Evidence of Possible Mucormycosis Coinfection, Detected by Plasma Mucorales PCR, in Patients with Proven or Probable Aspergillosis

Abstract

Background: Data on coinfection with Aspergillus and Mucorales are limited, although identifying such coinfection is important for its management. The diagnosis of mucormycosis remains challenging owing to the lack of reliable antigen tests and the low sensitivity of fungal culture, especially when biopsy is not feasible. Thus, we investigated mucormycosis coinfection in cases of proven or probable aspergillosis, using plasma Mucorales polymerase chain reaction (PCR). Materials and Methods: Adult patients with proven or probable aspergillosis who consented to blood sampling were prospectively enrolled at a tertiary hospital between January 2017 and April 2020, and again between June 2023 and February 2025. Aspergillosis was classified according to the European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG) criteria. Plasma 18S PCR was performed to detect Aspergillus- and Mucorales-specific DNA. Results: A total of 82 patients (28 with proven and 54 with probable aspergillosis) were analyzed. No Mucorales were detected in sterile or non-sterile cultures. Among the 28 patients with proven aspergillosis, 4 (14.3%) showed evidence of mucormycosis coinfection: 2 had a positive Mucorales-specific PCR result, and 2 had positive PCR results for both Aspergillus and Mucorales. Among the 54 patients with probable aspergillosis, 12 (22.2%) showed evidence of mucormycosis coinfection: 7 had a positive Mucorales-specific PCR result, and 5 had positive results for both Aspergillus and Mucorales. Overall, 16 (19.5%) of the 82 patients with proven or probable aspergillosis showed molecular evidence of possible mucormycosis coinfection. In-hospital mortality did not significantly differ between patients with mucormycosis coinfection who were treated with voriconazole and those with aspergillosis alone treated with voriconazole (38.5% [5/13] vs. 30.6% [15/49]; P=0.74). Conclusion: Approximately 10–20% of patients with proven or probable aspergillosis had molecular evidence of possible mucormycosis coinfection, as detected by plasma Mucorales PCR.