In vitro activity of cefiderocol against Pseudomonas aeruginosa demonstrating evolved resistance to novel β-lactam/β-lactamase inhibitors.
In vitro activity of cefiderocol against Pseudomonas aeruginosa demonstrating evolved resistance to novel β-lactam/β-lactamase inhibitors.
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DOI：
10.1093/jacamr/dlad107
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发表时间：
2023-10
影响因子：
3.4
通讯作者：
中科院分区：
文献类型：
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Cefiderocol对MDR铜绿假单胞菌表现出优异的活性;然而，对来自既往接受β-内酰胺类药物治疗的患者的分离株的活性尚不清楚。我们的目的是确定头孢地罗可对铜绿假单胞菌的活性，在使用传统β-内酰胺类和新型β-内酰胺/β-内酰胺酶抑制剂治疗之前和之后收集。在铁耗尽的阳离子调节的Mueller-Hinton肉汤中一式三份测定头孢地罗可MIC，并与通过标准方法检测的β-内酰胺MIC进行比较。对所有分离株进行WGS分析，以鉴定与耐药性相关的突变。对178株铜绿假单胞菌分离株进行了评价; 48%（86/178）对头孢他啶/阿维巴坦、头孢洛扎/他唑巴坦和/或亚胺培南/曲马巴坦不敏感。头孢地罗可的MIC 50和MIC 90分别为0.12和1 mg/L。 与非MDR分离株相比，分类为MDR、XDR或对头孢他啶/阿维巴坦、头孢洛扎/他唑巴坦和/或亚胺培南/曲马巴坦不敏感的分离株的中位头孢地罗可MIC无差异。从既往接受过头孢洛扎/他唑巴坦治疗的患者中采集的分离株中，头孢德罗可MIC较基线增加4倍。在21%（3/14）对头孢洛扎/他唑巴坦治疗后出现耐药的患者中发现了对头孢地罗可的交叉耐药。总体而言，6%（11/178）的分离株显示头孢德罗可MIC ≥2 mg/L，这些分离株不成比例地采集自既往接受过头孢洛扎/他唑巴坦治疗的患者（73%; 8/11）。 头孢地罗敏感性降低的分离株在ampC、tonB依赖性受体、反应调节因子pirR和ftsI中存在突变。头孢地罗可对暴露于其他新型β-内酰胺类药物的铜绿假单胞菌分离株表现出优异的体外活性;然而，也发现了一些例外情况。头孢地罗可与头孢洛扎/他唑巴坦之间的交叉耐药性明显，但与头孢他啶/阿维巴坦或亚胺培南/曲马巴坦之间的交叉耐药性不明显。ampC和tonB依赖性受体的突变介导了头孢地罗敏感性的降低。
Cefiderocol demonstrates excellent activity against MDR Pseudomonas aeruginosa; however, the activity against isolates from patients previously treated with β-lactam agents is unknown. We aimed to determine the activity of cefiderocol against P. aeruginosa collected before and after treatment with traditional β-lactams and new β-lactam/β-lactamase inhibitors. Cefiderocol MICs were determined in triplicate in iron-depleted cation-adjusted Mueller–Hinton broth and compared with β-lactam MICs tested by standard methods. All isolates underwent WGS analysis to identify mutations associated with resistance. One hundred and seventy-eight P. aeruginosa isolates were evaluated; 48% (86/178) were non-susceptible to ceftazidime/avibactam, ceftolozane/tazobactam and/or imipenem/relebactam. The cefiderocol MIC50 and MIC90 were 0.12 and 1 mg/L, respectively. Median cefiderocol MICs did not vary against isolates classified as MDR, XDR, or those non-susceptible to ceftazidime/avibactam, ceftolozane/tazobactam and/or imipenem/relebactam when compared with non-MDR isolates. Against isolates collected from patients previously treated with ceftolozane/tazobactam, cefiderocol MICs were increased 4-fold compared with baseline. Cross-resistance to cefiderocol was identified in 21% (3/14) of patients who developed treatment-emergent resistance to ceftolozane/tazobactam. Overall, 6% (11/178) of isolates demonstrated cefiderocol MICs ≥2 mg/L, which were disproportionately collected from patients previously treated with ceftolozane/tazobactam (73%; 8/11). Isolates with reduced cefiderocol susceptibility harboured mutations in ampC, tonB-dependent receptors, the response regulator pirR and ftsI. Cefiderocol demonstrates excellent in vitro activity against P. aeruginosa isolates exposed to other novel β-lactam agents; however, some exceptions were identified. Cross-resistance between cefiderocol and ceftolozane/tazobactam was evident, but not with ceftazidime/avibactam or imipenem/relebactam. Reduced cefiderocol susceptibility was mediated by mutations in ampC and tonB-dependent receptors.
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影响因子：
4.9
作者：
Kawai, Akito;McElheny, Christi L.;Doi, Yohei
通讯作者：
Doi, Yohei
影响因子：
2.6
作者：
Nordmann, Patrice;Shields, Ryan K.;Doi, Yohei;Takemura, Miki;Echols, Roger;Matsunaga, Yuko;Yamano, Yoshinori
通讯作者：
Yamano, Yoshinori
DOI：
10.1007/s10096-022-04526-0
发表时间：
2023-01
影响因子：
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作者：
Sadek, Mustafa;Le Guern, Remi;Kipnis, Eric;Gosset, Philippe;Poirel, Laurent;Dessein, Rodrigue;Nordmann, Patrice
通讯作者：
Nordmann, Patrice
影响因子：
4.9
作者：
Haidar, Ghady;Clancy, Cornelius J.;Nguyen, M. Hong
通讯作者：
Nguyen, M. Hong
影响因子：
14.2
作者：
Magiorakos, A. -P.;Srinivasan, A.;Monnet, D. L.
通讯作者：
Monnet, D. L.