In Vitro and In Vivo Antibacterial Activities of S-4661, a New Carbapenem

Abstract

ABSTRACT The in vitro and in vivo antibacterial activities of S-4661, a new 1β-methylcarbapenem, were compared with those of imipenem, meropenem, biapenem, cefpirome, and ceftazidime. The activity of S-4661 against methicillin-susceptible staphylococci and streptococci was comparable to that of imipenem, with an MIC at which 90% of the strains tested were inhibited (MIC 90 ) equal to 0.5 μg/ml or less. S-4661 was highly active against members of the family Enterobacteriaceae , Haemophilus influenzae , and Moraxella catarrhalis , with MIC 90 s ranging from 0.032 to 0.5 μg/ml. Against imipenem-resistant Pseudomonas aeruginosa , S-4661 was the most active among test agents (MIC 90 , 8 μg/ml). Furthermore, S-4661 displayed a high degree of activity against many ceftazidime-, ciprofloxacin-, and gentamicin-resistant isolates of P. aeruginosa . The in vivo efficacy of S-4661 against experimentally induced infections in mice caused by gram-positive and gram-negative bacteria, including penicillin-resistant Streptococcus pneumoniae and drug-resistant P. aeruginosa , reflected its potent in vitro activity and high levels in plasma in mice. We conclude that S-4661 is a promising new carbapenem for the treatment of infections caused by gram-positive and -negative bacteria, including penicillin-resistant S. pneumoniae and drug-resistant P. aeruginosa.