Diagnosis Of Invasive Fungal Disease Research Articles

Fungal infections in children with haematologic malignancies and stem cell transplant recipients.

Children with haematologic malignancies and haematopoietic stem cell transplant recipients are at high risk for invasive fungal diseases (IFD). There has been an increased number of at-risk children over the past two decades due to improvements in cancer therapies resulting in improved survival of children with high-risk and refractory malignancies. The predominant organisms that cause IFD include Candida spp., Aspergillus spp. and the Mucorales molds. Clinical presentations of IFD vary based on host immune status and the causative organism. Though serum biomarkers such as the galactomannan assay and beta-D-glucan assay have been validated in adults, there are limited data regarding their diagnostic value in children. Thus, the gold standard for IFD diagnosis remains tissue biopsy with histopathological and microbiological evaluation. Treatment of IFD is multimodal and involves antifungal drugs, correction of immune dysfunction and surgical resection when feasible. Paediatric practice regarding IFD is largely extrapolated from data generated in adult patients; in this review, we evaluate both primary paediatric studies and guidelines intended for adult patients that are applied to paediatric patients. There remain significant knowledge gaps with respect to the prevention, diagnosis and treatment of IFD in immunocompromised children, and further research is needed to help guide management decisions.

Utility of Fungal Cell Markers in Pediatric Bone Marrow Transplant Recipients for Screening and Diagnosis of Invasive Fungal Infections

Invasive fungal disease (IFD) is a significant contributor to morbidity and mortality in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). Early detection and timely initiation of antifungal therapy is important for improved outcome, but diagnosis remains difficult, especially when relying on conventional microbiology methods such as culture and microscopy. Data on the use of fungal biomarkers for screening and diagnosis of IFD in HSCT pediatric patients are limited, precluding the development of specific guidelines in this population. In this review, we have summarized available literature on kinetics, diagnostic and prognostic performance, and limitations of fungal biomarkers for screening and diagnosis of IFD in pediatric HSCT recipients to help guide their use and interpretation.

Nucleic Acid Tools for Invasive Fungal Disease Diagnosis

This review has incorporated the knowledge and experience of the leads of each of the laboratory working parties of the fungal PCR initiative in order to provide up-to-date information on the performance and developments of PCR methods for the detection of fungi that commonly cause invasive fungal disease (IFD). Molecular diagnosis of IFD enhances the current repertoire of mycological investigations. Providing superior sensitivity and turn-around-time over classical approaches, yet maintaining the benefits of classical tests (e.g. species level identification and identifying resistance). Standardization for Aspergillus PCR is almost complete; the recent release of commercial PCR assays for a wide range fungi (Aspergillus, Candida, Pneumocystis, Mucorales and Pan-fungal) and availability of external quality control schemes (e.g. Quality Control of Molecular Diagnostics for Aspergillus, Candida, Pneumocystis) means that fungal PCR testing is robust and ready for use, globally. Further work is needed to ascertain the utility of PCR in routine practice and to determine whether combining it with other biomarkers is an optimal strategy. PCR for detecting Mucorales sp. and on tissue, together with direct antifungal resistance detection in body fluids, may increase its diagnostic value across the board. This and the ability to diagnose Pneumocystis pneumonia and invasive candidiasis would go a long way towards attaining the long-held ambition of medical mycology to provide a comprehensive range of tests that can be relied upon to diagnose, at least, the common IFD. In short, PCR has a clear future and is close to achieving its full potential in our laboratories.

A population-based analysis of attributable hospitalisation costs of invasive fungal diseases in haematological malignancy patients using data linkage of state-wide registry and costing databases: 2009-2015.

