In Vitro Activity of Clarithromycin Against Penicillin-Susceptible and Penicillin-Resistant Strains of Streptococcus pneumoniae in a Pharmacodynamic Simulation Model

Abstract

Clarithromycin has shown enhanced activity against Streptococcus pneumoniae, but increased resistance to macrolides has been observed in recent years. Our aim was to investigate its activity against strains of S. pneumoniae with variable susceptibility to this antibiotic and to penicillin. We determined killing curves using the Centriprep-10 pharmacodynamic simulation model, which permits using varying antibiotic concentrations to mimic a pharmacoki-netic human profile in serum (corresponding to an oral dose of 500 mg). Four strains of S. pneumoniae were tested. In susceptible strains, clarithromycin showed bactericidal activity (reductions of up to 2.97 log₁₀ cfu/ml of the initial inoculum). In resistant strains, clarithromycin showed a bacteriostatic effect (<1 log₁₀ cfu/ml reduction). Penicillin-susceptible strains showed higher reductions than penicillin-resistant strains. This effect is important owing to the high minimum inhibitory concentration (MIC) of one of the resistant strains (32 μg/ml). More studies are needed to explain this bacteriostatic activity.