哌拉西林/舒巴坦对临床分离菌的体外抗菌活性研究

In vitro comparative activities study of piperacillin/sulbactam against clinical isolates

目的 比较研究哌拉西林、舒巴坦、哌拉西林与舒巴坦不同比例联合及阿莫西林 /舒巴坦 (2∶1) ,对临床分离 3 0 9株需氧菌和 3 0株厌氧菌的体外抗菌活性及其影响因素 (研究哌拉西林 /舒巴坦 (2∶1)对金葡球菌、大肠埃希氏菌和铜绿假单胞菌的的杀菌曲线 )。方法 采用琼脂平板稀释法及肉汤稀释法测定MIC值 ,Nitrocefin纸片法测定细菌产生的 β 内酰胺酶 ,时间杀菌曲线采用肉汤 10倍稀释法。结果 对临床分离的3 3 9株需氧菌及厌氧菌体外抗菌活性研究结果显示 ,哌拉西林及其与舒巴坦联合时 ,对革兰氏阳性球菌及厌氧菌的体外抗菌活性MIC50 为 1～ 4μg/ml,MIC90 多数低于 12 8μg/ml,优于革兰氏阴性杆菌 ,其MIC50 为 1～12 8μg/ml ,MIC90 多数高于 12 8μg/ml;单用舒巴坦对各种细菌的体外抗菌活性极差 ,多数菌的MIC50 及MIC90 分别为 64及 2 5 6μg/ml。对革兰氏阴性杆菌及厌氧菌 ,哌拉西林与舒巴坦联合时体外抗菌活性明显优于单用哌拉西林 ;对于革兰氏阳性球菌 ,哌拉西林联合舒巴坦后体外抗菌活性改善不如革兰氏阴性杆菌及厌氧菌。哌拉西林对产酶株的MIC高于非产酶株 ,联合舒巴坦后 ,产酶株MIC降低而非产酶株MIC变化不明显。不同比例联合的体外抗菌活性比较发现 ,以哌拉西林 /舒巴坦 2∶1联合时效果较好。

Aims To compare the in vitro activities of piperacillin, sulbactam, piperacillin combined with sulbactam in various proportions, amoxicillin/sulbactam (2∶1) aganist 309 strains of areobes and 30 strains of anaerobes. To study the factors affecting the in vitro activities. To study the time kill curve of piperacillin/sulbactam 2∶1 against S.aureus, E coli and P.aeruginosa . Method The MICs were tested by two fold agar dillution method and two fold broth dillution method. The β lactamases were examined by Nitrocefin disc method. The time kill effect was tested with broth ten fold dilution. Result The in vitro activities of piperacillin, piperacillin/sulbactam, amoxicillin against 339 strains areobes and anaerobes showed that MIC 50 of piperacillin, amoxicillin and piperacillin/sulbactam and amoxicillin/sulbactam against gram positive coccus and anaerobes were 1～4μg/ml, MIC 90 were less than 128μg/ml, better than those against gram negative bacteria (MIC 50 , 1～128μg/ml, MIC 90 >128μg/ml). Sulbactam was the worst active to all of the isolates among these agents, MIC 50 and MIC 90 were 64μg/ml and 256μg/ml respectively. The in vitro activity of piperacillin combined with sulbactam against gram negative bacteria and anaerobes was better than that of piperacillin alone. The improvement of in vitro activities of piperacillin combined with sulbactam against gram positive coccus was less than that against gram negative bacteria and anaerobes. The in vitro activity study of piperacillin combined with sulbactam in various proportions showed that piperacillin/sulbactam 2∶1 was better than other composition, similar to that of amoxicillin/sulbactam 2∶1. The activity of piperacillin/sulbactam against the Pseudomonas spp. was better than that of amoxicillin/sulbactam. Among these clinical isolates, the resistant rate of Pseudomonas spp. was the highest (61.5%), followed by E.coli and Enterobacter spp. (50.8% and 50.0% respectively). The resistant rates of all clinical isolates decreased when piperacillin combined with sulbactam. The time kill curve of piperacillin/sulbactam 2∶1 showed that when the concentration of 4×MIC acted to S.aureus, E.coli and P.aeruginosa , the number of bacteria decreased in logical grade. At 8th hour point, the concentration of piperacillin/sulbactam 2∶1 killed all of the tested bacteria. The effects of 1×MIC and 2×MIC concentration of piperacillin/sulbactam were less than that of 4×MIC. The MICs of piperacillin/sulbactam was mainly affected by pH in media and the concentration of bacteria. The concentration of bovine serum albumin had no effect on in vitro activities. Conclusion Results showed that piperacillin had the poor activity against these clinical isolates due to the β lactamase productivity. When piperacillin was combined with sulbactam, the in vitro activity was improved apparently. Piperacillin/sulbactam 2∶1 had the best activity against most of the clinical isolates. 4×MIC concentration of piperacillin/sulbactam 2∶1 had the best killing effects to bacteria. The in vitro activities was mainly affected by pH in media and the concentration of bacteria.