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Record W4200284047 · doi:10.1093/ofid/ofab466.1466

1274. Activity of Ceftolozane/Tazobactam, Imipenem/Relebactam, and Comparators Against <i>Pseudomonas aeruginosa</i> Isolates from Patients with Bloodstream and Other Infection Types—SMART United States/Canada 2018-2019

2021· article· en· W4200284047 on OpenAlexaboutno aff
Sibylle Lob, Meredith Hackel, C Andrew DeRyke, Kelly Harris, Katherine Young, Mary Motyl, Daniel F. Sahm

Bibliographic record

VenueOpen Forum Infectious Diseases · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicAntibiotic Resistance in Bacteria
Canadian institutionsnot available
Fundersnot available
KeywordsMedicineImipenemBroth microdilutionPseudomonas aeruginosaMicrobiologyAmikacinCefepimeTazobactamCephalosporinMeropenemCarbapenemAntibioticsInternal medicineMinimum inhibitory concentrationAntibiotic resistanceBiologyBacteria

Abstract

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Abstract Background Ceftolozane/tazobactam (C/T), an antipseudomonal cephalosporin combined with a β-lactamase inhibitor, was approved for treatment of complicated urinary tract (cUTI) and intraabdominal infections (cIAI), and hospital-acquired/ventilator-associated bacterial pneumonia (HAP/VAP). Imipenem/relebactam (IMI/REL) is a combination of imipenem/cilastatin with relebactam, an inhibitor of class A and C β-lactamases. IMI/REL was approved for HAP/VAP and for infections due to aerobic gram-negative organisms in adults with limited treatment options (e.g., cUTI, cIAI). We compared the activity of C/T and IMI/REL against P. aeruginosa from bloodstream infections (BSI) to those from other infection types. Methods As part of the SMART program, 24 hospitals in the US and 8 in Canada each collected up to 250 consecutive gram-negative isolates per year in 2018-2019 from patients with BSI, lower respiratory tract infections (LRTI), IAI, and UTI. A total of 2351 Pa isolates were collected. MICs were determined using CLSI broth microdilution and breakpoints. Results Pa isolates from BSI tended to show higher susceptibility than IAI, UTI, and especially LRTI isolates (Table). Susceptibility to the tested comparator β-lactams was 11-12 percentage points lower among LRTI than BSI isolates, while C/T and IMI/REL susceptibility was only 2-5% lower. Even among BSI isolates, the comparator β-lactams were active against only 75-88% of isolates, while C/T and IMI/REL were active against &amp;gt;95%. Only amikacin showed higher activity. Analyzing coverage by either C/T or IMI/REL, 98.7% of Pa isolates from BSI were susceptible to one or both agents. C/T and IMI/REL maintained activity against 89% and 69% of meropenem-nonsusceptible (MEM-NS) Pa isolates from BSI (n=36), respectively, and 87% and 76% of piperacillin/tazobactam (P/T)-NS Pa (n=38). Results Table Conclusion Even among BSI isolates, which were generally more susceptible than those from other infection types, Pa susceptibility to commonly used β-lactams like MEM and P/T was &amp;lt; 90%, 7-23% lower than C/T and IMI/REL. Given the desirability of β-lactams among clinicians and the &amp;gt;98% coverage by either C/T or IMI/REL of Pa isolates from BSI, both agents represent important options in the treatment of patients with BSI. Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) C. Andrew DeRyke, PharmD, Merck &amp; Co., Inc. (Employee, Shareholder) Kelly Harris, PharmD, BCPS, Merck &amp; Co. Inc (Employee) Katherine Young, MS, Merck (Employee) Mary Motyl, PhD, Merck &amp; Co., Inc. (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)

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 distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.056
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.004
GPT teacher head0.207
Teacher spread0.203 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designObservational
Domainnot available
GenreEmpirical

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".

Quick stats

Citations0
Published2021
Admission routes1
Has abstractyes

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