312. Impact of Patient Subgroups on the Efficacy of Ceftazidime-Avibactam (CZA) versus Ceftolozane-Tazobactam (C/T) for Multidrug-resistant (MDR) Pseudomonas aeruginosa infections in the United States (CACTUS)
Authors: Veve Michael P , 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 , Hyoung Lee Jae , 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 , Wangchinda Walaiporn , Witt Lucy S , Shields Ryan K 
Published: January 2025

Abstract

Background
CACTUS is a retrospective, matched, multicenter study comparing the efficacy of C/T and CZA for treatment of bacteremia or pneumonia due to MDR P. aeruginosa. We found that treatment with C/T resulted in higher rates of clinical success compared to CZA after controlling for baseline differences between cohorts. The objective of this study is to determine the impact of patient subgroups on the overall findings.

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 primary outcome was clinical success at day 30, defined as survival, resolution of signs/symptoms of infection with the intended treatment course, and absence of recurrent infection. For subgroups of interest, the proportion with clinical success in each group was compared using an unadjusted odds ratio (OR) and 95% confidence interval.

Results
Among 420 cases from 28 sites, 60.95% (128/210) of C/T- and 51.9% (109/210) of CZA-treated patients experienced clinical success. Groups were overall well-balanced by matching; however, CT-treated patients were older, more likely to have immunocompromising conditions, and to receive suboptimal dosing (Table 1). After conditional logistic regression, the adjusted OR for clinical success with C/T treatment was 1.97 (95% CI: 1.11 – 3.49; P=0.02).
Unadjusted OR for patient subgroups are listed in Table 2. Overall, the effect size was consistent across all subgroups. Key factors are highlighted in Figure 1. Significantly higher rates of clinical success were found for treatment with C/T compared to CZA for patients with pneumonia, SOFA ≤7, mechanical ventilation, and optimal dosing. Table 3 displays comparative 30-day mortality rates. Higher mortality rates were identified in both C/T- and CZA-treated patients who were critically-ill, received suboptimal dosing, and were treated within 72 hours of index culture (Table 3); rates did not vary by treatment.

Conclusion
The consistency of the results in this subgroup analysis of CACTUS reinforces the primary finding of higher rates of clinical success for patients with MDR P. aeruginosa pneumonia or bacteremia treated with C/T compared to CZA.

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