脑膜炎抗生素的治疗(英文教学)Antibiotics for Gram Positive Meningitis重点培训.pptVIP

Antibiotics for Gram Positive Meningitis Bhakti Patel M4 Medical Therapeutics Case (adapted from ID consult 8/2006) 62 yo woman with history of Hep C presenting with GBS cervical osteomyelitis refractory to initial medical management. She required a C5-7 anterior corpectomy with posterior C4-C7 spinal fusion, which was unfortunately complicated by a persistent dural leak, requiring surgical exploration with placement of a lumbar drain for repair. Post-operatively, CSF cultures grew E. Faecium sensitive to vancomycin. Despite prolonged treatment with vancomycin CSF cultures continued to grow E. faecium and the patient’s neurological status worsened. What would be your next step in the management of this patient? Choosing the Right AntibioticPharmacokinetics of Antibiotics in CSF Blood Brain Barrier Cerebral capillary endothelial cells have tight junctions instead of fenestrations; Consequently only water, most ions, and lipids pass freely. Glucose and other nutrients are transported via surface enzymes and transport molecules expressed by the endothelium. Pharmacokinetics The concentration of antibiotics in CSF depends on the balance between drug penetration and elimination through the blood brain barrier. Choosing the Right AntibioticCrossing the Blood Brain Barrier Factors Influencing antibiotic concentrations in CSF Factor Example Effect Drug Lipophilicity Fluoroquinolones Rifampin Rapid entry into CSF, Relatively good CSF conc Half life similar to serum High degree of ionization Beta-lactams Low lipid solubility with poor BBB penetration High serum protein binding Ceftriaxone Delayed entry into CSF Long CSF and serum half-life Active Transport system Penicillin Relatively rapid entry into CSF Short duration of effective CSF levels Inflammation Meningitis Increased penetration of hydrophilic agents Minimal effect on lipophilic agents Infecting organism Listeria, Haemophilus E coli, Strep pneumoniae Greater antibiotic penetration Lesser antibiotic