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A Multicenter, Observational Study to Compare the Effectiveness of Ceftazidime-Avibactam Versus Ceftolozane-Tazobactam for Multidrug-Resistant Pseudomonas Aeruginosa Infections in the United States (Cactus)

23 Pages Posted: 15 Jul 2024

See all articles by Ryan K. Shields

Ryan K. Shields

University of Pittsburgh

Lilian M. Abbo

Jackson Memorial Hospital

Renee Ackley

Atrium Health

Samuel L. Aitken

University of Michigan at Ann Arbor - College of Pharmacy

Benjamin Albrecht

Emory University School of Medicine

Ahmed Babiker

Emory University School of Medicine

Rachel Burgoon

Medical University of South Carolina

Renzo Cifuentes

University of Miami

Kimberly C. Claeys

University of Maryland - School of Pharmacy

Brooke N. Curry

University of Illinois at Chicago - College of Pharmacy

Kathryn E. DeSear

University of Florida Health/Shands Hospital - Department of Pharmacy

Jason C. Gallagher

Temple University - Department of Pharmacology

Esther Y. Golnabi

University of Texas at Dallas - The University of Texas Southwestern Medical Center

Alan E. Gross

University of Illinois at Chicago - College of Pharmacy

Jonathan Hand

Ochsner Health

Emily L. Heil

University of Maryland - School of Pharmacy

Krutika M. Hornback

Medical University of South Carolina

Keith S. Kaye

Rutgers University, Piscataway - Robert Wood Johnson Medical School

Trieu-Vi Khuu

University of North Carolina (UNC) at Chapel Hill

Megan E. Klatt

University of Kansas - The University of Kansas Health System

Ellen G. Kline

University of Pittsburgh

Ryan C. Kubat

University of Kansas - The University of Kansas Health System

Wesley D. Kufel

State University of New York (SUNY) - School of Pharmacy and Pharmaceutical Sciences

Jae Hyoung Lee

Johns Hopkins University School of Medicine

Alexander J. Lepak

University of Wisconsin - Madison - School of Medicine and Public Health

Ahmi Lim

University of California

Justin M. Ludwig

University of Pittsburgh Medical Center

Conan Macdougall

University of California

Anjali Majumdar

Rutgers University, Piscataway - Robert Wood Johnson Medical School

Amy J. Mathers

University of Virginia

Erin K. McCreary

University of Pittsburgh

William R. Miller

Houston Methodist Hospital

Marguerite L. Monogue

University of Texas at Dallas - The University of Texas Southwestern Medical Center

W. Justin Moore

Northwest School of Medicine

Shannon Olson

Detroit Médica Center Sinai-Grace Hospital

Jessica Oxer

Cornell University - Weill Cornell Medicine

Jeffrey C. Pearson

Brigham and Women’s Hospital

Christine Pham

University of California

Paulette Pinargote

Ochsner Health

Christopher Polk

Wake Forest University - Section on Infectious Diseases

Michael J. Satlin

Cornell University - Department of Medicine

Sarah W. Satola

Emory University School of Medicine

Sunish Shah

University of Pittsburgh Medical Center

Pranita D. Tamma

Johns Hopkins University School of Medicine

Truc T. Tran

Houston Methodist Hospital

David van Duin

University of North Carolina (UNC) at Chapel Hill - Institute for Global Health and Infectious Diseases

Mollie VanNatta

Ochsner Health

Ana Vega

Jackson Memorial Hospital

Veena Venugopalan

University of Florida

Michael P. Veve

Henry Ford Health System - Henry Ford Hospital

Walaiporn Wangchinda

University of Michigan at Ann Arbor - College of Pharmacy

Lucy S. Witt

Emory University School of Medicine

Janet Y. Wu

Cleveland Clinic

Jason M. Pogue

University of Michigan at Ann Arbor - College of Pharmacy

PRECEDENT Network

Independent

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Abstract

Background. Ceftolozane-tazobactam (C/T) and ceftazidime-avibactam (CZA) are preferred treatment options for multidrug-resistant (MDR) Pseudomonas aeruginosa infections; however, real-world comparative-effectiveness studies are lacking.

Methods. To compare the efficacy of C/T and CZA, adult patients with MDR P. aeruginosa pneumonia or bacteremia treated with C/T or CZA for >48 hours were enrolled. Patients were matched 1:1 by study site, severity of illness, time to treatment initiation, and infection type. The primary outcome was clinical success at day 30.

