Intracalvariosseous Plus Intravenous Antibiotics for Moderate-to-Severe Bacterial Meningitis

Inclusion Criteria: * 1\. Age 18-75 years, gender not limited; * 2\. Meeting the diagnostic criteria for moderate to severe bacterial meningitis: 1. Meeting the diagnostic criteria for bacterial meningitis, i.e., meeting at least item i: i. Abnormal body temperature (\>38℃ or \<36℃), turbid or purulent Cerebrospinal fluid (CSF) , CSF leukocytosis (\>500×10⁶/L), CSF glucose/serum glucose concentration \<0.4, CSF protein concentration \>50mg/dL, meeting the clinical diagnosis; ii. In addition to item i, positive microbial tests or cultures of specimen smears, drainage tube heads, implants, and CSF (excluding contamination and colonization), meeting the etiological diagnosis; 2. GCS score ≤12 points or a decrease of 2 points from the previous score; 3. At least one of the following conditions is present: altered consciousness, seizures, brain parenchymal involvement, severe manifestations such as mechanical ventilation or circulatory support. * 3\. After 48-72 hours of antibiotic treatment, if the investigator determines that the patient's condition shows no significant improvement or continues to worsen, or if at least one of the following conditions is present: 1. Symptoms and signs related to intracranial infection show no trend of relief or worsen; 2. CSF white blood cell count shows no trend of decrease, or increases after decreasing; 3. CSF protein concentration shows no trend of decrease, or increases after decreasing; 4. CSF/serum glucose concentration shows no trend of increase, or decreases after increasing; 5. CSF bacterial culture remains positive or becomes positive again after initially being negative. * 4\. Based on the patient's condition, treatment with polymyxin B, tigecycline, or vancomycin may be necessary. * 5\. Obtain informed consent. Exclusion Criteria: * 1\. History of allergy to polymyxin B, tigecycline, or vancomycin; * 2\. Received intrathecal or intraventricular antibiotic treatment before randomization; * 3\. Patients with severe pulmonary infection/acute respiratory distress syndrome (PaO₂/FiO₂ \< 150 mmHg, FiO₂ ≥ 0.6, PEEP ≥ 5 cmH₂O) or whose primary cause of mechanical ventilation is not determined to be intracranial infection; * 4\. Patients with a primary extracranial infection focus (e.g., lungs, abdomen, urinary tract, etc.) who, after adequate fluid resuscitation, require vasoactive drugs to maintain MAP ≥ 65 mmHg (e.g., norepinephrine ≥ 0.25 μg/kg/min) and lactate \> 2 mmol/L, or whose primary cause of critical illness is not determined to be intracranial infection; * 5\. Patients with contraindications to transcranial administration, such as severe skull fracture, poor visualization of the skull diploic, or planned decompressive craniectomy, which may affect transcranial administration. * 6\. Clinical signs of brain herniation, such as unilateral or bilateral pupillary dilation and fixation; or loss of other brainstem reflexes determined by the investigator to be caused by meningitis or brain herniation; or other uncontrollable signs of unstable vital signs; * 7\. Bleeding tendency deemed unfavorable for the procedure by the investigator: abnormal coagulation function (e.g., platelet count \<50×10⁹/L; prothrombin time \[PT\]\>3s), patients with a previous diagnosis of hemophilia or other coagulation disorders; * 8\. Patients with severe hepatic or renal insufficiency (where severe hepatic insufficiency is defined as alanine aminotransferase (ALT) value ≥3 times the upper limit of normal (ULN) or aspartate aminotransferase (AST) value ≥3 times the ULN; severe renal insufficiency is defined as serum creatinine (CRE) ≥1.5 times the ULN or glomerular filtration rate (eGFR) \<40 mL/min/1.73m²; * 9\. Within the past 3 months, the patient has experienced an acute ST-segment elevation myocardial infarction and/or decompensated heart failure (meeting New York Heart Association \[NYHA\] functional class III or IV). * 10\. Patients with severe or extremely severe anemia (hemoglobin \< 60 g/L) at the time of randomization; * 11\. Patients with active hepatitis B infection (positive hepatitis B surface antigen and/or positive serum HBV DNA or serum HBV DNA \> 2 × 10⁸ IU/ml); * 12\. Patients with positive hepatitis C virus antibody or a history of positive testing; * 13\. Patients with positive HIV test or a history of positive testing; * 14\. Pregnant, lactating, or potentially pregnant patients, or patients planning to become pregnant; * 15\. Patients currently participating in other interventional trials or who have used other investigational drugs within one month or five drug half-lives; * 16\. Patients deemed unsuitable for participation in this study by the investigator.