Peryton: a manual collection of experimentally supported microbe-disease associations.

We present Peryton (https://dianalab.e-ce.uth.gr/peryton/), a database of experimentally supported microbe-disease associations. Its first version constitutes a novel resource hosting more than 7900 entries linking 43 diseases with 1396 microorganisms. Peryton's content is exclusively sustained by manual curation of biomedical articles. Diseases and microorganisms are provided in a systematic, standardized manner using reference resources to create database dictionaries. Information about the experimental design, study cohorts and the applied high- or low-throughput techniques is meticulously annotated and catered to users. Several functionalities are provided to enhance user experience and enable ingenious use of Peryton. One or more microorganisms and/or diseases can be queried at the same time. Advanced filtering options and direct text-based filtering of results enable refinement of returned information and the conducting of tailored queries suitable to different research questions. Peryton also provides interactive visualizations to effectively capture different aspects of its content and results can be directly downloaded for local storage and downstream analyses. Peryton will serve as a valuable source, enabling scientists of microbe-related disease fields to form novel hypotheses but, equally importantly, to assist in cross-validation of findings.

The High Diversity and Variable Susceptibility of Clinically Relevant Acremonium-Like Species in China.

Acremonium-like fungi are emerging as important opportunistic pathogens in cutaneous, subcutaneous and serious invasive infections, especially in immunocompromised and debilitated individuals, and Acremonium infections are usually resistant to antifungal therapy. Several molecular studies have demonstrated that many species in the genus Acremonium are polyphyletic, and currently, the genus is restricted to the family Bionectriaceae (Hypocreales). Molecular identification and in vitro antifungal susceptibility tests of Acremonium-like fungi isolated from human clinical specimens in China were performed in this study. Three genetic loci: the large subunit ribosomal RNA gene (LSU), ribosomal internal transcribed spacer and elongation factor 1-α (EF1-α), were used to assess their taxonomic position for correct identification among various species. The multilocus study of twenty-eight strains showed that these strains were distributed in three main lineages: egyptiacum, Cordycipitaceae and Sarocladium; Acremonium egyptiacum and Sarocladium kiliense were the main species of these strains, and three isolates were too phylogenetically distant to be considered undescribed species. Relatively low minimum inhibitory concentrations (MICs) of 0.25-2 and 0.031-0.5 µg/mL were found for voriconazole and terbinafine for most species, respectively. Varied antifungal activities of ciclopirox olamine, amorolfine and posaconazole were found in our study. However, no antifungal effect of sertaconazole, itraconazole or fluconazole was observed against most strains. This is the first study on Acremonium-like species diversity by multilocus sequence analyses and antifungal susceptibility of clinically relevant isolates in China.

Acute Invasive Fungal Rhinosinusitis: Presentation of 19 Cases, Review of the Literature, and a New Classification System.

PURPOSE: The aim of this study was to determine the correlation between acute invasive fungal rhinosinusitis (AIFRS) and underlying diseases, micro-organisms, presenting symptoms, extent of disease, radiologic findings, and outcomes and propose a new classification system. MATERIALS AND METHODS: The data of 19 AIFRS cases were analyzed retrospectively. Magnetic resonance imaging and computed tomography were performed in all patients preoperatively. All patients underwent at least 1 surgical debridement. RESULTS: Hematologic diseases were the most common (52%) underlying diseases. Patients with type 2 diabetes and those with multiple etiologies causing immunosuppression had the lowest survival. Aspergillus and Mucoraceae species were isolated in 9 patients but were not associated with poor prognosis. Headache and nasal discharge or crusting were the most common presenting symptoms. Premaxillary involvement was significantly correlated with poor prognosis (P = .001). Unilateral involvement was correlated with poor prognosis, although this finding was not significant (P = .111). The overall mortality rate was 61.2%. Patients with neutropenia that was corrected had 80% survival (P = .014). Cessation of corticosteroids and regulating blood glucose levels in patients with immunosuppression from corticosteroid use resulted in 75% survival. CONCLUSION: There is no single curative treatment for AIFRS. For a favorable prognosis, underlying conditions must be treated in addition to surgical debridement and antifungals.

Overview of Fungal Infections--The Italian Experience.

