Optimization of antibiotic dosing schedules in the light of increasing antibiotic resistance.

The development of antibiotic-resistant bacteria is an increasing problem throughout the world and is, without doubt, due to the increasing use of antibiotics themselves. As organisms become more resistant, treatment options become more limited and treatment failures increasingly likely. The need to reverse, or at least minimize this pattern of increasing resistance is therefore essential. Numerous strategies to achieve this have been postulated and there is no doubt that a combination of these will ultimately prove to be most effective. Among them, using antibiotic dosing regimens that may be less likely to promote resistance is one measure which could be beneficial, and this will be the focus of this review. Individual antibiotics will be discussed under the headings of the patterns of killing activity that they produce. Namely whether they exhibit concentration-dependent killing with prolonged persistent effects, time-dependent killing with minimal or no persistent effects, or time-dependent killing with prolonged persistent effects. The available evidence for optimal dosing regimens, as far as minimizing antibiotic resistance is concerned, will be reviewed. Where possible, recommendations relating to clinical practice will be made, or failing that, an indication of where further research would be of benefit.