Reduced susceptibility mechanism to cefiderocol, a siderophore cephalosporin, among clinical isolates from a global surveillance programme (SIDERO-WT-2014)
Reduced susceptibility mechanism to cefiderocol, a siderophore cephalosporin, among clinical isolates from a global surveillance programme (SIDERO-WT-2014)
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DOI：
10.1016/j.jgar.2020.07.009
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发表时间：
2020-09-01
影响因子：
4.6
通讯作者：
Yamano, Yoshinori
中科院分区：
文献类型：
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作者：
Kohira, Naoki;Hackel, Meredith A.;Yamano, Yoshinori
目的：为了研究可能的机制因素来解释头孢地罗克（CFDC）的非敏感性，我们从一项多国监测研究中鉴定了38株CFDC最低抑菌浓度（MIC）>4 μ g/mL的临床分离株。方法：在β-内酰胺酶抑制剂存在下进行MIC测量并进行全基因组测序。观察到β-内酰胺酶抑制剂对所有供试分离株的CFDC MIC降低。在38株分离株中，NDM基因阳性5株，PER基因阳性25株。在其他8株分离株中未发现导致高MIC的其他β-内酰胺酶。CDFC对引入NDM和PER β-内酰胺酶的大肠杆菌等基因菌株的MIC增加>= 16倍，表明NDM和PER对CFDC不敏感的贡献。对NDM生产者，只有当同时加入丝氨酸和金属型β-内酰胺酶抑制剂时，才观察到MIC增加>= 8倍。此外，许多PER或NDM生产商仍然容易受到CFDC的影响。结论：NDM、PER等多种因素可能与CFDC易感性降低有关。(C)2020作者（S）由Elsevier Ltd代表国际抗微生物化疗学会发表。
Objective: To investigate possible mechanistic factors to explain cefiderocol (CFDC) non-susceptibility, we characterized 38 clinical isolates with a CFDC minimum inhibitory concentration (MIC) of >4 mu g/mL from a multi-national surveillance study.Methods: The MIC measurement in the presence of beta-lactamase inhibitors and whole genome sequencing were performed.Results: The MIC decrease of CFDC by beta-lactamase inhibitors was observed against all of the test isolates. Among the 38 isolates, NDM and PER genes were observed in 5 and 25 isolates, respectively. No other beta-lactamases responsible for high MIC were identified in the other eight isolates. The MIC of CDFC against Escherichia coli isogenic strains introduced with NDM and PER beta-lactamase increased by >= 16-fold, suggesting the contribution of NDM and PER to the non-susceptibility to CFDC. Against NDM producers, a >= 8-fold MIC increase was observed only when both serine- and metallo-type beta-lactamase inhibitors were added. In addition, many of the PER or NDM producers remained susceptible to CFDC. These results suggested that the presence of only NDM or PER would not lead to non-susceptibility to CFDC and that multiple factors would be related to CFDC resistance.Conclusion: Multiple factors including NDM and PER could be related to reduced susceptibility to CFDC. (C) 2020 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.