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Journal of Antimicrobial Chemotherapy (1993) 31, 533-541
© 1993 The British Society for Antimicrobial Chemotherapy

other

Synergic activity of imipenem/cilastatin combined with cefotiam against methiclillin-resistant Staphylococcus aureus

Shinichi Okaa, Mieko Gotoa, Yoshiko Kajia, Satoshi Kimuraa, Kouji Matsudab,*, Yoshinari Asahib, Minoru Sanadab, Susumu Nakagawahb, Matsuhisa Inouec and Kaoru Shlmadaa

aDepartment of Infectious Diseases, Institute of Medical Science, University of Tokyo 4-6-1, Shirokanedai, Minato-ku, Tokyo, 108 bAntimicrobial Screening and Evaluation, New Drug Discovery Research Laboratories, Tsukuba Research Institute Banyu Pharmaceutical Co. Ltd. cMicrobiology, School of Medicine, Kitazato University 1-15-1 Kitazato, Sagamihara, Kanagawa, 228, Japan

Received 18 December 1991; accepted 23 November 1992

*Correspondence to: Dr Kouji Matsuda, Antimicrobial Screening & Evaluation, New Drug Discovery Research Laboratories, Tsukuba Research Institute, Banyu Pharmaceutical Co. Ltd., Tsukuba Techno-Park Oho, Okubo 3, Tsukuba 300-33, Japan

The synergic activity of imipenem/cilastatin combined with cefotiam was studied in a mouse bacteraemia mod.el. Combinations of imipenem plus cefotiam in ratios from 1: 5 to I : 160 were more effective than either imipenem alone or cefotiam alone (P < 0·05). Synergy was observed against both ß-lactamase producing and ß-lactamase non-producing MRSA. Staggered combinations of imipenem with cefotiam (each drug was administered at a different time) were studied in an in-vitro pharmacokinetic system to clarify relationships between killing kinetics and pharmacodynamics of the combinations. In the in-vitro system, cefotiam (1 g over 30 mm) administered 2 h after imipenem administration (250 mg over 30 mm) reduced viable cell counts to an undetectable level and maintained this for 4 h, while the simultaneous administration of imipenem and cefotiam maintained an undetectable cell count for only 2 h. Furthermore, imipenem administered after cefotiam showed no synergy. These results indicate that the timing of dosing of each antibiotic influences synergy, and administration of cefotiam 2 h after imipenemis more effective than the other regimens.


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