Management Of Invasive Fungal Diseases Research Articles

Epidemiology and management burden of invasive fungal infections after autologous hematopoietic stem cell transplantation: 10-year experience at a European Pediatric Cancer Center.

Autologous hematopoietic stem cell transplantation (HSCT) carries risks of infectious morbidity. We analysed epidemiology and management burden associated with invasive fungal diseases (IFDs) in children and adolescents undergoing autologous HSCT. In a retrospective, single-centre observational study, epidemiology and management burden associated with IFDs were analysed in all paediatric cancer patients who underwent autologous HSCT between 2005 and 2014. Clinical, radiographic and microbiological data were assessed up to 100days post-transplant. The primary endpoint was the incidence of proven, probable and possible IFDs. Further endpoints included the use of systemic antifungal agents for prevention and management of IFDs; infectious and non-infectious comorbidities; and survival until day+100. Of 95 patients (median age: 8years; r, 0.75-20) underwent 103 HSCT procedures for solid tumours (92) or lymphoma (11). Primary antifungal prophylaxis was administered in 49 procedures (47.5%). No single case of proven/probable IFD was diagnosed. Nine cases (8.7%) fulfilled criteria of possible pulmonary mould infection and received treatment for a median of 14days (r, 7-35). In an additional 12 procedures, empiric antifungal therapy with mould active agents was given for a median of 8days (r, 3-105). Microbiologically documented non-fungal infections were observed in 17 procedures, and five patients were transferred to the ICU. There was one death from biopsy documented toxic endothelial damage at day 83 post-transplant. Autologous HSCT for solid tumours or lymphoma was associated with low morbidity from IFDs. However, utilisation of systemic antifungal agents for prevention and management of suspected IFDs was considerable.

Effect of an intervention to improve the prescription of antifungals in pediatric hematology-oncology.

The use of antifungals has expanded in pediatric hematology-oncology, and the need to develop pediatric-based surveillance and education activities is becoming crucial. The aims of this study were to evaluate the impact of a multidisciplinary protocol on the adequacy of antifungal prescription in a pediatric hematology-oncology unit and to assess the effect of an educational intervention to improve the knowledge of prescribing pediatricians over time. A multidisciplinary team established a protocol for the management of invasive fungal disease (IFD). The use of antifungals before (January 2012-May 2013) and after the protocol (June 2013-December 2015) was evaluated. Prescribing pediatricians attended a training course on IFD and were evaluated before 0, 6, and 12 months after the intervention. During the study period, antifungal agents were used in 185 episodes (56 children, 39.3% females), and were administered as prophylaxis (58.9%), empiric (34.6%), or targeted therapy (6.5%). Antifungal prescriptions were inadequate in 7% of the episodes, related to drug selection (53.8%), dosage (38.5%) and route of administration (7.7%). After protocol implementation, inadequate prescriptions decreased 9.9% (15.2% vs 5.3%; P=.04). Following the educational activity, the percentage of adequate responses to the questionnaire improved significantly compared to baseline, and persisted over time (19.7% improvement at 0 months [P<.0001]; 21.1% at 6 months [P<.0001]; 16.6% at 12 months [P=.002]). The establishment of multidisciplinary protocols and education activities improved the quality of antifungal prescription and the knowledge of prescribers regarding antifungal therapy. Therefore, these activities may be important for the implementation of antifungal stewardship programs in pediatrics.

Advances in the Diagnosis and Management of Invasive Fungal Disease

Advances in the Diagnosis and Management of Invasive Fungal Disease

National mycology laboratory diagnostic capacity for invasive fungal diseases in 2017: Evidence of sub-optimal practice

