دورية أكاديمية
Defining Baseline Mechanisms of Cefiderocol Resistance in the Enterobacterales.
| العنوان: | Defining Baseline Mechanisms of Cefiderocol Resistance in the Enterobacterales. |
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| المؤلفون: | Simner PJ; Division of Medical Microbiology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Beisken S; Ares Genetics, Vienna, Austria., Bergman Y; Division of Medical Microbiology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Ante M; Ares Genetics, Vienna, Austria., Posch AE; Ares Genetics, Vienna, Austria., Tamma PD; Division of Pediatric Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. |
| المصدر: | Microbial drug resistance (Larchmont, N.Y.) [Microb Drug Resist] 2022 Feb; Vol. 28 (2), pp. 161-170. Date of Electronic Publication: 2021 Oct 06. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Mary Ann Liebert Country of Publication: United States NLM ID: 9508567 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1931-8448 (Electronic) Linking ISSN: 10766294 NLM ISO Abbreviation: Microb Drug Resist Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Larchmont, N.Y. : Mary Ann Liebert, c1995- |
| مواضيع طبية MeSH: | Anti-Bacterial Agents/*pharmacology , Carbapenem-Resistant Enterobacteriaceae/*genetics , Cephalosporins/*pharmacology , Genes, Bacterial/*genetics, Drug Resistance, Multiple, Bacterial ; Microbial Sensitivity Tests ; Whole Genome Sequencing ; beta-Lactamases/genetics ; Cefiderocol |
| مستخلص: | The objective of this study was to identify putative mechanisms contributing to baseline cefiderocol resistance among carbapenem-resistant Enterobacterales (CRE). We evaluated 56 clinical CRE isolates with no previous exposure to cefiderocol. Cefiderocol and comparator agent minimum inhibitory concentrations (MICs) were determined by broth microdilution. Short-read and/or long-read whole genome sequencing was pursued. Cefiderocol nonwild type (NWT; i.e., MICs ≥4 mg/L) CRE were compared with species-specific reference genomes and with cefiderocol wild type (WT) CRE isolates to identify genes or missense mutations, potentially contributing to elevated cefiderocol MICs. A total of 14 (25%) CRE isolates met cefiderocol NWT criteria. Of the 14 NWT isolates, various β-lactamases ( e.g., carbapenemases in Klebsiella pneumoniae and AmpC β-lactamases in Enterobacter cloacae complex) in combination with permeability defects were associated with a ≥ 80% positive predictive value in identifying NWT isolates. Unique mutations in the sensor kinase gene baeS were identified among NWT isolates. Cefiderocol NWT isolates were more likely to be resistant to colistin than WT isolates (29% vs. 0%). Our findings suggest that no consistent antimicrobial resistance markers contribute to baseline cefiderocol resistance in CRE isolates and, rather, cefiderocol resistance results from a combination of heterogeneous mechanisms. |
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| معلومات مُعتمدة: | R21 AI153580 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: carbapenem-resistant Enterobacterales; cefiderocol; mechanisms of resistance |
| المشرفين على المادة: | 0 (Anti-Bacterial Agents) 0 (Cephalosporins) EC 3.5.2.6 (beta-Lactamases) |
| تواريخ الأحداث: | Date Created: 20211007 Date Completed: 20220228 Latest Revision: 20231213 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC8885434 |
| DOI: | 10.1089/mdr.2021.0095 |
| PMID: | 34619049 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1931-8448 |
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| DOI: | 10.1089/mdr.2021.0095 |