The post-antibiotic effect

Pharmacodynamics are being applied increasingly to the design of antibiotic dosing regimens. One characteristic of pharmacodynamics is the post-antibiotic effect (PAE), the delayed regrowth of bacteria following exposure to an antibiotic. In this review the various laboratory techniques which have been used to determine the PAE are critically evaluated and compared with the standard viable counting method. The potential sources of error associated with these methods are considered and recommendations are made for the optimum testing system; on the basis of current evidence the bioluminescence and impedence techniques appear to be the most suitable in terms of being the least labour-intensive and producing the most reliable results. Whichever technique is used, the properties of the growth medium, including osmolality and pH, the size of the bacterial inoculum, the initial antibiotic concentration, the exposure time to the antibiotic and the method of antibiotic removal should be standardized. Other post-(antibiotic) exposure events and their relationships with the PAE and theories concerning the mechanism (or mechanisms) by which antibiotics produce PAEs are discussed. Finally, consideration is given to the clinical significance of the PAE and how it, in conjunction with other pharmaco-dynamic parameters, might be used to allow antibiotic dosing regimens to be developed on a more scientific basis.