The incidence of severe fungal infections has increased worldwide and represents a serious threat, especially among immunocompromised and critically ill patients. Most common pulmonary fungal infections include aspergillosis, cryptococcosis, and Pneumocystis jiroveci pneumonia. Among nosocomial bloodstream infections, Candida spp. is the most common isolated fungus. Mortality rates up to 60% in critically ill patients with Candida infections and 90% in hematological patients with invasive aspergillosis are reported. Furthermore, fungal infections contribute to high morbidity and prolonged hospitalizations. Since standard cultural methods can show low sensitivity or provide delayed responses, new non-culture-dependent methods such as galactomannan ß-D-glucan are now available. Novel antifungal compounds (e.g., amphotericin B lipid formulations, last-generation azoles, and echinocandins) have been introduced in the recent years. Nevertheless, despite new advances the appropriate use of diagnostic assays along with a thorough therapeutic management remain the key to ensure an early appropriate targeted treatment that represents the crucial factor to attain a successful approach to severe fungal infections.

Posaconazole: Use in the Prophylaxis and Treatment of Fungal Infections.

Posaconazole, a fluorinated triazole antifungal drug, is approved by the U.S. Food and Drug Administration (FDA) for (1) prophylaxis against Aspergillus and Candida infections in immunocompromised patients at high risk for these infections and (2) oropharyngeal candidiasis (OPC), including cases refractory to fluconazole and/or itraconazole. The European Medicines Agency (EMA) has approved posaconazole for (1) treatment of aspergillosis, fusariosis, chromoblastomycosis, and coccidioidomycosis in patients who are refractory to or intolerant of other azoles or amphotericin B; (2) first-line therapy for OPC for severe disease or in those unlikely to respond to topical therapy; and (3) prophylaxis of invasive fungal infections in high-risk hematologic patients and stem cell transplant recipients. In addition to approved indications, posaconazole has been used with success as salvage therapy for invasive mold infections and endemic mycoses in patients who are refractory to or intolerant of other antifungal agents, and as prophylaxis or salvage therapy in children, for whom indications are more limited owing to a paucity of data. Posaconazole has potent in vitro activity against a broad range of fungi and molds, including Aspergillus, Candida, Cryptococcus, filamentous fungi, and endemic mycoses including coccidioidomycosis, histoplasmosis, and blastomycosis. Importantly, posaconazole is much more active than other azoles against many Mucorales species and the combination of posaconazole with other antifungal agents may be synergistic. Hence, posaconazole is a potential candidate as a single or combination agent for difficult-to-treat fungal infections. Posaconazole has an excellent safety profile; to date, serious side effects are rare, even with prolonged use. However, newer posaconazole formulations achieve higher blood levels and it remains to be seen whether this may lead to an increase in the rate of adverse effects. Currently, posaconazole is used predominantly for prophylaxis and salvage therapy of fungal infections in adults. Indications for use as initial therapy of fungal infections and for broader use in children will depend on the accrual of additional clinical data.

Voriconazole: How to Use This Antifungal Agent and What to Expect.

Voriconazole is an important agent in the antifungal armamentarium. It is the treatment of choice for invasive aspergillosis, other hyaline molds, and many brown-black molds. It is also effective for infections caused by Candida species, including those that are fluconazole resistant, and for infections caused by the endemic mycoses, including those that occur in the central nervous system. It has the advantage of being available in both an intravenous and an oral formulation that is well absorbed. Drawbacks to the use of voriconazole are that it has unpredictable, nonlinear pharmacokinetics with extensive interpatient and intrapatient variation in serum levels. Some of the adverse effects seen with voriconazole are related to high serum concentrations, and, as a result, therapeutic drug monitoring is essential when using this agent. Drug-drug interactions are common, and possible interactions must be sought before voriconazole is prescribed. With prolonged use, newly described adverse effects, including periostitis, alopecia, and development of skin cancers, have been noted.

Migration and mycoses.

In recent years, the incidence of fungal infections of the skin, one of the most frequent forms of infection, has been steadily increasing in Europe. One of the main factors contributing to this increase is the gradual raise of migratory flows towards Europe. In the last decades Italy has witnessed an ever-increasing growth of the migrant population, and has become, to this day, one of the European countries with the highest number of immigrants. This phenomenon has had significant implications in clinical practice of dermatologic mycology as it is increasingly common to see unusual clinical isolate causal agents absent in our latitudes until a short time ago. This review provides an update on the epidemiology, classification, pathogenesis, clinical manifestations and treatment of the most important dermato-mycosis observed in the immigrant population, through the most typical cases, investigated by microscopic and cultural findings. These diseases continue to expand and are often difficult to detect. The special relationship between host-environment interaction-parasite plays a crucial role as, even more than in other categories, it is widely widespread among the immigrants.

