A 25-year-old female with poorly controlled type 1 diabetes mellitus presented to hospital for the second time in two weeks with recurrent, antibiotic-refractory left sided facial swelling and pain complicated by diabetic ketoacidosis (DKA). There was no history of antecedent dental manipulation. Two weeks prior, she was seen in an ambulatory clinic for the same symptoms and took a three-day course of amoxicillin-clavulanic acid 875/125 mg twice daily but was admitted to hospital three days later for DKA. During this index hospitalization, her diagnosis was correlated radiographically and presumed to be sinusitis complicated by DKA. A two-day course of ceftriaxone 2 g intravenously once daily and vancomycin 1 g intravenously twice daily was administered before transitioning to doxycycline 100 mg twice daily for an additional ten-day course.
She returned to hospital a mere ten days later with progressive left-sided facial swelling and was found to meet biochemical criteria for DKA. She was afebrile and hemodynamically stable but had profound left periorbital edema with necrotic lesions along her left maxillary region and forehead.
Three sets of blood cultures, each consisting of an aerobic and anaerobic bottle pair (20 mL per bottle), were drawn before any further parenteral antibiotics were given remained negative after 4-days of incubation in a BacT-Alert automated system (bioMérieux, Laval, Quebec). HIV serology was negative. Comparison of a repeat computed tomography (CT) scan of her sinuses with CT images performed during her prior hospitalization demonstrated improved aeration of the left maxillary sinus but progressive left facial soft tissue swelling complicated by subcutaneous emphysema. Subsequent CT-angiogram of the neck revealed an internal maxillary artery occlusion.
Although initial nasal rhinoscopy revealed normal appearing sinus tissue, surgical debridement to the epicranial aponeurosis revealed necrotic tissue with poor vascular supply but no microbiological diagnosis.
She was started empirically on parenteral therapies of piperacillin-tazobactam 3.375 g every six hours, vancomycin 1250 mg every twelve hours and liposomal amphotericin B at 7.5 mg/kg once daily before transfer to a tertiary care center for further surgical consultation. The ischemic changes on her face was originally thought to be secondary to the internal maxillary artery occlusion from surrounding inflamed tissue. Given the extent of her rhino-orbital disease, she underwent surgical debridements. Her timeline is outlined in Fig. 1.
Original tissue cultures, including anaerobic, fungal and acid-fast bacilli cultures set-up under various growth, differential and selective media for pathogen identification were negative. Four subsequent deeper debridements were done, which extended down to the sternocleidomastoid muscle and up to the auditory canal and as deep as the skull base. Histopathology from biopsied tissue and bone from these sites revealed pauci-septated, ribbon shaped elements with liquefactive skin necrosis consistent with mucormycosis (Fig. 2 a and b). Microbiological 18 s RNA sequencing ultimately identified Rhizopus oryzae as the causative organism. Her hospitalization was complicated by kidney injury secondary to hypovolemia and amphotericin B, necessitating intermittent hemodialysis but she subsequently recovered her renal function. Due to disfiguration from extensive debridement, she underwent a facial skin graft reconstruction after achieving surgical care of her invasive fungal infection. She was transitioned to isavuconazole for three months and then to posaconazole which she continues indefinitely.