Objectives
Fusarium species can cause severe infections in both immuno-compromised and immune-competent hosts, ranging from superficial, locally invasive to disseminated infections. Disseminated infections occur mainly in hemato-oncology patients and have an exceedingly high mortality of >90%, partly because of the high resistance rate of Fusarium species against antifungals. Data on the epidemiology of fusariosis in Germany are limited. Given the difficult species identification and the low number of clinical studies which provide identification using reliable molecular identification, the true epidemiology of fusariosis is only incompletely understood. Therefore, this study investigates the epidemiology of Fusarium infections by application of molecular identification of isolates and in vitro susceptibility testing using reference methods.

Methods
Eighty five non-copy patient isolates from seven medical centers in Germany were included in the study. All strains were isolated from human infections. Species identification was carried out using morphological, mass spectrometry and molecular methods (sequencing of EF1 alpha and RPB2 and comparison to the CBS Fusarium database and an in-house database). Susceptibility testing was done using the EUCAST microdilution reference method.

Results
Fusarium fujikuroi species complex was the most frequent species complex (N=40) with F. proliferatum as the most frequent species (N=26), followed by FSSC (N=30) with F. petroliphilum as the most common species (N=16), F. oxysporum complex (N=12) and F. dimerum species complex (N=3). Interestingly, in blood cultures the newly described F. musae was the most frequent species (8/28; 28.6%), in contrast to FSSC which was the most common species complex in skin/soft tissue infections (11/19; 57.6%). Resistance to common antifungals was frequent. MIC50 were 2 mg/L for amphotericin B, 4 mg/L for voriconazole, >16 mg/L for itraconazole and 8 mg/L for posaconazole . Among FSSC isolates, higher MICs were observed for voriconazole (MIC50 8 mg/L) compared to other species complexes. 

Conclusion
Fusarium infections in Germany seem to be caused by a limited number of species, with F. fujikuroi species complex and F. solani species complex being the most frequent ones. F. musae seems to be an emerging species in BSI and reported for the first time in Germany. Species identification is not sufficient for the prediction of susceptibility; susceptibility testing is required to optimize therapy, ideally using a microdilution method. Resistance to most antifungals was common in isolates of German origin, with amphotericin and voriconazole retaining the best in vitro activity.

5 / Epidemiology and in vitro susceptibility of Fusarium species from human infections in Germany – results of a retrospective multicenter study