Cherubin C E, Eng R H, Smith S M, Tan E N
Department of Medicine, Mercy Hospital of Medical Center, Chicago, Illinois 60616-2477.
J Antimicrob Chemother. 1991 Jul;28(1):61-70. doi: 10.1093/jac/28.1.61.
Reference strains of Escherichia coli (ampicillin-susceptible and -resistant ATCC strains, and known TEM-1 and TEM-2 beta-lactamase producers) were tested in vitro and in the in-vivo mouse thigh infection model against four beta-lactamase inhibitor compounds (BICs: amoxycillin/clavulanic acid, ampicillin/sulbactam, ticarcillin/clavulanic acid, and piperacillin/tazobactam), selected cephalosporins, and imipenem. The ATCC strains (ampicillin-susceptible and -resistant) were susceptible to the BICs in disc and MIC tests. Three or more logs of killing were observed at the NCCLS breakpoint concentrations. However, the TEM-1 and TEM-2 producers were resistant in disc tests to ampicillin/sulbactam and amoxycillin/clavulanic acid, and showed intermediate susceptibility to ticarcillin/clavulanic acid. MICs were at or near the breakpoint, but bactericidal activity was only noted at the probable breakpoint concentration of piperacillin/tazobactam. Cefoxitin, cefotaxime, cefpirome and imipenem, but not cephalothin, showed greater bactericidal activity and lower MICs for the TEM-producing strains than the BICs. The viable count of the TEM-1 producer was not reduced in the mouse thigh model by ampicillin/sulbactam or amoxycillin/clavulanic acid, but cefpirome and cefotaxime reduced the viable count by approximately three logs. There was a 50% mortality rate in mice receiving the two BICs. The ampicillin-susceptible ATCC strain of E. coli was killed to a similar degree by all agents tested. Overall, the BICs appeared inferior, in both in-vivo and in-vitro tests to selected cephalosporins and imipenem when tested against reference strains of E. coli producing TEM-1 or TEM-2 beta-lactamase. The large inoculum effect and poor bactericidal activity observed with the BICs suggest they could be less effective in certain clinical situations.
针对四种β-内酰胺酶抑制剂化合物（BICs：阿莫西林/克拉维酸、氨苄西林/舒巴坦、替卡西林/克拉维酸和哌拉西林/他唑巴坦）、选定的头孢菌素以及亚胺培南，在体外和体内小鼠大腿感染模型中对大肠杆菌参考菌株（氨苄西林敏感和耐药的ATCC菌株，以及已知的TEM-1和TEM-2β-内酰胺酶产生菌）进行了测试。在纸片扩散试验和MIC试验中，ATCC菌株（氨苄西林敏感和耐药）对BICs敏感。在NCCLS断点浓度下观察到了三个或更多对数的杀菌效果。然而，TEM-1和TEM-2产生菌在纸片扩散试验中对氨苄西林/舒巴坦和阿莫西林/克拉维酸耐药，对替卡西林/克拉维酸表现出中度敏感性。MIC处于或接近断点，但仅在哌拉西林/他唑巴坦的可能断点浓度下才观察到杀菌活性。头孢西丁、头孢噻肟、头孢匹罗和亚胺培南，而不是头孢噻吩，对产生TEM的菌株显示出比BICs更高的杀菌活性和更低的MIC。在小鼠大腿模型中，氨苄西林/舒巴坦或阿莫西林/克拉维酸未降低TEM-1产生菌的活菌数，但头孢匹罗和头孢噻肟使活菌数减少了约三个对数。接受两种BICs的小鼠死亡率为50%。所有测试药物对氨苄西林敏感的大肠杆菌ATCC菌株的杀灭程度相似。总体而言，在针对产生TEM-1或TEM-2β-内酰胺酶的大肠杆菌参考菌株进行测试时，无论是在体内还是体外试验中，BICs似乎都不如选定的头孢菌素和亚胺培南。BICs观察到的大接种量效应和较差的杀菌活性表明它们在某些临床情况下可能效果较差。
