Here, the incidence of voriconazole, posaconazole and itraconazole resistance in clinical isolates from high-risk patients from either the haematology ward or the ICU of the University Medical Center Utrecht in the period 2011–13 is analysed. Putative clonality of resistant strains was tested through cyp51A and microsatellite typing.
This study reveals a high incidence of voriconazole resistance (16.2%) in A. fumigatus in high-risk patients. The data stresses the need for laboratory detection of azole resistance prior to treatment.
Fungal aerosols consist of spores and fragments with diverse array of morphologies; however, the size, shape, and origin of the constituents require further characterization. In this study, we characterize the profile of aerosols generated from Aspergillus fumigatus, A. versicolor, and Penicillium chrysogenum grown for 8 weeks on gypsum boards. We observed spore particle fraction consisting of single spores and spore aggregates in four size categories, and a fragment fraction that contained submicronic fragments and three size categories of larger fragments. Single spores dominated the aerosols from A. fumigatus(median: 53%), while the submicronic fragment fraction was the highest in the aerosols. This study shows that fungal particles of various size, shape, and origin are aerosolized, and supports the need to include a broader range of particle types in fungal exposure assessment.
OBJECTIVE: To establish the role of therapeutic bronchoalveolar lavage in addition to conventional treatment among two groups, with allergic bronchopulmonary aspergillosis, in terms of regression in serum IgE levels and clinical recurrence at 3 and 6 months of follow-up.
RESULTS: There was a statistically significant reduction in the mean serum IgE levels at 3 (p < 0.00) and 6 months (p < 0.001) of follow-up in BAL as compared to conventional group. CONCLUSION: Therapeutic bronchoalveolar lavage may be a useful adjunct to treatment in patients with allergic bronchopulmonary aspergillosis, serum in terms of IgE level reduction.
The aim of this study was to investigate the effect of prior azole exposure on AmB sensitivity in Aspergillus fumigatus biofilms. It was hypothesised that sequential antifungal therapy has the potential to impact adaptive resistance mechanisms. The in vitro data revealed that A. fumigatus sensitivity to AmB was decreased when it was tested in combination with AmB±voriconazole (VRZ). In addition, a two- to four-fold decreased sensitivity to AmB was recorded against VRZ-exposed germlings compared with controls. It was also shown that depletion of extracellular DNA (eDNA) by DNase treatment enhanced AmB activity against VRZ-exposed cells by eight-fold, which visually could be explained by destabilisation of the biofilm when examined microscopically. Pharmacological inhibition of Hsp90 by
geldanamycin (GDA) significantly improved biofilm susceptibility to AmB by four- to eight-fold. In conclusion, A. fumigatus pre-exposure to VRZ concomitantly induces eDNA release and activates the stress response, which collectively confers AmB resistance in vitro.