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[估算舒巴坦/头孢哌酮有效给药剂量的临床实验室方法]

[Clinical laboratory approach for estimating effective administrative dose of sulbactam/cefoperazone].

作者信息

Uete T, Matsuo K

机构信息

Department of Clinical Investigation, Kitano Hospital, Tazuke Kofukai Medical Research Institute.

出版信息

Jpn J Antibiot. 1988 Nov;41(11):1578-90.

PMID:3210296
Abstract

Sulbactam/cefoperazone (SBT/CPZ) is a preparation containing CPZ and SBT, an inhibitor of beta-lactamases, at the ratio 1:1. The reliability of the SBT/CPZ disc susceptibility test in estimating approximate values of MICs and the utilization of the test in the evaluation of proper administrative doses were studied using 365 strains of clinical isolates. The antimicrobial activity of SBT/CPZ was stronger than that of CPZ alone. This increase in the antimicrobial activity due to the addition of SBT was well observed in the disc diffusion susceptibility test and MIC values. The MIC80 of SBT/CPZ against Staphylococcus aureus was 12.5 micrograms/ml, while that of CPZ alone was 50 micrograms/ml. MIC80s of SBT/CPZ against Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens and Enterobacter aerogenes were smaller than those of CPZ, and were 0.20, 12.5, 25 and 3.13 micrograms/ml, respectively. However, MIC80s of SBT/CPZ against Staphylococcus epidermidis, Klebsiella pneumoniae, Proteus mirabilis and Proteus vulgaris were not changed compared to those of CPZ alone, and MIC80s were 6.25, 0.20, 0.78, and 0.78 micrograms/ml, respectively. The reliability of the SBT/CPZ disc diffusion susceptibility test in the quantitative estimation of antimicrobial activities was well demonstrated using commercialized 8 mm diameter discs (Showa) and 6 mm diameter discs prepared in this laboratory, both of which contained 30 micrograms of CPZ and 30 micrograms of SBT. These disc susceptibility test results were well correlated with MICs, hence the SBT/CPZ disc susceptibility test should be useful for the estimation of approximate MIC values. To interpret results of the Showa SBT/CPZ disc test, the following 4 category classification was used: (¿) MIC less than or equal to 3 micrograms/ml, (¿ 3 micrograms/ml less than MIC less than or equal to 15 micrograms/ml, (¿15 micrograms/ml less than MIC less than or equal to 60 micrograms/ml, (-) MIC greater than 60 micrograms/ml. In both 6 and 8 mm diameter disc tests, when uniform break points of inhibitory zone diameter were similarly applied to all strains isolated clinically, some strains of S. aureus, E. faecalis, and P. aeruginosa, brought false positive (susceptible) results showing slightly greater inhibitory zone diameters compared to MICs. However, if different break points against P. aeruginosa as indicated in this study were applied and E. faecalis was excluded from the test, excellent results were obtained in the quantitative estimation of MICs. Antimicrobial activities of antibiotic agents have been reported to be reduced by serum protein binding.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

舒巴坦/头孢哌酮(SBT/CPZ)是一种含有头孢哌酮和β-内酰胺酶抑制剂舒巴坦的制剂,二者比例为1:1。使用365株临床分离菌株研究了SBT/CPZ纸片药敏试验在估计最低抑菌浓度(MIC)近似值方面的可靠性以及该试验在评估合适给药剂量中的应用。SBT/CPZ的抗菌活性强于单独使用头孢哌酮。在纸片扩散药敏试验和MIC值中均能很好地观察到由于添加舒巴坦而导致的抗菌活性增强。SBT/CPZ对金黄色葡萄球菌的MIC80为12.5微克/毫升,而单独使用头孢哌酮时为50微克/毫升。SBT/CPZ对大肠杆菌、铜绿假单胞菌、粘质沙雷氏菌和产气肠杆菌的MIC80小于头孢哌酮,分别为0.20、12.5、25和3.13微克/毫升。然而,SBT/CPZ对表皮葡萄球菌、肺炎克雷伯菌、奇异变形杆菌和普通变形杆菌的MIC80与单独使用头孢哌酮相比没有变化,分别为6.25、0.20、0.78和0.78微克/毫升。使用商业化的8毫米直径纸片(昭和)和本实验室制备的6毫米直径纸片(均含有30微克头孢哌酮和30微克舒巴坦)很好地证明了SBT/CPZ纸片扩散药敏试验在抗菌活性定量估计中的可靠性。这些纸片药敏试验结果与MICs具有良好的相关性,因此SBT/CPZ纸片药敏试验对于估计近似的MIC值应该是有用的。为了解释昭和SBT/CPZ纸片试验结果,采用了以下4类分类法:(+)MIC小于或等于3微克/毫升,(±)3微克/毫升<MIC≤15微克/毫升,(±±)15微克/毫升<MIC≤60微克/毫升,(-)MIC>60微克/毫升。在6毫米和8毫米直径纸片试验中,当对所有临床分离菌株同样应用抑菌圈直径的统一断点时,一些金黄色葡萄球菌、粪肠球菌和铜绿假单胞菌菌株出现假阳性(敏感)结果,其抑菌圈直径比MIC略大。然而,如果应用本研究中针对铜绿假单胞菌的不同断点并将粪肠球菌排除在试验之外,则在MIC的定量估计中可获得优异结果。据报道,抗生素的抗菌活性会因血清蛋白结合而降低。(摘要截短至250字)

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