The morbidity and mortality of patients with fungal infections before and during extracorporeal membrane oxygenation support.

OBJECTIVE: To evaluate the prevalence of fungal infections (both pre-cannulation and post-cannulation) while on extracorporeal membrane oxygenation support and the associated morbidity and mortality. DESIGN: Retrospective cohort study. PATIENT AND METHODS: The Extracorporeal Life Support Organization database is an international voluntary registry of clinical data for patients placed on extracorporeal membrane oxygenation. The database was queried for all patients on extracorporeal membrane oxygenation from 1997 to 2009. Patient and extracorporeal membrane oxygenation data collected included age, support type, length of support, infection status and organism code, discharge status, complications, and component failures. Outcomes of interest were mortality, extracorporeal membrane oxygenation-related patient complications, and mechanical component failures. RESULTS: From 1997 to 2009, there were 21,073 patients' extracorporeal membrane oxygenation runs analyzed of which 12,933 were in the neonatal group (0-30 days), 6,073 were in the pediatric group (31 days to <18 yrs old), and 2,067 were in the adult group (≥18 yrs). The prevalence of fungal infection during extracorporeal membrane oxygenation varied by age group and timing of infection and ranged from 0.04% to 5%. Fungal infections pre-extracorporeal membrane oxygenation and on-extracorporeal membrane oxygenation conferred a statistically significant higher relative risk of mortality for all age groups and varied by support type and timing of infection. Extracorporeal membrane oxygenation-related complications and component failures were not statistically significantly affected by infection status. CONCLUSIONS: Fungal infection before or during extracorporeal membrane oxygenation increases the odds of mortality and the magnitude of this effect is dependent upon age-group and timing of infection. This increased mortality was not the result of increased patient or mechanical complications during extracorporeal membrane oxygenation. For patients with fungal infections pre-extracorporeal membrane oxygenation, 82%-89% demonstrated presumed clearance during extracorporeal membrane oxygenation. Although the risk of mortality increased with fungal infections, it does not appear that fungal infection before or during extracorporeal membrane oxygenation is a contraindication to initiation or continuation of support.

On chronic rhinosinusitis and the prevalence of fungal sinus disease: problems of diagnostic accuracy and a proposed classification of chronic rhinosinusitis.

There is considerable controversy in the diagnosis and classification of the type of inflammation that is attributed to various forms of chronic rhinosinusitis (CRS). Specimens obtained during surgical treatment of CRS have been invaluable resources for identifying the underlying inflammatory process. The classification of sinus inflammation is based on histopathologic examination of these surgical specimens. Accurate identification of the pathology and standardized reporting are invaluable for postsurgical treatment options and our understanding of CRS. In a large multispecialty referral hospital where multiple surgeons and pathologists are involved in clinical practice, the lack of standardization in specimen collection, specimen processing, and reporting introduce several variables that make it extremely difficult for retrospective analysis. This report focuses on consecutive endoscopic sinus surgical procedures performed by 4 different sinus surgeons over a period of 4 years in a Central Texas multispecialty hospital. This is an analysis of the reality of clinical practice without intervention. At the core of this analysis are pathology reporting practices for fungal sinus disease and the undesirable variables introduced by nonstandardized reporting. A practical classification of CRS based on pathology is proposed.

A global call for talaromycosis to be recognised as a neglected tropical disease.

Talaromycosis (penicilliosis) is an invasive mycosis that is endemic in tropical and subtropical Asia. Talaromycosis primarily affects individuals with advanced HIV disease and other immunosuppressive conditions, and the disease disproportionally affects people in low-income and middle-income countries, particularly agricultural workers in rural areas during their most economically productive years. Approximately 17 300 talaromycosis cases and 4900 associated deaths occur annually. Talaromycosis is highly associated with the tropical monsoon season, when flooding and cyclones can exacerbate the poverty-inducing potential of the disease. Talaromycosis can present as localised or disseminated disease, the latter causing cutaneous lesions that are disfiguring and stigmatising. Despite up to a third of diagnosed cases resulting in death, talaromycosis has received little attention and investment from regional and global funders, policy makers, researchers, and industry. Diagnostic and treatment modalities remain extremely insufficient, however control of talaromycosis is feasible with known public health strategies. This Viewpoint is a global call for talaromycosis to be recognised as a neglected tropical disease to alleviate its impact on susceptible populations.

