In vitro antibacterial activities of S-013420, a novel bicyclolide, against respiratory tract pathogens


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Abstract

ObjectivesThe in vitro activity of S-013420, a novel bicyclolide, was investigated.MethodsAll test strains for this study were isolated from Japanese medical facilities. MICs were determined by the microbroth dilution method or agar dilution method according to the CLSI guidelines. In time–kill kinetics, viable cells were measured at 1, 2.5, 4 and 6 h after exposure to antimicrobials. The frequencies of single-step resistance acquisition at 4× MIC and 8× MIC were determined using 107 cfu of bacterial cells.ResultsS-013420 showed MIC90 values of 0.125, 0.125, 8 and 0.5 mg/L for Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae and Moraxella catarrhalis, respectively. S-013420 showed the most potent activity against erythromycin-intermediate and -resistant S. pneumoniae with an MIC90 of 0.25 mg/L and inhibited the growth of all strains of S. pyogenes with macrolide resistance genes at 1 mg/L. The MICs of S-013420 for atypical pathogens such as erythromycin-susceptible Mycoplasma pneumoniae and Chlamydophila pneumoniae were 0.00049–0.001 and 0.0039 mg/L, respectively, although the activity of S-013420, as well as other macrolide agents, against erythromycin-resistant M. pneumoniae was significantly weak. S-013420 caused a 3 log10 reduction in viable cells against all test strains of S. pneumoniae and H. influenzae. Acquisition of resistance to S-013420 was not observed for three strains of S. pneumoniae.ConclusionsS-013420 shows potent in vitro activity against respiratory tract pathogens. Against streptococci, including erythromycin-resistant strains, S-013420 demonstrated the most potent in vitro activity among the antimicrobials tested.

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