Activity of imipenem/relebactam and comparators against KPC-producing Klebsiella pneumoniae and imipenem-resistant Pseudomonas aeruginosa,European Journal of Clinical Microbiology & Infectious Diseases

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Activity of imipenem/relebactam and comparators against KPC-producing Klebsiella pneumoniae and imipenem-resistant Pseudomonas aeruginosa
European Journal of Clinical Microbiology & Infectious Diseases ( IF 3.7 ) Pub Date : 2023-12-29 , DOI: 10.1007/s10096-023-04735-1
Mercedes Delgado-Valverde _{1,

2} , Inés Portillo-Calderón _{1,

2} , Manuel Alcalde-Rico _{2,

3} , M Carmen Conejo ₄ , Carmen Hidalgo ₁ , Carlos Del Toro Esperón ₄ , Álvaro Pascual _{1,

2,

4}

Affiliation

Purpose

Relebactam is a novel β-lactamase inhibitor, which, when combined with imipenem/cilastatin, is active against both class A and class C β-lactamases. To evaluate in vitro antimicrobial activity of imipenem/relebactam against a collection of recent clinical isolates of carbapenem-non-susceptible P. aeruginosa and K. pneumoniae ST258 and ST512 KPC producers belonging to different lineages from hospitals in Southern Spain.

Methods

Six hundred and seventy-eight isolates were tested: 265 K. pneumoniae (230 ST512/KPC-3 and 35 ST258/KPC-3) and 413 carbapenem-non-susceptible P. aeruginosa. Imipenem, piperacillin/tazobactam, ceftazidime, cefepime, aztreonam, ceftolozane/tazobactam, meropenem, amikacin, ciprofloxacin, colistin, and ceftazidime/avibactam were used as comparators against P. aeruginosa. Against K. pneumoniae ceftazidime, cefepime, aztreonam, and ceftolozane/tazobactam were not tested, and tigecycline was studied instead. MICs were determined in duplicate by broth microdilution according to EUCAST guidelines.

Results

Imipenem/relebactam displayed potent in vitro activity against both sequence types of KPC-3-producing K. pneumoniae. MIC₅₀ and MIC₉₀ values were 0.25 mg/L and 1 mg/L, respectively, with percent of susceptible isolates >97%. Only three K. pneumoniae ST512/KPC-3 isolates and one ST258/KPC-3 were resistant to imipenem/relebactam. Relebactam sensitized 98.5% of K. pneumoniae isolates resistant to imipenem. The activity of imipenem/relebactam against P. aeruginosa was moderate (susceptibility rate: 62.7%). Analysis of the acquired and mutational resistome of isolates with high levels of resistance to imipenem/relebactam has not shown a clear association between them.

Conclusion

Imipenem/relebactam showed excellent activity against K. pneumoniae KPC-3. The activity of imipenem/relebactam against imipenem-resistant P. aeruginosa was moderate.

中文翻译：

亚胺培南/瑞莱巴坦和对照物对产 KPC 肺炎克雷伯菌和亚胺培南耐药铜绿假单胞菌的活性

目的

Relebactam 是一种新型 β-内酰胺酶抑制剂，与亚胺培南/西司他丁联合使用时，可有效对抗 A 类和 C 类 β-内酰胺酶。评估亚胺培南/瑞莱巴坦对来自西班牙南部医院的不同谱系的碳青霉烯类不敏感铜绿假单胞菌和肺炎克雷伯菌ST258 和 ST512 KPC 生产者的最新临床分离株的体外抗菌活性。

方法

测试了 678 株分离株：265株肺炎克雷伯菌（230 株 ST512/KPC-3 和 35 株 ST258/KPC-3）和 413 株碳青霉烯类不敏感铜绿假单胞菌。使用亚胺培南、哌拉西林/他唑巴坦、头孢他啶、头孢吡肟、氨曲南、头孢洛扎/他唑巴坦、美罗培南、阿米卡星、环丙沙星、粘菌素和头孢他啶/阿维巴坦作为针对铜绿假单胞菌的比较物。没有测试针对肺炎克雷伯菌的头孢他啶、头孢吡肟、氨曲南和头孢噻嗪/他唑巴坦，而是研究了替加环素。根据 EUCAST 指南，通过肉汤微量稀释一式两份测定 MIC。

结果

亚胺培南/瑞莱巴坦对产生 KPC-3 的肺炎克雷伯菌的两种序列类型均表现出有效的体外活性。 MIC ₅₀和 MIC ₉₀值分别为 0.25 mg/L 和 1 mg/L，敏感菌株百分比>97%。只有 3株肺炎克雷伯菌ST512/KPC-3 分离株和 1 株 ST258/KPC-3 对亚胺培南/瑞巴坦耐药。 Relebactam 使 98.5% 的肺炎克雷伯菌分离株对亚胺培南耐药。亚胺培南/瑞来巴坦对铜绿假单胞菌的活性中等（敏感率：62.7%）。对亚胺培南/瑞莱巴坦高水平耐药菌株的获得性和突变耐药性组分析并未显示出它们之间存在明确的关联。