University of Queensland Centre for Clinical Research, Brisbane, QLD, Australia; Department of Infectious Diseases, National University Hospital, Singapore; University Medicine Cluster, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Department of Infectious Diseases, National University Hospital, Singapore; University Medicine Cluster, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Lancet Infect Dis. 2015 Apr;15(4):475-85. doi: 10.1016/S1473-3099(14)70950-8. Epub 2015 Feb 23.
The spread of extended-spectrum β-lactamase (ESBL) genes in Enterobacteriaceae such as Escherichia coli or Klebsiella spp is a major challenge to modern medical practice. Carbapenems are the treatment of choice for serious infections caused by ESBL producers; however, carbapenem resistance has increased globally. ESBL producers might be susceptible to β-lactam-β-lactamase inhibitor (BLBLI) combination antibiotics such piperacillin-tazobactam or amoxicillin-clavulanate. These drugs are frequently avoided in serious infections caused by ESBL producers because of the inoculum effect in-vitro (especially for piperacillin-tazobactam), animal data suggesting inferior efficacy when compared with carbapenems, concerns about pharmacokinetic-pharmacodynamic drug target attainment with standard doses, and poor outcomes shown in some observational studies. Prospective cohort data and a meta-analysis suggest that BLBLIs are non-inferior to carbapenems in the treatment of bloodstream infections caused by ESBL producers. We examine why BLBLIs are perceived as inferior in the treatment of infection with ESBL producers, and discuss data that suggest these concerns might not be strongly supported by clinical evidence.
肠杆菌科（如大肠杆菌或克雷伯菌属）中扩展谱β-内酰胺酶（ESBL）基因的传播是现代医学实践的主要挑战。碳青霉烯类抗生素是治疗由 ESBL 产生菌引起的严重感染的首选药物；然而，碳青霉烯类耐药性在全球范围内不断增加。ESBL 产生菌可能对β-内酰胺-β-内酰胺酶抑制剂（BLBLI）联合抗生素敏感，如哌拉西林-他唑巴坦或阿莫西林-克拉维酸。由于体外（尤其是哌拉西林-他唑巴坦）的接种效应、与碳青霉烯类药物相比疗效较差的动物数据、对标准剂量下药代动力学-药效学药物靶标达到的担忧，以及一些观察性研究显示的不良结局，这些药物在由 ESBL 产生菌引起的严重感染中常被避免使用。前瞻性队列数据和荟萃分析表明，BLBLIs 在治疗由 ESBL 产生菌引起的血流感染方面与碳青霉烯类药物相当。我们研究了为什么 BLBLIs 在治疗 ESBL 产生菌感染时被认为不如碳青霉烯类药物，并且讨论了一些数据，这些数据表明这些担忧可能没有得到临床证据的有力支持。
