Methods: MIC was measured by broth microdilution method according to Clinical and Laboratory Standard Institute except that iron deficient broth, which was prepared by treatment with Chelex resin, was used for evaluation of ‘266.
Study 1: In vitro activity of ‘266 against Gram-negative bacteria isolated from multiple hospitals in Japan in 2012 was determined using Chelex-treated ISB. Test strains were 173 E. coli, 108 K. pneumoniae, 80 E. cloacae, 103 S. marcescens, 123 P. aeruginosa, 29 B. cepacia, 69 S. maltophilia, and 91 Acinetobacter species.
Study 2: In vitro activity of ‘266 against carbapenem-resistant Enterobacteriaceae (29 E. coli, 25 K. pneumoniae, 21 K. oxytoca, 11 E. cloacae, and 4 C. freundii) such as IMP-type metallo b-lactamase-producers isolated in Japan was determined using Chelex-treated MHB.
Results: The MIC90s of ‘266 against E. coli, K. pneumoniae, E. cloacae and S. marcescens ranged from 0.063 to 0.5 µg/mL. The MIC90 of ceftazidime and meropenem ranged from 0.5 to 64 µg/mL and 0.031 to 0.125 µg/mL, respectively. In the case of P. aeruginosa, S. maltophilia, B. cepacia and Acinetobacter spp., the MIC90s of ‘266 ranged from 0.016 to 0.5 µg/mL, which were significantly lower than those of ceftazidime and meropenem (8 to >64 µg/mL and 1 to >64 µg/mL, respectively). The MIC90 of S-649266 against carbapenem-resistant Enterobacteriaceae was 1 µg/mL. The MIC90 of cefepime and meropenem were >32 and 32 µg/mL, respectively.
Conclusion: ‘266 showed potent antimicrobial activity against Gram-negative bacteria including carbapenem-resistant Enterobacteriaceae. These data suggest that ‘266 is a promising siderophore cephalosporin antibiotic for treatment of infections caused by these problematic pathogens.
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