of two tests. The GM test and G tests are both useful in diagnosis of IFI with the cutoff values of 0.5 and 20 x 10(3) pg/L. A better sensitivity is acquired if there is a combined utility of two tests.