Comparative pharmacodynamics of clarithromycin and azithromycin against respiratory pathogens.
The differences between the antibacterial activities of new macrolides such as clarithromycin (CLA) and azithromycin (AZI) against common respiratory tract pathogens are only minor. However, CLA and AZI constitute macrolides with extremely different pharmacokinetic profiles. This constellation presents an opportunity to evaluate the effect of the pharmacokinetic profile on antibacterial kinetics comparatively. In a pharmacodynamic model simulating the dynamics of serum concentrations in bacterial cultures, both CLA and AZI demonstrate bactericidal activity at concentrations reached in human blood at recommended dosages (CLA 250 mg b.i.d., AZI 500 mg o.i.d.). Bactericidal activity of CLA against the variety of pathogens included is superior to that of AZI in the rate and the extent of killing in this model. These results are considered to correlate with the antibacterial effect of macrolides in vivo in cases where pathogens enter the blood stream. Furthermore, mutants with susceptibility reduced between 8 and 16 times in relation to the initial strain of all strains having an initial minimal inhibitory concentration (MIC) < or = 0.25 mg/l, are selected during exposure to AZI, but not to CLA. The pharmacokinetic profiles of CLA and AZI thus strongly influence their antibacterial effect in the pharmacodynamic model, allowing both higher bactericidal activity and greater reduction of the risk of selection of resistant mutants with CLA than with AZI. As a whole, the pharmacodynamics of these macrolides are determined more by the proportion of the MICs to the maximum serum concentration than by the relation of the MICs to the area under the curve.
Bauernfeind
A
A
Max von Pettenkofer Institut, Universität München, Germany.
Jungwirth
R
R
Eberlein
E
E
D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D017963:Azithromycin / Q000493:pharmacokinetics / Q000494:pharmacology*; D001424:Bacterial Infections / Q000097:blood / Q000188:drug therapy*; D017291:Clarithromycin / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D012141:Respiratory Tract Infections / Q000097:blood / Q000188:drug therapy*
D000900:Anti-Bacterial Agents; D017963:Azithromycin; D017291:Clarithromycin