Identifying Spectra of Activity and Therapeutic Niches for Ceftazidime-Avibactam and Imipenem-Relebactam against Carbapenem-Resistant Enterobacteriaceae
Identifying Spectra of Activity and Therapeutic Niches for Ceftazidime-Avibactam and Imipenem-Relebactam against Carbapenem-Resistant Enterobacteriaceae
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DOI：
10.1128/aac.00642-17
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发表时间：
2017-09-01
影响因子：
4.9
通讯作者：
Nguyen, M. Hong
中科院分区：
文献类型：
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作者：
Haidar, Ghady;Clancy, Cornelius J.;Nguyen, M. Hong
我们测定了亚胺培南、亚胺培南-阿贝巴坦、头孢他啶和头孢他啶-阿维巴坦对100株进行全基因组测序的CRE分离株的MICs。肺炎克雷伯菌碳青霉烯酶（KPC）是最常见的碳青霉烯酶。46株细菌携带超广谱β-内酰胺酶（ESBLs）。随着阿曲巴坦的加入，亚胺培南的敏感性从8%增加到88%。添加阿维巴坦后，头孢他啶敏感性从0%增加至85%。亚胺培南-曲马巴坦和头孢他啶-阿维巴坦对金属β-内酰胺酶（MBL）产生菌均无活性。头孢他啶-阿维巴坦（而非亚胺培南-阿维巴坦）对OXA-48样产酶菌具有活性，包括不携带任何ESBL的菌株。主要OmpK 36孔蛋白突变与较高的亚胺培南-阿维巴坦MIC独立相关（P < 0.0001），并显示出与较高的头孢他啶-阿维巴坦MIC独立相关的趋势（P = 0.07）。变异KPC-3的存在与头孢他啶-阿维巴坦耐药相关（P < 0.0001）。总之，亚胺培南-曲马巴坦和头孢他啶-阿维巴坦具有重叠的活性谱和生态位，其中每种均具有上级优势。KPC-K中的主要OmpK 36突变。肺炎克雷伯氏菌可能为亚胺培南-阿维巴坦和头孢他啶-阿维巴坦耐药的逐步出现提供了基础。
We determined imipenem, imipenem-relebactam, ceftazidime, and ceftazidime-avibactam MICs against 100 CRE isolates that underwent whole-genome sequencing. Klebsiella pneumoniae carbapenemases (KPCs) were the most common carbapenemases. Forty-six isolates carried extended-spectrum beta-lactamases (ESBLs). With the addition of relebactam, imipenem susceptibility increased from 8% to 88%. With the addition of avibactam, ceftazidime susceptibility increased from 0% to 85%. Neither imipenem-relebactam nor ceftazidime-avibactam was active against metallo-beta-lactamase (MBL) producers. Ceftazidime-avibactam (but not imipenem-relebactam) was active against OXA-48-like producers, including a strain not harboring any ESBL. Major OmpK36 porin mutations were independently associated with higher imipenem-relebactam MICs (P < 0.0001) and showed a trend toward independent association with higher ceftazidime-avibactam MICs (P = 0.07). The presence of variant KPC-3 was associated with ceftazidime-avibactam resistance (P < 0.0001). In conclusion, imipenem-relebactam and ceftazidime-avibactam had overlapping spectra of activity and niches in which each was superior. Major OmpK36 mutations in KPC-K. pneumoniae may provide a foundation for stepwise emergence of imipenem-relebactam and ceftazidime-avibactam resistance.