311. Defining the magnitude of desirability of outcome ranking (DOOR) differences in effectiveness of Ceftazidime-Avibactam (CZA) versus Ceftolozane-Tazobactam (C/T) for multidrug-resistant (MDR) Pseudomonas aeruginosa infections in the United States (CACTUS)
Authors: Pogue jason M , Abbo Lilian M , Ackley Renee , Aitken Samuel L , Albrecht Benjamin , Babiker Ahmed , Burgoon Rachel , Claeys Kimberly C , Curry Brooke , DeSear Kate , Gallagher Jason C , Golnabi Esther , Green Sarah B , Gross Alan E , Heil Emily L , Hornback Krutika M , Kaye Keith S , Khuu Trieu-Vi , Klatt Megan , Kline Ellen G , Kubat Ryan C , Kufel Wesley D , Lepak Alexander , MacDougall Conan , Majumdar Anjali , Mathers Amy , McCreary Erin K , Miller William R , Monogue Marguerite , Moore W Justin , Olson Shannon , Oxer Jessica , Pearson Jeffrey C , Pham Christine , Pinargote Paulette , Polk Christopher , Satlin Michael J , Satola Sarah W , Shah Sunish , Tamma Pranita , Cecilia Tran Truc , van Duin David , VanNatta Mollie , Vega Ana , Veena Venugopalan , Veve Michael P , Wangchinda Walaiporn , Witt Lucy S , Wu Janet , Shields Ryan K 
Published: January 2025

Background

CACTUS is a retrospective, matched, multicenter study comparing the efficacy of C/T and CZA for the treatment of bacteremia or pneumonia due to MDR P. aeruginosa. We previously demonstrated that treatment with C/T resulted in higher rates of clinical success compared to CZA. The objective of this analysis is to compare the day 30 Desirability of Outcome Ranking (DOOR) between matched patient pairs.

Methods

C/T and CZA patients were matched 1:1 within each study site based on severity of illness, infection type, and time to treatment initiation. The DOOR scale applied is described in Figure 1. Each matched pair was compared for a better ranking. The frequency of an improved DOOR for C/T compared to CZA was determined for the entire cohort (n = 210 pairs) and pneumonia subgroup (n = 175 pairs) where a DOOR of 50% would represent no difference. In addition, we measured the magnitude of DOOR differences within matched pairs.

Results

C/T was not associated with an improved DOOR relative to CZA in the overall cohort (53.3% (95% CI 47.2 – 59.4)) or pneumonia subgroup (54.6% (95% CI 47.9 – 61.2); Figure 1). Specifically, 37% of pairs had the same DOOR, 33% had a lower (better) DOOR with C/T, and 30% had a lower DOOR with CZA. Figure 2 shows the magnitude of DOOR differences for patient pairs. The magnitude was greater for pairs when C/T was associated with a better outcome as compared to the magnitude for pairs when CZA was associated with a better outcome. This difference was more pronounced among patients with pneumonia (Figure 3). A summary of major comparisons is shown in Figure 4. For the entire cohort, an improved DOOR by ≥2 categories within matched pairs occurred more commonly with C/T vs. CZA (p=0.03). In the subgroup of patients with pneumonia, a greater proportion of pairs showed the greatest possible difference (success without complications (DOOR=1) versus death (DOOR=5)) in favor of C/T compared to pairs in favor of CZA; 14% vs. 7%; p = 0.06.

Conclusion

These data demonstrate the power of matched data for analyzing DOOR endpoints. While there was no difference in the overall DOOR, the magnitude of improved outcomes consistently favored C/T over CZA and suggests clinically important differences in these agents for patients with MDR P. aeruginosa pneumonia or bacteremia.

Disclosures

jason M. Pogue, PharmD, Entasis: Advisor/Consultant|GSK: Advisor/Consultant|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Venatorx: Advisor/Consultant Samuel L. Aitken, PharmD, MPH, Basilea: Advisor/Consultant|bioMerieux: Advisor/Consultant|Melinta: Advisor/Consultant|Shionogi: Advisor/Consultant Ahmed Babiker, MBBS, Beckman Coulter Inc.: Advisor/Consultant Kimberly C. Claeys, PharmD, PhD, bioMérieux: Advisor/Consultant|bioMérieux: Honoraria Kate DeSear, PharmD, BCIDP, AAHIVP, FIDSA, AbbVie Inc: Advisor/Consultant|Basilea Pharmaceutica: Advisor/Consultant|GSK: Advisor/Consultant|La Jolla (Entasis): Advisor/Consultant|Melinta Therapuetics: Advisor/Consultant Alan E. Gross, PharmD, Becton Dickinson Co: Advisor/Consultant Keith S. Kaye, MD, MPH, Allecra: Advisor/Consultant|CARB-X: Advisor/Consultant|GSK: Advisor/Consultant|Merck: Advisor/Consultant|Shionogi: Advisor/Consultant|Spero: Advisor/Consultant Wesley D. Kufel, Pharm.D., BCPS, BCIDP, Merck & Co.: Grant/Research Support|Shionogi, Inc: Grant/Research Support Conan MacDougall, PharmD, MAS, Merck: Grant/Research Support Erin K. McCreary, PharmD, Abbvie: Advisor/Consultant|Basilea: Advisor/Consultant|Ciadara: Advisor/Consultant|Entasis: Advisor/Consultant|Ferring: Advisor/Consultant|GSK: Advisor/Consultant|GSK: Honoraria|Melinta: Advisor/Consultant|Merck: Advisor/Consultant|Pfizer: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Honoraria William R. Miller, M.D., Merck: Grant/Research Support|UptoDate: Royalties Jeffrey C. Pearson, PharmD, inflarx: Advisor/Consultant Michael J. Satlin, MD, AbbVie: DSMB participant|bioMerieux: Grant/Research Support|Merck: Grant/Research Support|Selux Diagnostics: Grant/Research Support|SNIPRBiome: Grant/Research Support David van Duin, MD, PhD, Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Qpex: Advisor/Consultant|Roche: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support Ryan K. Shields, PharmD, MS, Allergan: Advisor/Consultant|Cidara: Advisor/Consultant|Entasis: Advisor/Consultant|GSK: Advisor/Consultant|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Menarini: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Roche: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Utility: Advisor/Consultant|Venatorx: Advisor/Consultant|Venatorx: Grant/Research Support