Matsuda K, Inoue M
Banyu Pahrmaceutical Co., Ltd., 2-3 Nihonbashi-Honcho 2-Chome, Chuo-ku, Tokyo 103-8416, Japan.
Jpn J Antibiot. 2000 Dec;53(12):667-71.
Minimum inhibitory concentration (MIC) has been generally used to evaluate the activity of antimicrobial agents. However, there is some discrepancy between clinical efficacy and the MIC value. We studied the relationship between initial bactericidal activity of imipenem (IPM), panipenem (PAPM), meropenem (MEPM), ceftazidime (CAZ) and amikacin (AMK) and the respective MIC values against Pseudomonas aeruginosa PAO1. Initial bactericidal activity was defined as percent reduction of initial bacterial cell concentration (10(6) cells/ml) after 1 hour incubation following addition of antibiotic. The concentration of antibiotic used in this experiment was the blood level of each antibiotic at 3 hours after administration by drip infusion of the usual dose (IPM, PAPM and CAZ were 1 g for 1 hour drip infusion, MEPM was 1 g for 0.5 hours drip infusion and AMK was 200 mg for 1 hour drip infusion, respectively). The antibiotic concentration of IPM, PAPM, MEPM, CAZ and AMK were 8.77 micrograms/ml, 6.37 micrograms/ml, 4.12 micrograms/ml, 12.0 micrograms/ml and 5.18 micrograms/ml, respectively. MICs of IPM, PAPM, MEPM, CAZ and AMK were 2 micrograms/ml, 64 micrograms/ml, 1 microgram/ml, 1 microgram/ml and 2 micrograms/ml, respectively. Initial bactericidal activity of IPM, PAPM, MEPM, and CAZ against P. aeruginosa PAO1 was 98.2%, 86.1%, 48.1%, and 43.4% reduction in bacterial concentration, respectively. AMK shows the strongest initial bactericidal activity with more than 99.9%. The killing speed of IPM was obviously the most rapid among the three carbapenems. The MIC of PAPM was significantly higher than the other antibiotics, and the initial bactericidal activity of PAPM was second to IPM. We can classify antibiotics into two groups based on initial bactericidal activity against P. aeruginosa; one class is antibiotics having rapid initial killing such as AMK, IPM and PAPM, the other is CAZ, MEPM showing slow initial killing.
最低抑菌浓度（MIC）通常用于评估抗菌药物的活性。然而，临床疗效与MIC值之间存在一些差异。我们研究了亚胺培南（IPM）、帕尼培南（PAPM）、美罗培南（MEPM）、头孢他啶（CAZ）和阿米卡星（AMK）对铜绿假单胞菌PAO1的初始杀菌活性与各自MIC值之间的关系。初始杀菌活性定义为添加抗生素后孵育1小时后初始细菌细胞浓度（10⁶个细胞/毫升）的降低百分比。本实验中使用的抗生素浓度是常规剂量静脉滴注给药3小时后每种抗生素的血药浓度（IPM、PAPM和CAZ为1克静脉滴注1小时，MEPM为1克静脉滴注0.5小时，AMK为200毫克静脉滴注1小时）。IPM、PAPM、MEPM、CAZ和AMK的抗生素浓度分别为8.77微克/毫升、6.37微克/毫升、4.12微克/毫升、12.0微克/毫升和5.18微克/毫升。IPM、PAPM、MEPM、CAZ和AMK的MIC分别为2微克/毫升、64微克/毫升、1微克/毫升、1微克/毫升和2微克/毫升。IPM、PAPM、MEPM和CAZ对铜绿假单胞菌PAO1的初始杀菌活性分别使细菌浓度降低98.2%、86.1%、48.1%和43.4%。AMK显示出最强的初始杀菌活性，超过99.9%。在三种碳青霉烯类药物中，IPM的杀菌速度明显最快。PAPM的MIC显著高于其他抗生素，其初始杀菌活性仅次于IPM。基于对铜绿假单胞菌的初始杀菌活性，我们可以将抗生素分为两组；一类是具有快速初始杀菌作用的抗生素，如AMK、IPM和PAPM，另一类是CAZ、MEPM，显示出缓慢的初始杀菌作用。
