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头孢他啶/阿维巴坦聚焦:耐多药革兰氏阴性菌感染的新选择。

Spotlight on ceftazidime/avibactam: a new option for MDR Gram-negative infections.

作者信息

Falcone Marco, Paterson David

机构信息

Department of Public Health and Infectious Diseases, 'Sapienza' University, Rome, Italy

University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital Campus, Brisbane, Australia.

出版信息

J Antimicrob Chemother. 2016 Oct;71(10):2713-22. doi: 10.1093/jac/dkw239. Epub 2016 Jul 17.

Abstract

During the last decade infections caused by MDR Gram-negative bacteria (GNB) have become increasingly prevalent. Because of their high morbidity and mortality rates, these infections constitute a serious threat to public health worldwide. Ceftazidime/avibactam is a new approved agent combining ceftazidime and a novel β-lactamase inhibitor with activity against various β-lactamases produced by MDR GNB. Avibactam has a spectrum of inhibition of class A and C β-lactamases, including ESBLs, AmpC and Klebsiella pneumoniae carbapenemase (KPC) enzymes. Thus, combination with this inhibitor expands ceftazidime's spectrum of activity to MDR Enterobacteriaceae and Pseudomonas aeruginosa strains. In Phase II clinical trials of patients with complicated intra-abdominal infections and complicated urinary tract infections ceftazidime/avibactam exhibited clinical efficacy comparable to those of meropenem and imipenem/cilastatin, respectively. A Phase III clinical trial confirmed the efficacy of ceftazidime/avibactam in patients with MDR Enterobacteriaceae and P. aeruginosa infections. Microbiological surveillance studies, in vivo animal models of infection and pharmacokinetic/pharmacodynamic target attainment analyses are also discussed, to assess the potential role of this new drug in the treatment of infections caused by MDR GNB.

摘要

在过去十年中,耐多药革兰氏阴性菌(GNB)引起的感染日益普遍。由于其高发病率和死亡率,这些感染对全球公共卫生构成严重威胁。头孢他啶/阿维巴坦是一种新批准的药物,它将头孢他啶与一种新型β-内酰胺酶抑制剂结合,对耐多药GNB产生的各种β-内酰胺酶具有活性。阿维巴坦对A类和C类β-内酰胺酶具有抑制谱,包括超广谱β-内酰胺酶(ESBLs)、AmpC酶和肺炎克雷伯菌碳青霉烯酶(KPC)。因此,与这种抑制剂联合使用可将头孢他啶的活性谱扩展到耐多药肠杆菌科细菌和铜绿假单胞菌菌株。在复杂性腹腔内感染和复杂性尿路感染患者的II期临床试验中,头孢他啶/阿维巴坦分别显示出与美罗培南和亚胺培南/西司他丁相当的临床疗效。一项III期临床试验证实了头孢他啶/阿维巴坦对耐多药肠杆菌科细菌和铜绿假单胞菌感染患者的疗效。还讨论了微生物监测研究、体内感染动物模型以及药代动力学/药效学达标分析,以评估这种新药在治疗耐多药GNB引起的感染中的潜在作用。

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