1720. <i>In Vitro</i> Activity of Aztreonam-Avibactam and Comparator Agents Against Enterobacterales from Patients with Urinary Tract Infections Collected During the ATLAS Global Surveillance Program, 2017-2020
Bibliographic record
Abstract
Abstract Background β-lactamase-producing Enterobacterales (Eba) frequently carry resistance mechanisms for multiple drug classes, limiting treatment options. Avibactam (AVI) inhibits class A, class C, and some class D serine β-lactamases, while aztreonam (ATM) is refractory to hydrolysis by class B metallo-β-lactamases (MBLs). ATM-AVI is being developed for use against drug-resistant isolates of Eba, especially those co-producing MBLs and serine β-lactamases. This study evaluated the in vitro activity of ATM-AVI and comparators against Eba collected in 2017-2020 from patients with urinary tract infections (UTI) as part of the ATLAS global surveillance program. Methods Non-duplicate clinical isolates were collected from 239 sites in 55 countries in Europe, Latin America, Asia/Pacific (excluding mainland China and India), and Middle East/Africa. Susceptibility testing was performed by CLSI broth microdilution and interpreted using CLSI 2022 and FDA (tigecycline) breakpoints. PCR and sequencing were used to determine the β-lactamase genes present in all isolates with meropenem MIC &gt;1 µg/mL, and Escherichia coli, Klebsiella spp. and Proteus mirabilis with ATM or ceftazidime MIC &gt;1 µg/mL. Results Based on MIC90 values, ATM-AVI was at least as active as every comparator agent tested against all 15085 Eba isolates collected from UTI (0.12 µg/ml; table), with only five isolates testing with MIC values &gt;8 µg/ml (not shown). Against resistant subsets of isolates, MIC90 values for ATM-AVI were 0.25-0.5 µg/ml, 4- to 8-fold lower than any comparator tested. Against MBL-positive isolates, ATM-AVI MIC values ranged from ≤0.015-2 µg/ml with the exception of one Escherichia coli isolate testing with an MIC value of 16 µg/ml that carried NDM-5, CMY-145, CTX-M-55 and TEM (not shown). Conclusion Based on MIC90 values, ATM-AVI was the most potent agent tested against drug-resistant and MBL-positive subsets of Eba collected from UTI. Based on the potent in vitro activity of ATM-AVI, continued development of this combination for treatment of UTI caused by drug-resistant Eba is warranted. Disclosures All Authors: No reported disclosures.
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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".