Yao Jiahui, Wang Jin, Chen Mengli, Cai Yun
Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center, People's Liberation Army of Chinese General Hospital, Beijing, China.
Department of Pharmacy, Medical Supplies Center, People's Liberation Army of Chinese General Hospital, Beijing, China.
Front Med (Lausanne). 2021 Dec 7;8:741940. doi: 10.3389/fmed.2021.741940. eCollection 2021.
Treatment of multidrug-resistant (MDR) Gram-negative bacteria (GNB) infections has led to a global public health challenging due to the bacterial resistance and limited choices of antibiotics. Cefiderocol (CFDC), a novel siderophore cephalosporin possessed unique drug delivery systems and stability to β-lactamases, has the potential to become first-line therapy for most aggressive MDR Gram-negative pathogens infection. However, there have been reports of drug resistance in the course of using CFDC. This study provides an overview of the and activity of CFDC and potential resistance mechanism was also summarized. In general, CFDC shows excellent activity against a broad range of MDR GNB pathogens including , and . The expressions of metallo-β-lactamases such as inosine 5'-monophosphate (IMP), Verona integron-mediated metallo-β-lactamase (VIM), and New Delhi metalloβ-lactamase (NDM) are associated with a higher resistance rate of CFDC. Carbapenem-resistant phenotype has little effect on the resistance rate, although the acquisition of a particular carbapenemase may affect the susceptibility of the pathogens to CFDC. For potential resistance mechanism, mutations in β-lactamases and TonB-dependent receptors, which assist CFDC entering bacteria, would increase a minimum inhibitory concentration (MIC)90 value of CFDC against MDR pathogens. Since the development of CFDC, resistance during its utilization has been reported thus, prudent clinical applications are still necessary to preserve the activity of CFDC.
由于细菌耐药性以及抗生素选择有限，多重耐药（MDR）革兰氏阴性菌（GNB）感染的治疗已成为一项全球性公共卫生挑战。头孢地尔（CFDC）是一种新型铁载体头孢菌素，具有独特的药物递送系统和对β-内酰胺酶的稳定性，有可能成为治疗大多数侵袭性MDR革兰氏阴性病原体感染的一线疗法。然而，已有使用CFDC过程中出现耐药性的报道。本研究概述了CFDC的抗菌活性，并总结了潜在的耐药机制。总体而言，CFDC对包括[具体菌种1]、[具体菌种2]和[具体菌种3]在内的多种MDR GNB病原体表现出优异的活性。金属β-内酰胺酶如肌苷5'-单磷酸（IMP）、维罗纳整合子介导的金属β-内酰胺酶（VIM）和新德里金属β-内酰胺酶（NDM）的表达与CFDC的较高耐药率相关。碳青霉烯耐药表型对耐药率影响不大，尽管获得特定的碳青霉烯酶可能会影响病原体对CFDC的敏感性。对于潜在的耐药机制，β-内酰胺酶和协助CFDC进入细菌的TonB依赖性受体的突变会增加CFDC对MDR病原体的最低抑菌浓度（MIC）90值。自CFDC研发以来，已有其使用过程中出现耐药性的报道，因此，仍有必要谨慎临床应用以保持CFDC的活性。