A survey of laboratory testing capabilities for systemic fungal pathogens was undertaken in the UK, to identify where improved compliance with published standards and guidelines is required and to inform antifungal stewardship (AFS). The survey captured information from laboratories in the UK on diagnostic capacity for invasive fungal diseases (IFD), including identification, serology, molecular diagnostics and susceptibility testing. The survey was circulated in March 2017 through key networks. Of 154 laboratories providing diagnostic mycology services in the UK, 80 (52%) responded to the survey. Results indicated that 85% of respondents identified fungal isolates from high risk patients to species level, and that many laboratories (78%) could access local susceptibility testing for yeasts, whereas 17% could for Aspergillus species. However, direct microscopy was only used in 49% as a first line investigation on samples where it would be appropriate. A low number of respondents identified yeasts cultured from intravascular line tips to species level (63%) and even fewer fully identified urine isolates from critically ill patients (42%) or the immunocompromised (39%). Less than half of respondents advised therapeutic drug monitoring (TDM) for flucytosine. Few laboratories had access to local β-glucan (4%) or galactomannan (20%) testing. The survey highlights that the current level of fungal diagnostics in the UK is below accepted best practice with an urgent need to improve across many diagnostic areas including the timely accessibility of fungal biomarkers, susceptibility testing and provision of TDM testing. Improvements are important to facilitate the delivery of diagnostic driven AFS strategies as well as appropriate management of IFD.

Management of Invasive Fungal Disease in Neonates and Children.

Invasive fungal diseases (IFD) are an important cause of morbidity and mortality in premature neonates and immunocompromised pediatric patients. Their diagnostic and therapeutic management remains a challenge. A nationwide survey was conducted among 13 of the largest pediatric units in the United Kingdom, to obtain insight in the current management of IFD in neonates and children. All responding centers were tertiary teaching centers. The use of fungal diagnostic tools and imaging modalities varied among centers. Antifungal prophylaxis was prescribed in most centers for extreme-low birth weight (LBW) infants and high-risk hemato-oncologic patients, but with a huge variety in antifungals given. An empirical treatment was favored by most centers in case of febrile neutropenia. First line therapy for candidemia consists of either fluconazole or liposomal amphotericin B, with voriconazole being first-line therapy for invasive aspergillosis. Disseminated invasive aspergillosis was most often mentioned as a reason to prescribe combination antifungal therapy. In conclusion, this survey reinforces the fact that there are still important aspects in the management of pediatric IFD which should ideally be addressed in pediatric clinical trials. Attention needs to be given the knowledge gaps as observed in the results of our survey to optimize the management of IFD in children and neonates.

Diagnostic-driven management of invasive fungal disease in hematology in the era of prophylaxis and resistance emergence: Dutch courage?

Patients receiving intensive anti-leukemic treatment or recipients of allogeneic hematopoietic stem cell transplantation (HSCT) are prone to develop invasive fungal disease caused by both Aspergillus and non-Aspergillus moulds. Overall mortality following invasive mould disease (IMD) is high; adequate and timely antifungal treatment seems to ameliorate the outcome, yet early diagnosis in the haematological patient remains a challenge for most clinicians. Prophylaxis and the empiric addition of antifungal therapy to neutropaenic patients with fever persisting or recurring during broad-spectrum antibiotic treatment is therefore standard of care in many institutions. However, aside from the potential for overtreatment and important side effects, the emergence of resistance to medical triazoles in Aspergillus fumigatus poses a risk for inadequate initial treatment. Initial voriconazole therapy in patients with azole-resistant invasive aspergillosis was recently shown to be associated with a 23% increased mortality rate compared to the patients with azole-susceptible infection, despite changing to appropriate antifungal therapy once resistance was detected. Moreover, fever is not always present with IMD; therefore, cases may be missed when relying solely on this symptom for starting diagnostic procedures and antifungal treatment. At our institution, a diagnostic-driven treatment approach for IMD was implemented relying on clinical but also laboratory markers to start antifungal treatment. We describe the basis and clinical implementation of our diagnostic-driven approach in this review.

Invasive fungal disease and cytomegalovirus infection: is there an association?

