Efficacy of piperacillin-tazobactam and cefotaxime against Escherichia coli hyperproducing TEM-1 in a mouse peritonitis infection model
Efficacy of piperacillin-tazobactam and cefotaxime against Escherichia coli hyperproducing TEM-1 in a mouse peritonitis infection model
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DOI：
10.1016/j.ijantimicag.2022.106543
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发表时间：
2022-04-10
影响因子：
10.8
通讯作者：
Schonning, Kristian
中科院分区：
文献类型：
--
作者：
Hertz, Frederik Boetius;Andreasen, Minna Rud;Schonning, Kristian
目的：阿伐他西林-他唑巴坦（TZP）是医院常用的抗生素。报告表明，尽管对头孢菌素敏感的分离株在体外具有耐药性，但TZP在体内仍有效。大肠杆菌（E.高产TEM-1 β-内酰胺酶的菌株具有这种表型。本研究探讨了他唑巴坦（TAZ）浓度对哌拉西林（PIP）抑制这些菌株的影响，并在感染模型中比较了TZP和头孢噻肟（CTX）的体内疗效。在棋盘设置中使用增加浓度的TAZ来确定大肠杆菌分离株，所述大肠杆菌分离株或者由于启动子置换（n = 4）或者由于基因扩增（n = 2）而超产生TEM-1，或者产生耐药TEM-35（IRT）（n = 1）。此外，使用模拟人类条件的抗生素暴露，在小鼠腹膜炎模型中研究了TZP和CTX对分离株的功效。结果：使用TAZ浓度= 64 mg/L时，一个过度产生TEM-1的分离株在TAZ浓度为16 mg/L时的PIP MIC为8，另外两个分离株在TAZ浓度为64 mg/L时的PIP MIC为8。在小鼠腹膜炎感染模型中，对于产生CTX-M-15的分离株，TZP对腹膜中细菌负荷的减少大于仅CTX。对于剩余的8个测试分离株中的7个，观察到CTX治疗后细菌负荷比TZP治疗后更大的减少。超产TEM-1的大肠杆菌分离株比CTX处理效果差，并且对于某些分离株，可能与产生确定的抗性标记物如IRT或OXA-48的分离株的TZP处理相当。(c)2022年，任作家。爱思唯尔有限公司出版
Objectives: Piperacillin-tazobactam (TZP) is a frequently prescribed antibiotic in hospital settings. Reports suggest in vivo efficacy of TZP, despite in vitro resistance of isolates susceptible to cephalosporins. Escherichia coli (E. coli) isolates hyperproducing TEM-1 beta-lactamase possess this phenotype. This study investigated the influence of tazobactam (TAZ) concentration on piperacillin (PIP) inhibition of such isolates and compared the in vivo efficacy of TZP with cefotaxime (CTX) in an infection model.Methods: The PIP MICs for E. coli isolates, either hyperproducing TEM-1 because of promoter substitutions (n = 4) or because of gene amplification (n = 2) or producing an inhibitor-resistant TEM-35 (IRT) (n = 1), were determined using increasing concentrations of TAZ in a checkerboard setup. Furthermore, the efficacy of TZP and CTX against the isolates was investigated in a mouse peritonitis model using antibiotic exposures mimicking human conditions. Isolates producing either OXA-48 or CTX-M-15 beta-lactamases were included as controls.Results: Using TAZ concentrations = 64 mg/L, one isolate hyperproducing TEM-1 had a PIP MIC of 8 at TAZ 16 mg/L and two additional isolates at TAZ 64 mg/L. In the mouse peritonitis infection model, reduction of bacterial load in the peritoneum was larger for TZP than CTX only for the CTX-M-15-producing isolate. Larger reductions in bacterial load were observed after CTX treatment than TZP treatment for seven of the eight remaining test isolates.Conclusions: Piperacillin-tazobactam treatment of E. coli isolates hyperproducing TEM-1 was less effective than CTX treatment and may, for some isolates, be comparable with TZP treatment of isolates producing established resistance markers as IRT or OXA-48. (c) 2022 The Authors. Published by Elsevier Ltd.