Article ; Online: Citrobacter freundii resistant to novel β-lactamase inhibitor combinations and cefiderocol, co-producing class A, B and D carbapenemases encoded by transferable plasmids.
The Journal of antimicrobial chemotherapy
2023 Volume 78, Issue 7, Page(s) 1677–1682
Abstract: Objectives: To characterize a carbapenem-resistant Citrobacter freundii (Cf-Emp) co-producing class A, B and D carbapenemases, resistant to novel β-lactamase inhibitor combinations (BLICs) and cefiderocol.: Methods: Carbapenemase production was ... ...
| Abstract | Objectives: To characterize a carbapenem-resistant Citrobacter freundii (Cf-Emp) co-producing class A, B and D carbapenemases, resistant to novel β-lactamase inhibitor combinations (BLICs) and cefiderocol. Methods: Carbapenemase production was tested by an immunochromatography assay. Antibiotic susceptibility testing (AST) was performed by broth microdilution. WGS was performed using short- and long-read sequencing. Transfer of carbapenemase-encoding plasmids was assessed by conjugation experiments. Results: Cf-Emp was isolated on selective medium for carbapenem-resistant Enterobacterales from the surveillance rectal swab taken at hospital admission from a patient of Moroccan origin. Cf-Emp produced three different carbapenemases, including KPC-2, OXA-181 and VIM-1, and was resistant to all β-lactams including carbapenems, novel BLICs (ceftazidime/avibactam, meropenem/vaborbactam and imipenem/relebactam) and cefiderocol. MIC of aztreonam/avibactam was 0.25 mg/L. The strain belonged to ST22, one of the C. freundii lineages of global diffusion, known to be associated with carbapenemase production. Each carbapenemase gene was located aboard a different plasmid (named pCf-KPC, pCf-OXA and pCf-VIM, respectively), which also carried other clinically relevant resistance genes, such as armA (pCf-KPC), blaSHV-12 (pCf-VIM) and qnrS1 (pCf-OXA). Transferability to Escherichia coli J53 by conjugation was observed for all plasmids. Conclusions: The finding of enterobacterial strains carrying multiple carbapenemase genes on transferable plasmids is alarming, because similar strains could provide an important reservoir for disseminating these clinically relevant resistance determinants. |
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| MeSH term(s) | Humans ; beta-Lactamase Inhibitors/pharmacology ; Citrobacter freundii ; Bacterial Proteins/genetics ; beta-Lactamases/genetics ; Anti-Bacterial Agents/pharmacology ; Carbapenems/pharmacology ; Plasmids/genetics ; Drug Combinations ; Microbial Sensitivity Tests ; Cefiderocol |
| Chemical Substances | carbapenemase (EC 3.5.2.6) ; avibactam (7352665165) ; beta-Lactamase Inhibitors ; Bacterial Proteins ; beta-Lactamases (EC 3.5.2.6) ; Anti-Bacterial Agents ; Carbapenems ; Drug Combinations |
| Language | English |
| Publishing date | 2023-05-16 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 191709-2 |
| ISSN | 1460-2091 ; 0305-7453 |
| ISSN (online) | 1460-2091 |
| ISSN | 0305-7453 |
| DOI | 10.1093/jac/dkad150 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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