Can antibiotics dripped through the skull bone reach the brain better than IV drugs alone?

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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.