Choosing an antibiotic on the basis of pharmacodynamics

Although standard parameters of antimicrobial activity such as minimal inhibitory concentration (MIC) and minimal bactericidal concentration are useful, they do not provide information about the time course or rate of kill relative to concentration or whether post-antibiotic effects on leukocytes contribute to activity. Antibiotics can be divided into two major groups: those that exhibit concentration-dependent killing and prolonged persistent effects and those that exhibit time-dependent killing and minimal-to-moderate persistent effects. With drugs that fall into the former group, the area under the concentration-time curve (AUC) and peak levels are the major parameters correlating with efficacy. The ratio of peak concentration to MIC is a measure of potency that also indicates the efficacy of the drug. With drugs that exhibit time-dependent killing and minimal-to-moderate persistent effects, time above MIC is the major parameter determining efficacy. Beta-lactam and macrolide antibiotics fall into this second group. Studies in otitis media show that there appears to be a relationship between the time above MIC in serum and in middle ear fluid (MEF) for beta-lactam antibiotics. It is predicted that to achieve at least 80-85% bacteriologic cure in otitis media, serum concentrations should exceed the MIC of pathogens for at least 40% of the dosing interval. For the same cure rate, the peak MEF to MIC ratio should be in the range of 3-6. If the MICs for pathogens are known, it will be possible to predict those for which adequate concentrations can be achieved.