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Antimicrobial Agents and Chemotherapy, January 1998, p. 94-99, Vol. 42, No. 1
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

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

Masakatsu Tsuji,* Yoshikazu Ishii, Akira Ohno, Shuichi Miyazaki, and Keizo Yamaguchi

Department of Microbiology, Toho University School of Medicine, 5-21-16, Omori-nishi, Ota-ku, Tokyo 143, Japan

Received 18 April 1997/Returned for modification 25 August 1997/Accepted 20 October 1997

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 µg/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 µg/ml. Against imipenem-resistant Pseudomonas aeruginosa, S-4661 was the most active among test agents (MIC90, 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.

* Corresponding author. Present address: Department of Antimicrobial Program, Discovery Research Laboratories II, Shionogi & Co. Ltd., 3-1-1, Futaba-cho, Toyonaka, Osaka 561, Japan. Phone: 81 (6) 331-8081. Fax: 81 (6) 331-8612. E-mail: masakatsu.tsuji{at}shionogi.co.jp.

Antimicrobial Agents and Chemotherapy, January 1998, p. 94-99, Vol. 42, No. 1
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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