Pharmacodynamic Target Attainment Potential of Azithromycin, Clarithromycin and Telithromycin in Serum and Epithelial Lining Fluid (ELF) of Community Acquired Pneumonia (CAP) Patients with Penicillin-Susceptible, Intermediate and Resistant Streptococcus pneumoniae

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Objective To compare the probability of target attainment (PTA) for macrolides and ketolides against penicillin-susceptible, intermediate, and resistant Streptococcus pneumoniae in both serum and epithelial lining fluid (ELF) of patients with community-acquired pneumonia (CAP).

Methods Monte Carlo simulations were used to assess the attainment of the bacterial eradication-linked pharmacodynamic index of the free drug area under the concentration–time curve over 24 hours to minimum inhibitory concentration (fAUC0–24/MIC90) by azithromycin, clarithromycin, and telithromycin, at therapeutic doses, against penicillin-susceptible, intermediate, and resistant S. pneumoniae.

Results In serum, azithromycin and clarithromycin were found to have a probability of attaining the recommended fAUC0–24/MIC90 ratio of 30 in 50.2% and 74.6%, respectively, of CAP patients with penicillin-intermediate strains, and a probability of 36.9% and 60.7%, respectively, in cases of penicillin-resistant strains. Telithromycin maintained a probability of reaching the fAUC0–24/MIC90 ratio of 30 in serum and ELF in 89.1% of CAP patients, regardless of the penicillin resistance of the strain.

Conclusions Clarithromycin results in a higher PTA than azithromycin in the treatment of penicillin-susceptible S. pneumoniae, but both of these agents exhibit a decreasing efficacy as S. pneumoniae penicillin resistance increases. When compared to clarithromycin and azithromycin, telithromycin maintains higher PTA in CAP patients with penicillin-resistant strains of S. pneumoniae.


This article was originally published in International Journal of Infectious Diseases, volume 13, issue 4, in 2009. DOI: 10.1016/j.ijid.2008.08.016


International Society for Infectious Diseases

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