Invasive fungal breakthrough infections, fungal colonization and emergence of resistant strains in high-risk patients receiving antifungal prophylaxis with posaconazole: real-life data from a single-centre institutional retrospective observational study

The broad-spectrum triazole posaconazole showed promising results in preventing invasive fungal infections (IFIs) in high-risk patients. Concerns rise over the relevance of breakthrough IFIs (bIFIs) and the emergence of azole-resistant strains. The current retrospective analysis was undertaken to evaluate the incidence of bIFIs and to study fungal colonization and resistance following posaconazole exposure. Ninety-five patients who underwent 202 courses of primary antifungal prophylaxis with 200 mg of posaconazole three times daily during neutropenia after chemotherapy/haematopoietic stem cell transplantation between September 2008 and September 2010 were evaluated. An IFI was considered to be a bIFI if its occurrence was detected epsilon 4 days after initiation of preventative posaconazole prophylaxis. The incidence of bIFIs was 13 (27/202), with 11/27 (41) proven and 16/27 (59) probable bIFIs. Proven infections were mainly localized in the lungs (85). Species diagnosis exclusively revealed non-Aspergillus species, i.e. mucormycetes in 55 and yeasts in 45. The median overall survival for patients with bIFIs was 5.2 months. Sixteen of 27 patients with bIFIs (proven and probable) succumbed. Regarding only proven cases, 8/11 patients died, whereas only 1/16 deaths was caused by fungal disease. Prospective screening confirmed colonization with yeasts in 42/202 (21) courses; moulds were not identified. The spectrum of colonizing yeasts changed slightly over time, shifting to more rare yeasts. There were no deaths due to invasive yeast infections. A significant proportion of bIFIs, compared with historical data, with a shift to non-Aspergillus spp. and in particular to mucormycetes was observed in patients at high risk for IFI during posaconazole prophylaxis.