Saionji K, Shitara M, Miyake N, Inoue K, Kobayashi I
Department of Clinical Laboratory, Kosei General Hospital, Tokyo.
Jpn J Antibiot. 1990 Oct;43(10):1685-97.
Imipenem (IPM) and beta-lactams have been reported to possess a synergistic relationship in their activities against methicillin (DMPPC)-resistant strains of Staphylococcus aureus (MRSA). The purpose of this study was to determine activities of IPM and ampicillin (ABPC) singly and in combination against MRSA. Activities of the 2 antibiotics against 19 strains of S. aureus resistant to DMPPC were investigated by means of the checkerboard method, the disk diffusion technique and the killing-curve method. MICs of DMPPC against these strains determined using the agar dilution method were greater than or equal to 100 micrograms/ml and MICs of IPM and ABPC ranged from 12.5 to 100 micrograms/ml and from 12.5 to 50 micrograms/ml, respectively, when used singly. The following results were obtained with the checkerboard method: Synergistic effects and additive effects were found against 13/19 and against 6/19 strains, respectively, and no antagonistic effect was found according to the FIC (fractionary inhibitory concentration) index. The disk diffusion technique indicated synergistic results. Killing-curves with the following drug concentration combinations were examined in Mueller-Hinton broth against 5 fosfomycin(FOM)-resistant and 5 FOM-susceptible stains: (1) IPM 12.5 micrograms/ml, (2) ABPC 25 micrograms/ml, (3) IPM 12.5 micrograms/ml + ABPC 25 micrograms/ml, (4) IPM 6.25 micrograms/ml + ABPC 25 micrograms/ml, (5) IPM 6.25 micrograms/ml + ABPC 12.5 micrograms/ml, (6) IPM 6.25 micrograms/ml + ABPC 12.5 micrograms/ml + FOM (fosfomycin) 25 micrograms/ml, (7) IPM 12.5 micrograms/ml + ABPC 25 micrograms/ml + FOM 50 micrograms/ml, (8) FOM 50 micrograms/ml. The following results were obtained with the killing-curve method; (1) Synergistic effects were found against 8/10 strains and no antagonistic effect was found with the combinations of IPM and ABPC. (2) Synergistic effects were found against 3/5 strains and no antagonistic effect was found with the combinations of IPM, ABPC and FOM against 5 FOM-susceptible strains.
IPM in combination with ABPC produced synergistic effects against MRSA. This combination therapy should be evaluated in treating MRSA infections.
据报道，亚胺培南（IPM）和β-内酰胺类药物在抗耐甲氧西林（DMPPC）金黄色葡萄球菌（MRSA）菌株的活性方面具有协同关系。本研究的目的是确定IPM和氨苄西林（ABPC）单独及联合使用对MRSA的活性。采用棋盘法、纸片扩散法和杀菌曲线法研究了这两种抗生素对19株耐DMPPC金黄色葡萄球菌的活性。使用琼脂稀释法测定DMPPC对这些菌株的最低抑菌浓度（MIC）大于或等于100微克/毫升，单独使用时IPM和ABPC的MIC分别为12.5至100微克/毫升和12.5至50微克/毫升。棋盘法得到以下结果：分别对13/19株和6/19株发现协同作用和相加作用，根据分数抑菌浓度（FIC）指数未发现拮抗作用。纸片扩散法显示协同结果。在 Mueller-Hinton肉汤中，用以下药物浓度组合的杀菌曲线检测了5株耐磷霉素（FOM）和5株对FOM敏感的菌株：（1）IPM 12.5微克/毫升，（2）ABPC 25微克/毫升，（3）IPM 12.5微克/毫升 + ABPC 25微克/毫升，（4）IPM 6.25微克/毫升 + ABPC 25微克/毫升，（5）IPM 6.25微克/毫升 + ABPC 12.5微克/毫升，（6）IPM 6.25微克/毫升 + ABPC 12.5微克/毫升 + FOM（磷霉素）25微克/毫升，（7）IPM 12.5微克/毫升 + ABPC 25微克/毫升 + FOM 50微克/毫升，（8）FOM 50微克/毫升。杀菌曲线法得到以下结果：（1）对8/10株发现协同作用，IPM和ABPC联合使用未发现拮抗作用。（2）对3/5株发现协同作用，IPM、ABPC和FOM联合使用对5株FOM敏感菌株未发现拮抗作用。
IPM与ABPC联合使用对MRSA产生协同作用。这种联合疗法在治疗MRSA感染方面应进行评估。
