抗生素的药效动力学Pharmacodynamics of Antibiotics课件.ppt

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” Concepts 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. 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. Static versus Cidal Questions Can this antibiotic inhibit/kill these bacteria? Can this antibiotic reach the site of bacterial replication? What concentration of this antibiotic is needed to inhibit/kill bacteria? Will the antibiotic kill better or faster if we increase its concentration? Do we need to keep the antibiotic concentration always high throughout the day? Can this antibiotic inhibit/kill these bacteria? In vitro susceptibility testing Mixing bacteria with antibiotic at different concentrations and observing for bacterial growth. 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? 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, glycopept