P-1507. <i>In Vitro</i> Activity of Ceftazidime-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 Ceftazidime-avibactam (CAZ-AVI) is a β-lactam/β-lactamase inhibitor combination approved to treat infections caused by Gram-negative organisms. Notably, CAZ-AVI has activity against Enterobacterales producing Class A, C, and D β-lactamases, but not Class B metallo-β-lactamases (MBLs). The in vitro activity of CAZ-AVI and comparator agents against clinical Enterobacterales isolates producing one or more β-lactamase collected as a part of the ATLAS global surveillance program (2018-2022) was evaluated. Methods 89,316 isolates from 228 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 &gt;1 µg/mL or Escherichia coli, Klebsiella pneumoniae, K. oxytoca, or Proteus mirabilis isolates testing with ceftazidime and/or aztreonam MIC values &gt;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), acquired AmpC, serine-carbapenemase, or MBL was identified among 17,348/18,798 isolates characterized. Against isolates producing ESBLs (51.1%), susceptibility to CAZ-AVI was similar if the isolate carried one ESBL (99.4%) or two ESBLs (98.4%). Against acquired AmpC-producing isolates (5.9%), CAZ-AVI susceptibility was similar if the isolates co-carried 0, 1, or 2 ESBLs (98.9%, 97.1%, and 100% susceptible, respectively). Against isolates carrying serine-carbapenemases (18.6%), CAZ-AVI activity was similar regardless of co-carriage of acquired AmpC and/or one or more ESBLs (95.5-100% susceptible). CAZ-AVI was not active against isolates that carried an MBL (16.6%), regardless of other enzyme carriage (0-2.9% susceptible). Conclusion These results highlight that the number of distinct β-lactamases have little association with susceptibility to CAZ-AVI, while the type of β-lactamase (MBL or non-MBL) has a greater association. 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 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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".