抗生素的药效动力学Pharmacodynamics of Antibiotics资料汇总.pptVIP

Pharmacodynamics of Antibiotics Hail M. Al-Abdely, MD Concepts Pharmacokinetics describe how drugs behave in the human host Pharmacodynamics the relationship between drug concentration and antimicrobial effect. “Time course of antimicrobial activity” Minimum Inhibitory Concentration (MIC) The lowest concentration of an antibiotic that inhibits bacterial growth after 16-20 hrs incubation. Minimum Bacteriocidal Concentrations. The lowest concentration of an antibiotic required to kill 99.9% bacterial growth after 16-20 hrs exposure. C-p Peak antibiotic concentration Area under the curve (AUC) Amount of antibiotic delivered over a specific time. Concepts Antimicrobial-micro-organism interaction Antibiotic must reach the binding site of the microbe to interfere with the life cycle. Antibiotic must occupy “sufficient” number of active sites. Antibiotic must reside on the active site for “sufficient” time. Antibiotics are not contact poisons. What concentration of this antibiotic is needed to inhibit/kill bacteria? In vitro offers some help Concentrations have to be above the MIC. How much above the MIC? How long above the MIC? Time Conc MIC Patterns of Microbial Killing Concentration dependent Higher concentration greater killing Aminoglycosides, Flouroquinolones, Ketolides, metronidazole, Ampho B. Time-dependent killing Minimal concentration-dependent killing (4x MIC) More exposure more killing Beta lactams, glycopeptides, clindamycin, macrolides, tetracyclines, bactrim Persistent Effects Persistent suppression of bacterial growth following antimicrobial exposure. Moderate to prolonged against all GM positives (In vitro) Moderate to prolonged against GM negatives for protein and nucleic acid synthesis inhibitors. Minimal or non against GM negatives for beta lactams (except carabapenems against P. aeruginosa) Post-antibiotic sub-MIC effect. Prolonged drug level at sub-MIC augment the post-antibiotic effect. Post-antibiotic leukocyte killing enh