Pharmacodynamic target attainment potential of azithromycin, clarithromycin, and telithromycin in serum and epithelial lining fluid of community-acquired pneumonia patients with penicillin-susceptible, intermediate, and resistant Streptococcus pneumoniae☆

Summary 

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 24hours to minimum inhibitory concentration (fAUC_0–24/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 fAUC_0–24/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 fAUC_0–24/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.

Keywords: Macrolides, Ketolides, Streptococcus pneumoniae, Monte Carlo simulation, Bacterial resistance