312. Impact of Patient Subgroups on the Efficacy of Ceftazidime-Avibactam (CZA) versus Ceftolozane-Tazobactam (C/T) for Multidrug-resistant (MDR) <i>Pseudomonas aeruginosa</i> infections in the United States (CACTUS)

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 &amp; 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

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Publication Details

Journal
Open Forum Infectious Diseases
Published
2025-01-29
DOI
https://doi.org/10.1093/ofid/ofae631.102
Primary Topic
Antibiotic Resistance in Bacteria
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article
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0.00
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article

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)

Michael J. Satlin, Lucy S Witt, Marguerite L. Monogue, Walaiporn Wangchinda et al.
Open Forum Infectious Diseases
Antibiotic Resistance in Bacteria
article

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)

Michael J. Satlin, Lucy S Witt, Marguerite L. Monogue, Walaiporn Wangchinda, Ellen G Kline, Keith S. Kaye, Michael P. Veve, Sarah W. Satola, William R. Miller, Conan MacDougall, Sarah B. Green, Pranita D. Tamma, Jason C Gallagher, Erin K McCreary, Emily L. Heil, Sunish Shah, Mollie VanNatta, Christine Pham, Wesley D. Kufel, Rachel Burgoon, Esther Y. Golnabi, Ana Vega, Amy J. Mathers, R Kubát, Veena Venugopalan, Alan E. Gross, Shannon Olson, Truc Cecilia Tran, Christopher Polk, Jeffrey C Pearson, David van Duin, Lilian M. Abbo, Krutika Mediwala Hornback, Megan Klatt, Kimberly C. Claeys, Renee Ackley, Jason M. Pogue, Paulette Pinargote, Benjamin Albrecht, W Justin Moore, Ryan K. Shields, Samuel L Aitken, Jessica Oxer, Anjali Majumdar, Jae Hyoung Lee, Alexander J. Lepak, Brooke N Curry, Ahmed Babiker, Trieu-Vi Khuu, Kate DeSear
article en

Abstract

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 &amp; 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

Open Forum Infectious DiseasesVol. 12(Supplement_1)
Rutgers, The State University of New Jersey (US), University of North Carolina at Chapel Hill (US), Eugene Applebaum College of Pharmacy and Health Sciences (US), Binghamton University (US), University of Maryland, Baltimore (US), Brigham and Women's Hospital (US), Houston Methodist (US), UF Health Shands Hospital (US), University of Wisconsin–Madison (US), Johns Hopkins University (US), University of Miami (US), University of Kansas (US), Emory University (US), Medical University of South Carolina (US), University of California, Los Angeles (US), University of Pittsburgh (US), University of California, San Francisco (US), Cornell University (US), University of Michigan (US), Detroit Medical Center (US), Emory University Hospital (US), Sinai Grace Hospital (US), Johnson University (US), Jackson Memorial Hospital (US), University of Florida (US), University of Illinois Chicago (US), Jackson Health System (US), Presbyterian Hospital (US), Southwestern Medical Center (US), Atrium Medical Cente (US), Michigan Medicine (US), UPMC Presbyterian (US), University of Pittsburgh Medical Center (US), Northwestern Medicine (US), Weill Cornell Medicine (US), University of Virginia (US), University of Baltimore (US), Louisiana State University Health Sciences Center Shreveport (US), Temple University (US), The University of Texas Southwestern Medical Center (US), Florida College (US)
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