P-1508. <i>In Vitro</i> Activity of Aztreonam-avibactam against Enterobacterales Isolates Producing Multiple β-lactamases Collected Globally as a Part of the ATLAS Global Surveillance Program from 2018-2022
Bibliographic record
Abstract
Abstract Background Aztreonam-avibactam (ATM-AVI) is a β-lactam/β-lactamase inhibitor combination to treat infections caused by Gram-negative organisms, particularly those carrying metallo-β-lactamases (MBLs) and other β-lactamases. Aztreonam is stable to hydrolysis by MBLs and avibactam inhibits Class A, C, and some Class D enzymes. We examined ATM-AVI activity against Enterobacterales isolates producing one or more β-lactamase collected as a part of the ATLAS global surveillance program (2018-2022). Methods 88,750 isolates from 227 medical centers in 57 countries (excluding mainland China, Canada, and the USA) were collected and tested for susceptibility using the broth microdilution method according to CLSI guidelines. Analysis was performed with CLSI 2024 breakpoints. Isolates testing with meropenem MIC values >1 µg/mL or Escherichia coli, Klebsiella pneumoniae, K. oxytoca, or Proteus mirabilis isolates testing with ceftazidime and/or aztreonam MIC values >2 µg/mL were screened for β-lactamase genes by PCR, which were sequenced when identified. Results One or more extended-spectrum β-lactamase (ESBL), serine-carbapenemase, MBL, or acquired AmpC was identified among 17,013/18,408 isolates characterized. Among isolates carrying one or two ESBLs (51.4%), 99.9-100% tested with ATM-AVI MICs ≤8 µg/mL (MIC90 values of 0.12 and 0.5 µg/mL, respectively). Among isolates with a serine-carbapenemase and one or more ESBL (18.3%), 99.9-100% tested with ATM-AVI MICs ≤8 µg/mL (MIC90 values of 0.5-1 µg/mL). MBL-positive isolates with or without serine-carbapenemases and/or ESBLs (13.7%) demonstrated MICs ≤8 µg/mL among 98.3-100% of isolates in each category (MIC90 values of 0.5-1 µg/mL). Isolates carrying acquired AmpC as well as any combination of additional β-lactamases (9%) tested with ATM-AVI MICs ≤8 µg/mL among 93.6-100% of each population (MIC90 values of 0.5-8 µg/mL). Conclusion ATM-AVI demonstrated potent in vitro activity against Enterobacterales isolates regardless of the number of β-lactamases carried. Slightly reduced potency was observed in populations that carried acquired AmpC. This may be expected as some variants of AmpC with extended-spectrum activity are known to increase ATM-AVI MICs. Disclosures Mark Estabrook, MS, Pfizer, Inc.: Advisor/Consultant Henry Li, MS in Biotechnology, Pfizer, Inc.: Advisor/Consultant Daniel F. Sahm, PhD, Pfizer, Inc.: Advisor/Consultant
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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".