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Item does not contain fulltext Aspergillus terreus species complex is recognized as a frequent agent of invasive aspergillosis in Tyrol. The reason for this specific epidemiological situation is unclear. Aspergillus terreus strains isolated from environmental and clinical sources were genotyped using a novel panel of short tandem repeats and were evaluated for virulence. Three major endemic genotypes collected from the Inn region and its side valleys were found to cause the majority of invasive A. terreus infections. All of these genotypes were of the same mating type, which suggests that a mating barrier is present between these geographically well-adapted strains which is found to persist for at least 11 years. The three major genotypes were prevalent in both human infections and the environment. No major differences in virulence were observed using Galleria mellonella as model. Our data suggest a specific environmental exposure being responsible for the high incidence of A. terreus infections in Innsbruck, the Inn valley and side valleys (Tyrol, Austria).

Invasive aspergillosis (IA) is associated with significant morbidity and mortality, and, among other factors, this is due to a delay in diagnosis performed with conventional techniques. A prospective, multicentre study was conducted to evaluate the efficacy of Aspergillus DNA screening in the early diagnosis of IA. Patients undergoing haematopoietic stem cell transplantation or chemotherapy for acute leukaemia were enrolled for biomarker screening. Three centres applied the same protocol for in-house PCR, which was compliant with the European Aspergillus PCR Initiative recommendations, to guarantee the highest diagnostic standards. Two thousand one hundred and twenty-eight sera from 213 patients were investigated and stratified according to the revised European Organization for the Research and Treatment of Cancer/Mycoses Study Group criteria for invasive fungal disease. The incidence rates of probable and possible IA were 18% and 38%, respectively. The sensitivity, specificity and positive predictive value (PPV) of PCR were superior in antifungal drug-naive patients, being 71.4%, 92.3%, and 62.5%, respectively. The last of these key performance indicators (PPV) was moderate in patients receiving primary prophylaxis, at 5.4%. Negative predictive values for both strategies applied were 100% with and 98.3% without antifungal mould prophylaxis. PCR has the potential to play a decisive role in the diagnosis and management of Aspergillus infections in centres not applying primary antifungal mould prophylaxis.

These European Society for Clinical Microbiology and Infectious Diseases and European Confederation of Medical Mycology Joint Clinical Guidelines focus on the diagnosis and management of mucormycosis. Only a few of the numerous recommendations can be summarized here. To diagnose mucormycosis, direct microscopy preferably using optical brighteners, histopathology and culture are strongly recommended. Pathogen identification to species level by molecular methods and susceptibility testing are strongly recommended to establish epidemiological knowledge. The recommendation for guiding treatment based on MICs is supported only marginally. Imaging is strongly recommended to determine the extent of disease. To differentiate mucormycosis from aspergillosis in haematological malignancy and stem cell transplantation recipients, identification of the reverse halo sign on computed tomography is advised with moderate strength. For adults and children we strongly recommend surgical debridement in addition to immediate first-line antifungal treatment with liposomal or lipid-complex amphotericin B with a minimum dose of 5 mg/kg/day. Amphotericin B deoxycholate is better avoided because of severe adverse effects. For salvage treatment we strongly recommend posaconazole 4 × 200 mg/day. Reversal of predisposing conditions is strongly recommended, i.e. using granulocyte colony-stimulating factor in haematological patients with ongoing neutropenia, controlling hyperglycaemia and ketoacidosis in diabetic patients, and limiting glucocorticosteroids to the minimum dose required. We recommend against using deferasirox in haematological patients outside clinical trials, and marginally support a recommendation for deferasirox in diabetic patients. Hyperbaric oxygen is supported with marginal strength only. Finally, we strongly recommend continuing treatment until complete response demonstrated on imaging and permanent reversal of predisposing factors.

Clin Microbiol Infect 2012; 18 (Suppl. 7): 918 Abstract As the mortality associated with invasive Candida infections remains high, it is important to make optimal use of available diagnostic tools to initiate antifungal therapy as early as possible and to select the most appropriate antifungal drug. A panel of experts of the European Fungal Infection Study Group (EFISG) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) undertook a data review and compiled guidelines for the clinical utility and accuracy of different diagnostic tests and procedures for detection of Candida infections. Recommendations about the microbiological investigation and detection of candidaemia, invasive candidiasis, chronic disseminated candidiasis, and oropharyngeal, oesophageal, and vaginal candidiasis were included. In addition, remarks about antifungal susceptibility testing and therapeutic drug monitoring were made.

