Sino-Cranial Aspergillosis in an ABO-Incompatible Renal Transplant Recipient Following a "March of Infections"

We report the clinical management and pharmacologic challenges of sino‑cranial aspergillosis in a renal allograft recipient. A 60‑year‑old male patient underwent ABO‑incompatible (ABOi) kidney transplantation and, after a 15‑month "march of infections" that included multidrug‑resistant bacterial sepsis, rifamycin‑sparing antitubercular therapy, and new‑onset diabetes, presented with persistent unilateral headache. Four months earlier, functional endoscopic sinus surgery (FESS) for frontal sinusitis had yielded maxillary debris that cultured Aspergillus fumigatus but was interpreted as colonization. Magnetic resonance imaging demonstrated a left frontal pyocele with posterior frontal sinus table erosion and skull-base extension, and craniotomy specimens confirmed A. fumigatus on microscopy, histopathology, and culture. Surgical source control followed by systemic voriconazole (intravenous followed by oral), in the context of a high net state of immunosuppression, resulted in clinical improvement and radiologic resolution by 10 weeks with preserved graft function. Voriconazole therapy was complicated by a marked tacrolimus interaction that required major dose reduction and intensive therapeutic drug monitoring (TDM), with tacrolimus troughs normalizing by day 75. This case underscores that in immunosuppressed transplant recipients, sinus isolation of Aspergillus spp. should not be dismissed as benign colonization; even in the absence of unequivocal focal signs, it warrants timely imaging, otolaryngology reassessment, and early consideration of central nervous system (CNS)-penetrant triazole therapy with close TDM to prevent invasive CNS aspergillosis.