Invasive fungal diseases (IFD) are associated with significant treatment-related costs in patients with haematological malignancies (HM). The objectives of this study were to characterise the gross and attributable hospitalisation costs of a variety of IFD in patients with HM by linking state-wide hospital administrative and costing datasets. We linked the Victorian Admitted Episodes Dataset, Victorian Cancer Registry and the Victorian Cost Data Collection from 1 July 2009 to 30 June 2015. IFD cases and uninfected controls were matched 1:1 based on age within ten years, same underlying HM and length of stay prior to IFD diagnosis. The cost difference between surviving cases and controls, indexed to 2019 Australian dollars (AUD) calculated twelve months from IFD diagnosis, was determined using Poisson and negative binomial regression (NBR). From 334 matched pairs, the gross hospitalisation cost of cases was AUD$67277 compared to AUD$51158 among uninfected controls, associated with an excess median hospitalisation cost of AUD$16119 (P<.001) attributable to IFD, approximating to USD$11362 and €10154 at purchasing power parity. Median attributable costs were highest for patients with invasive aspergillosis (AUD$55642; P<.001) and mucormycosis (AUD$51272; P=.043) followed by invasive candidiasis AUD$24572 (P<.001). No change in median excess attributable costs was observed over the study period (P=.90) Analyses by NBR revealed a 1.36-fold increase (P<.001) in total hospitalisation costs among cases as compared to controls twelve months from IFD diagnosis. Invasive aspergillosis and mucormycosis have high attributable hospitalisation costs but the overall excess IFD cost of AUD$16119 is modest, potentially reflecting missed or miscoded fungal episodes arguing for better quality surveillance data at hospital level.

The Use of Whole Genome and Next-Generation Sequencing in the Diagnosis of Invasive Fungal Disease

This review examines how next-generation nucleic acid sequencing (NGS) is being used in the diagnosis of invasive fungal disease (IFD) and how well its implementation compares to PCR-based diagnosis. The comparison allows for the assessment of the advantages and potential limitations of NGS in the diagnosis of IFD. NGS is established as a method for sequencing of microbial genomes. It is increasingly being tested as a direct diagnostic method from various sample types including samples such as plasma, formalin fixed and paraffin embedded specimens, and bronchoalveolar lavage. In these cases, the methodology was generally able to identify the causative agents of IFD. NGS-based methods will play an increasingly important role in diagnosis of IFD. The major limitation is currently cost, the need to standardise methods of nucleic acid isolation, and sequence analysis to enable broad uptake and application of the method.

Epidemiology, utilisation of healthcare resources and outcome of invasive fungal diseases following paediatric allogeneic haematopoietic stem cell transplantation.

Epidemiology and management practices of invasive fungal diseases (IFD) after allogeneic haematopoietic stem cell transplantation (HSCT) are a subject of constant change. We investigated the contemporary incidence, diagnostics, antifungal management and outcome at a major paediatric transplant centre in Germany. The single-centre retrospective observational study included all paediatric allogeneic HSCT patients (pts) transplanted between 2005 and 2015. Patient-related data were assessed up to 365days post-transplant. The primary endpoint was the incidence of possible, probable and proven IFDs. Secondary endpoints included diagnostics and antifungal treatment; analysis of risk factors; and overall survival with the last follow-up in January 2017. A total of 221 first (196), second (21) or third (4) procedures were performed in 200 pts (median age: 9years, range, 0.5-22) for leukaemia/lymphoma (149) and non-malignant disorders (72). Prophylaxis was administered in 208 HSCT procedures (94%; fluconazole, 116, mould-active agents, 92). At least one computed tomography scan of the chest was performed in 146, and at least one galactomannan antigen assay in 60 procedures. There were 15 cases of proven (candidemia, 4; aspergillosis, 4) or probable (aspergillosis, 7) IFDs, accounting for an incidence rate of 6.8%. Overall mortality at last follow-up was 30%; the occurrence of proven/probable IFDs was associated with a reduced survival probability (P<.001). Morbidity and mortality from IFDs at our institution were consistent with data reported from other centres. Utilisation of healthcare resources for prevention, diagnosis and management of IFDs was considerable.

