Saionji K
Department of Clinical Pathology, School of Medicine, Juntendo University.
Jpn J Antibiot. 1988 Oct;41(10):1390-406.
Influence of human albumin on bactericidal or antibacterial activities of 11 beta-lactams were examined. The 11 beta-lactams included second generation cephems (cefsulodin, cefotiam and cefmetazole), third generation cephems (ceftazidime, latamoxef, cefmenoxime, cefoperazone, cefotetan and cefpiramide) and monobactams (carumonam and aztreonam). The micro-broth-dilution method was used to determine antibacterial activities. Bactericidal activities were determined using the time-kill method. Used in the broth-dilution method were 2 media, MUELLER-HINTON broth (MHB) and the same medium supplemented with 5 g human albumin/d1 (MHB-A). The first experiment was to compare minimum inhibitory concentrations (MICs) determined in MHB were compared with those in MHB-A of 6 antibiotics against Staphylococcus aureus FDA 209P JC-1, of 7 antibiotics against Escherichia coli ATCC 25922 and of 5 antibiotics against Pseudomonas aeruginosa NCTC 10490. MICs using MHB-A were higher than MIC using MHB for 2 of the 6 antibiotics against S. aureus, and for all the 7 antibiotics against E. coli, and for 3 of the 5 antibiotics against P. aeruginosa. The second experiment was done to compare MICs of 5 antibiotics determined in MHB-A with those determined in MHB against 10 clinical isolates of S. aureus, of 6 antibiotics against 10 clinical isolates of Klebsiella pneumoniae and of 6 antibiotics against 10 clinical isolates of P. aeruginosa. The results obtained in the second experiment were varied for different antibiotics and different strains of organisms, and same antibiotics produced different results for different strains. MICs determined in MHB-A were lower than those in MHB for antibiotics with relatively low protein binding rates against 22 of 170 isolates tested (12.9%), whereas the former was higher than the latter against 103 out of 170 isolates tested (60.6%). MICs of antibiotics with relatively high protein binding rates showed an opposite trend. In the third experiment, time-kill curves were determined in the 2 media for 5 antibiotics against S. aureus FDA 209P JC-1, for 6 drugs against E. coli ATCC 25922 and for 5 drugs against P. aeruginosa NCTC 10490. The concentrations of these antibiotics used were 1/2 x MIC, 1 x MIC and 2 x MIC. MICs determined in the first experiment were used here. Time-kill curves determined in MHB-A didn't reflect MICs determined in MHB. Using MHB-A, antibiotics with lower MICs determined in MHB-A showed bactericidal activities in lower concentrations. Human albumin influenced antibacterial or bactericidal activities of beta-lactams.(ABSTRACT TRUNCATED AT 400 WORDS)
研究了人白蛋白对11种β-内酰胺类药物杀菌或抗菌活性的影响。这11种β-内酰胺类药物包括第二代头孢菌素(磺苄西林、头孢替安和头孢美唑)、第三代头孢菌素(头孢他啶、拉氧头孢、头孢甲肟、头孢哌酮、头孢替坦和头孢匹胺)以及单环β-内酰胺类药物(卡芦莫南和氨曲南)。采用微量肉汤稀释法测定抗菌活性,使用时间杀菌法测定杀菌活性。在肉汤稀释法中使用了2种培养基,即MUELLER-HINTON肉汤(MHB)和添加了5 g人白蛋白/d1的相同培养基(MHB-A)。第一个实验是比较在MHB中测定的6种抗生素对金黄色葡萄球菌FDA 209P JC-1、7种抗生素对大肠埃希菌ATCC 25922以及5种抗生素对铜绿假单胞菌NCTC 10490的最低抑菌浓度(MIC)与在MHB-A中的MIC。在针对金黄色葡萄球菌的6种抗生素中,有2种使用MHB-A时的MIC高于使用MHB时的MIC;针对大肠埃希菌的所有7种抗生素,以及针对铜绿假单胞菌的5种抗生素中有3种,使用MHB-A时的MIC高于使用MHB时的MIC。第二个实验是比较在MHB-A中测定的5种抗生素对10株金黄色葡萄球菌临床分离株、6种抗生素对10株肺炎克雷伯菌临床分离株以及6种抗生素对10株铜绿假单胞菌临床分离株的MIC与在MHB中测定的MIC。第二个实验的结果因不同抗生素和不同菌株而异,相同抗生素对不同菌株产生不同结果。对于蛋白结合率相对较低的抗生素,在170株测试菌株中有22株(12.9%)使用MHB-A测定的MIC低于使用MHB时的MIC,而在170株测试菌株中有103株(60.6%)前者高于后者。蛋白结合率相对较高的抗生素的MIC呈现相反趋势。在第三个实验中,测定了在2种培养基中5种抗生素对金黄色葡萄球菌FDA 209P JC-1、6种药物对大肠埃希菌ATCC 25922以及5种药物对铜绿假单胞菌NCTC 10490的时间杀菌曲线。所用这些抗生素的浓度为1/2×MIC、1×MIC和2×MIC。这里使用第一个实验中测定的MIC。在MHB-A中测定的时间杀菌曲线未反映在MHB中测定的MIC。使用MHB-A时,在MHB-A中测定的MIC较低的抗生素在较低浓度下显示出杀菌活性。人白蛋白影响β-内酰胺类药物的抗菌或杀菌活性。(摘要截于400字)