Stability and low induction propensity of cefiderocol against chromosomal AmpC β-lactamases of Pseudomonas aeruginosa and Enterobacter cloacae.
Stability and low induction propensity of cefiderocol against chromosomal AmpC β-lactamases of Pseudomonas aeruginosa and Enterobacter cloacae.
复制标题
DOI：
10.1093/jac/dky317
复制
发表时间：
2018-11-01
期刊：
影响因子：
--
通讯作者：
Yamano Y
中科院分区：
文献类型：
--
作者：
Ito A;Nishikawa T;Ota M;Ito-Horiyama T;Ishibashi N;Sato T;Tsuji M;Yamano Y
铁载体头孢菌素头孢地罗可具有抗MDR革兰氏阴性菌的体外活性。头孢地罗可对丝氨酸型和金属型碳青霉烯酶的稳定性先前已有报道，但头孢地罗可如何与染色体AmpC β-内酰胺酶相互作用知之甚少。我们研究了头孢地罗可的一些特性，即对AmpC过度生产者的抗菌活性、对AmpC β-内酰胺酶的稳定性以及使用铜绿假单胞菌和阴沟肠杆菌诱导AmpC的倾向。根据CLSI指南，通过肉汤微量稀释法测定MIC。在铁耗尽的CAMHB中测定头孢地罗可的MIC。通过监测AmpC β-内酰胺酶存在下吸光度的变化来确定抗生素的水解，并通过双纸片扩散和头孢硝肟降解试验来评估AmpC诱导。头孢他啶和头孢吡肟对PAO 1的MIC随着ampD或dacB的失活而增加4- 16倍，而头孢地罗可MIC几乎不受这些失活的影响（增加<2倍）。Cefiderocol对铜绿假单胞菌SR 24 -12和大肠杆菌的AmpC具有40倍和>940倍的低亲和力（较高Ki）。与头孢他啶比较，纸片扩散法和头孢硝肟降解试验均表明头孢地罗可对铜绿假单胞菌PAO 1和ATCC 27853及大肠杆菌的AmpC酶无诱导作用。Clopectin ATCC 13047，而亚胺培南则有此作用。Cefiderocol对AmpC高产菌株具有体外活性，对染色体AmpC β-内酰胺酶的亲和力低，对铜绿假单胞菌和大肠杆菌AmpC β-内酰胺酶的时间诱导倾向低。clothing.这些与染色体AmpC相关的特征可以解释头孢地罗可对产AmpC酶的耐药菌株的强效抗菌活性。
The siderophore cephalosporin cefiderocol possesses in vitro activity against MDR Gram-negative bacteria. The stability of cefiderocol against serine- and metallo-type carbapenemases has been reported previously, but little is known about how cefiderocol interacts with chromosomal AmpC β-lactamases. We investigated a number of features of cefiderocol, namely antibacterial activity against AmpC overproducers, stability against AmpC β-lactamases and propensity for AmpC induction using Pseudomonas aeruginosa and Enterobacter cloacae. MICs were determined by broth microdilution according to CLSI guidelines. The MIC of cefiderocol was determined in iron-depleted CAMHB. Hydrolysis of the antibiotics was determined by monitoring the changes in the absorbance in the presence of AmpC β-lactamase, and AmpC induction was evaluated by double disc diffusion and nitrocefin degradation assays. The MICs of ceftazidime and cefepime for PAO1 increased 4- to 16-fold with inactivation of either ampD or dacB, whereas cefiderocol MICs were little affected by these inactivations (<2-fold increase). Cefiderocol has 40- and >940-fold lower affinity (higher Ki) to AmpCs of P. aeruginosa SR24-12 and E. cloacae P99, respectively, compared with ceftazidime. Both disc diffusion and nitrocefin degradation assays indicated that cefiderocol did not induce AmpC β-lactamases of P. aeruginosa PAO1 and ATCC 27853 and E. cloacae ATCC 13047, whereas imipenem did. Cefiderocol showed in vitro activity against the AmpC-overproducing strains, low affinity for chromosomal AmpC β-lactamases, and a low propensity of temporal induction of AmpC β-lactamases of P. aeruginosa and E. cloacae. These features relating to chromosomal AmpC could explain the potent antibacterial activity of cefiderocol against drug-resistant strains producing AmpC β-lactamases.
登录
查看更多内容
影响因子：
3.5
作者：
SCHWEIZER, HP;HOANG, TT
通讯作者：
HOANG, TT
影响因子：
9.4
作者：
Peter-Getzlaff, S.;Polsfuss, S.;Bloemberg, G. V.
通讯作者：
Bloemberg, G. V.
影响因子：
5.2
作者：
Majewski P;Wieczorek P;Ojdana D;Sieńko A;Kowalczuk O;Sacha P;Nikliński J;Tryniszewska E
通讯作者：
Tryniszewska E
影响因子：
4.9
作者：
Quale, J;Bratu, S;Landman, D
通讯作者：
Landman, D
DOI：
10.1073/pnas.2036282100
发表时间：
2003-11-25
影响因子：
11.1
作者：
Jacobs, MA;Alwood, A;Manoil, C
通讯作者：
Manoil, C