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中国台湾地区耐碳青霉烯类肠杆菌科细菌的体外药敏研究:亚胺培南/雷利巴坦、美罗培南/比阿培南、头孢他啶/阿维巴坦、头孢吡肟/他唑巴坦和其他新型抗生素的活性。

In vitro activity of imipenem/relebactam, meropenem/vaborbactam, ceftazidime/avibactam, cefepime/zidebactam and other novel antibiotics against imipenem-non-susceptible Gram-negative bacilli from Taiwan.

机构信息

National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.

Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

出版信息

J Antimicrob Chemother. 2021 Jul 15;76(8):2071-2078. doi: 10.1093/jac/dkab141.

Abstract

OBJECTIVES

To investigate the susceptibility of imipenem-non-susceptible Escherichia coli (INS-EC), Klebsiella pneumoniae (INS-KP), Acinetobacter baumannii (INS-AB) and Pseudomonas aeruginosa (INS-PA) to novel antibiotics.

METHODS

MICs were determined using the broth microdilution method. Carbapenemase and ESBL phenotypic testing and PCR for genes encoding ESBLs, AmpCs and carbapenemases were performed.

RESULTS

Zidebactam, avibactam and relebactam increased the respective susceptibility rates to cefepime, ceftazidime and imipenem of 17 INS-EC by 58.8%, 58.8% and 70.6%, of 163 INS-KP by 77.9%, 88.3% and 76.1% and of 81 INS-PA by 45.7%, 38.3% and 85.2%, respectively. Vaborbactam increased the meropenem susceptibility of INS-EC by 41.2% and of INS-KP by 54%. Combinations of β-lactams and novel β-lactamase inhibitors or β-lactam enhancers (BLI-BLE) were inactive against 136 INS-AB. In 58 INS-EC and INS-KP with exclusively blaKPC-like genes, zidebactam, avibactam, relebactam and vaborbactam increased the susceptibility of the partner β-lactams by 100%, 96.6%, 84.5% and 75.9%, respectively. In the presence of avibactam, ceftazidime was active in an additional 85% of 20 INS-EC and INS-KP with exclusively blaOXA-48-like genes while with zidebactam, cefepime was active in an additional 75%. INS-EC and INS-KP with MBL genes were susceptible only to cefepime/zidebactam. The β-lactam/BLI-BLE combinations were active against INS-EC and INS-KP without detectable carbapenemases. For INS-EC, INS-KP and INS-AB, tigecycline was more active than omadacycline and eravacycline but eravacycline had a lower MIC distribution. Lascufloxacin and delafloxacin were active in <35% of these INS isolates.

CONCLUSIONS

β-Lactam/BLI-BLE combinations were active in a higher proportion of INS-EC, INS-KP and INS-PA. The susceptibility of novel fluoroquinolones and tetracyclines was not superior to that of old ones.

摘要

目的

研究耐亚胺培南大肠埃希菌(INS-EC)、肺炎克雷伯菌(INS-KP)、鲍曼不动杆菌(INS-AB)和铜绿假单胞菌(INS-PA)对新型抗生素的敏感性。

方法

采用肉汤微量稀释法测定 MIC。进行碳青霉烯酶和 ESBL 表型检测以及 ESBLs、AmpC 和碳青霉烯酶基因的 PCR 检测。

结果

齐他培南、阿维巴坦和雷利巴坦分别使 17 株 INS-EC 对头孢吡肟、头孢他啶和亚胺培南的敏感性增加了 58.8%、58.8%和 70.6%,使 163 株 INS-KP 对头孢吡肟、头孢他啶和亚胺培南的敏感性增加了 77.9%、88.3%和 76.1%,使 81 株 INS-PA 对头孢吡肟、头孢他啶和亚胺培南的敏感性增加了 45.7%、38.3%和 85.2%。沃巴坦使 41.2%的 INS-EC 和 54%的 INS-KP 对美罗培南的敏感性增加。β-内酰胺类药物与新型β-内酰胺酶抑制剂或β-内酰胺增强剂(BLI-BLE)的联合用药对 136 株 INS-AB 无效。在仅携带 blaKPC 样基因的 58 株 INS-EC 和 INS-KP 中,齐他培南、阿维巴坦、雷利巴坦和沃巴坦分别使伙伴β-内酰胺类药物的敏感性提高了 100%、96.6%、84.5%和 75.9%。在阿维巴坦存在的情况下,头孢他啶对另外 85%的仅携带 blaOXA-48 样基因的 20 株 INS-EC 和 INS-KP 有效,而齐他培南使另外 75%的 cefepime 有效。仅携带 MBL 基因的 INS-EC 和 INS-KP 仅对头孢吡肟/齐他培南敏感。β-内酰胺类药物/BLI-BLE 联合用药对未检测到碳青霉烯酶的 INS-EC、INS-KP 和 INS-AB 有效。对于 INS-EC、INS-KP 和 INS-AB,替加环素比奥马环素和依拉环素更有效,但依拉环素的 MIC 分布较低。拉司氟沙星和德拉沙星对这些 INS 分离株的活性低于 35%。

结论

β-内酰胺类药物/BLI-BLE 联合用药在更高比例的 INS-EC、INS-KP 和 INS-PA 中有效。新型氟喹诺酮类药物和四环素类药物的敏感性并不优于旧药物。

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