Estimates of serious fungal infection burden in Côte d'Ivoire and country health profile.

Due to limited access to more powerful diagnostic tools, there are few data on the burden of fungal infections in Côte d'Ivoire, despite a high HIV and TB burden and many cutaneous diseases. Here we estimate the burden of serious fungal infections in this sub-Saharan country with a health profiling description. National demographics were used and PubMed searches to retrieve all published articles on fungal infections in Côte d'Ivoire and other bordering countries in West Africa. When no data existed, risk populations were used to estimate frequencies of fungal infections, using previously described methodology by LIFE (www.LIFE-Worldwide.org). The population of Côte d'Ivoire is around 25 million; 37% are children (≤14 years), and 9% are>65 years. Tinea capitis in children is common, measured at 13.9% in 2013. Considering the prevalence of HIV infection (2.6% of the population, a total of ∼500,000) and a hospital incidence of 12.7% of cryptococcosis, it is estimated that 4590 patients per year develop cryptococcosis. For pneumocystosis, it is suggested that 2640 new cases occur each year with the prevalence of 11% of newly diagnosed HIV adults, and 33% of children with HIV/AIDS. Disseminated histoplasmosis is estimated a 1.4% of advanced HIV disease - 513 cases. An estimated 6568 news cases of chronic pulmonary aspergillosis (CPA) occur after pulmonary tuberculosis (a 5-year prevalence of 6568 cases [26/100,000]). Allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitisation (SAFS) were estimated in 104/100,000 and 151/100,000 respectively, in 1,152,178 adult asthmatics. Vulvovaginal candidiasis (VVC) is common and recurrent VVC affects ∼6% of women in their fertile years - 421,936 women. An unknown number develop candidaemia and invasive aspergillosis. The annual incidence of fungal keratitis is estimated at 3350. No cases of sporotrichosis, mucormycosis and chromoblastomycosis are described, although some cases of mycetoma and Conidiobolus infection have been reported. This study indicates that around to 7.25% (1.8 million) of the population is affected by a serious fungal infection, predominently tinea capitis in children and rVVC in women. These data should be used to inform epidemiological studies, diagnostic needs and therapeutic strategies in Côte d'Ivoire.

[Amphotericin B deoxycholate prescription and adverse events in a Chilean university hospital]. / Uso de anfotericina B deoxicolato y sus reacciones adversas en un hospital universitario en Chile.

UNLABELLED: Amphotericin B deoxycholate is associated with infusion-related toxicity and renal toxicity. PURPOSE: To evaluate medical indications of this compound in a tertiary care center, analyze adverse reactions, infusion protocols and outcome of treated patients. PATIENTS AND METHODS: Retrospective analysis of 39 treatments indicated in 33 patients during 2007, exploring indications, infusion protocols and renal protective measures, infusion-related adverse reactions, nephrotoxicity, hypokalemia and outcomes. RESULTS: On average, therapy lasted 12 days (2 to 39) and reached 600 mg of accumulated dose (100 to 1950) respectively. 24-hours infusions were applied in 63.2% of prescriptions and 35.9% received a 4-6 hour infusion schedule. In addition, 36.8% received daily a saline infusion before amphotericin. Adverse reactions were observed in 40% of treatments, predominating fever (25%). Nonetheless, nephrotoxicity was infrequent (9.4%), of low magnitude, only affecting patients without previous renal disease, and not requiring dialysis. Hypokalemia developed in 21.6% of treatments. More than half of medical indications were empirical (59%), for presumed infections by either filamentous fungi or yeasts. In the subgroup with microbiological information, main indications were invasive aspergillosis (15.4% of total), systemic candidiasis (12.8%) or meningeal cryptococcosis (10.3%). A favorable response was registered in 41%, and only 48.5% of patients survived. In a multivariate analysis, only age > 60 years remained as an independent factor for developing infusion-related adverse reactions. In the same manner, a SOFA score > 3 and corticosteroids administration at the same time than amphotericin B, were independently associated to a fatal outcome. CONCLUSION: infusion-related adverse reactions are frequent during amphotericin B deoxycholate therapy, but renal toxicity is occasionally observed. Amphotercin B was used mainly as empirical therapy in this study.

Spectrum of fungal rhinosinusitis; histopathologist's perspective.

