Aspergillus calidoustus and Talaromyces columbinus infections in chronic graft-versus-host disease

Abstract

Advancements in allogeneic haematopoietic stem cell transplant (alloHSCT) procedures have improved patient outcomes over the last two decades, though invasive fungal infections (IFIs) remain a significant risk. The incidence of IFIs in alloHSCT recipients is estimated at 6%, with a mortality rate of 13%, and Aspergillus species are the most common pathogens involved. Posaconazole is effective in preventing IFIs post-transplant and is standard care during neutropenia or when managing graft-versus-host disease (GvHD) with high-dose steroids. However, azole prophylaxis may cause resistant Aspergillus species like A. calidoustus, which are difficult to treat. We report a case from our institution where a patient developed a dual infection with Aspergillus calidoustus and Talaromyces columbinus after alloHSCT and posaconazole prophylaxis. While A. calidoustus is known to cause IFIs in HSCT recipients, T. columbinus represents a previously unreported occurrence in medical literature. This case underscores the importance of a multifaceted diagnostic strategy, integrating BAL diagnosis, mycological cultures, direct microscopy, fungal speciation, susceptibility testing, and biomarkers. These comprehensive approaches are indispensable for accurate pathogen identification and effective management of IFIs with appropriate antifungal agents.

Keywords: A. calidoustus; Allogeneic stem cell transplant; BAL; GVHD; IFIs; Posaconazole-resistant; T. Colombinus.

Fig. 1

(A) Serial measurements of serum β-D-glucan and galactomannan over time with indication when respiratory samples were collected, (B) Direct microscopic examination of bronchoalveolar lavage (BAL) fluid using Calcofluor-white stain. Solid white arrows show Aspergillus hyphal fragments and dashed white arrows demonstrated fungal hyphae that belong to Talaromyces species. Both hyphae are septated, however Talaromyces hyphae are narrower when compared to Aspergillus species. (C) Macroscopic colony features and microscopic characteristics of both isolates with their corresponding antifungal susceptibility profiles using standard CLSI broth microdilution method. Green: sensitive, orange: intermediate, and red: resistant. (BALF: bronchoalveolar lavage fluid, BDG: β-D-glucan, GM: galactomannan, MIC: minimum inhibitory concentration, ND: not done, scale bar = 10 μm)