OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVES: The broad-spectrum triazoleposaconazole 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Mariana Castanheira; Shawn A Messer; Paul R Rhomberg; Rachel R Dietrich; Ronald N Jones; Michael A Pfaller Journal: Mycopathologia Date: 2014-06-21 Impact factor: 2.574
Authors: Jeffrey D Jenks; Sharon L Reed; Danila Seidel; Philipp Koehler; Oliver A Cornely; Sanjay R Mehta; Martin Hoenigl Journal: Int J Antimicrob Agents Date: 2018-08-09 Impact factor: 5.283
Authors: Anastasia Wasylyshyn; Kathleen A Linder; Caroline G Castillo; Shiwei Zhou; Carol A Kauffman; Marisa H Miceli Journal: Mycopathologia Date: 2020-01-14 Impact factor: 2.574
Authors: Gloria Castellano-González; Helen M McGuire; Fabio Luciani; Leighton E Clancy; Ziduo Li; Selmir Avdic; Brendan Hughes; Mandeep Singh; Barbara Fazekas de St Groth; Giorgia Renga; Marilena Pariano; Marina M Bellet; Luigina Romani; David J Gottlieb Journal: Blood Adv Date: 2020-07-28
Authors: A F Schmalreck; M Lackner; K Becker; W Fegeler; V Czaika; H Ulmer; C Lass-Flörl Journal: Antimicrob Agents Chemother Date: 2013-12-23 Impact factor: 5.191