Surgical resection for persistent localized pulmonary fungal infection prior to allogeneic hematopoietic stem cell transplantation: Analysis of six cases

ObjectiveAlthough invasive fungal disease (IFD) is an important complication in allogeneic hematopoietic stem cell transplantation (HSCT), the clinical significance of surgery, including the role of surgical resection for persistent pulmonary fungal disease prior to allogeneic HSCT in the current era with a variety of available antifungal agents, is controversial. We investigated the role of surgical resection. MethodsWe retrospectively investigated six patients who underwent surgical resection of suspected pulmonary fungal disease prior to allogeneic HSCT between April 2007 and June 2016 at our medical center. ResultsWe present six patients who underwent surgical resection of suspected pulmonary fungal disease prior to allogeneic HSCT. In our case series, three of four patients who were given a presurgical diagnosis of possible IFD were given a proven diagnosis after surgery, including two cases of invasive aspergillosis (IA) and one case of mucormycosis. All surgeries were performed by video-assisted thoracic surgery (VATS) for lobectomy without major complications. Recurrence of IFD was not observed after allogeneic HSCT in any of the six patients. ConclusionOur experience indicated that surgical resection of persistent localized pulmonary lesions of IFD before allogeneic HSCT was helpful for obtaining a definitive diagnosis and might be useful for reducing recurrence after HSCT.

A consensus document for the clinical management of invasive fungal diseases in pediatric patients with hematologic cancer and/or undergoing hematopoietic stem cell transplantation in Brazilian medical centers

In the present paper we summarize the suggestions of a multidisciplinary group including experts in pediatric oncology and infectious diseases who reviewed the medical literature to elaborate a consensus document (CD) for the diagnosis and clinical management of invasive fungal diseases (IFDs) in children with hematologic cancer and those who underwent hematopoietic stem-cell transplantation. All major multicenter studies designed to characterize the epidemiology of IFDs in children with cancer, as well as all randomized clinical trials addressing empirical and targeted antifungal therapy were reviewed. In the absence of randomized clinical trials, the best evidence available to support the recommendations were selected. Algorithms for early diagnosis and best clinical management of IFDs are also presented. This document summarizes practical recommendations that will certainly help pediatricians to best treat their patients suffering of invasive fungal diseases.

Diagnostic Value of G and GM Tests in Acute Leukemia Patients with Invasive Fungal Disease

To analyze the diagnostic value of (1, 3) -β-D-glucan and galactomannan (GM) tests in the patients with acute leukemia complicated by invasive fungal disease, and explore the application of serological detection (G/GM) and lung CT for early diagnosis of invasive fungal disease (IFD). A total of 493 patients with acute leukemia complicated by high risk invasive fungal infection, also receival G and GM tests, in Department of hematology of our hospital from June 2016 to December 2016 were selected and were divided into IFD-confirmed group (62 cases) including confirmed and clinical diagnesed IFD, and IFD-unconfirmed group (431 cases) including suspected IFD and non-IFD according to the diagnostic criteria of IFD. The results of G and GM tests in patients of 2 groups were analyzed, then the diagnostic efficacy of G and GM done and combination evaluated. In addition, 26 patients whose lung CT negative at hospitalization, moreover, presentation of changes in lung by CT during hospitalization and serological G and GM test positive were selected, and the difference of time between serological that postive and presentation of changes in lung by CT were compared for the estimation of early diagnotic value. The positive rate of (1, 3) -β-D-glucan in IFD-confirmed group and IFD-unconfirmed group was 56.5% and 10.4%, respectively. Meanwhile, that of galactomannan test was 41.9% and 9.0%, respectively. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of (1, 3) -β-D-glucan was 56%, 90%, 44% and 92%, and that of galactomannan was 42%、91%、40% and 93%, respectively. Moreover, the combination of (1, 3) -β-D-glucan and galactomannan could raise the sensitivity to 69% and specificity to 98%. The positive results of serological detection (G/GM) come earlier about five days than CT changes. Both (1, 3) -β-D-glucan and galactomannan test have high sensitivity and specificity, and the combination of them can improve the diagnostic efficacy, and make the clinical antifungal therapy more precisely. In the early clinical diagnosis of IFD, the positive results of serological detection coming earlier than lung CT.