AIMS: Clinical presentation can provide a clue to the subcategories of fungal rhinosinusitis (FRS); however, tissue examination provides accurate classification. The aim was to analyse the incidence and histopathological spectrum of FRS. METHODS AND RESULTS: A retrospective analysis of all the cases of rhinosinusitis reported in the last 5 years was carried out. Haematoxylin and eosin-stained sections along with special stains such as periodic acid-Schiff and Grocott's were examined. These cases were subclassified based on the presence of allergic mucin, mycelial elements and tissue reaction. Out of a total of 665 cases of rhinosinusitis, 284 (42.7%) were of FRS. On histopathological examination they were broadly categorized as: (i) non-invasive FRS (n = 171, 60.2%), which included 160 cases (56.3%) of allergic fungal rhinosinusitis (AFRS) and eleven (3.9%) of fungal ball; (ii) invasive FRS (n = 101, 35.6%), which included 48 cases (16.9%) of chronic invasive granulomatous FRS, four (1.4%) of chronic invasive FRS and 49 (17.3%) of acute fulminant FRS; and (iii) mixed pattern FRS, comprising 12 cases (4.25%). CONCLUSIONS: AFRS is the most common type of FRS. Cases with mixed reaction pattern suggest that different types of FRS represent a progressive spectrum of disease. An exact histopathological categorization of FRS is important as regards treatment.

Controversies surrounding the categorization of fungal sinusitis.

Though rhinosinusitis is a common disorder, controversies surround the categorization of chronic rhinosinusitis (CRS) and the role of fungus in CRS. The diagnosis of each category is important for optimum therapy and predicting the course. Based on histopathological findings, fungal rhinosinusitis (FRS) can be broadly divided into two categories: the invasive and non-invasive depending on invasion of the mucosal layer. Three types of FRS are tissue-invasive: acute invasive, chronic invasive, & granulomatous. The two non-invasive FRS disorders are fungal ball, and fungus related eosinophilic rhinosinusitis including allergic fungal rhinosinusitis (AFRS). The distinction of granulomatous from chronic invasive type is not beyond controversy as both types have a chronic course and predominant orbital involvement. Maximum confusion surrounds the entity of fungus-related eosinophilic rhinosinusitis, and the definition of AFRS. In the diagnosis of AFRS, the detection of fungi in allergic mucin is considered important, although hyphae are sparse in sinus content. This leads to confusion in definition of this entity, especially with the description of two more closely related entities--eosinophilic fungal rhinosinusitis (EFRS) and eosinophilic mucin rhinosinusitis (EMRS). Recently reports of histologic invasion in possible cases of AFRS were also documented. Currently, there are more questions than answers concerning the categorization of FRS.

Mortality due to systemic mycoses as a primary cause of death or in association with AIDS in Brazil: a review from 1996 to 2006.

Deaths caused by systemic mycoses such as paracoccidioidomycosis, cryptococcosis, histoplasmosis, candidiasis, aspergillosis, coccidioidomycosis and zygomycosis amounted to 3,583 between 1996-2006 in Brazil. When analysed as the underlying cause of death, paracoccidioidomycosis represented the most important cause of deaths among systemic mycoses (approximately 51.2%). When considering AIDS as the underlying cause of death and the systemic mycoses as associated conditions, cryptococcosis (50.9%) appeared at the top of the list, followed by candidiasis (30.2%), histoplasmosis (10.1%) and others. This mortality analysis is useful in understanding the real situation of systemic mycoses in Brazil, since there is no mandatory notification of patients diagnosed with systemic mycoses in the official health system.

Biodiversity and new records of microfungi in the Ruhrarea (north Rhine Westfalia), Germany.

