In Vitro Antibacterial Activity of Modithromycin , a Novel 1 6 , 11 - Bridged Bicyclolide , against Respiratory Pathogens 2 including Macrolide - Resistant Gram - positive Cocci

20 In vitro activities of modithromycin against Gram-positive and -negative respiratory 21 pathogens including macrolide-resistant cocci with different resistant-mechanisms were 22 compared with those of other macrolide and ketolide agents. MICs were determined by broth 23 microdilution method. All 595 test strains used in this study were isolated from Japanese 24 medical facilities. The erm (ribosome methylase) and/or mef (efflux pump) genes, which 25 correlated with resistance to erythromycin as well as clarithromycin and azithromycin, were 26 found in 81.8%, 21.3% and 23.2% of Streptococcus pneumoniae, Streptococcus pyogenes and 27 methicillin-susceptible Staphylococcus aureus (MSSA), respectively. Modithromycin showed 28 MIC90s of 0.125 μg/ml against these three cocci including macrolide-resistant strains. In 29 particular, the MICs of modithromycin against ermB-carrying S. pyogenes were ≥32-fold 30 lower than that of telithromycin. The activities of modithromycin as well as telithromycin 31 were little affected by the presence of the mefA/E in both streptococci. Against Gram-negative 32 pathogens, modithromycin showed MIC90s of 0.5, 8 and 0.031 μg/ml against Moraxella 33 catarrhalis, Haemophilus influenzae and Legionella spp., respectively. The MICs of 34 modithromycin against M. catarrhalis and H. influenzae were higher than telithromycin and 35 azithromycin. However, modithromycin showed the most potent anti-Legionella activity 36 among the macrolide and ketolide agents tested. These results suggested that the bicyclolide 37 agent modithromycin was a novel class of macrolides with improved antibacterial activity 38 against Gram-positive cocci including telithromycin-resistant streptococci and intracellular 39 Gram-negative bacteria of the Legionella species. 40 41 on O cber 5, 2017 by gest httpaac.asm .rg/ D ow nladed fom