Dan Med Bull
-
The correlation between in vitro activity, pharmacokinetic properties and effect in vivo of antibiotics has so far received relatively little attention, and the optimal dosing strategy for most antibiotics is still a matter of dispute. A review on this subject is presented based on observations from an experimental pneumococcus infection model in mice. The pneumococcus is particularly suitable as pathogen in experimental infection models for antibiotic research, since it is clinically relevant, susceptible to a range of antibiotics, and naturally virulent to most laboratory animals without the need for potentiating factors. ⋯ The role of the time greater than MIC in context with other factors such as extravascular penetration of antibiotics, serum protein binding and the post-antibiotic effect is discussed. Most other experimental studies concerning dosing strategy for the beta-lactam antibiotics, including the few clinical studies available, confirm the importance of the time factor. The clinical implication for this group of antibiotics therefore is to strive for a constant, not necessarily high, concentration above the MIC.(ABSTRACT TRUNCATED AT 400 WORDS)