P1A Recombinant β-Lactamase Prevents Emergence of Antimicrobial Resistance in Gut Microflora of Healthy Subjects during Intravenous Administration of Ampicillin
P1A Recombinant β-Lactamase Prevents Emergence of Antimicrobial Resistance in Gut Microflora of Healthy Subjects during Intravenous Administration of Ampicillin
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DOI：
10.1128/aac.00853-08
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发表时间：
2009-06-01
影响因子：
4.9
通讯作者：
Nord, Carl Erik
中科院分区：
文献类型：
--
作者：
Tarkkanen, Ann-Mari;Heinonen, Tuula;Nord, Carl Erik
Ipsat P1a是一种能降解胃肠道中抗生素残留的重组β-内酰胺酶。在一项开放标签的单中心对照试验中，36名健康受试者被随机接受(I)氨苄西林(1g静脉注射)。每6h一次，(Ii)口服重组β-内酰胺酶(8.2 mg q6h)，或(Iii)氨苄西林(1g)静脉注射。Q6h)，联合口服P1a重组β-内酰胺酶(8.2 mg，q6h)，疗程5d。在治疗前、治疗期间(第3至5天)和随访(第12天)收集粪便样本。主要终点是(I)胃肠道微生物区系的变化(通过温度梯度凝胶电泳法[TGGE]确定)和(Ii)细菌耐药性的出现(通过常规微生物学和透射电子显微镜β-内酰胺酶基因的聚合酶链式反应(PCR)确定)。35名受试者完成了这项研究。在第3、4、5天，氨苄西林组TGGE图谱与每个治疗日样本之间的平均相似百分比显著低于氨苄西林组和P1a重组β-内酰胺酶组(P
Ipsat P1A is a recombinant beta-lactamase which degrades antibiotic residue in the gastrointestinal tract. In an open-label, single- center controlled trial, 36 healthy subjects were randomized to receive (i) ampicillin (1 g intravenously [i.v.] every 6 h [q6h]), (ii) oral P1A recombinant beta-lactamase (8.2 mg q6h), or (iii) ampicillin (1 g i.v. q6h) in combination with oral P1A recombinant beta-lactamase (8.2 mg q6h) for 5 days. Fecal samples were collected before treatment, during treatment (days 3 to 5), and at follow-up (day 12). The primary end points were (i) changes in gastrointestinal microflora (determined by temperature gradient gel electrophoresis [TGGE]) and (ii) emergence of bacterial resistance (determined by conventional microbiology and PCR of TEM beta-lactamase genes). Thirty-five subjects completed the study. The mean similarity percentages of TGGE profiles between baseline and each treatment day sample were significantly lower for the ampicillin group than for the group receiving ampicillin plus P1A recombinant beta-lactamase on days 3, 4, and 5 (P