Characterization of Ceftazidime-Avibactam-Resistant Carbapenem-Resistant Enterobacteriaceae, United States, 2015–2017
Bibliographic record
Abstract
Background: Carbapenem-resistant Enterobacteriaceae (CRE) are a major public health problem. Ceftazidime-avibactam (CZA) is a treatment option for CRE approved in 2015; however, it does not have activity against isolates with metallo-β-lactamases (MBLs). Emerging resistance to CZA is a cause for concern. Our objective was to describe the microbiologic and epidemiologic characteristics of CZA-resistant (CZA-R) CRE. Methods: From 2015 to 2017, 9 states participated in laboratory- and population-based surveillance for carbapenem-resistant Escherichia coli, Klebsiella pneumoniae, K. oxytoca, K. aerogenes, and Enterobacter cloacae complex isolates from a normally sterile site or urine. A convenience sample of isolates from this surveillance were sent to the CDC for antimicrobial susceptibility testing (AST) using reference broth microdilution (BMD) including an MBL screen, species confirmation with MALDI-TOF, and real-time PCR to detect blaKPC, blaNDM, and blaOXA-48–like genes. Additional AST by BMD was performed on CZA-R isolates using meropenem-vaborbactam (MEV), imipenem-relebactam (IMR), plazomicin (PLZ), and eravacycline (ERV). Epidemiologic data were obtained from a medical record review. Community-associated cases were defined as having no healthcare exposures in the year prior to culture, no devices in place 2 days prior to culture, and culture collected before calendar day 3 after hospital admission. Data were analyzed in 3 groups: CRE that were CZA-susceptible (CZA-S), CZA-R that were due to blaNDM, and CZA-R without blaNDM. Results: Among 606 confirmed CRE tested with CZA, 33 (5.4%) were CZA-R. Of the CZA-R isolates, 16 (48.5%) harbored a blaNDM gene, of which 2 coharbored blaNDM and blaOXA-48-like genes; 9 (27.3%) harbored only a blaKPC gene. Of the 17 CZA-R isolates without blaNDM, all were MBL screen negative. CZA-R due to blaNDM were more frequently community-associated (43.8%) than CZA-S or CZA-R without blaNDM (11.0% and 5.9%, respectively); a higher percentage of CZA-R cases due to blaNDM also had recent international travel (25%) compared to the other groups (1.8% and 5.9%, respectively). CZA-R without blaNDM were more susceptible to MEV (76%), IMR (71%), PLZ (88%), and ERV (65%) compared to CZA-R due to blaNDM (19%, 6%, 56%, and 44%, respectively). Conclusions: The emergence of CZA-R isolates without blaNDM are concerning; however, these isolates are more susceptible to newer antimicrobials than those with blaNDM. In addition to high rates of resistance to newer antimicrobials, isolates with blaNDM are more frequently community-associated than other CRE. This underscores the need for more aggressive measures to stop the spread of CRE. Funding: None Disclosures: None
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".