Lamp K C, Vickers M K
Veterans Affairs Medical Center, School of Pharmacy, University of Missouri-Kansas City, 64128, USA.
Antimicrob Agents Chemother. 1998 Feb;42(2):231-5. doi: 10.1128/AAC.42.2.231.
The activity of ampicillin-sulbactam against beta-lactamase-producing Escherichia coli has been questioned. Therefore, in this study, the killing activity of ampicillin-sulbactam was investigated in an in vitro infection model which simulates human pharmacokinetics. One ampicillin-sensitive strain (E. coli ATCC 25922, ampicillin-sulbactam MIC = 4/2 microg/ml) and three ampicillin-resistant TEM-1-producing strains with various levels of ampicillin-sulbactam resistance (EC11, MIC = 4/2 microg/ml; TIM2, MIC = 12/6 microg/ml; and GB85, MIC > 128/64 microg/ml) were studied. The E. coli strains were exposed to ampicillin-sulbactam at a starting inoculum of 6 to 7 log10 CFU/ml. Ampicillin-sulbactam was infused over 30 min to simulate doses of 3 and 1.5 g every 6 h for 24 h. The 3-g ampicillin-sulbactam dose was bactericidal against E. coli ATCC 25922, EC11, and TIM2. The 1.5-g dose displayed bactericidal activity against ATCC 25922 and EC11 similar to that of the higher dose but failed to kill TIM2 due to inadequate time above the MIC and increased MICs over 24 h. GB85 was highly resistant and grew similarly to controls. Despite an MIC at 10(7) CFU/ml indicating resistance (20/10 microg/ml), TIM2 was killed by the 3-g dose of ampicillin-sulbactam. Current MIC breakpoints may not adequately portray the activity of ampicillin-sulbactam, considering both the activity in in vitro infection models and clinical data.
氨苄西林-舒巴坦对产β-内酰胺酶的大肠杆菌的活性受到质疑。因此，在本研究中，在模拟人体药代动力学的体外感染模型中研究了氨苄西林-舒巴坦的杀菌活性。研究了一株对氨苄西林敏感的菌株（大肠杆菌ATCC 25922，氨苄西林-舒巴坦MIC = 4/2微克/毫升）和三株对氨苄西林耐药且产TEM-1酶、对氨苄西林-舒巴坦具有不同耐药水平的菌株（EC11，MIC = 4/2微克/毫升；TIM2，MIC = 12/6微克/毫升；GB85，MIC > 128/64微克/毫升）。将大肠杆菌菌株以6至7 log10 CFU/毫升的起始接种量暴露于氨苄西林-舒巴坦。氨苄西林-舒巴坦在30分钟内输注，以模拟每6小时3克和1.5克的剂量，持续24小时。3克氨苄西林-舒巴坦剂量对大肠杆菌ATCC 25922、EC11和TIM2具有杀菌作用。1.5克剂量对ATCC 25922和EC11显示出与高剂量相似的杀菌活性，但由于高于MIC的时间不足以及24小时内MIC增加，未能杀死TIM2。GB85具有高度耐药性，生长情况与对照相似。尽管TIM2在10(7) CFU/毫升时的MIC表明其耐药（20/10微克/毫升），但3克剂量的氨苄西林-舒巴坦仍可将其杀死。考虑到体外感染模型中的活性和临床数据，目前的MIC断点可能无法充分描述氨苄西林-舒巴坦的活性。
