In vitro and in vivo antibacterial activities of S-4661, a new carbapenem.
The in vitro and in vivo antibacterial activities of S-4661, a new 1beta-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 (MIC90) equal to 0.5 microg/ml or less. S-4661 was highly active against members of the family Enterobacteriaceae, Haemophilus influenzae, and Moraxella catarrhalis, with MIC90s ranging from 0.032 to 0.5 microg/ml. Against imipenem-resistant Pseudomonas aeruginosa, S-4661 was the most active among test agents (MIC90, 8 microg/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.
Tsuji
M
M
Department of Microbiology, Toho University School of Medicine, Tokyo, Japan. masakatsu.tsuji@shionogi.co.jp
Ishii
Y
Y
Ohno
A
A
Miyazaki
S
S
Yamaguchi
K
K
D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015780:Carbapenems / Q000097:blood / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D000077726:Doripenem; D004755:Enterobacteriaceae / Q000187:drug effects*; D006193:Haemophilus influenzae / Q000187:drug effects*; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D009016:Moraxella / Q000187:drug effects*; D010403:Penicillin Resistance; D011008:Pneumococcal Infections / Q000097:blood / Q000188:drug therapy*
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D000077726:Doripenem