1649. Ceftolozane-Tazobactam or Ceftazidime-Avibactam Versus Best Available Therapy in the Treatment of Difficult-to-Treat Pseudomonas aeruginosa Infections: a Retrospective Comparative Effectiveness Analysis of 195 U.S. Hospitals, 2016–2020
Bibliographic record
Abstract
Abstract Background Infections due to Pseudomonas aeruginosa displaying difficult-to-treat resistance (DTR-PA) necessitate the use of sub-efficacious and/or toxic “reserve” antibiotics and are associated with considerable morbidity and mortality. Ceftazidime-avibactam (CAZ-AVY) and ceftolozane-tazobactam (CEF-TAZO) are novel ß-lactam/ß-lactamase inhibitors (BLBLI) that tend to retain in vitro activity against DTR-PA. However, little is known about their in vivo effectiveness compared to reserve agents. Methods Inpatients aged ≥ 18 years with ≥1 blood, urine, respiratory, or body fluid culture growing DTR-PA who received targeted therapy with either CAZ-AVY, CEF-TAZO, or Best-Available Therapy (BAT) were identified in the Premier Healthcare Database. Primary outcome was in-hospital mortality or discharge to hospice and secondary outcome was length of hospital stay (LOS) for survivors. The primary outcome was compared for CAZ-AVY vs CEF-TAZO and novel agents (CAZ-AVY or CEF-TAZO) vs BAT using overlap weighting and binomial regression with downstream adjustment controlling for patient and treatment characteristics. The secondary outcomes were compared using overlap weighting and poisson regression with downstream adjustment controlling for patient and treatment characteristics. Results Between 2016 and 2020, 1,552 patients with DTR-PA infections were identified at 105 hospitals, of which 202 (13.0%) were treated with CAZ-AVY, 906 (58.4%) with CEF-TAZO, and 444 (28.6%) with BAT. Patient characteristics were similar among treatment groups (Table 1, Table 2). Overall crude mortality was 15.5%. The adjusted risk of mortality was lower in patients treated with CAZ-AVI (12.5%, 95% CI 7.9–17.1) vs CEF-TAZO (18.8%, 95% CI 15.9–21.8) for a risk difference of 6.3% (95% 1.1–11.5, p = 0.02). The novel agents were not associated with a reduced mortality risk when collectively compared to BAT (risk difference -1.1%, 95% CI -5.4; 3.2%). LOS favoured novel agents and were comparable for CAZ-AVY and CEF-TAZO. Conclusion In this real-world observational study of patients with DTR-PA infections, the novel ß-lactam/ß-lactamase inhibitors were comparably effective against BAT, though the use of CAZ-AVY was associated with a reduced mortality compared to CEF-TAZO. Disclosures All Authors: No reported disclosures.
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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 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".