Interestingly, in three patients (patient 10, patient 11 and patient 13), multiple genotypes were found GDC-0980 (up to five genotypes per patient always

involving colonisation with S. prolificans in CF patients. In one patient (patient 01), two different genotypes of P. apiosperma were found. Especially, the Scedosporium colonisation patient 13 was distinct, as this patient was persistently colonised for more than 4 years by the same genotype of S. prolificans, but during this period, at least four additional transient genotypes were recognised. Once, from a single sputum sample, two macro-morphologically different colonies were obtained (differing mainly in colony pigmentation). Both isolates were identified as S. prolificans, but were Vismodegib found to represent two different AFLP genotypes. Remarkably, the various isolates from patient 13 varied considerably in their antifungal susceptibility patterns (AFSP) (Table 1) with remarkably different combinations in susceptibility towards AMB, ISA, and/or MICA. Patient 1 suffering from gastric cancer was found to be colonised/infected with two different genotypes of P. apiosperma with different susceptibilities towards MICA and ISA; both were isolated within days of each other. Since 1991, when S. prolificans was first recognised as a causative

agent of disseminated infections in humans,17 more than 70 such cases have been reported. To date, 45.7% of all case studies concerned systemic infections.14 In this respect, the species is remarkably different from P. boydii and P. apiosperma, where subcutaneous cases are preponderant.18 In the murine model, strains of S. prolificans appear to be more virulent than those of the teleomorph genera Pseudallescheria.19,20 The results of this study from Northern-East Spain confirm S. prolificans as most frequently found Scedosporium in Spain, present in >50% of all isolates and >30% of all patients. Based on antifungal susceptibility, S. prolificans differs from the Pseudallescheria/Scedosporium

species by being pan-azole resistant.14 In concordance with other authors,21–24 we found that none of the currently available antifungal substances has a promising activity against S. prolificans Cobimetinib solubility dmso strains (Table 2); all MEC50 and MIC 50 values were ≥4 μg ml−1, and MEC90 and MIC90 values were ≥8 μg ml−1. The relatively low GM for AMB is the result of AMB susceptible isolates identified in patient 13. Such AMB susceptible strains appear to be very rare, but have also been published by others.12 Pseudallescheria boydii and P. apiosperma sensu Gilgado et al.5 strains have been isolated from clinical samples worldwide, and both species can be regarded as environmental opportunists provoking similar spectra of clinical manifestations. In Northern-Spain, we found P. boydii as the second most frequent species (≥25% of all samples and patients), followed by P. apiosperma (10% of all samples and >15% of all patients).