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
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.
Noreddin AM, El-Khatib WF, Aolie, J, Salem AH, Zanel GG. 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. International Journal of Infectious Diseases. 2009;13(4):483-7. doi: 10.1016/j.ijid.2008.08.016
International Society for Infectious Diseases
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