Progressive in vivo development of resistance to cefiderocol in Pseudomonas aeruginosa.
Progressive in vivo development of resistance to cefiderocol in Pseudomonas aeruginosa.
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DOI：
10.1007/s10096-022-04526-0
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发表时间：
2023-01
影响因子：
4.5
通讯作者：
Nordmann, Patrice
中科院分区：
文献类型：
--
作者：
Sadek, Mustafa;Le Guern, Remi;Kipnis, Eric;Gosset, Philippe;Poirel, Laurent;Dessein, Rodrigue;Nordmann, Patrice
我们报告了在没有暴露于FDC的情况下，从单个患者中回收的四个连续铜绿假单胞菌临床分离株ST 244中头孢地罗可（FDC）耐药性的体内发展，这引起了对这种新药有效性的关注。第一个回收的铜绿假单胞菌分离株（P-01）对FDC（2 μg/mL）敏感，尽管该MIC值高于野生型铜绿假单胞菌（0.12-0.25 μg/mL）。随后分离的菌株（P-02、P-03、P-04）显示FDC MIC水平升高（分别为8、16和64 μg/ml）。这些分离株对本研究中检测的大多数β-内酰胺类抗生素的耐药性水平也存在差异，且逐渐增加。令人惊讶的是，在这些分离株中均未鉴定出获得性β-内酰胺酶。全基因组序列分析表明，这种耐药性是由多因素机制驱动的，包括与FDC摄取相关的铁转运蛋白突变变化、ampC基因过度表达和mexAB-oprM过度表达。这些结果强调，在任何处方之前必须进行FDC敏感性试验。
We report in vivo development of cefiderocol (FDC) resistance among four sequential Pseudomonas aeruginosa clinical isolates ST244 recovered from a single patient, without exposure to FDC, which raises concern about the effectiveness of this novel drug. The first recovered P. aeruginosa isolate (P-01) was susceptible to FDC (2 μg/mL), albeit this MIC value was higher than that of a wild-type P. aeruginosa (0.12–0.25 μg/ml). The subsequent isolated strains (P-02, P-03, P-04) displayed increasing levels of FDC MICs (8, 16, and 64 μg/ml, respectively). Those isolates also showed variable and gradual increasing levels of resistance to most β-lactams tested in this study. Surprisingly, no acquired β-lactamase was identified in any of those isolates. Whole-genome sequence analysis suggested that this resistance was driven by multifactorial mechanisms including mutational changes in iron transporter proteins associated with FDC uptake, ampC gene overproduction, and mexAB-oprM overexpression. These findings highlight that a susceptibility testing to FDC must be performed prior to any prescription.
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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
影响因子：
4.9
作者：
Bagge, N;Ciofu, O;Hoiby, N
通讯作者：
Hoiby, N
DOI：
10.1016/j.diagmicrobio.2019.03.003
发表时间：
2019-08-01
影响因子：
2.9
作者：
Hackel, Meredith A.;Tsuji, Masakatsu;Sahm, Daniel F.
通讯作者：
Sahm, Daniel F.
影响因子：
4.6
作者：
Kohira, Naoki;Hackel, Meredith A.;Yamano, Yoshinori
通讯作者：
Yamano, Yoshinori
影响因子：
4.9
作者：
Malik, Saquib;Kaminski, Monica;Quale, John
通讯作者：
Quale, John