Rapid identification of invasive fungal species using sensitive universal primers-based PCR and restriction endonuclease digestions coupled with high-resolution melting analysis.

Conventional diagnosis of invasive fungal disease from blood cultures is often notoriously delayed and inadequately sensitive. We aimed to develop a universal primers-based polymerase chain reaction (PCR) assay and restriction fragment length polymorphisms (RFLP) for rapid identification of invasive fungal disease (IFD). We evaluated 16 clinical fungal species using a combination of PCR assays with 3 different restriction endonucleases targeting various internal transcribed spacer (ITS) regions and high resolution melting analysis (HRMA). Serial samples from 75 patients suspected to have IFD were analyzed for clinical verification. We have designed a universal PCR capable of amplifying a portion of the 18S rRNA gene of 16 clinically important fungal species. The restriction patterns of most PCR products generated by EcoRI or double digested by ClaI and AvaI were different, except Aspergillus niger and Aspergillus flavus had a similar pattern, and Aspergillus fumigatus and Aspergillus terreus had a similar pattern. All these species had a unique melting curve shape using the HRMA. Both HRMA and universal PCR had adequate sensitivity, and all sixteen reference fungal species can be clearly distinguished by the universal PCR-RFLP-HRMA assay. With a reference library of 176 clinically relevant fungal strains, and 75 clinical samples from patients with suspicious IFD were tested, our assay identified 100% and 61.1% of isolates from the reference library and clinical samples, respectively. Universal PCR and RFLP coupled with HRMA could be a highly discriminative and useful molecular diagnostic that could enhance the current diagnostic, treatment, and surveillance methods of invasive fungal disease.

PS1285 INVASIVE FUNGAL DISEASES IN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION RECIPIENTS WITH HODGKIN'S LYMPHOMA

Background:Data on invasive fungal disease (IFD) in allogeneic hematopoietic stem cell transplantation (allo‐HSCT) recipients with relapsed/refractory Hodgkin's lymphoma (r/r HL) are limited. Outcome of allo‐HSCT in patients with prior IFD is still a subject of controversy.Aims:The aim is to study the epidemiology of IFD in allo‐HSCT recipients with r/r HL.Methods:Single center prospective observational study included 86 patients with classical r/r HL who underwent allo‐HSCT from 2002 to 2018. The median age was 27 (13–49) y.o., children (&lt;18 yo) – 13% (n = 11). Allo‐HSCT from MUD was performed in 45,4% (n = 39), MRD – 24,4% (n = 21), MMUD – 15,1% (n = 13), haplo – 15,1% (n = 13), with RIC (100%) and predominantly PTCY‐based GvHD prophylaxis (71%). Primary antifungal prophylaxis was fluconazole in 85%, secondary – voriconazole (100%). EORTC/MSG 2008 criteria for diagnosis and response to therapy were used. In pts with CT‐scan lung lesions before allo‐HSCT bronchoscopy with BAL was used. “Active IFD” means IFD diagnosed just before HSCT. Median follow‐up time was 12 months [1–71].Results:Incidence of pre‐existing IFD in allo‐HSCT recipients with r/r HL was 12,8% (n = 11). All cases of IFD prior to HSCT were invasive aspergillosis (IA) with lungs involvement. Antifungal therapy before allo‐HSCT was used in 81,8% pts with median duration – 2 months. Complete response to antifungal therapy was in 45,4% pts, partial response or stabilization – 36,4%, and 18,2% pts had an “active IFD”. After allo‐HSCT all pts received voriconazole as an antifungal therapy or secondary prophylaxis. Cumulative incidence of relapse or progression of IA after allo‐HSCT was 18,2% with the median 49 day [19–79] of onset after HSCT, which were successfully treated with voriconazole. Incidence of IFD after allo‐HSCT for naïve patients was 17,6% (n = 13/74). Etiology of IFD after allo‐HSCT was IA – 69%, invasive candidiasis (IC) – 15%, mucormycosis – 8%, and combined IFD caused by Aspergillus fumigatus + Rhizopus stolonifer ‐ 8%. The median day of onset of IFD after allo‐HSCT was day+ 114 [1–489]. The main site of infection were lungs (88%), the main clinical symptom – febrile fever (100%). Antifungal therapy was following: voriconazole – 59%, micafungin – 17%, posaconazole – 8%, lipid amphotericin B – 8% and combination lipid amphotericin B with caspofungin – 8%. Overall survival (OS) at 12 weeks from the IFD diagnosis after allo‐HSCT was 80%. The 2‐year OS in children and adult with r/r HL after allo‐HSCT was 73,3%. Development of IFD after allo‐HSCT do not decrease the 2‐year OS rate (69,2% vs 74%, p = 0,77). The impact of prior IFD on 2‐year OS in allo‐HSCT recipients was not statistically significant in all group (63,6% vs 74,7%, p = 0,47), and separately in children and adults.Summary/Conclusion:Incidence of pre‐existing IFD in children and adults with r/r Hodgkin's lymphoma allo‐HSCT recipients was 12,8%. Incidence of IFD after allo‐HSCT in naïve patients with Hodgkin's lymphoma was 17,6%. The major etiology agent as before as after allo‐HSCT were Aspergillus spp. IFD was a late complication after allo‐HSCT. Despite the high incidence of IFD before or after allo‐HSCT didn’t influence the outcome in children and adults with r/r Hodgkin lymphoma.

