1567. <i>In Vitro</i> Activity of Aztreonam-Avibactam and Comparator Agents Against Multidrug-Resistant Enterobacterales Collected Globally as Part of the ATLAS Surveillance Program, 2016-2018
Bibliographic record
Abstract
Abstract Background Avibactam (AVI) is a serine-β-lactamase inhibitor in development with aztreonam (ATM) for treatment of infections caused by drug-resistant Enterobacterales (Ent), especially carbapenem-resistant isolates co-producing serine- and metallo-β-lactamases (MBL), which are often resistant to agents from multiple drug classes. This study evaluated the in vitro activity of ATM-AVI and comparators against Ent collected globally as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program. Methods 44,671 non-duplicate clinical isolates were collected in 2016-2018 in 52 countries in Europe, Asia/Pacific (excluding China and India), Middle East/Africa, and Latin America. Susceptibility testing was performed by CLSI broth microdilution and interpreted using CLSI 2020 and FDA (tigecycline) breakpoints. ATM-AVI was tested at a fixed concentration of 4 µg/mL AVI. Drug-resistant phenotypes were defined as: multidrug resistant (MDR), resistant (R) to ≥3 of 7 sentinel agents (amikacin [AMK], ATM, cefepime [FEP], colistin [CST], levofloxacin [LVX], meropenem [MEM], piperacillin-tazobactam [TZP]); extensively drug resistant (XDR), susceptible to ≤2 sentinel agents; and pandrug resistant (PDR), non-susceptible to all sentinel agents. Isolates with MEM MIC &gt;1 µg/mL were screened for β-lactamase genes by PCR and sequencing. Results 14.9%, 4.3%, 3.7%, 1.3%, and 0.3% of Ent collected globally were MDR, XDR, MEM-R, MBL-positive, and PDR, respectively. ATM-AVI tested with MIC90 values of 0.12 µg/mL against all Ent and 0.5 µg/mL against subsets of resistant isolates (Table). On the regional level, similar values were observed against all (MIC90, 0.12 µg/mL) and resistant isolates (MIC90, 0.25-1 µg/mL) (not shown). The tested comparators, excluding TGC, showed percentages of susceptibility &lt; 90% against regional and global subsets of resistant isolates. 99.97% (44658 of 44671) Ent, including all MBL-positive and PDR isolates, were inhibited by ≤8 µg/mL of ATM-AVI. Table Conclusion Based on MIC90 values, ATM-AVI demonstrated potent in vitro activity against resistant and MBL-positive subsets of Ent collected globally. ATM-AVI could be an effective therapy for difficult-to-treat infections caused by drug-resistant Ent. Disclosures Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Francis Arhin, PhD, Pfizer, Inc. (Employee) Greg Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (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 | 0.001 |
| 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".