Clinical data at admission
A 67-year-old male patient was admitted to our hospital on March 20, 2020 with a complaint of sudden disturbance of consciousness. The symptoms began six hours before admission, and included the inability to move the right limbs, irritability, and vomiting several times with no obvious cause. A head computed tomography (CT) performed at the local hospital showed left thalamic haemorrhage with intraventricular extension. After symptomatic and supportive treatments, the condition showed no significant improvement, and the blood pressure was not adequately controlled. Then, the patient was transferred to our hospital urgently. An emergency head CT scan showed: (1) left basal ganglia haemorrhage with intraventricular extension, (2) bilateral lacunar infarctions at basal ganglia and senile brain degeneration, and (3) mild bilateral inflammation of ethmoid sinuses. An emergency lung CT scan showed chronic bronchitis-emphysema, pulmonary bullae, and mild chronic inflammation of both lungs. The patient had a 9-year history of bipolar disorder with long-term use of lithium carbonate, and a 6-year-old fracture fixation of the right upper limb. Physical examination at admission showed a body temperature of 36.7 °C, a pulse of 100 bpm, a respiratory rate of 21 breaths per minute, and a blood pressure of 156/92 mm Hg. The patient was in a light coma and showed no response to instructions or questions. Rough respiratory sounds were detected in both lungs, and no moist rale was detected in either of the lower lungs. Neurological examination showed eye opening and vocalization with strong pricking, binocular gaze to the left side, and pupils equal in size with a diameter of 3 mm, round, and reactive to light. No rigidity was detected in the neck and the patient could not cooperate in muscle strength examination. Voluntary movements of the left limbs were observed while no movement was observed in the right limbs. The patient could not cooperate during the examination of muscle tone or tendon reflexes. A positive Babinski sign was observed on the right side but negative on the left side, while a positive Kernig sign was present bilaterally.
Clinical data after treatment
After admission, symptomatic treatments were provided, including haemostasis, dehydration to decrease intracranial pressure, neurotrophic treatment, blood pressure control, and fluid infusion. Bedside bilateral drill, craniotomy and ventricular drainage were performed, and urokinase was injected into bilateral ventricular drainage catheters. Bronchoscopy-guided nasotracheal intubation was performed. A repeat CT scan on March 21 showed that the right ventricular hematoma mostly resolved, and therefore the right ventricular drainage catheter was removed.
On March 23, the patient was still in a light coma, and moist rales in both lower lungs increased, along with an elevated white blood cell (WBC) count (15.36 × 109/L) and an elevated C-reactive protein (CRP) level (59.21 mg/L). Pulmonary infection was diagnosed, and intravenous infusion of piperacillin-tazobactam (4.5 g every 8 h) was used as an anti-infection treatment. A repeat head CT scan on March 25 showed a significant decrease in the volume of intraventricular hematoma. In order to avoid infection after long-term retention, the drainage catheter of the left ventricle was removed.
On March 30 (d10), the patient developed fever and was in the twilight state of consciousness with aggravation of neck rigidity. The WBC count increased to 17.17×109/L, and the first routine and biochemical tests of cerebrospinal fluid (CSF) showed significant increases in cell count and protein level (see Figure 1 for details), leading to a diagnosis of possible intracranial bacterial infection. Piperacillin-tazobactam was discontinued, and the anti-infective therapy of intravenous infusion of vancomycin (1 g every 12 h) combined with ceftriaxone (2 g every 12 h) was administered with lumbar cistern drainage performed concurrently.
The vancomycin trough serum concentration on April 3 was 18.3 µg/mL. On April 8, the patient still had fever with aggravated neck rigidity, accompanied by cough and sputum expectoration. Therefore, the combined anti-infective treatment was considered ineffective, and ceftriaxone was discontinued. A combination of vancomycin with continuous 2-hour intravenous infusion of meropenem (2 g every 8 h) was used.
On April 12 (d23), the patient was in the twilight state of consciousness with no fever. The volume of lumbar cisternal drainage was 150 ml with unobstructed CSF drainage, and the drainage fluid was light yellow and turbid. Repeat blood routine and CRP tests showed decreased WBC count and CRP, and repeat CSF routine and biochemical tests showed that cell count and protein level decreased significantly compared with previous results (Figure 1). On April 18, the results of the first two CSF cultures revealed the presence of Staphylococcus epidermidis, which was resistant to oxacillin and sensitive to vancomycin (MIC = 2 µg/mL) and linezolid (MIC = 4 µg/mL). The current anti-infective therapy was deemed effective, and the treatment of vancomycin combined with meropenem continued.
On April 27 (d38), patient's neck rigidity improved, and a repeat CSF examination showed that cell count and protein level further decreased. The lumbar cisternal drainage catheter was removed. On April 29, the CSF metagenomic sequencing revealed Staphylococcus epidermidis (read count 1,541), Propionibacterium acnes (read count 116) and Moraxella osloensis (read count 14), and the treatment of vancomycin combined with meropenem continued.
On May 6 (d47), the patient developed fever again, with a maximum body temperature of 38.4 °C. A repeat CSF examination showed turbid CSF with elevated WBC count, increased proportion of multinucleated cells, and elevated protein level compared with previous tests, leading to the conclusion that the infection aggravated again. The CSF concentration of vancomycin was 5.0 µg/mL. The anti-infective regimen was adjusted to 0.6 g linezolid every 12 h combined with 2 g ceftazidime every 8 h.
On May 10, the patient’s liver function test showed 528 U/L ALT and 323 U/L AST. Considering possible linezolid-induced liver injury, linezolid was discontinued and reduced glutathione and bicyclol were given for liver protection. On May 11 (d52), the patient had no fever and showed improved neck rigidity. The results of CSF routine and biochemical tests showed significant improvement, and Staphylococcus epidermidis was isolated from the CSF culture. On May 12, given the isolation of Staphylococcus epidermidis from several CSF cultures and the poor outcome of vancomycin treatment, anti-infective treatment with linezolid was resumed, combined with entecavir (0.5 mg once a day p.o.) for anti-HBV (hepatitis B virus) treatment. Liver-protective drugs were continued with close monitoring of liver function. A repeat blood biochemical test on May 16 showed 58 U/L aspartate aminotransferase and 125 U/L alanine aminotransferase. On May 24 (d64), routine repeat CSF and biochemical tests showed normal results (Figure 1). On May 25, repeat head and lung CT scans showed left thalamic post-haemorrhagic encephalomalacia, while the rest were similar to previous results.
On May 26, the patient was in the twilight state of consciousness. After tracheotomy, the patient exhibited smooth spontaneous breathing and was supported by liquid diet. The patient had no fever, and there was a slight improvement of neck rigidity. The antibacterial drugs, including linezolid and ceftazidime, were discontinued, while nutritional, supportive, and symptomatic treatments continued. On June 1, the patient regained consciousness and was transferred to the Department of Rehabilitation Medicine for comprehensive rehabilitation. On June 28, the recovery was satisfactory and the patient was discharged from the hospital. The treatment regimens and CSF cell counts during hospitalization in the Department of Neurosurgery are shown in Figure 1.