Matsuo K, Uete T
Department of Clinical Investigation, Kitano Hospital, Tazuke Kofukai Medical Research Institute.
Jpn J Antibiot. 1993 Feb;46(2):130-41.
Antimicrobial activities of cefmetazole (CMZ) and cefazolin (CEZ) in combination were studied against clinical isolates of Staphylococcus aureus (9 methicillin-sensitive and 47 methicillin-resistant strains) using the checkerboard MIC method and the disc diffusion test using Mueller-Hinton agar with or without addition of 4% NaCl. MICs of CMZ and CEZ individually against 9 methicillin-sensitive strains (MSSA) were 0.78-1.56 micrograms/ml and 0.39-0.78 micrograms/ml without 4% NaCl, and 1.56-3.13 micrograms/ml and 0.39-0.78 micrograms/ml with 4% NaCl, respectively. In combination of CMZ and CEZ, the MICs of CMZ and CEZ against these MSSA decreased to 0.012-0.39 micrograms/ml and 0.10-0.20 micrograms/ml without 4% NaCl, and 0.20-0.78 micrograms/ml and 0.20-0.39 micrograms/ml with 4% NaCl, respectively, showing minimum FIC indexes of 0.385 to 1.013. Minimum FIC indexes < or = 0.5 were seen in 7 out of 9 strains. MICs of CMZ and CEZ individually against 47 methicillin-resistant strains (MRSA) were 3.13-100 micrograms/ml and 3.13-400 micrograms/ml without 4% NaCl, and 6.25-50 micrograms/ml and 50-400 micrograms/ml with 4% NaCl, respectively. In combination of CMZ and CEZ, MICs of these drugs against MRSA were reduced to 0.10-50 micrograms/ml and 0.39-200 micrograms/ml without addition of 4% NaCl and 0.39-12.5 micrograms/ml and 3.13-100 micrograms/ml with 4% NaCl, respectively. Minimum FIC indexes observed were 0.047 to 0.625, and those with values < or = 0.5 were observed in 43 out of 47 strains. By the disc diffusion method, between the CMZ disc and CEZ disc, a synergistic interaction against MRSA was well observed. In addition, discs containing both drugs showed a greater inhibitory zone diameter than discs containing the equivalent amount of CMZ or CEZ alone. These in vitro observations reported here suggest that the use of CMZ and CEZ in combination is more effective than the use of these drugs individually for the treatment of MSSA and slight to moderate resistant MRSA infection, as well as for surgical prophylaxis. Therefore, further study was carried out to assess the synergistic enhancement of antimicrobial activity of CMZ and CEZ in combination using discs containing various amounts of these drugs at various ratios. Using discs containing CMZ/CEZ (20 micrograms/10 micrograms), disc inhibitory zone diameters against MSSA and MRSA were well correlated negatively with MICs of CMZ or CEZ in combination. From inhibitory zone diameters obtained with these combination discs, enhanced MICs of CMZ or CEZ in combination can be assessed.
采用棋盘微量肉汤稀释法和纸片扩散法，在添加或不添加4%氯化钠的穆勒-欣顿琼脂上，研究了头孢美唑（CMZ）和头孢唑林（CEZ）联合使用对金黄色葡萄球菌临床分离株（9株甲氧西林敏感株和47株甲氧西林耐药株）的抗菌活性。CMZ和CEZ单独对9株甲氧西林敏感株（MSSA）的最低抑菌浓度（MIC），在不添加4%氯化钠时分别为0.78～1.56微克/毫升和0.39～0.78微克/毫升，添加4%氯化钠时分别为1.56～3.13微克/毫升和0.39～0.78微克/毫升。CMZ和CEZ联合使用时，对这些MSSA的CMZ和CEZ的MIC分别降至不添加4%氯化钠时的0.012～0.39微克/毫升和0.10～0.20微克/毫升，添加4%氯化钠时的0.20～0.78微克/毫升和0.20～0.39微克/毫升，最低联合抑菌系数（FIC）指数为0.385至1.013。9株菌株中有7株的最低FIC指数≤0.5。CMZ和CEZ单独对47株甲氧西林耐药株（MRSA）的MIC，在不添加4%氯化钠时分别为3.13～100微克/毫升和3.13～400微克/毫升，添加4%氯化钠时分别为6.25～50微克/毫升和50～400微克/毫升。CMZ和CEZ联合使用时，这些药物对MRSA的MIC分别降至不添加4%氯化钠时的0.10～50微克/毫升和0.39～200微克/毫升，添加4%氯化钠时的0.39～12.5微克/毫升和3.13～100微克/毫升。观察到的最低FIC指数为0.047至0.625，47株菌株中有43株的值≤0.5。通过纸片扩散法，在CMZ纸片和CEZ纸片之间，观察到对MRSA有良好的协同相互作用。此外，含有两种药物的纸片显示出比单独含有等量CMZ或CEZ的纸片更大的抑菌圈直径。此处报道的这些体外观察结果表明，CMZ和CEZ联合使用比单独使用这些药物治疗MSSA和轻度至中度耐药MRSA感染以及手术预防更有效。因此，进一步开展研究以评估使用含有不同比例的各种量的这些药物的纸片联合使用时CMZ和CEZ抗菌活性的协同增强作用。使用含有CMZ/CEZ（20微克/10微克）的纸片，对MSSA和MRSA的纸片抑菌圈直径与CMZ或CEZ联合使用时的MIC呈良好的负相关。根据这些联合纸片获得的抑菌圈直径，可以评估CMZ或CEZ联合使用时的增强MIC。
