Pharmacodynamic effects of subinhibitory antibiotic concentrations

The pharmacodynamic effects of subinhibitory antibiotic concentrations (sub-MICs) on bacteria can be evaluated in different ways. A direct effect in vitro can be expressed as the minimum antibiotic concentration that produces a structural change in the bacteria seen by light or electron microscopy, or as the concentration that produces one log10 decrease in a bacterial population compared to controls. A direct effect of sub-MICs has also been reported in vivo, both in animals with normal host defenses and in humans. In these cases, it has been shown that subinhibitory antibiotic concentrations can be sufficient to clear an infection. Another effect of sub-MICs can be seen when bacteria are pretreated with suprainhibitory antibiotic concentrations and then exposed to subinhibitory concentrations. Here, sub-MICs may produce a long period of delay before regrowth and even yield a bactericidal effect, especially in antibiotic/bacterial combinations where a postantibiotic effect is present. It seems that subinhibitory antibiotic concentrations may be of great importance for the success of intermittent dosing in certain combinations of antibiotics and bacteria.