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

Abstract

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 ≥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.