Invasive fungal disease (IFD) and cytomegalovirus (CMV) infections occur frequently, either concomitantly or sequentially in immune-compromised hosts. Although there is extensive knowledge of the risk factors for these infections as single entities, the inter-relationship between opportunistic fungii and CMV has not been comprehensively explored. Both solid organ and stem cell transplant recipients who develop CMV invasive organ disease are at an increased risk of developing IFD, particularly aspergillosis and Pneumocystis pneumonia (PCP). Moreover, CMV viremia and recipient CMV serostatus also increased the risk of both early and late-onset IFD. Treatment-related factors, such as ganciclovir-induced neutropenia and host genetic Toll-like receptor (TLR) polymorphisms are likely to be contributory. Less is known about the relationship between CMV and IFD outside transplantation, such as in patients with hematological cancers or other chronic immunosuppressive conditions. Finally, few studies report on the relationship between CMV-specific treatments or the viral/antigen kinetics and its influence on IFD management. CMV infection is associated with increased risk of IFD in posttransplant recipients because of a number of overlapping and virus-specific risk factors. Better understanding of how CMV virus, its related treatment, CMV-induced immunosuppression and host genetic factors impact on IFD is warranted.

Diagnostic Imaging and Invasive Fungal Diseases in Children.

Invasive fungal disease (IFD) is a life-threatening condition, especially in immunocompromised children. The role of diagnostic imaging in children at risk for an IFD is multifactorial, including initially detecting it, evaluating for dissemination of infection beyond the primary site of disease, monitoring the response to antifungal therapy, and assessing for potential relapse. The objective of this review was to synthesize the published literature relevant to the use of various imaging modalities for the diagnosis and management of IFD in children.

The Chinese guidelines for the diagnosis and treatment of invasive fungal disease in patients with hematological disorders and cancers (the fifth revision)

Invasive fungal disease(IFD) is a common yet highly lethal complication in patients with hematological malignancies receiving chemotherapy or stem cell transplantation, as well as immune suppressive conditions including aplastic anemia and other malignancies. According to the diagnostic criteria, patients are defined as proven, probable, possible and undefined IFD based on the evidence provided by histopathologic/cytologic, culture, radiographic and biomarker examinations. For the management of IFD, the major treatment strategies consist of prophylaxis, empirical, diagnostic-driven and target therapy. The Chinese Invasive Fungal Infection Working Group has developed the Chinese consensus for the diagnosis and treatment of invasive fungal disease based on international guidelines and local experience. Recently, the working group revises the consensus by update international guidelines and clinical studies in China.

A prospective study of fungal biomarkers to improve management of invasive fungal diseases in a mixed specialty critical care unit

PurposeThe diagnosis of invasive fungal diseases (IFD) in critical care patients (CrCP) is difficult. The study investigated the performance of a set of biomarkers for diagnosis of IFD in a mixed specialty critical care unit (CrCU). MethodsA prospective observational study in patients receiving critical care for ≥7days was performed. Serum samples were tested for the presence of: (1-3) - β-d-glucan (BDG), galactomannan (GM), and Aspergillus fumigatus DNA. GM antigen detection was also performed on bronchoalveolar lavage (BAL) samples. The patients were classified using published definitions for IFD and a diagnostic algorithm for invasive pulmonary aspergillosis. Performance parameters of the assays were determined. ResultsIn patients with proven and probable IFD, the sensitivity, specificity, PPV and NPV of a single positive BDG were 63%, 83%, 65% and 83% respectively. Specificity increased to 86% with 2 consecutive positive results. The mean BDG value of patients with proven and probable IFD was significantly higher compared to those with fungal colonization and no IFD (p value<0.0001). ConclusionNew diagnostic criteria which incorporate these biomarkers, in particular BDG, and host factors unique to critical care patients should enhance diagnosis of IFD and positively impact antifungal stewardship programs.

The role of the multidisciplinary team in antifungal stewardship.

There are a variety of challenges faced in the management of invasive fungal diseases (IFD), including high case-fatality rates, high cost of antifungal drugs and development of antifungal resistance. The diagnostic challenges and poor outcomes associated with IFD have resulted in excessive empirical use of antifungals in various hospital settings, exposing many patients without IFD to potential drug toxicities as well as causing spiralling antifungal drug costs. Further complexity arises as different patient groups show marked variation in their risk for IFD, fungal epidemiology, sensitivity and specificity of diagnostic tests and the pharmacokinetics and pharmacodynamics of antifungal drugs. To address these issues and to ensure optimal management of IFD, specialist knowledge and experience from a range of backgrounds is required, which extends beyond the remit of most antibiotic stewardship programmes. The first step in the development of any antifungal stewardship (AFS) programme is to build a multidisciplinary team encompassing the necessary expertise in the management of IFD to develop and implement the AFS programme. The specific roles of the key individuals within the AFS team and the importance of collaboration are discussed in this article.

