Oka S, Goto M, Kaji Y, Kimura S, Matsuda K, Asahi Y, Sanada M, Nakagawa S, Inoue M, Shimada K
Department of Infectious Diseases, University of Tokyo, Japan.
J Antimicrob Chemother. 1993 Apr;31(4):533-41. doi: 10.1093/jac/31.4.533.
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.
在小鼠菌血症模型中研究了亚胺培南/西司他丁与头孢替安联合使用的协同活性。亚胺培南与头孢替安以1:5至1:160的比例联合使用比单独使用亚胺培南或单独使用头孢替安更有效（P < 0.05）。观察到对产β-内酰胺酶和不产β-内酰胺酶的耐甲氧西林金黄色葡萄球菌均有协同作用。在体外药代动力学系统中研究了亚胺培南与头孢替安的错开联合使用（每种药物在不同时间给药），以阐明联合用药的杀菌动力学与药效学之间的关系。在体外系统中，在亚胺培南给药（30分钟内给予250毫克）2小时后给予头孢替安（30分钟内给予1克）可将活菌数降至检测不到的水平并维持4小时，而同时给予亚胺培南和头孢替安仅能维持2小时的检测不到的细胞数。此外，在头孢替安之后给予亚胺培南未显示出协同作用。这些结果表明每种抗生素的给药时间会影响协同作用，并且在亚胺培南给药2小时后给予头孢替安比其他给药方案更有效。
