Pharmacodynamic effects of subinhibitory antibiotic concentrations.

The pharmacodynamics of antibiotics have become increasingly important for the determination of optimal dosing regimens. Studies over the past decade have demonstrated marked differences in the time course of antimicrobial activity for different classes of antibiotics both in vitro, in animals and in human trials. One of the explanations for the success of intermittent dosing regimens has been the delay in regrowth after the concentration has fallen under the MIC, the so called postantibiotic effect (PAE). In addition to the PAE, the success of discontinuous dosing regimens may be attributed to both the function of a normal host defence and to the effects of subinhibitory antibiotic concentrations (sub-MICs). It has been shown that there is a difference between the effects of sub-MICs following a suprainhibitory dose (postantibiotic sub-MIC effect; PA SME) and the effects of sub-MICs (SME) alone. It seems that the PA SME is more clinically relevant compared with the PAE, since exposure to suprainhibitory concentrations will always be followed by sub-MICs in vivo. A long PA SME could indicate that longer dosing intervals may be used for that antibiotic /bacterial combination and together with the known effects of sub-MICs on bacterial virulence and the influence of the immune system, it may explain the efficacy of antibiotics with short half-lives even of they are given infrequently.