During our investigations of the microflora in NRW (Duisburg, Düsseldorf and Essen incl. the greenhouse of the Botanical Garden) in 2007 and 2008, we were able to collect and identify about 55 species on trees, bushes and ornamental plants as parasites and saprophytes. Some of these species are new for Germany or have been only rarely found until now. Most of the species belong the Ascomycotina, Basidiomycotina and Deuteromycotina for example Arthrocladiella mougeotii (Lév.) Vassilkov. on Lycium barbarum L., Caudospora taleola (Fr.) Starb on Quercus robur L., Colletotrichum coffeanum F. Noak on Coffea arabica L. (new for Germany) Colletotrichum trichellum (Fr.) Duke on Hedera helix L., Erysiphe buhrii U. Braun on Lychnis cf. coronaria (L.) Desr. (Anamorph. Oidium dianthi Jacz.), Erysiphe spec. on Acer opalus Mill (new host), Erysiphe flexuosa (Peck) U. Braun & S. Takam. on Aesculus spec. (new for Europe)), Erysiphe heraclei DC. on Tinguarra montana (Webb ex Christ ) A.Hansen & G.Kunkel, Erysiphe necator Schwein. = Uncinula necator (Schwein.) Burrill on Cissus cf. rhombifolia Vahl. (new for NRW), Erysphe trifolii Grev. on Trigonella caerulea (L.) Ser., Golovinomyces cichoracearum (DC.) V.P.Gelyuta (Oidium spec.) on Argyranthemum pinnatifidum (L.f.) R.T. Lowe (new host), Lobatopedis foliicola P.M. Kirk on Quercus robur L. (new for NRW), Lophodermium juniperinum (Fr.) de Not. on Juniperus communis L., Mamiania coryli De Not. on Corylus avellana L., Marssonina juglandis (Lib.) Magnus on Juglans regia L., Oidium hortensia Jørst on Philadelphus coronarius L., Oidium spec. on Dahlia variabilis (Willd.) Desf. (new for Germany), Oidium longipes Noordeloos & Loerak on Petunia hybrida Vilm., Oidium pedilanthi M. Yen on Pedilanthus titymaloides (L.) Poit, Oidium pedaliacearum H.D. Shin sp. nov. (= Oidium sesami H.D. Shin) on Ibicella lutea (Lindl.) van Eselt. (= Martynia lutea Lindl.), Passalora pastinacae (Sacc.) U. Braun = Pseudocercosporella pastinacae (P. Karst.) U. Braun (new for Germany) on Pastinaca sativa L., Podosphaera tridactyla (WalIr.) de Bary on Prunus laurocerasus L., Septoria cornicola Desm. on Cornus sanguinea L., Stigmina tinea (Sacc.) M.B.Ellis on Viburnum opulus L., Torula herbarum (Pers.) Link on Potentilla argentea L., etc. All species are located in the herbarium Mycotheca parva collection G.B. Feige and N. Ale-Agha.

Definition of Opportunistic Infections in Immunocompromised Children on the Basis of Etiologies and Clinical Features: A Summary for Practical Purposes.

Opportunistic Infections (OIs) still remain a major cause of morbidity and death in children with either malignant or nonmalignant disease. OIs are defined as those infections occurring due to bacteria, fungi, viruses or commensal organisms that normally inhabit the human body and do not cause a disease in healthy people, but become pathogenic when the body's defense system is impaired. OIs can also be represented by unusually severe infections caused by common pathogens. An OI could present itself at the onset of a primary immunodeficiency syndrome as a life-threatening event. More often, OI is a therapyassociated complication in patients needing immunosuppressive treatment, among long-term hospitalised patients or in children who undergo bone marrow or solid organ transplantation. The aim of the present review is to provide a comprehensive and 'easy to read' text that briefly summarises the currently available knowledge about OIs in order to define when an infection should be considered as opportunistic in pediatrics as a result of an underlying congenital or acquired immune-deficit.

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.

BACKGROUND: Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies. METHODS: After the introduction of the original 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 definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved. RESULTS: The revised definitions retain the original classifications of "proven," "probable," and "possible" invasive fungal disease, but the definition of "probable" has been expanded, whereas the scope of the category "possible" has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only. CONCLUSIONS: These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients.

Antifungal management practices in liver transplant recipients.

We sought to determine the approach to antifungal prophylaxis, and diagnostic and therapeutic practices for the management of invasive aspergillosis in liver transplant recipients. Data were collected by an electronic survey questionnaire sent to all active liver transplant programs in North America; 63% (67/106) of the sites completed the survey. Overall, 91% of the sites employed antifungal prophylaxis; 28% used universal prophylaxis and 72% targeted it toward high-risk patients. Fluconazole was the most commonly used agent for universal and targeted prophylaxis. The leading choice for mold-active agents for antifungal prophylaxis was the echinocandins. Combination therapy was used as primary therapy for invasive aspergillosis in 47%, and as salvage in 80%. Thus, a vast majority of the surveyed programs employ antifungal prophylaxis and most use targeted prophylaxis. Consideration of these practices could guide clinical trial design to optimize antifungal prophylaxis in these patients. Our findings also merit investigations to better define the role of diagnostic assays and combination therapeutic strategies for invasive aspergillosis in liver transplant recipients.