Antifungal prophylaxis of patients undergoing allogenetic hematopoietic stem cell transplantation in China: a multicenter prospective observational study.

BackgroundAntifungal prophylaxis is currently regarded as the gold standard in situations with allo-genetic hematopoietic stem cell transplantation (allo-HSCT). However, the epidemiological information regarding prophylaxis of invasive fungal diseases (IFDs) is not clear in China.MethodsWe report the first large-scale (1053 patients) observational study of the prophylaxis and management of IFDs among patients with allo-HSCT in China.ResultsThe incidence rates of IFD after primary antifungal prophylaxis (PAP), secondary antifungal prophylaxis (SAP), and non-prophylaxis were 22.7 vs. 38.6 vs. 68.6 %, respectively (P = 0.0000). The median time from transplantation to IFD was 45 days in PAP patients, 18 days in SAP patients, and 12 days in non-prophylaxis patients. Aspergillus spp. represents the most common type of fungal infection. Independent risk factors for IFD in allo-HSCT patients with PAP were age, having human leukocyte antigen (HLA)-haploidentical or matched unrelated donor, decreased albumin levels, and the use of itraconazole as the prophylactic antifungal agent. Among SAP transplant recipients, there was no significant risk factor for IFDs. The incidence rates of overall survival (OS) in the PAP, SAP, and no prophylaxis groups were 85.07, 78.80, and 74.82, respectively (P = 0.01).ConclusionsThis observational study indicates that prophylaxis of IFD is helpful to reduce the incidence of IFDs and improve the OS of patients after allo-HSCT.

Radiologic Imaging Techniques for the Diagnosis and Management of Invasive Fungal Disease

Invasive fungal diseases (IFDs) are an important cause of morbidity and mortality, especially in immunocompromised patients. Prompt antifungal therapy is essential for favorable outcomes, but clinical signs and symptoms are nonspecific and mycologic confirmation is often not possible. Radiographic testing is an important adjunct to the diagnosis and management of IFDs. Early imaging has been associated with improved survival, particularly in neutropenic patients with fungal pneumonia or acute invasive fungal sinusitis. This review summarizes common radiologic appearances of IFDs of the lung, sinus, and brain. The advantages and limitations of computed tomography (CT) and magnetic resonance (MR) imaging are discussed as are recent developments in nuclear medicine and proton MR spectroscopy technology.

Risk and prognostic factors for invasive fungal diseases in paediatric patients with malignancy

Background Invasive fungal diseases (IFDs) remain a challenge in the treatment of patients with haematological malignancies. Aims The aim of the study was to evaluate factors that are thought to favour the onset of IFDs and identify prognostic factors that could predict the eventual outcome of these infections. Patients and methods A systematic review of the literature was conducted for an explicit identification of risk and prognostics factors for IFDs in immunocompromised children. We retrospectively reviewed two age-matched and sex-matched patients with refractory acute myeloid leukaemia who had undergone allogeneic bone marrow transplantation. Results Both patients were exposed to the same hospital conditions and had been admitted for the first time at nearly the same period. They had two different paths as regards the development and outcome of IFD. Conclusion Several factors may have an impact on the onset and outcome of IFDs, and identification of these factors is essential to the evaluation and management of IFD and for timely establishment of appropriate antifungal therapy. Egyptian J Haematol 40:-0 ͹ 2015 The Egyptian Society of Haematology.