Defining standards of CARE for invasive fungal diseases in adult haematology patients: antifungal prophylaxis versus treatment.

Despite the availability of four different classes of antifungal agents, invasive fungal infections, in particular mould diseases, continue to have a high crude mortality rate in adult haematology patients, especially when diagnosed late. Early diagnosis, resulting in prompt and adequate antifungal intervention, is of great importance when trying to improve the overall outcome of these infections, but depends on the availability of rapid and sensitive diagnostic tools. The medical community has developed and continues to evaluate a continuum of antifungal strategies (starting with prophylaxis followed by empirical therapy and more recently a diagnostic-driven or pre-emptive approach) to better tackle these life-threatening diseases. While the empirical approach seems to have lost some of its popularity, the jury is still out about the pros and cons of universal antifungal prophylaxis in at-risk adult haematology patients compared with an approach that uses radiological and mycological diagnostic methods with good to excellent negative predictive values (also erroneously called pre-emptive), trying to exclude the presence of an invasive fungal disease. Whilst awaiting the results of comparative clinical studies, believers and non-believers around the globe continue to argue about the advantages and shortcomings of both strategies. The debate presented here provides a rationale for both prophylaxis for 'high-risk' haematology patients as well as for a more targeted approach based on the appropriate use of mycological, radiological, immunological (and genetic) methods for the diagnosis of invasive fungal diseases.

Molecular diagnostics in fungal infections

Invasive fungal disease (IFD) causes significant morbidity and mortality in hospitalised patients, despite advances in antifungal therapies. Rapid, accurate diagnostic tests are essential for improving patient outcomes. Molecular diagnostic methods, including both broad-range and specific PCR assays, and proteomic approaches such as matrix-assisted laser desorption ionisation-time of flight mass spectroscopy (MALDI-TOF MS) have great potential to enhance sensitivity and speed to diagnosis of IFD, but have varying specificities. These assays are mainly used to complement conventional methods as they lack clinical validation and require standardisation before they can be recommended for widespread implementation. To date no molecular based assays have been incorporated into diagnostic criteria for defining IFD, however the development of commercial assays is likely to assist standardisation. The emergence of antifungal drug resistance in Candida spp. and Aspergillus spp. is concerning. Molecular methods, including PCR and next generation sequencing, have been developed for the detection of azole and echinocandin resistance in Candida species and azole resistance in Aspergillus species. These tests are not widely available to diagnostic laboratories, but are likely to be key for epidemiological surveillance of antifungal resistance in coming years.

