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Mutations in That Confer Ceftazidime-Avibactam Resistance Encode Novel KPC-3 Variants That Function as Extended-Spectrum β-Lactamases.赋予头孢他啶-阿维巴坦耐药性的突变编码新型KPC-3变体，其作为超广谱β-内酰胺酶发挥作用。
Antimicrob Agents Chemother. 2017 Apr 24;61(5). doi: 10.1128/AAC.02534-16. Print 2017 May.
2
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本文引用的文献

1
Emergence of Ceftazidime-Avibactam Resistance Due to Plasmid-Borne Mutations during Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infections.耐碳青霉烯类肺炎克雷伯菌感染治疗期间因质粒介导的突变导致头孢他啶-阿维巴坦耐药的出现
Antimicrob Agents Chemother. 2017 Feb 23;61(3). doi: 10.1128/AAC.02097-16. Print 2017 Mar.
2
Clinical Outcomes, Drug Toxicity, and Emergence of Ceftazidime-Avibactam Resistance Among Patients Treated for Carbapenem-Resistant Enterobacteriaceae Infections.耐碳青霉烯类肠杆菌科细菌感染患者的临床结局、药物毒性及头孢他啶-阿维巴坦耐药性的出现
Clin Infect Dis. 2016 Dec 15;63(12):1615-1618. doi: 10.1093/cid/ciw636. Epub 2016 Sep 13.
3
Association between the Presence of Aminoglycoside-Modifying Enzymes and In Vitro Activity of Gentamicin, Tobramycin, Amikacin, and Plazomicin against Klebsiella pneumoniae Carbapenemase- and Extended-Spectrum-β-Lactamase-Producing Enterobacter Species.氨基糖苷类修饰酶的存在与庆大霉素、妥布霉素、阿米卡星和普拉佐米星对产肺炎克雷伯菌碳青霉烯酶和超广谱β-内酰胺酶的肠杆菌属细菌的体外活性之间的关联。
Antimicrob Agents Chemother. 2016 Aug 22;60(9):5208-14. doi: 10.1128/AAC.00869-16. Print 2016 Sep.
4
In vitro selection of ceftazidime-avibactam resistance in Enterobacteriaceae with KPC-3 carbapenemase.携带KPC-3碳青霉烯酶的肠杆菌科细菌对头孢他啶-阿维巴坦耐药性的体外筛选
Antimicrob Agents Chemother. 2015 Sep;59(9):5324-30. doi: 10.1128/AAC.00678-15. Epub 2015 Jun 22.
5
Activity of ceftazidime/avibactam against isogenic strains of Escherichia coli containing KPC and SHV β-lactamases with single amino acid substitutions in the Ω-loop.头孢他啶/阿维巴坦对含KPC和SHVβ-内酰胺酶且Ω环有单个氨基酸取代的大肠杆菌同基因菌株的活性。
J Antimicrob Chemother. 2015 Aug;70(8):2279-86. doi: 10.1093/jac/dkv094. Epub 2015 May 8.
6
β-lactam and β-lactamase inhibitor combinations in the treatment of extended-spectrum β-lactamase producing Enterobacteriaceae: time for a reappraisal in the era of few antibiotic options?β-内酰胺类和β-内酰胺酶抑制剂联合治疗产超广谱β-内酰胺酶肠杆菌科细菌感染：在抗生素选择有限的时代，是否需要重新评估？
Lancet Infect Dis. 2015 Apr;15(4):475-85. doi: 10.1016/S1473-3099(14)70950-8. Epub 2015 Feb 23.
7
Editorial commentary: Bloodstream infection caused by extended-spectrum β-lactamase-producing Gram-negative bacteria: how to define the best treatment regimen?编辑评论：产超广谱β-内酰胺酶革兰氏阴性菌引起的血流感染：如何确定最佳治疗方案？
Clin Infect Dis. 2015 May 1;60(9):1326-9. doi: 10.1093/cid/civ007. Epub 2015 Jan 13.
8
Carbapenem therapy is associated with improved survival compared with piperacillin-tazobactam for patients with extended-spectrum β-lactamase bacteremia.对于产超广谱β-内酰胺酶菌血症患者，与哌拉西林-他唑巴坦相比，碳青霉烯类治疗与生存率提高相关。
Clin Infect Dis. 2015 May 1;60(9):1319-25. doi: 10.1093/cid/civ003. Epub 2015 Jan 13.
9
Microbiological features of KPC-producing Enterobacter isolates identified in a U.S. hospital system.在美国一家医院系统中鉴定出的产KPC肠杆菌分离株的微生物学特征。
Diagn Microbiol Infect Dis. 2014 Oct;80(2):154-8. doi: 10.1016/j.diagmicrobio.2014.06.010. Epub 2014 Jun 23.
10
Treating infections caused by carbapenemase-producing Enterobacteriaceae.治疗产碳青霉烯酶肠杆菌科细菌感染。
Clin Microbiol Infect. 2014 Sep;20(9):862-72. doi: 10.1111/1469-0691.12697. Epub 2014 Jul 12.

赋予头孢他啶-阿维巴坦耐药性的突变编码新型KPC-3变体，其作为超广谱β-内酰胺酶发挥作用。

Mutations in That Confer Ceftazidime-Avibactam Resistance Encode Novel KPC-3 Variants That Function as Extended-Spectrum β-Lactamases.

作者信息

Haidar Ghady, Clancy Cornelius J, Shields Ryan K, Hao Binghua, Cheng Shaoji, Nguyen M Hong

机构信息

University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

University of Pittsburgh, Pittsburgh, Pennsylvania, USA

出版信息

Antimicrob Agents Chemother. 2017 Apr 24;61(5). doi: 10.1128/AAC.02534-16. Print 2017 May.

DOI:10.1128/AAC.02534-16
PMID:28223379
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5404534/
Abstract

We identified four mutations in ceftazidime-avibactam-resistant clinical isolates, corresponding to D179Y, T243M, D179Y/T243M, and EL165-166 KPC-3 variants. Using site-directed mutagenesis and transforming vectors into , we conclusively demonstrated that mutant encoded enzymes that functioned as extended-spectrum β-lactamases; mutations directly conferred higher MICs of ceftazidime-avibactam and decreased the MICs of carbapenems and other β-lactams. Impact was strongest for the D179Y mutant, highlighting the importance of the KPC Ω-loop.

摘要

我们在对头孢他啶-阿维巴坦耐药的临床分离株中鉴定出四种突变，分别对应于D179Y、T243M、D179Y/T243M和EL165 - 166 KPC - 3变体。通过定点诱变并将载体转化入……，我们最终证明突变体编码的酶发挥超广谱β-内酰胺酶的作用；这些突变直接导致头孢他啶-阿维巴坦的最低抑菌浓度（MIC）升高，并降低了碳青霉烯类和其他β-内酰胺类药物的MIC。对D179Y突变体的影响最为显著，突出了KPC Ω环的重要性。