SP-017 PRODUCTS SITUATION OF THE BIOSIMILARS IN TURKEY AND IN THE WORLD

SP-017 – Table 1. Registered biosimiliars in Turkey (2009–2013) Product name Active substance Production site Reg. year, licensee LEUCOSTIM FILGRASTIM SOUTH KOREA (DONG-A) 2009, DEMMEDIKAL VE ECZA DEPOSU SAN VE TIC. LTD. STI. EPOBEL EPOETIN ZETA GERMANY (STADA) 2009, NOBEL ILAC PAZARLAMA VE SAN. LTD. STI. EPORON EPOETIN ALFA SOUTH KOREA (DONG-A) 2011, DEMMEDIKAL VE ECZA DEPOSU SAN VE TIC. LTD. STI. OMNITROPE SOMATROPIN AUSTRIA (SANDOZ) 2011, SANDOZ ILAC SAN. VE TIC. A.S. OKSAPAR ENOXAPARIN SODIUM TURKEY 2012, KOCAK FARMA ILAC VE KIMYA SAN. A.S. CLOTINAB ABCIXIMAB SOUTH KOREA (DONG-A) 2012, DEMMEDIKAL VE ECZA DEPOSU SAN VE TIC. LTD. STI. EPOPLUS EPOETIN ALFA CUBA 2013 HASBIOTECH ILAC SAN. VE TIC. A.S. ENOX ENOXAPARIN SODIUM TURKEY 2013, ATABAY KIMYA SAN. VE TIC. A.S. DROPOETIN EPOETIN ALFA TURKEY 2013, DROGSAN ILACLARI SAN. VE TIC. A.S. within 5 years of diagnosis. Thrombosis and CKD are leading causes of death in PNH: 40–67% of death are due to venous and arterial thrombosis, 64% of patients have CKD, which causes mortality in 8–18% of those patients. aHUS is a severe life-threatening disorder of uncontrolled complement activation resulting in thrombotic microangiopathy (TMA) in children and adults. TMA has a devastating impact on kidneys and other vital organs, 60% pf patients require dialysis, undergo kidney transplant or die within 1 year of diagnosis. The humanized monoclonal antibody eculizumab inhibits the terminal complement cascade by binding to human complement protein C5, inhibiting the formation of proinflammatory, prothrombotic C5a and C5b, with subsequent inhibition of assembly of the membrane attack complex. Multinational clinical studies in patients with PNH and aHUS demonstrated that eculisumab induces a rapid and clinically significant reduction in intravascular hemolysis and thrombotic events in PNH patients and TMA control and improvement of renal function in patients with aHUS. The data from Russian PNH and aHUS Registry present the demographic and clinical characteristics, incidence of complications and experience of patient treatment. Russian cohort in PNH Registry counts app 500 pts, aHUS app 40 pts. Recent achievements in diagnostic and treatment of PNH and aHUS made us responsible for the National guidelines development. There are several disease models described in the PNH guidelines where Russian experts recommend to use pathogenetic treatment. aHUS diagnostic and treatment experience also resulted in the Experts position paper and requires further consolidated efforts to prepare useful document for the medical community. SP-020 DIAGNOSIS, CLINICAL MANAGEMENT AND STEWARDSHIP FOR INVASIVE FUNGAL DISEASE IN HAEMATO-ONCOLOGY S.G. Agrawal. Department of Haemato-Oncology, Stem Cell Laboratory and Immunophenotyping Sections, Barts Health NHS Trust, London; Pathology Group, Blizard Institute, Queen Mary University of London, UK Antimicrobial stewardship has become a headline priority for governments and for international bodies, such as WHO. Antifungal stewardship is a highly specialized subset of this approach. I will discuss stewardship in the context of Haemato-Oncology as a further tool to ensure optimal patient management and resource utilization, over and beyond the development of care pathways for invasive fungal disease (IFD). A successful pathway requires “ownership” of the pathway by the clinical team looking after the patient, radiology, microbiology, infectious disease and respiratory physicians. . . My presentation will focus on the current debate on management strategies for IFD in Haemato-Oncology and the changes in our management algorithms over the last 12 years at St Bartholomew’s Hospital, London. I will present our updated diagnostic strategy, which uses three tests directed at Aspergillus detection – PCR, galactomannan and the LFD assay. The introduction of this triple testing strategy – “TRIADx” – will support the antifungal stewardship team, which will work closely with the Haemato-Oncology physicians and guide all aspects of IFD management.

