1252. <i>In Vitro</i> Activity of Aztreonam-Avibactam and Comparator Agents Against Enterobacterales from Patients with Bloodstream Infections collected during the ATLAS Global Surveillance Program, 2015-2019
Bibliographic record
Abstract
Abstract Background Treatment options for β-lactamase-producing Enterobacterales are limited, particularly for infections caused by metallo-β-lactamase (MBL)-producing strains. The β-lactam/non-β-lactam β-lactamase inhibitor combination aztreonam-avibactam (ATM-AVI) is active in vitro against Enterobacterales isolates carrying MBLs, including those co-producing β-lactamases of Class A, C, and some class D enzymes. This study evaluated the in vitro activity of ATM-AVI and comparators against Enterobacterales isolates collected in 2015-2019 from patients with bloodstream infections (BSI) as part of the ATLAS program. Methods Non-duplicate clinical isolates were collected in 53 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 2021 and FDA (tigecycline) breakpoints. ATM-AVI was tested at a fixed concentration of 4 µg/mL AVI. MDR was defined as resistant (R) to ≥3 of 7 sentinel drugs: amikacin, aztreonam, cefepime, colistin, levofloxacin, meropenem, and piperacillin-tazobactam. 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 phenotypically positive for ESBL activity (2015) or with aztreonam or ceftazidime MIC &gt;1 µg/mL (2016-2019). Results ATM-AVI was active in vitro against Enterobacterales isolates from BSI (MIC90, 0.12 µg/mL), with 99.97% of isolates inhibited by ≤8 µg/mL of ATM-AVI, including 100% of isolates that produced MBLs. ATM-AVI tested with MIC90 values of 0.5 µg/mL against subsets of cefepime-nonsusceptible (NS), meropenem-NS, amikacin-NS, colistin-resistant, and MBL-positive Enterobacterales (Table). The tested β-lactam comparators showed susceptibility of &lt; 79% against these subsets of resistant isolates. Results Table Conclusion Based on MIC90 values, ATM-AVI was the most potent agent tested against drug-resistant and MBL-positive subsets of Enterobacterales collected from BSI. The promising in vitro activity of ATM-AVI warrants further development of this combination for treatment of BSI caused by drug-resistant Enterobacterales. Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Francis Arhin, PhD, Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)
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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 | 0.000 |
| 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".