Frequency, Antimicrobial Susceptibility, and Molecular Characterization of Carbapenem-Resistant Enterobacterales Stratified by United States Census Divisions: Results From the INFORM Program (2018–2022)
Bibliographic record
Abstract
Abstract Background Recently approved β-lactamase inhibitor combinations, such as ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam, have demonstrated a broad spectrum of activity against carbapenem-resistant Enterobacterales (CRE) from US hospitals, but resistance may emerge with the increasing use of these compounds. Aztreonam-avibactam was recently approved in Europe and it is under clinical development in the United States. We evaluated the activity of aztreonam-avibactam and comparators against CREs from US hospitals. Methods A total of 45 497 Enterobacterales isolates were consecutively collected from 79 US medical centers (36 states) and susceptibility tested by broth microdilution. Aztreonam-avibactam was tested with avibactam at a fixed 4 mg/L and a susceptible breakpoint of ≤4 mg/L was applied for comparison. CRE isolates were screened for carbapenemase by whole-genome sequencing. Results Aztreonam-avibactam inhibited >99.9% of Enterobacterales at ≤4 mg/L. CRE frequencies varied from 0.2% (New England) to 2.4% (Middle Atlantic). Aztreonam-avibactam was active (minimum inhibitory concentration ≤4 mg/L) against 98.6% (408/414) of CREs overall, whereas susceptibility to ceftazidime-avibactam and meropenem-vaborbactam were lowest in the Mountain division (67.7% and 74.2%, respectively) and highest (100.0%) in West North Central. Klebsiella pneumoniae carbapenemase was the most common carbapenemase (65.5% of CREs), followed by New Delhi MBL (10.6%) and oxacillinase-48–like (2.7%). The occurrence of Klebsiella pneumoniae carbapenemase among CREs varied from 14.3% (New England) to 77.8% (East South Central), whereas the frequency of MBLs ranged from ≤3.0% (4 divisions) to 19.4% in Mountain and 42.9% in New England. Conclusions Aztreonam-avibactam showed potent activity against CRE, including MBL producers. Resistance to ceftazidime-avibactam and meropenem-vaborbactam was observed among CRE because of increasing occurrence of MBL-producing isolates.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".