Progress for diagnosis of invasive fungal disease in children

Invasive fungal disease(IFD)is common in immunocompromised children, particularly in those with hematological malignancies.IFD is associated with onset complications and can cause high morbidity and mortality.In recent years, the incidence of IFD is increasing.More cases are reported in non-neutropenic and immunocompetent children without apparent underlying conditions.Early diagnosis and prompt therapy is key to better prognosis.This review focuses on the diagnostic methods on IFD. Key words: Invasive fungal disease; Children; Diagnosis

Lung Ultrasound to Evaluate Invasive Fungal Diseases after Allogeneic Hematopoietic Stem Cell Transplantation.

Invasive fungal diseases (IFDs) are a leading cause of infection-related-mortality after allogeneic hematopoietic stem cell transplantation (HSCT). In this prospective pilot study, we investigated the use of bedside lung ultrasound (US) in IFD management. Ten consecutive hematological patients, who developed pulmonary IFD after HSCT, were included in the study. Standard computed tomography scan and lung US were performed at IFD diagnosis and 10 days after antifungal treatment. The lung US demonstrated a high sensitivity in the detection of lung lesions at IFD diagnosis and in the follow-up examinations. It is of potential clinical relevance for IFD management in hematological patients.

Detection and identification of fungi in bronchoalveolar lavage fluid from immunocompromised patients using panfungal PCR.

Rapid diagnostics of fungal pneumonia and initiation of appropriate therapy are still challenging. In this study, we used two panfungal assays to test bronchoalveolar lavage fluid (BALF) samples to prove their ability to confirm invasive fungal disease diagnosis and identify causative agents. Two methods targeting different fungal rDNA regions were used, and the obtained PCR products were sequenced directly or after cloning. In total, 106 BALF samples from 104 patients were tested. After sequencing, we obtained 578 sequences. Four hundred thirty-seven sequences were excluded from further analysis due to duplication (n = 335) or similarity with sequences detected in the extraction control sample (n = 102); 141 unique sequences were analyzed. Altogether, 23/141 (16%) of the fungi detected belonged to pathogenic species, and 63/141 (45%) were identified as various yeasts; a variety of environmental or very rare fungal human pathogens represented 29/141 (21%) of the total and 26/141 (18%) were described as uncultured fungus. Panfungal PCR detected fungal species that would be missed by specific methods in only one case (probable cryptococcosis). Panfungal PCR followed by sequencing has limited use for testing BALF samples due to frequent commensal or environmental fungal species pickup.

A Risk Prediction Model for Invasive Fungal Disease in Critically Ill Patients in the Intensive Care Unit

PurposeDeveloping a risk prediction model for invasive fungal disease based on an analysis of the disease-related risk factors in critically ill patients in the intensive care unit (ICU) to diagnose the invasive fungal disease in the early stages and determine the time of initiating early antifungal treatment. MethodsData were collected retrospectively from 141 critically ill adult patients with at least 4 days of general ICU stay at Sun Yat-sen Memorial Hospital, Sun Yat-sen University during the period from February 2015 to February 2016. Logistic regression was used to develop the risk prediction model. Discriminative power was evaluated by the area under the receiver operating characteristics (ROC) curve (AUC). ResultsSequential organ failure assessment (SOFA) score, antibiotic treatment period, and positive culture of Candida albicans other than normally sterile sites are the three predictors of invasive fungal disease in critically ill patients in the ICU. The model performs well with an ROC-AUC of .73. ConclusionThe risk prediction model performs well to discriminate between critically ill patients with or without invasive fungal disease. Physicians could use this prediction model for early diagnosis of invasive fungal disease and determination of the time to start early antifungal treatment of critically ill patients in the ICU.

Diagnosis of invasive fungal diseases in haematology and oncology: 2018 update of the recommendations of the infectious diseases working party of the German society for hematology and medical oncology (AGIHO).

