Aspergillus-Mucorales co-infections: implications for first-line antifungal treatment?

The at-risk population for invasive mold infections is expanding with broader immunosuppression; because Aspergillus and Mucorales share clinical/imaging features and Mucorales lacks accessible biomarkers, dual infections are often missed. This review synthesizes current evidence on epidemiology, diagnostics, and therapy and proposes a pragmatic threshold to guide initial treatment while tests are pending.

Invasive aspergillosis is ~10-fold more common than mucormycosis, yet mucormycosis progresses rapidly and carries high mortality; co-infection further worsens outcomes. When systematic PCR is used, reported possible co-infection rates rise (~7-30%). Biomarkers for differentiation are missing; biopsies are often unsuitable. Mucorales PCR has high specificity; bronchoalveolar lavage fluid is more sensitive than blood. Therapeutically, liposomal amphotericin B and isavuconazole usually cover both; voriconazole lacks Mucorales activity. Early active therapy improves survival; fosmanogepix is promising.

Clinicians should estimate Mucorales probability from host factors, prior prophylaxis, imaging, and local epidemiology and deploy PCR early. If the estimated probability is ~10% (consider at 5%), start a Mucorales-active first-line therapy while diagnostics proceed. Decisions must balance toxicity and organ function against the high cost of delay. Research should validate risk models, refine definitions/algorithms, and test new agents up-front.