Abstract
Abstract Background Ceftolozane-tazobactam (CT) and ceftazidime-avibactam (CZA) are front-line agents for treatment of multidrug-resistant (MDR) Pseudomonas aeruginosa; however, real-world comparative-effectiveness data are lacking. Methods CACTUS is a retrospective, matched, multicenter study to compare the efficacy of CT and CZA among patients with bacteremia or pneumonia due to MDR P. aeruginosa. CT and CZA patients were matched 1:1 within each study site by the presence/absence of septic shock/severe sepsis, infection site, and time to treatment initiation. The primary outcome was clinical success at day 30 defined as survival, resolution of signs/symptoms with the intended treatment course, and absence of recurrent infections. Patients with cystic fibrosis or COVID-19 infection within 90 days were excluded. Results 234 patients were included from 20 sites. Patient demographics, severity of illness, infection types, and treatment durations were similar for patients treated with CT or CZA (Table 1). The overall median age was 61 years, 61% were male, and the median Charlson score was 5. At study drug initiation, 77% of patients were in the ICU, 67% received mechanical ventilation and the median SOFA score was 7. 79% of patients were treated for pneumonia; 72% of which occurred in ventilated patients. The median time from index culture to treatment initiation was 72 hours in both groups; CT patients were more likely to receive a prolonged infusion of ≥3 hours (36% vs 19%; P=0.005). Clinical success occurred in 62% and 55% of patients receiving CT and CZA, respectively (P=0.35; Table 1). Corresponding rates of success for pneumonia were 63% and 52%, respectively (P=0.13; Figure 1). All-cause, 30-day mortality rate was 20% and 19%, respectively. Microbiologic failures, recurrent infections, and development of resistance within 90 days were similar between groups. Time to a composite endpoint of recurrent infection or death within 90 days was similar between groups in the overall analysis and the subgroup of patients with pneumonia (Figure 2). Conclusion In this interim analysis of the CACTUS study, patients treated with CT and CZA had similar clinical outcomes. We plan to continue enrollment up to 420 patients to detect if any differences exist in the efficacy of CT and CZA for MDR P. aeruginosa infections. Disclosures 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 Lilian M. Abbo, MD, MBA, Ferring: Advisor/Consultant|Pfizer: Advisor/Consultant|Regeneron: Grant/Research Support|Shionogi: Advisor/Consultant Ahmed Babiker, MBBS, Roche: Advisor/Consultant Kimberly C. Claeys, PharmD, Abbvie: Advisor/Consultant|bioMérieux Inc.: Advisor/Consultant|bioMérieux Inc.: Speaker|La Jolla Pharmaceuticals: Advisor/Consultant|Melinta Therapeutics: Advisor/Consultant Jason C. Gallagher, PharmD, Entasis: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Qpex: Advisor/Consultant|Shionogi: Advisor/Consultant|Spero: Advisor/Consultant Emily L. Heil, PharmD, MS, Wolters Kluwer-LexiComp: Advisor/Consultant Wesley D. Kufel, PharmD, BCPS, BCIDP, AAHIVP, Merck and Co: Grant/Research Support Amy Mathers, MD, D(ABMM), Merck: Advisor/Consultant Erin K. McCreary, PharmD, Abbvie: Advisor/Consultant|Ferring: Advisor/Consultant|GSK: Honoraria|La Jolla (Entasis): Advisor/Consultant|LabSimply: Advisor/Consultant|Merck: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Honoraria Christopher Polk, MD, ViiVHealthcare: Job change to work for ViiV as Medical Director Michael J. Satlin, MD, AbbVie: IDMC member|Biomerieux: Grant/Research Support|Merck: Grant/Research Support|SNIPRBiome: Grant/Research Support Michael Veve, PharmD, MPH, National Institutes of Health: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support jason M. Pogue, PharmD, AbbVie: Advisor/Consultant|Entasis: Advisor/Consultant|Ferring: Advisor/Consultant|GSK: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Qpex: Advisor/Consultant|Shionogi: Advisor/Consultant