PMC10315538_01
Timeline of the patient's disease course. (A) The patient's treatment course and clinical testing data. Routine blood workup results were shown in the top panel, including neutrophil, hemoglobin, and platelet on the left and white blood cells (WBCs) on the right. The patient's treatment course was shown in the bottom panel. (B) Images showing the development of the rhinocerebral L. ramosa infection from DAO 8 to DAO 16.
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Starting from DAO 0, routine peripheral blood testings were performed regularly to monitor the patient's conditions, which showed constantly low levels of white blood cells, neutrophils, platelets, and Hemoglobin (Figure 1A). Up till DAO13, the patient was empirically suspected of having a bacterial infection post-chemotherapy and treated as follows (Figure 1A): piperacillin/tazobactam (45 mg/kg, q8h), cefazoxime (50 mg/kg, bid), cefoperazone sulbactam (50 mg/kg, q12h), meropenem (20 mg/kg, q8h), vancomycin (10 mg/kg, q6h), and metronidazole (7.5 mg/kg, q8h) treatment. After the whole antibacterial treatment, the patient still experienced intermittent fever, nasal bleeding, and mouth pain (Figures 1A,B). The following treatments were given to relieve the severe symptoms (Figure 1A): meropenem (40 mg/kg, q8h, three days), vancomycin (15 mg/kg, q6h, three days), piperacillin/tazobactam (112.5 mg/kg, q8h, one day), micafungin (2 mg/kg, qd, three days), infusion of platelet (1 U, DAO 14), hemoglobin (1 U, DAO 15), and albumin (10 g, DAOs 14-16), and rhGCSF (150 microg, qd, DAOs 2-13). However, the patient showed no noticeable improvement (Figures 1A,B), and his CRP remained above 160 mg/l.
Representative radiographs. (A,B) CT images demonstrating scalp abscess on DAO 14. (C,D) CT images demonstrating pulmonary infarctions on DAO 14. (E,F) CT images demonstrating evidence of osteomyelitis on DAO 14.
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Computed tomography (CT) showed scalp abscess (Figures 2A,B), pulmonary infarction (Figures 2C,D), and evidence of osteomyelitis (Figures 2E,F).
Laboratory investigations. (A) mNGS results showing the read depth throughout the L. ramosa genome derived from the patient's blood sample on DAO 14. (B-E) Fluorescence staining of the tissue samples collected from the nasal gangrene region. Microscopic examination showed direct evidence of presence ribbon-shaped broad sparsely septate hyphae (B-D, 400x) and clusters of sporangiospores (E, 200x), suggestive of the Mucorales order.
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On DAO 16, L. ramosa was identified by mNGS with unique DNA sequences covering 8.11% of the L. ramosa genome (Figure 3A), supporting the diagnosis of mucormycosis by L. ramosa infection. Amphotericin B deoxycholate (5 mg/kg, ivgtt) was immediately administered, and tissue samples were collected from the nasal gangrene region for microscopic examination, which confirmed the diagnosis of L. ramosa infection shortly thereafter (Figures 3B-E).