Telithromycin post-antibiotic and post-antibiotic sub-MIC effects for 10 gram-positive cocci

Abstract

Post-antibiotic effects (PAE) and post-antibiotic sub-MIC effects (PA-SME) of the ketolide telithromycin (HMR 3647) were determined for 10 Gram-positive cocci with various macrolide resistance mechanisms, including inducible and constitutive ribosomal methylase and macrolide efflux resistance genes. Strains tested included four Streptococcus pneumoniae, three Streptococcus pyogenes and three Staphylococcus aureus. Telithromycin MICs were 0.008-0.015 mg/L for pneumococci, 0.015-4.0 mg/L for S. pyogrenes and 0.03 mg/L for staphylococci. PAE were determined after exposure of strains at 10 × MIC for 1 h. PA-SME were determined in the presence of 0.12×, 0.25× and 0.5× MIC of the agent after the initial 1 h exposure period. The PAE of telithromycin varied from 0.3 to 3.8 h; the PA-SME varied from 0.8 to 4.6 h, with maximal PA-SME varying from 1.5 to 4.6 h. PAE tended to be shortest for S. pyogenes (0.4-2.7 h) and S. aureus (0.3-2.4 h), compared to 1.5-3.8 h for S. pneumoniae. The duration of the PA-SME was similar for the three species tested. The low MICs for many strains as well as the PAE and PA-SME demonstrated in this study for telithromycin show promise for increasing the dosing interval of this ketolide, but will need verification by pharmacokinetic/pharmacodynamic and clinical studies.