In vitro activity of imipenem/relebactam against Gram-negative ESKAPE pathogens isolated in 17 European countries: 2015 SMART surveillance programme
Bibliographic record
Abstract
Objectives: Relebactam is an inhibitor of class A β-lactamases, including KPC β-lactamases, and class C β-lactamases, and is currently under clinical development in combination with imipenem. The objective of the current study was to evaluate the in vitro activity of imipenem/relebactam against Gram-negative ESKAPE pathogens (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) submitted by clinical laboratories in 17 European countries to the Study for Monitoring Antimicrobial Resistance Trends (SMART) global surveillance programme in 2015. Methods: MICs were determined using the CLSI standard broth microdilution method and interpreted using EUCAST clinical breakpoints. Relebactam was tested at a fixed concentration of 4 mg/L in combination with doubling dilutions of imipenem. Imipenem/relebactam MICs were interpreted using breakpoints for imipenem. Results: Rates of susceptibility to imipenem and imipenem/relebactam for isolates of P. aeruginosa (n = 1705), K. pneumoniae (n = 1591) and Enterobacter spp. (n = 772) were 72.0/94.7%, 88.7/94.8% and 95.6/96.8%, respectively. Relebactam restored imipenem susceptibility to 81.1%, 54.2% and 26.5% of imipenem-non-susceptible isolates of P. aeruginosa (n = 477), K. pneumoniae (n = 179) and Enterobacter spp. (n = 34). Most imipenem/relebactam-non-susceptible isolates carried MBLs, OXA-48 or GES carbapenemases. Relebactam did not increase the number of isolates of A. baumannii (n = 486) susceptible to imipenem. Conclusions: Relebactam restored susceptibility to imipenem for the majority of imipenem-non-susceptible isolates of P. aeruginosa and K. pneumoniae tested as well as some isolates of imipenem-non-susceptible Enterobacter spp. Based on our results, imipenem/relebactam appears to be a promising therapeutic option for treating patients with infections caused by antimicrobial-resistant Gram-negative bacilli.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".