Matsuo K, Uete T
Department of Clinical Investigation, Kitano Hospital, Tazuke Kofukai Medical Research Institute.
Jpn J Antibiot. 1993 Mar;46(3):222-33.
Antimicrobial activities of cefmetazole (CMZ) and cefotiam (CTM) in combination were studied against clinical isolates of Staphylococcus aureus (9 methicillin-susceptible strains and 47 methicillin-resistant strains) by the checkerboard MIC method and the disc diffusion test using Mueller-Hinton agar with or without addition of 4% NaCl. MICs of CMZ and CTM individually against 9 methicillin-susceptible strains (MSSA) were 0.78 approximately 1.56 micrograms and 0.39 approximately 0.78 micrograms/ml without 4% NaCl, and 1.56 approximately 3.13 micrograms/ml and 0.78 approximately 1.56 micrograms/ml with 4% NaCl, respectively. In combination of CMZ and CTM, MICs of CMZ and CTM against these MSSA decreased to 0.20 approximately 0.39 micrograms/ml and 0.20 micrograms/ml without 4% NaCl, and 0.20 approximately 0.78 micrograms/ml and 0.10 approximately 0.78 micrograms/ml with 4% NaCl, respectively, showing minimum FIC indexes of 0.313 to 0.628. FIC indexes < or = 0.5 were observed against 7 out of 9 strains. MICs of CMZ and CTM individually against 47 methicillin-resistant strains (MRSA) were 6.25 approximately 100 micrograms/ml and 3.13 approximately 800 micrograms/ml in the absence of 4% NaCl, and 6.25 approximately 100 micrograms/ml and 50 approximately greater than 800 micrograms/ml in the presence of 4% NaCl, respectively. In combination of CMZ and CTM, MICs of these drugs against MRSA were reduced to 0.20 approximately 25 micrograms/ml without 4% NaCl and 0.39 approximately 25 micrograms/ml and 3.13 approximately 200 micrograms/ml with 4% NaCl, respectively. The strains studied showed minimum FIC indexes of 0.02 to 0.5 either with 4% NaCl or not. By the disc diffusion method, between CMZ disc and CTM disc a synergistic interaction against MRSA was well observed. In addition, discs containing both drugs showed a greater inhibitory zone than discs containing the equivalent amount of CMZ or CTM alone. These in vitro observations reported here suggest that the use of CMZ and CTM in combination is more effective than the use of these drugs individually for the treatment of MSSA and slight to moderate resistant MRSA infection. Prophylactic use of CMZ and CTM in combination for surgical infection would be also more effective than the use of these drugs individually. The synergistic enhancement of antimicrobial activity of CMZ and CTM in combination was assessed using discs containing various amounts of these drugs at various ratios. In this investigation, discs containing CMZ/CTM (20 micrograms/10 micrograms) was selected. Using discs containing CMZ/CTM (20 micrograms/10 micrograms), disc inhibitory zone diameters against MSSA and MRSA were well correlated negatively with MICs of CMZ or CTM in combination.(ABSTRACT TRUNCATED AT 400 WORDS)
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-欣顿琼脂培养基上，研究了头孢美唑（CMZ）和头孢替安（CTM）联合应用对金黄色葡萄球菌临床分离株（9株甲氧西林敏感菌株和47株甲氧西林耐药菌株）的抗菌活性。CMZ和CTM单独对9株甲氧西林敏感菌株（MSSA）在无4%氯化钠时的MIC分别为0.78～1.56微克/毫升和0.39～0.78微克/毫升，有4%氯化钠时分别为1.56～3.13微克/毫升和0.78～1.56微克/毫升。CMZ和CTM联合应用时，对这些MSSA的MIC在无4%氯化钠时分别降至0.20～0.39微克/毫升和0.20微克/毫升，有4%氯化钠时分别降至0.20～0.78微克/毫升和0.10～0.78微克/毫升，最低FIC指数为0.313至0.628。9株菌株中有7株的FIC指数≤0.5。CMZ和CTM单独对47株甲氧西林耐药菌株（MRSA）在无4%氯化钠时的MIC分别为6.25～100微克/毫升和3.13～800微克/毫升，有4%氯化钠时分别为6.25～100微克/毫升和50～＞800微克/毫升。CMZ和CTM联合应用时，对MRSA的MIC在无4%氯化钠时降至0.20～25微克/毫升，有4%氯化钠时分别降至0.39～25微克/毫升和3.13～200微克/毫升。所研究的菌株无论有无4%氯化钠，最低FIC指数均为0.02至0.5。通过纸片扩散法，在CMZ纸片和CTM纸片之间观察到对MRSA有良好的协同作用。此外，含两种药物的纸片比单独含等量CMZ或CTM的纸片显示出更大的抑菌圈。此处报道的这些体外观察结果表明，CMZ和CTM联合应用治疗MSSA和轻度至中度耐药MRSA感染比单独使用这些药物更有效。CMZ和CTM联合预防性用于外科感染也比单独使用这些药物更有效。使用含有不同比例不同量这些药物的纸片评估CMZ和CTM联合抗菌活性的协同增强作用。在本研究中，选择了含CMZ/CTM（20微克/10微克）的纸片。使用含CMZ/CTM（20微克/10微克）的纸片，对MSSA和MRSA的纸片抑菌圈直径与CMZ或CTM联合的MIC呈良好的负相关。
