抗生素英文课件精品Antibiotics for Gram Positive .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 Choosing the Right AntibioticPharmacodynamics of Antibiotics in CSF Pharmacodynamics: concerned with the time course of antimicrobial activity at the site of infection The CSF has poor immune response because there are very low concentrations of pathogen-specific antibodies and complement factors even during meninigitis. Therefore antibiotics should have rapid bactericidal activity for successful treatment (J Antimicrobial Chemo. 1993; 31, Suppl D, 61-70) Concentration-dependent killing: efficacy depends on high peak concentrations and prolonged recovery period after drug levels fall below MIC. The recovery period is characterized by po