Subinhibitory concentration effects

After the MIC has been determined, it is necessary to decide whether the results suggest whether the organisms are susceptible to the tested antimicrobial in vivo. This decision requires an understanding of the PK of the dmg (see Chapter 2 for discussion) and other factors. For example, in vitro assessments of activity may underestimate the in vivo activity because of a post-antibiotic effect and post-antibiotic leukocyte enhancement. The post-antibiotic ejfect (PAE) refers to a persistent antibacterial effect at subinhibitory concentrations, whereas the term post-antibiotic leukocyte enhancement term (PALE) refers to the increased susceptibility to phagocytosis and intracellular killing demonstrated by bacteria following exposure to an antimicrobial agent. ... 

The coadministration of 22a-25b and a subinhibitory concentration of ciprofloxacin led to an observed synergistic effect with a number of silver compounds, with the most pronounced effects in 22c, 25a, and 25b. Compound 25a demonstrated the largest reduction in MIC value, with an eightfold decrease (64 to 8 pgrnl ), while 22c and 25b each exhibited a fourfold decrease in their MIC... 

In the environment of the burn the compound slowly dissociates into silver and sulfadiazine (30). The silver ion is the antimicrobially active part of the compound and acts by interaction with the micro-organism. Possibly sulfadiazine has a supportive antibacterial effect, but the concentration seems to be subinhibitory (30). The role of sulfadiazine may be to create a sustained delivery of silver ions into the wound environs. 

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