Article ; Online: Activity of cefiderocol and innovative β-lactam/β-lactamase inhibitor combinations against isogenic strains of Escherichia coli expressing single and double β-lactamases under high and low permeability conditions.
International journal of antimicrobial agents
2024 Volume 63, Issue 5, Page(s) 107150
Abstract: Objectives: To analyse the impact of the most clinically relevant β-lactamases and their interplay with low outer membrane permeability on the activity of cefiderocol, ceftazidime/avibactam, aztreonam/avibactam, cefepime/enmetazobactam, cefepime/ ... ...
| Abstract | Objectives: To analyse the impact of the most clinically relevant β-lactamases and their interplay with low outer membrane permeability on the activity of cefiderocol, ceftazidime/avibactam, aztreonam/avibactam, cefepime/enmetazobactam, cefepime/taniborbactam, cefepime/zidebactam, imipenem/relebactam, meropenem/vaborbactam, meropenem/xeruborbactam and meropenem/nacubactam against recombinant Escherichia coli strains. Methods: We constructed 82 E. coli laboratory transformants expressing the main β-lactamases circulating in Enterobacterales (70 expressing single β-lactamase and 12 producing double carbapenemase) under high (E. coli TG1) and low (E. coli HB4) permeability conditions. Antimicrobial susceptibility testing was determined by reference broth microdilution. Results: Aztreonam/avibactam, cefepime/zidebactam, cefiderocol, meropenem/xeruborbactam and meropenem/nacubactam were active against all E. coli TG1 transformants. Imipenem/relebactam, meropenem/vaborbactam, cefepime/taniborbactam and cefepime/enmetazobactam were also highly active, but unstable against most of MBL-producing transformants. Combination of β-lactamases with porin deficiency (E. coli HB4) did not significantly affect the activity of aztreonam/avibactam, cefepime/zidebactam, cefiderocol or meropenem/nacubactam, but limited the effectiveness of the rest of carbapenem- and cefepime-based combinations. Double-carbapenemase production resulted in the loss of activity of most of the compounds tested, an effect particularly evident for those E. coli HB4 transformants in which MBLs were present. Conclusions: Our findings highlight the promising activity that cefiderocol and new β-lactam/β-lactamase inhibitors have against recombinant E. coli strains expressing widespread β-lactamases, including when these are combined with low permeability or other enzymes. Aztreonam/avibactam, cefiderocol, cefepime/zidebactam and meropenem/nacubactam will help to mitigate to some extent the urgency of new compounds able to resist MBL action, although NDM enzymes represent a growing challenge against which drug development efforts are still needed. |
|---|---|
| MeSH term(s) | Escherichia coli/drug effects ; Escherichia coli/genetics ; beta-Lactamases/genetics ; beta-Lactamases/metabolism ; Cephalosporins/pharmacology ; Microbial Sensitivity Tests ; beta-Lactamase Inhibitors/pharmacology ; Azabicyclo Compounds/pharmacology ; Anti-Bacterial Agents/pharmacology ; Drug Combinations ; Cyclooctanes/pharmacology ; Cefiderocol ; Ceftazidime/pharmacology ; Cefepime/pharmacology ; Boronic Acids/pharmacology ; Meropenem/pharmacology ; Aztreonam/pharmacology ; Imipenem/pharmacology ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Heterocyclic Compounds, 1-Ring/pharmacology ; Cell Membrane Permeability/drug effects ; Borinic Acids ; Carboxylic Acids ; Lactams ; Triazoles |
| Chemical Substances | beta-Lactamases (EC 3.5.2.6) ; Cephalosporins ; beta-Lactamase Inhibitors ; Azabicyclo Compounds ; Anti-Bacterial Agents ; Drug Combinations ; Cyclooctanes ; Cefiderocol (SZ34OMG6E8) ; Ceftazidime (9M416Z9QNR) ; Cefepime (807PW4VQE3) ; Boronic Acids ; Meropenem (FV9J3JU8B1) ; Aztreonam (G2B4VE5GH8) ; avibactam, ceftazidime drug combination ; Imipenem (71OTZ9ZE0A) ; nacubactam (832O37V7MZ) ; taniborbactam (8IGQ156Z07) ; enmetazobactam (80VUN7L00C) ; meropenem and vaborbactam ; relebactam (Y1MYA2UHFL) ; carbapenemase (EC 3.5.2.6) ; Bacterial Proteins ; Heterocyclic Compounds, 1-Ring ; Borinic Acids ; Carboxylic Acids ; Lactams ; Triazoles |
| Language | English |
| Publishing date | 2024-03-19 |
| Publishing country | Netherlands |
| Document type | Journal Article |
| ZDB-ID | 1093977-5 |
| ISSN | 1872-7913 ; 0924-8579 |
| ISSN (online) | 1872-7913 |
| ISSN | 0924-8579 |
| DOI | 10.1016/j.ijantimicag.2024.107150 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
Full text online
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 3368: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG) |
|||
| Zs.MO 500: Show issues |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.