Findings. 420 patients were enrolled from 28 study sites; 83% and 17% had pneumonia and bacteremia, respectively. Baseline demographics, comorbidities, and severity of illness indicators were all similar between groups. Upon treatment initiation 80% (336/420) of patients were in the intensive care unit, 70% (296/420) received mechanical ventilation, and 40% (168/420) required vasopressor support. Clinical success was achieved in 61% (128/210) and 52% (109/210) of patients treated with C/T and CZA, respectively (P=0.05). By conditional logistic regression analysis, the adjusted odds ratio (aOR) of success following treatment with C/T compared to CZA was 1·97 [95% CI:1·10–3·53]. Corresponding rates of success for patients with pneumonia were 63% (110/175) and 51% (89/175), respectively (aOR=2·23 [95% CI:1·17–4·26]). There were no differences in 30- or 90-day mortality rates. Resistance developed in 22% (38/173) and 23% (40/177) of patients treated with C/T and CZA, respectively.

Interpretation. Treatment with C/T resulted in higher rates of clinical success compared to CZA for MDR P. aeruginosa pneumonia. Resistance development was common with both agents.

Funding: Investigator-initiated grant from Merck Sharp & Dohme, LLC.

Declaration of Interest: RKS has served as a consultant for AbbVie, Biomerieux, Cidara, Shionogi, Menarini, Melinta, Merck, Entasis, Utility, GlaxoSmithKline, and Venatorx, and has received investigator-initiated funding from Merck, Melinta, Shionogi, and Venatorx. LMA has served on advisory boards for Biomerieux, Roche, Pfizer, Shionogi, La Jolla/Innoviva, Ferrig, and AbbVie, and has received speaker honorarium from Gilead. SLA has served on advisory boards for Shionogi, GlaxoSmithKline, Melinta, and Basilea. AB has served on an advisory board for Beckman Coulter. RB has received travel funds from Biomerieux. KCC has served as a consultant for Biomerieux. KED has served on advisory boards for Shionogi, Spero, Melinta, Entasis, AbbVie, Melinta, Basilea, and GlaxoSmithKline, has received a speaker honorarium from MAD- ID, and has received travel funds from Society of Infectious Diseases Pharmacists where she serves as Treasurer. JCG has received honoraria from MJH, Inc where he serves as Associate Editor for Clinical Infectious Diseases, has received payment for expert testimony from German, Gallagher, & Murtagh, has served on advisory boards for Allergan, GlaxoSmithKline, Merck, Novavax, Qpex, Shionogi, and Spero. He serves as Editor in Chief for Contagion and received authorship royalties from JB Learning. ELH has served as a consultant for Wolters-Kluwer. KMH has served on a speaker’s bureau for Cepheid Diagnostics and has received travel funds from Biomerieux. KSK has served as a consultant for Merck, GlaxoSmithKline, Allecra, Shionogi, MicuRx, VenatoRx, and AbbVie. WDK has received funding from Merck and Shionogi. AM has received funding from F2G Biotech GmbH. EKM has served as a consultant for Abbvie, Merck, Basilea, Shionogi, Melinta, Ferring, Cidara, Entasis, LabSimply, Pfizer, and GlaxoSmithKline, received speaker honorarium from GlaxoSmithKline, Shionogi, and Pfizer, and has served as a safety monitor for the SNAP Trial and DMID. She is President Elect for the Society of Infectious Diseases Pharmacists. WRM has received funding from the NIH and royalties from UpToDate. JMP has served as a consultant for Merck, Shionogi, Melinta, Entasis, GlaxoSmithKline, and VenatoRx. He has received investigator-initiated funding from Merck, and has research grants from Merck, Shionogi, and Melinta. MJS has received funding from Merck, Biomerieux, and Selux Diagnostics, has served as a consultant from Shionogi, and has served on an advisory board for AbbVie. DV has received funding from Merck, has served as a consultant for Utility, Shionogi, Merck, Union, Roche, and Qpex, has received honoraria from Pfizer, Entasis, and Clinical Care Options, has received fees from the British Society of Antimicrobial Chemotherapy and Universidade Federal do Rio Grande do Sul. MV has served on an advisory board for Shionogi. VV has received funding from the Florida Department of Health, has received honoraria from the American College of Clinical Pharmacy, the American Society of Health-System Pharmacists, ID Week, the American Society of Microbiologists, and Merck, has received payment for expert testimony from Silver, Golub, & Teitell, LLP. All other authors have nothing to declare.

Ethical Approval: The CACTUS study was approved by local Institutional Review Boards at each participating site. The University of Pittsburgh was also approved as a coordinating center by local IRB, STUDY22020151.