SP-019 PATHOGENETIC TREATMENT OF PNH AND AHUS: RUSSIAN EXPERIENCE

SP-017 – Table 1. Registered biosimiliars in Turkey (2009–2013) Product name Active substance Production site Reg. year, licensee LEUCOSTIM FILGRASTIM SOUTH KOREA (DONG-A) 2009, DEMMEDIKAL VE ECZA DEPOSU SAN VE TIC. LTD. STI. EPOBEL EPOETIN ZETA GERMANY (STADA) 2009, NOBEL ILAC PAZARLAMA VE SAN. LTD. STI. EPORON EPOETIN ALFA SOUTH KOREA (DONG-A) 2011, DEMMEDIKAL VE ECZA DEPOSU SAN VE TIC. LTD. STI. OMNITROPE SOMATROPIN AUSTRIA (SANDOZ) 2011, SANDOZ ILAC SAN. VE TIC. A.S. OKSAPAR ENOXAPARIN SODIUM TURKEY 2012, KOCAK FARMA ILAC VE KIMYA SAN. A.S. CLOTINAB ABCIXIMAB SOUTH KOREA (DONG-A) 2012, DEMMEDIKAL VE ECZA DEPOSU SAN VE TIC. LTD. STI. EPOPLUS EPOETIN ALFA CUBA 2013 HASBIOTECH ILAC SAN. VE TIC. A.S. ENOX ENOXAPARIN SODIUM TURKEY 2013, ATABAY KIMYA SAN. VE TIC. A.S. DROPOETIN EPOETIN ALFA TURKEY 2013, DROGSAN ILACLARI SAN. VE TIC. A.S. within 5 years of diagnosis. Thrombosis and CKD are leading causes of death in PNH: 40–67% of death are due to venous and arterial thrombosis, 64% of patients have CKD, which causes mortality in 8–18% of those patients. aHUS is a severe life-threatening disorder of uncontrolled complement activation resulting in thrombotic microangiopathy (TMA) in children and adults. TMA has a devastating impact on kidneys and other vital organs, 60% pf patients require dialysis, undergo kidney transplant or die within 1 year of diagnosis. The humanized monoclonal antibody eculizumab inhibits the terminal complement cascade by binding to human complement protein C5, inhibiting the formation of proinflammatory, prothrombotic C5a and C5b, with subsequent inhibition of assembly of the membrane attack complex. Multinational clinical studies in patients with PNH and aHUS demonstrated that eculisumab induces a rapid and clinically significant reduction in intravascular hemolysis and thrombotic events in PNH patients and TMA control and improvement of renal function in patients with aHUS. The data from Russian PNH and aHUS Registry present the demographic and clinical characteristics, incidence of complications and experience of patient treatment. Russian cohort in PNH Registry counts app 500 pts, aHUS app 40 pts. Recent achievements in diagnostic and treatment of PNH and aHUS made us responsible for the National guidelines development. There are several disease models described in the PNH guidelines where Russian experts recommend to use pathogenetic treatment. aHUS diagnostic and treatment experience also resulted in the Experts position paper and requires further consolidated efforts to prepare useful document for the medical community. SP-020 DIAGNOSIS, CLINICAL MANAGEMENT AND STEWARDSHIP FOR INVASIVE FUNGAL DISEASE IN HAEMATO-ONCOLOGY S.G. Agrawal. Department of Haemato-Oncology, Stem Cell Laboratory and Immunophenotyping Sections, Barts Health NHS Trust, London; Pathology Group, Blizard Institute, Queen Mary University of London, UK Antimicrobial stewardship has become a headline priority for governments and for international bodies, such as WHO. Antifungal stewardship is a highly specialized subset of this approach. I will discuss stewardship in the context of Haemato-Oncology as a further tool to ensure optimal patient management and resource utilization, over and beyond the development of care pathways for invasive fungal disease (IFD). A successful pathway requires “ownership” of the pathway by the clinical team looking after the patient, radiology, microbiology, infectious disease and respiratory physicians. . . My presentation will focus on the current debate on management strategies for IFD in Haemato-Oncology and the changes in our management algorithms over the last 12 years at St Bartholomew’s Hospital, London. I will present our updated diagnostic strategy, which uses three tests directed at Aspergillus detection – PCR, galactomannan and the LFD assay. The introduction of this triple testing strategy – “TRIADx” – will support the antifungal stewardship team, which will work closely with the Haemato-Oncology physicians and guide all aspects of IFD management.

