Exploring the Combination of Intracalvariosseous and 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: Meeting the diagnostic criteria for bacterial meningitis (at least item i must be satisfied): i. Clinical diagnosis: abnormal body temperature (\>38 ℃ or \<36 ℃), turbid or purulent cerebrospinal fluid (CSF), CSF leukocytosis (\>500 × 10⁶/L), CSF glucose/serum glucose ratio \< 0.4, CSF protein concentration \> 50 mg/dL; ii. Etiological diagnosis: on the basis of item i, positive microbial detection or culture from specimen smears, drainage catheter tips, implants or CSF (excluding contamination and colonization). Glasgow Coma Scale (GCS) score ≤ 12, or a decrease of ≥ 2 points from the previous assessment; At least one of the following: altered consciousness, seizures, brain parenchymal involvement, mechanical ventilation, or circulatory support. * 3\. No significant improvement or progressive worsening of the condition after empirical or targeted antibiotic therapy, as confirmed by at least 2 consecutive treatment evaluations, with at least one of the following: No relief or worsening of intracranial infection-related signs and symptoms; No decreasing trend in CSF white blood cell count, or re elevation after an initial decrease; No decreasing trend in CSF protein concentration, or re elevation after an initial decrease; No increasing trend in CSF/serum glucose concentration ratio, or re decrease after an initial increase; Persistently positive CSF bacterial culture, or re positivity after initial negative conversion. * 4\. Treatment with polymyxin B, tigecycline or vancomycin is clinically indicated for intracranial anti infective therapy, as judged by the investigator. * 5\. Written informed consent obtained. Exclusion Criteria: * 1\. History of allergy to polymyxin B, tigecycline or vancomycin; * 2\. Unilateral skull craniotomy edge within 30 mm of the parietal eminence, as confirmed by cranial imaging or physical measurement; * 3\. Severe pulmonary infection / acute respiratory distress syndrome (PaO₂/FiO₂ \< 150 mmHg, FiO₂ ≥ 0.6, PEEP ≥ 5 cmH₂O), or mechanical ventilation whose primary cause is not intracranial infection; * 4\. Primary extracranial focus of infection (e.g., lung, abdomen, urinary tract) requiring vasoactive agents to maintain MAP ≥ 65 mmHg (e.g., norepinephrine ≥ 0.25 μg/kg/min) and lactate \> 2 mmol/L after adequate fluid resuscitation, or critical illness whose primary cause is not intracranial infection; * 5\. Contraindications to intracalvariosseous (ICO) administration: severe skull fracture, poor visualization of the calvarial diploic space, planned decompressive craniectomy, or other conditions that may interfere with ICO drug delivery; * 6\. Clinical signs of brain herniation: unilateral or bilateral pupillary dilation and fixation; loss of other brainstem reflexes judged by the investigator to be caused by meningitis or brain herniation; or other uncontrollable signs of vital sign instability; * 7\. Bleeding tendency considered unfavorable for the procedure by the investigator: coagulopathy (e.g., platelet count \< 50 × 10⁹/L; prothrombin time \[PT\] prolongation \> 3 seconds), or previously diagnosed hemophilia or other coagulation disorders; * 8\. Severe hepatic or renal insufficiency: Severe hepatic insufficiency: alanine aminotransferase (ALT) ≥ 3 × upper limit of normal (ULN) or aspartate aminotransferase (AST) ≥ 3 × ULN; Severe renal insufficiency: serum creatinine (CRE) ≥ 1.5 × ULN or estimated glomerular filtration rate (eGFR) \< 40 mL/min/1.73 m²; * 9\. Acute ST segment elevation myocardial infarction and/or decompensated heart failure (New York Heart Association \[NYHA\] class III or IV) within the past 3 months; * 10\. Active hepatitis B infection (positive hepatitis B surface antigen and/or serum HBV DNA positive, or serum HBV DNA \> 2 × 10⁸ IU/mL); * 11\. Positive hepatitis C virus antibody or history of positive testing; * 12\. Positive HIV test or history of positive testing; * 13\. Pregnant, lactating, or potentially pregnant patients, or patients planning pregnancy; * 14\. Currently participating in other interventional trials, or having received other investigational drugs within 1 month or 5 drug half lives; * 15\. Patients deemed unsuitable for the study by the investigator.