A 70-year-old woman (60 kg, 160 cm) was admitted to the hospital with chest and back pain, and limited mobility for five months. Five months ago, the patient felt continuous pain in the chest and back without significant cause. The pain area was fixed and accompanied by fever (the highest temperature was 39  C). There were no chills or convulsions, chest tightness or wheezing, numb lower limbs, or other symptoms. Four months before admission, thoracic magnetic resonance imaging (MRI) revealed abnormal signals in the appendages of the T9, T11, and T12 vertebrae, consistent with tuberculosis. Therefore, she was treated with isoniazid, rifampicin, ethambutol, and pyrazinamide. However, her symptoms did not improve.
Physical examination on admission was as follows: temperature 37  C, pulse rate 81 times/min, respiration rate 20 times/min, blood pressure 124/87 mmHg. A focused physical examination revealed kyphosis deformity, tenderness of the spinous process of T11-12 vertebrae, and pain to percussion. The admission diagnosis was bony destruction of the T11-12 vertebrae of unknown cause.
The patient continued to take isoniazid (0.3 g, once a day), rifampicin (0.6 g, once a day), ethambutol (0.75 g, once a day), pyrazinamide (0.5 g, three times a day) for anti-tuberculosis treatment, and tiopronin (200 mg, once a day, intravenous) was given for liver protection. On the second day of hospitalization, computed tomography (CT) of the thoracolumbar vertebrae revealed bony destruction of T11 and T12 vertebral bodies with a slight swelling of the surrounding soft tissues. MRI of the lumbar spine and hip showed presumptive infectious lesions in the T11-12 vertebral bodies and the right appendage of T12, consistent with tuberculosis. Subcutaneous fascial edema was observed in the lumbar region. A T-score of less than -2.5 indicated osteoporosis.
Laboratory tests showed a white blood cell count of 2.5x109/L, low neutrophil counts, uric acid 487 micromol/L, and positive T SPOT-TB testing. Leucogen tablets (20.0 mg, three times a day), calcitonin injection (20 U, twice a week), and calcitriol soft capsules (0.25 microg, twice a day) were added. On the fifth hospital day, a needle biopsy of the affected vertebrae revealed no evidence of tuberculosis.
On the tenth hospital day, the patient was treated with debridement, decompression, instrumentation, and fusion surgery and was given cefazolin (1.0 g every eight hours) to prevent surgical site infection. The day after surgery, body temperature increased to 39  C, and C-reactive protein (CRP) increased to 129.08 mg/L. Considering the possibility of surgical incision infection, we continued cefazolin. On the thirteenth hospital day, cefazolin was discontinued after the body temperature returned to normal.
On the sixteenth hospital day, the CRP was 21.37 mg/L, and next-generation sequencing of the vertebral body indicated the sequence number of Aspergillus tubingensis was 28. The patient was diagnosed with Aspergillus tubingensis spondylitis. Because the tuberculosis evidence of thoracic vertebral lesions was insufficient, anti-tuberculosis treatment was discontinued. The clinical pharmacist recommended caspofungin (initial loading agent 70 mg, maintaining 50 mg, intravenous injection, once a day) for anti-Aspergillus treatment, and switching it to VRZ after rifampicin discontinuation for 7-14 days, considering the continuous induction effect of rifampicin on drug-metabolizing enzymes.
On the twenty-ninth hospital day, caspofungin was discontinued due to stomach discomfort. The treatment regimen was changed to oral VRZ (200 mg every 12 hours). However, the patient complained of blurred vision, hallucinations, and sleeplessness at night after taking two doses of VRZ tablets. The clinical pharmacist suggested that VRZ tablets be adjusted to 200 mg daily and instructed the patient to stop eating grapefruit on the thirtieth hospital day.
On the thirty-third hospital day, the trough concentration of VRZ was 0.82 mg/L (effective range: 1.0-5.0 microg/mL); therefore, the clinical pharmacist suggested it should be adjusted to 150 mg every 12 hours, but this regimen was not accepted. The patient was discharged in stable condition, on VRZ tablets (200 mg every 12 hours), calcitriol soft capsules (0.25 microg twice a day), and leucogen tablets (20 mg three times per day), and the patient was instructed present for complete blood count, erythrocyte sedimentation, liver and kidney function tests, electrolytes, CRP, and VRZ levels regularly. The patient was followed up and measured VRZ concentrations at eleven days, three months, and six months after discharge. The VRZ dose was adjusted based on monitoring results. Liver functions remained normal during VRZ treatment. The timeline of the treatment process is displayed in Table 1. The dosing regimen and trough concentration changes of VRZ during the treatment are presented in Figure 1. Radiographic images, including CT scans and MRIs, are shown in Figure 2.