Role of Management Strategies in Reducing Mortality From Invasive Fungal Disease in Children With Cancer or Receiving Hemopoietic Stem Cell Transplant

In the last decades, several diagnostic and therapeutic strategies have been implemented for management of invasive fungal diseases (IFD) in patients with cancer or receiving allogeneic hemopoietic stem cell transplant. Few data are available on their impact on mortality in children. All IFD episodes diagnosed at tertiary care center during a 30-year period between 1983 and 2012 were analyzed for 90-day mortality and risk factors. Diagnoses were coded according to international (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) criteria. Four treatment eras (1983-1990, 1991-1999, 2000-2005 and 2006-2012) were defined according to availability of diagnostic technologies, new antifungal drugs and use of a diagnostic-driven approach without empiric antifungal therapy. A total of 198 IFD were diagnosed in 191 patients; 71.2% were proven/probable infections; 39.9% were caused by yeasts and 31.3% by molds. Within 90 days from IFD diagnosis, 58 (30.4%) patients died for a 28.3% cumulative probability of death. A multivariable analysis showed that the highest risk of death was associated with alternative donor-hemopoietic stem cell transplant [hazard ratio (HR): 3.96] and mold etiology (HR: 1.34). The risk of death significantly decreased across the treatment eras, with almost a 3-fold reduced risk for patients diagnosed during the 2006-2012 period (HR: 0.24). Also if the variable year of diagnosis was considered as continuous, the hazard of death significantly decreased by 5% per year (HR: 0.95). New management strategies resulted in a better prognosis of IFD in children with cancer or hemopoietic stem cell transplant. A diagnostic-driven approach was not associated with an increase in mortality.

A multidisciplinary team approach to the management of patients with suspected or diagnosed invasive fungal disease

Implementation of evidence-based guidelines for the treatment of invasive fungal disease (IFD) requires collaboration among numerous clinical and laboratory services, as partners in patient care. The multidisciplinary team (MDT) approach has emerged as a way of providing comprehensive medical care by bringing together professionals from a wide range of disciplines in a coordinated and effective manner. Here, we propose an MDT model for IFD management aimed at facilitating communication among consultants, adherence to clinical pathways and optimized use of resources available at each centre.

Care pathways for managing invasive mould diseases

In the last decade, there have been some favourable developments in the management of invasive fungal diseases, including definitions, diagnosis and drugs for treatment. This has led to a gradual awareness that caring for patients at risk need not solely rely on an empirical therapy approach but that a degree of individualisation is possible, provided certain prerequisites are met.

Prevention and diagnosis of invasive fungal disease in high-risk patients within an integrative care pathway

The aim of this study was to assess the clinical utility of enhanced diagnostics on the management of invasive fungal disease in high risk patients within an integrated care pathway and to audit compliance and efficacy of antifungal prophylaxis. A cohort of 549 high risk haematology and stem-cell transplant recipients was followed over a 5 year period. The routine standard of care involved the use of antimould prophylaxis and a neutropenic care pathway utilizing twice weekly antigen and PCR testing. Prophylaxis with itraconazole was poorly tolerated and therapeutic levels could not be maintained. Antigen testing and PCR showed good clinical utility in the management of invasive aspergilosis with high sensitivity (98%) and negative predictive value (99.6%) when both tests were used together, allowing a diagnosis IA to be excluded and obviating the need for empirical antifungal agents. When used serially, multiple positive PCR and antigen test results enabled accurate diagnosis of IA with a specificity of 95% and a positive likelihood ratio of 11. Biomarkers preceded clinical signs in 85% of proven and probable invasive disease. The combination of both tests showed optimum clinical utility for the diagnosis and management of IA in this high risk group.