INTRODUCTIONAntifungal susceptibility tests are performed onfungi that cause disease, especially if they belongto a species exhibiting resistance to commonlyused antifungal agents. Antifungal susceptibilitytesting is also important for resistance surveil-lance, for epidemiological studies and forcomparing the in-vitro activity of new and exist-ing agents.Dilution methods are used to establish theMICs of antimicrobial agents. These are thereference methods for antimicrobial susceptibilitytesting, and are used mainly to establish theactivity of a new antifungal agent, to confirm thesusceptibility of organisms that give equivocalresults in routine tests, and to determine thesusceptibility of fungi where routine dilution testsmay be unreliable. Fungi are tested for theirability to produce visible growth in microdilutionplate wells containing broth culture media andserial dilutions of the antifungal agents (brothmicrodilution). The MIC is defined as the lowestconcentration (in mg⁄L) of an antifungal agentthat inhibits the growth of a fungus. The MICprovides information concerning the susceptibil-ity or resistance of an organism to the antifungalagent and can help in making correct treatmentdecisions.The method described in this document isintended for testing the susceptibility ofyeasts that cause clinically significant infections(primarily Candida spp.). The method encom-passes only those yeasts that are able to fermentglucose. Thus, the susceptibility of non-fermenta-tive yeasts, e.g., Cryptococcus neoformans, cannotbe determined by the current procedure, and themethod is not suitable for testing the yeast formsof dimorphic fungi.SCOPEThe standard method described in this documentprovides a valid method for testing the suscepti-bility of glucose-fermenting yeasts to antifungalagents by determination of the MIC. MICs indi-cate the activity of a given antifungal drug underthe described test conditions, and can be used inmaking decisions concerning patient manage-ment after taking into account other factors, e.g.,pharmacokinetics, pharmacodynamics and resis-tance mechanisms. The MIC also allows fungi tobe categorised as ‘susceptible’ (S), ‘intermediate’(I) or ‘resistant’ (R) to a drug. In addition, MICdistributions can be used to define wild-type ornon-wild-type fungal populations.This method is intended primarily to facilitatean acceptable degree of conformity, i.e., agree-ment within specified ranges among laboratories,in measuring the susceptibility of yeasts to anti-fungal agents. The method is designed to be easyto perform, rapid, economical, and suitable forreading by microdilution plate readers in order toallow direct transfer, storage and manipulation ofthe data by computer. The method is alsointended to yield results that are concordantwith those obtained using the procedure

A multicentre study involving seven laboratories was performed using techniques recommended by the Antifungal Susceptibility Testing Subcommittee of the European Committee on Antimicrobial Susceptibility Testing (AFST-EUCAST) to evaluate and propose quality control ranges and strains for susceptibility testing of fermentative yeasts and filamentous fungi. Participating laboratories tested the susceptibilities of a panel of 12 encoded isolates to amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole and posaconazole. In total, 15 lots of assay medium were tested, with one lot being common to all laboratories, and 18 144 MIC values were determined. Intra- and inter-laboratory agreements and intra-class correlation coefficients (ICCs) of the results for each drug/strain/lot combination were calculated. An average value of 85% agreement was selected for validation purposes. The average percentage of intra-laboratory agreement was 90–95%, with ICC values of 0.90–0.95 (p

Species of Candida and Aspergillus remain the most common causes of invasive fungal infections, but other yeasts and filamentous fungi are emerging as significant pathogens. Opportunistic yeast-like fungi and moulds such as Zygomycetes, Fusarium spp. and Scedosporium spp. are increasingly being recognised in patient groups such as those with leukaemia and in bone marrow transplant recipients. Recognition of these epidemiological changes is critical to patient care. The key elements in selecting an appropriate antifungal agent are the type of patient (solid-organ or stem-cell transplant), severity of immunosuppression, history of prolonged exposure to antifungal drugs, and knowledge of the genera and species of the infecting pathogen and its typical susceptibility pattern.

Mucormycosis is an emerging fungal infection worldwide, with devastating disease symptoms and diverse clinical manifestations. The most important underlying risk factors are immunosuppression, poorly controlled diabetes, iron overload and major trauma. The aetiological agents involved in the disease have been re-classified due to changes in taxonomy and nomenclature, which also led to appropriately naming the disease ‘mucormycosis’. This article shortly explains the new nomenclature, clinical manifestations and risk factors and focuses on putative virulence traits associated with mucormycosis, mainly in the group of diabetic ketoacidotic patients.

The aetiological agents of many invasive fungal infections are saprobes and opportunistic pathogens. Some of these fungi are darkly pigmented due to melanin production and traditionally have been named ‘dematiaceous’. The melanized fungi cause a wide array of clinical syndromes ranging from superficial to deep-seated infections. Diagnosis relies on histopathological examination of clinical specimens and on examination of cultures. Sequencing is recommended for accurate species identification, especially for unusual or newly described pathogens. In cases of mycetoma and chromoblastomycosis, pathognomonic histological findings are useful and the Fontana–Masson stain, specific for melanin, usually confirms the diagnosis. There are no standardized therapies but voriconazole, posaconazole and itraconazole demonstrate the most consistent in vitro activity against this group of fungi. Oral itraconazole has been considered the drug of choice, given the extensive clinical experience with this drug. However, voriconazole may presumably be superior for central nervous system infections because of its ability to achieve good levels in the cerebrospinal fluid. Posaconazole is a well-tolerated alternative drug, backed by less clinical experience but with excellent salvage treatment results after failure of other antifungals. Amphotericin B has been useful as alternative therapy in some cases. Combination antifungal therapy is recommended for cerebral abscesses when surgery is not possible and for disseminated infections in immunocompromised patients.