Answer 16: Dosing of antibiotics for HAP, VAP, and HCAP

20 June, 2018

 

 

The mechanism of action of certain antibiotics can affect dosing regimens, efficacy, and toxicity. Agents such as the aminoglycosides and fluoroquinolones are bactericidal in a concentration-dependent fashion, killing more rapidly at high concentrations. Another difference is that some antibiotics have a post-antibiotic effect (PAE), which means that these agents are able to suppress bacterial growth even after the antibiotic level falls below the MIC of the organism (5,85,86). The specific pharmacodynamic effects of antibiotics lead to drug-specific dosing regimens (45). Fluoroquinolones can be dosed less often because of the prolonged PAE. In addition, because of their concentration-dependent killing mechanism, efficacy may be improved by using a regimen that maximizes initial serum concentrations. Combining an entire day of therapy into a single daily dose (every 24 hours) can take advantage of both the concentration-dependent killing mechanism and the PAE. This dosing regimen has been applied to levofloxacin to maximize efficacy and minimize toxicity, and there is clinical data supporting the once daily 750 mg dose for HAP and VAP (87).