دورية أكاديمية
Cefiderocol Activity Against Clinical Pseudomonas aeruginosa Isolates Exhibiting Ceftolozane-Tazobactam Resistance.
| العنوان: | Cefiderocol Activity Against Clinical Pseudomonas aeruginosa Isolates Exhibiting Ceftolozane-Tazobactam Resistance. |
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| المؤلفون: | Simner PJ; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Beisken S; Ares Genetics, Vienna, Austria., Bergman Y; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Posch AE; Ares Genetics, Vienna, Austria., Cosgrove SE; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Tamma PD; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. |
| المصدر: | Open forum infectious diseases [Open Forum Infect Dis] 2021 Jun 12; Vol. 8 (7), pp. ofab311. Date of Electronic Publication: 2021 Jun 12 (Print Publication: 2021). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Published by Oxford University Press on behalf of the Infectious Diseases Society of America Country of Publication: United States NLM ID: 101637045 Publication Model: eCollection Cited Medium: Print ISSN: 2328-8957 (Print) Linking ISSN: 23288957 NLM ISO Abbreviation: Open Forum Infect Dis Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Cary, NC : Published by Oxford University Press on behalf of the Infectious Diseases Society of America, [2014]- |
| مستخلص: | Background: Mutations in the AmpC-AmpR region are associated with treatment-emergent ceftolozane-tazobactam (TOL-TAZ) and ceftazidime-avibactam (CAZ-AVI) resistance. We sought to determine if these mutations impact susceptibility to the novel cephalosporin-siderophore compound cefiderocol. Methods: Thirty-two paired isolates from 16 patients with index P. aeruginosa isolates susceptible to TOL-TAZ and subsequent P. aeruginosa isolates available after TOL-TAZ exposure from January 2019 to December 2020 were included. TOL-TAZ, CAZ-AVI, imipenem-relebactam (IMI-REL), and cefiderocol minimum inhibitory concentrations (MICs) were determined using broth microdilution. Whole-genome sequencing of paired isolates was used to identify mechanisms of resistance to cefiderocol that emerged, focusing on putative mechanisms of resistance to cefiderocol or earlier siderophore-antibiotic conjugates based on the previously published literature. Results: Analyzing the 16 pairs of P. aeruginosa isolates, ≥4-fold increases in cefiderocol MICs occurred in 4 of 16 isolates. Cefiderocol nonsusceptibility criteria were met for only 1 of the 4 isolates, using Clinical and Laboratory Standards Institute criteria. Specific mechanisms identified included the following: AmpC E247K (2 isolates), MexR A66V and L57D (1 isolate each), and AmpD G116D (1 isolate) substitutions. For both isolates with AmpC E247K mutations, ≥4-fold MIC increases occurred for both TOL-TAZ and CAZ-AVI, while a ≥4-fold reduction in IMI-REL MICs was observed. Conclusions: Our findings suggest that alterations in the target binding sites of P. aeruginosa -derived AmpC β-lactamases have the potential to reduce the activity of 3 of 4 novel β-lactams (ie, ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol) and potentially increase susceptibility to imipenem-relebactam. These findings are in need of validation in a larger cohort. (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.) |
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| فهرسة مساهمة: | Keywords: AmpC; antimicrobial resistance; ceftazidime-avibactam; omega loop |
| تواريخ الأحداث: | Date Created: 20210715 Latest Revision: 20240402 |
| رمز التحديث: | 20240402 |
| مُعرف محوري في PubMed: | PMC8275882 |
| DOI: | 10.1093/ofid/ofab311 |
| PMID: | 34262990 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2328-8957 |
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| DOI: | 10.1093/ofid/ofab311 |