In Vitro and In Vivo Antibacterial Activities of SM-216601, a New Broad-Spectrum Parenteral Carbapenem

Abstract

ABSTRACT SM-216601 is a novel parenteral 1β-methylcarbapenem. In agar dilution susceptibility testing, the MIC of SM-216601 for 90% of the methicillin-resistant Staphylococcus aureus (MRSA) strains tested (MIC 90 ) was 2 μg/ml, which was comparable to those of vancomycin and linezolid. SM-216601 was also very potent against Enterococcus faecium , including vancomycin-resistant strains (MIC 90 = 8 μg/ml). SM-216601 exhibited potent activity against penicillin-resistant Streptococcus pneumoniae , ampicillin-resistant Haemophilus influenzae , Moraxella catarrhalis , Escherichia coli , Klebsiella pneumoniae , and Proteus mirabilis , with MIC 90 s of less than 0.5 μg/ml, and intermediate activity against Citrobacter freundii , Enterobacter cloacae , Serratia marcescens , and Pseudomonas aeruginosa . The therapeutic efficacy of SM-216601 against experimentally induced infections in mice caused by S. aureus , E. faecium , E. coli , and P. aeruginosa reflected its in vitro activity and plasma level. Thus, SM-216601 is a promising candidate for nosocomial bacterial infections caused by a wide range of gram-positive and gram-negative bacteria, including multiresistant pathogens.