Invasive fungal diseases (IFD) are a primary cause of morbidity and mortality in patients with haematological malignancies. These infections are mostly life-threatening and an early diagnosis and initiation of appropriate antifungal therapy are essential for the clinical outcome. Most commonly, Aspergillus and Candida species are involved. However, other Non-Aspergillus moulds are increasingly identified in case of documented IFD. For definite diagnosis of IFD, a combination of diagnostic tools have to be applied, including conventional mycological culture and non-conventional microbiological tests such as antibody/antigen and molecular tests, as well as histopathology and radiology. Although varying widely in cancer patients, the risk of invasive fungal infection is highest in those with allogeneic stem cell transplantation and those with acute leukaemia and markedly lower in patients with solid cancer. Since the last edition of Diagnosis of Invasive Fungal Diseases recommendations of the German Society for Hematology and Oncology in 2012, integrated care pathways have been proposed for the management and therapy of IFDs with either a diagnostic driven strategy as opposed to a clinical or empirical driven strategy. This update discusses the impact of this additional evidence and effective revisions.

The diagnosis and treatment of invasive aspergillosis in Dutch haematology units facing a rapidly increasing prevalence of azole-resistance. A nationwide survey and rationale for the DB-MSG 002 study protocol.

Patients with haematological malignancies are at risk for invasive fungal diseases (IFD). A survey was conducted in all Dutch academic haematology centres on their current diagnostic, prophylactic and therapeutic approach towards IFD in the context of azole-resistance. In all 8 centres, a haematologist and microbiologist filled in the questionnaire that focused on different subgroups of haematology patients. Fungal prophylaxis during neutropaenia was directed against Candida and consisted of fluconazole and/or amphotericin B suspension. Mould-active prophylaxis was given to acute myeloid leukaemia patients during chemotherapy in 2 of 8 centres. All centres used azole prophylaxis in a subset of patients with graft-versus-host disease. A uniform approach towards the diagnosis and treatment of IFD and in particular azole-resistant Aspergillus fumigatus was lacking. In 2017, all centres agreed to implement a uniform diagnostic and treatment algorithm regarding invasive aspergillosis with a central role for comprehensive diagnostics and PCR-based detection of azole-resistance. This study (DB-MSG 002) will re-evaluate this algorithm when 280 patients have been treated. A heterogeneous approach towards antifungal prophylaxis, diagnosis and treatment was apparent in the Netherlands. Facing triazole-resistance, consensus was reached on the implementation of a uniform diagnostic approach in all 8 centres.

Diagnosis of invasive fungal disease in hospitalized patients with chronic obstructive pulmonary disease

BackgroundThe role of culture-independent techniques (galactomannan, (1-3)-β-d-glucan) in the early diagnosis of invasive fungal diseases (IFD) is well assessed in hematological patients, but there are no clear conclusions in patients with chronic obstructive pulmonary disease (COPD). AimsTo study the usefulness of nonculture-based techniques in the diagnosis of IFD in COPD-patients at risk for IFD. MethodsA prospective observational study based on monitoring COPD patients at risk for IFD during 2007–2010 was carried out. The presence of galactomannan, (1-3)-β-d-glucan and an indirect immunofluorescence of Candida albicans germ tube specific antibodies (CAGTA) were performed. ResultsAmong 43 COPD patients, 16 (37.2%) were diagnosed with IFD: seven cases were proven IFD (five invasive candidemia – IC, one invasive aspergillosis – IA and a rhinocerebral zygomycosis) and nine probable IFD (seven IA and two IC). In the diagnosis of IC and IA, the negative predictive value (NPV) of (1-3)-β-d-glucan was 100%. Regarding CAGTA in IC, NPV was 96.2%. Finally, NPV of galactomannan in IA was 91.2%. The area under the ROC curve for (1-3)-β-d-glucan in IC and for the rest of the IFD cases was 0.86 (95% CI, 0.79–0.93) and 0.60 (95% CI, 0.43–0.77), for CAGTA in IC was 0.83 (95% CI, 0.74–0.91) and for galactomannan in IA was 0.71 (95% CI, 0.56–0.85). Positive (1-3)-β-d-glucan preceded the growth of Candida (average of 1.7 days) in blood culture. ConclusionsIn COPD patients at risk for IFD the assayed techniques are especially useful to rule out the presence of IFD.