Synergic activity of imipenem/cilastatin combined with cefotiam against methicillin-resistant Staphylococcus aureus.
The synergic activity of imipenem/cilastatin combined with cefotiam was studied in a mouse bacteraemia model. Combinations of imipenem plus cefotiam in ratios from 1:5 to 1:160 were more effective than either imipenem alone or cefotiam alone (P < 0.05). Synergy was observed against both beta-lactamase producing and beta-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 min) administered 2 h after imipenem administration (250 mg over 30 min) 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 imipenem is more effective than the other regimens.
Department of Infectious Diseases, University of Tokyo, Japan.
S
S
Oka
M
M
Goto
Y
Y
Kaji
S
S
Kimura
K
K
Matsuda
Y
Y
Asahi
M
M
Sanada
S
S
Nakagawa
M
M
Inoue
K
K
Shimada
D000818:Animals; D015310:Cefotiam / Q000493:pharmacokinetics / Q000494:pharmacology; D015377:Cilastatin / Q000493:pharmacokinetics / Q000494:pharmacology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000493:pharmacokinetics / Q000494:pharmacology*; D015378:Imipenem / Q000493:pharmacokinetics / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D016106:Methicillin Resistance; D051379:Mice; D008813:Mice, Inbred ICR; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000187:drug effects*
D015377:Cilastatin; D015378:Imipenem; D015310:Cefotiam