Antibacterial activity of RU 64004 (HMR 3004), a novel ketolide derivative active against respiratory pathogens

Abstract

The antibacterial activity of RU 64004, a new ketolide, was evaluated against more than 600 bacterial strains and was compared with those of various macrolides and pristinamycin. RU 64004 had good activity against multiresistant pneumococci, whether they were erythromycin A resistant or not, including penicillin-resistant strains. RU 64004 inhibited 90% of pneumococci resistant to erythromycin A and penicillin G at 0.6 and 0.15 microg/ml, respectively. Unlike macrolides, RU 64004 did not induce the phenotype of resistance to macrolides-lincosamides-streptogramin B. Its good antibacterial activity against multiresistant pneumococci ran in parallel with its well-balanced activity against all bacteria involved in respiratory infections (e.g., Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes). In contrast to all comparators (14- and 16-membered-ring macrolides and pristinamycin), RU 64004 displayed high therapeutic activity in animals infected with all major strains, irrespective of the phenotypes of the strains. The results suggest that RU 64004 has potential for use in the treatment of infections caused by respiratory pathogens including multiresistant pneumococci.