Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline.

The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended. Serum and BAL galactomannan measures are recommended as markers for the diagnosis of IA. PCR should be considered in conjunction with other diagnostic tests. Pathogen identification to species complex level is strongly recommended for all clinically relevant Aspergillus isolates; antifungal susceptibility testing should be performed in patients with invasive disease in regions with resistance found in contemporary surveillance programmes. Isavuconazole and voriconazole are the preferred agents for first-line treatment of pulmonary IA, whereas liposomal amphotericin B is moderately supported. Combinations of antifungals as primary treatment options are not recommended. Therapeutic drug monitoring is strongly recommended for patients receiving posaconazole suspension or any form of voriconazole for IA treatment, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended. Primary prophylaxis with posaconazole is strongly recommended in patients with acute myelogenous leukaemia or myelodysplastic syndrome receiving induction chemotherapy. Secondary prophylaxis is strongly recommended in high-risk patients. We strongly recommend treatment duration based on clinical improvement, degree of immunosuppression and response on imaging.

Invasive Aspergillus niger complex infections in a Belgian tertiary care hospital.

The incidence of invasive infections caused by the Aspergillus niger species complex was 0.043 cases/10 000 patient-days in a Belgian university hospital (2005-2011). Molecular typing was performed on six available A. niger complex isolates involved in invasive disease from 2010 to 2011, revealing A. tubingensis, which has higher triazole minimal inhibitory concentrations, in five out of six cases.

Azole-resistant Aspergillus fumigatus due to TR46/Y121F/T289A mutation emerging in Belgium, July 2012.

A new azole resistance mechanism in Aspergillus fumigatus consisting of a TR46/Y121F/T289A alteration in the cyp51A gene was recently described in the Netherlands. Strains containing these mutations are associated with invasive infection and therapy failure. This communication describes the first case of fatal invasive aspergillosis caused by TR46/Y121F/T289A outside the Netherlands, in the neighboring country of Belgium, suggesting geographical spread. TR46/Y121F/T289A leads to a recognisable phenotypic susceptibility pattern which should trigger cyp51A genotyping to monitor further spread.

Azole resistance in Aspergillus: an emerging problem?

Reports of Aspergillus' azole resistance are emerging, and resistance is now recognised as a cause of treatment failure. The scope of this article is to describe the problem of resistance in Aspergillus: the epidemiology, clinical impact and the underlying molecular mechanisms. In patients with acute invasive aspergillosis, the probability that the patient harbours a resistant strain depends on the emergence of resistant strains in the environment (acquired resistance due to CYP51A mutations and/or natural resistant Aspergillus species). As environmental pan-azole resistance of Aspergillus fumigatus is reported in increasing numbers in the Netherlands, surveillance is warranted. Voriconazole currently remains the first line therapeutic agent for invasive aspergillosis in Belgium. In chronic (and chronically treated) Aspergillus infections,"in-patient" resistance development is possible, especially in the setting of aspergilloma. Culturing an isolate during therapy should therefore be a trigger to test susceptibility.

Fungemia at a tertiary care hospital: incidence, therapy, and distribution and antifungal susceptibility of causative species.

The aim of this study was to review fungal bloodstream infections at a large tertiary care hospital to evaluate the incidence of fungemia and the distribution of causative species during the period 2001-2005. Another aim was to assess the extent of antifungal resistance. A review of all episodes of fungemia at the University Hospitals of Leuven (Belgium) was conducted between January 2001 and December 2005. For the first yeast isolate collected from each non-mould fungemic episode during a 1-year period (June 2004-June 2005), susceptibility to seven antifungal agents was determined using Sensititre YeastOne plates (Trek Diagnostic Systems, East Grinstead, UK), and the antifungal therapy was reviewed. The annual incidence of fungemia ranged between 1.30 and 1.68 episodes per 10,000 patient-days (on a total of 2,680,932 patient-days), with a decreasing trend observed over the 5-year study period. The most common species were Candida albicans (59%), Candida glabrata (22%), Candida parapsilosis (10%), and Candida tropicalis (4%). Overall, fluconazole resistance was rare (1.6%) and was detected only in C. glabrata and C. krusei. Voriconazole and caspofungin inhibited 100% of the isolates at a concentration of