1584. <i>In Vitro</i> Activity of Imipenem/Relebactam against Gram-Negative Pathogens from Patients with Bloodstream Infections in the United States and Canada – SMART 2018
Bibliographic record
Abstract
Abstract Background Relebactam (REL) inhibits class A and C β-lactamases, including KPC, and was approved in the United States combined with imipenem (IMI) and cilastatin for complicated urinary tract and intraabdominal infections. We evaluated the activity of IMI/REL against non-Morganellaceae (NME) and P. aeruginosa collected as part of the global SMART surveillance program from patients with bloodstream infections (BSI) in the US and Canada. Methods In 2018, 24 US and 8 Canadian hospitals each collected up to 50 consecutive aerobic or facultative gram-negative pathogens from patients with BSI. MICs were determined using CLSI broth microdilution and interpreted with 2020 CLSI breakpoints. Multidrug-resistance (MDR) was defined as resistance to ≥3 of the following sentinel drugs: amikacin, aztreonam, cefepime, ceftazidime (NME only), ciprofloxacin, colistin, imipenem, and piperacillin/tazobactam. Results The 5 most common species among 1463 collected BSI isolates were E. coli (46.9%), K. pneumoniae (16.0%), P. aeruginosa (8.5%), P. mirabilis (4.8%), and E. cloacae (4.3%). Susceptibility to IMI/REL and comparators of selected species and subsets of resistant phenotypes is shown in the table. IMI/REL was active against 99.8% of NME isolates; only meropenem, ceftazidime/avibactam, and amikacin showed comparable activity. Per 2020 CLSI guidelines, Enterobacterales and P. aeruginosa isolates are no longer considered susceptible to colistin. IMI/REL maintained activity against 89-100% of NME isolates that were nonsusceptible (NS) to β-lactams or MDR. Among P. aeruginosa, IMI/REL was active against 94.4% of isolates; a susceptibility rate only exceeded by amikacin. The addition of relebactam lowered the MIC90 for P. aeruginosa from 16 µg/mL to 1 µg/mL. IMI/REL maintained activity against 40-77% of P. aeruginosa isolates NS to β-lactams or MDR; susceptibility rates only exceeded by amikacin. Susceptibility to IMI/REL was similar in the US (99.8% of NME [n=846]; 93.8% of P. aeruginosa [n=96]) and Canada (99.7% of NME [n=339]; 96.4% of P. aeruginosa [n=28]). Table Conclusion In the US and Canada, IMI/REL could provide an important treatment option for patients with BSI caused by resistant gram-negative organisms. Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co, Inc (Employee, Shareholder) 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 | 0.000 |
| 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".