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 distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".