Pharmacodynamic properties of HMR 3647, a novel ketolide, on respiratory pathogens, enterococci and Bacteroides fragilis demonstrated by studies of time-kill kinetics and postantibiotic effect

Abstract

The pharmacodynamic properties of a novel ketolide (a new class of macrolide), HMR 3647, were investigated by studying time-kill kinetics and postantibiotic effect (PAE). The time-kill kinetics were studied at two inocula against three strains each of Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, Streptococcus pyogenes, Enterococcus faecalis, Enterococcus faecium and Bacteroides fragilis. The PAEs of HMR 3647 were also investigated on these organisms at concentrations equivalent to 1, 4 and 10 x MIC. The time-kill kinetic data demonstrated that HMR 3647 is predominantly bacteriostatic and only slowly bactericidal at higher concentrations. HMR 3647 exhibited a significant PAE with all strains studied, ranging from 1.2 h to 8.2 h at 10 x MIC. The bacteriostatic activity and significant PAE demonstrated by HMR 3647 are similar to those previously obtained with other macrolides.