Activity of Imipenem-Relebactam (MK-7655) Against Enterobacteriaceae and Pseudomonas aeruginosa From Respiratory Tract Infections in North America—SMART 2015
Bibliographic record
Abstract
Background. Relebactam (formerly MK-7655) (REL) is a newly developed beta-lactamase inhibitor of class A and class C carbapenemases. REL restores the in vitro activity of imipenem (IMI) against Enterobacteriaceae, including those producing KPC, and Pseudomonas aeruginosa (PA). In this study we evaluated the ability of REL to restore IMI susceptibility to a collection of gram-negative isolates from respiratory tract infections (RTI) from North America collected as part of the 2015 SMART surveillance program. Methods. Twenty-six hospitals in the US (19) and Canada (7) collected up to 50 consecutive gram-negative pathogens from RTIs. MICs were determined for 96 PA and 981 nonproteae Enterobacteriaceae (NPE) using CLSI broth microdilution. Proteae were excluded due to intrinsic non-susceptibility to IMI. REL was tested at a fixed concentration of 4 µg/mL in combination with IMI. The percentage susceptible (S) was assessed using CLSI breakpoints. IMI S breakpoints of ≤1 µg/mL (NPE) and ≤2 µg/mL (PA) were applied to IMI/REL. Results. The cumulative percentage of isolates at each IMI and IMI/REL MIC is shown in the table. Shaded area indicates susceptible by CLSI 2016 imipenem breakpoint; MIC90 bolded; NPE, nonproteae Enterobacteriaceae; IMI, imipenem; REL, relebactam; NS, non-susceptible Among 769 PA, 69% (528) were S to IMI; of the 241 non-susceptible (NS) isolates, 181 (75%) were rendered S by the addition of REL, for a final 92% S. Among 1060 NPE, 92% (978) were S to IMI; of the 82 NS isolates, 58 (71%) were rendered S by the addition of REL, for a final 98% S. Conclusion. Relebactam exhibited strong potential for restoring the in vitro activity of IMI against many RTI pathogens otherwise NS to carbapenems. Further development of this compound could provide a valuable therapeutic option for treating infections caused by resistant gram-negative bacilli. Disclosures. M. Hackel, IHMA, Inc: Independent Contractor, Research support K. Young, Merck & Co, Inc: Employee, Salary M. Motyl, Merck & Co, Inc: Employee, Salary D. Sahm, IHMA, Inc: Independent Contractor, Research support
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| 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".