Keywords: Pseudomonas aeruginosa, pneumonia, ceftolozane-tazobactam, ceftazidime-avibactam, Gram negatives, multidrug resistance

Suggested Citation

Shields, Ryan K. and Abbo, Lilian M. and Ackley, Renee and Aitken, Samuel L. and Albrecht, Benjamin and Babiker, Ahmed and Burgoon, Rachel and Cifuentes, Renzo and Claeys, Kimberly C. and Curry, Brooke N. and DeSear, Kathryn E. and Gallagher, Jason C. and Golnabi, Esther Y. and Gross, Alan E. and Hand, Jonathan and Heil, Emily L. and Hornback, Krutika M. and Kaye, Keith S. and Khuu, Trieu-Vi and Klatt, Megan E. and Kline, Ellen G. and Kubat, Ryan C. and Kufel, Wesley D. and Lee, Jae Hyoung and Lepak, Alexander J. and Lim, Ahmi and Ludwig, Justin M. and Macdougall, Conan and Majumdar, Anjali and Mathers, Amy J. and McCreary, Erin K. and Miller, William R. and Monogue, Marguerite L. and Moore, W. Justin and Olson, Shannon and Oxer, Jessica and Pearson, Jeffrey C. and Pham, Christine and Pinargote, Paulette and Polk, Christopher and Satlin, Michael J. and Satola, Sarah W. and Shah, Sunish and Tamma, Pranita D. and Tran, Truc T. and van Duin, David and VanNatta, Mollie and Vega, Ana and Venugopalan, Veena and Veve, Michael P. and Wangchinda, Walaiporn and Witt, Lucy S. and Wu, Janet Y. and Pogue, Jason M. and Network, PRECEDENT, A Multicenter, Observational Study to Compare the Effectiveness of Ceftazidime-Avibactam Versus Ceftolozane-Tazobactam for Multidrug-Resistant Pseudomonas Aeruginosa Infections in the United States (Cactus). Available at SSRN: https://ssrn.com/abstract=4891722 or http://dx.doi.org/10.2139/ssrn.4891722

Ryan K. Shields

University of Pittsburgh ( email )

135 N Bellefield Ave
Pittsburgh, PA 15260
United States

Lilian M. Abbo

Jackson Memorial Hospital ( email )

USA

Renee Ackley

Atrium Health ( email )

Charlotte, NC
United States

Samuel L. Aitken

University of Michigan at Ann Arbor - College of Pharmacy ( email )

Benjamin Albrecht

Emory University School of Medicine ( email )

Ahmed Babiker

Emory University School of Medicine ( email )

Rachel Burgoon

Medical University of South Carolina ( email )

Renzo Cifuentes

University of Miami ( email )

Kimberly C. Claeys

University of Maryland - School of Pharmacy ( email )

Brooke N. Curry

University of Illinois at Chicago - College of Pharmacy ( email )

Kathryn E. DeSear

University of Florida Health/Shands Hospital - Department of Pharmacy ( email )

PO Box 117165, 201 Stuzin Hall
Gainesville, FL 32610-0496
United States

Jason C. Gallagher

Temple University - Department of Pharmacology ( email )

Esther Y. Golnabi

University of Texas at Dallas - The University of Texas Southwestern Medical Center ( email )

Alan E. Gross

University of Illinois at Chicago - College of Pharmacy ( email )

Jonathan Hand

Ochsner Health ( email )

2700 Napoleon Ave
New Orleans, LA
United States

Emily L. Heil

University of Maryland - School of Pharmacy ( email )

Krutika M. Hornback

Medical University of South Carolina ( email )

Keith S. Kaye

Rutgers University, Piscataway - Robert Wood Johnson Medical School ( email )

Trieu-Vi Khuu

University of North Carolina (UNC) at Chapel Hill ( email )

Megan E. Klatt

University of Kansas - The University of Kansas Health System ( email )

Kansas City, KS
United States

Ellen G. Kline (Contact Author)

University of Pittsburgh ( email )

135 N Bellefield Ave
Pittsburgh, PA 15260
United States

Ryan C. Kubat

University of Kansas - The University of Kansas Health System ( email )

Kansas City, KS
United States

Wesley D. Kufel

State University of New York (SUNY) - School of Pharmacy and Pharmaceutical Sciences ( email )

Jae Hyoung Lee

Johns Hopkins University School of Medicine ( email )

Alexander J. Lepak

University of Wisconsin - Madison - School of Medicine and Public Health ( email )

Ahmi Lim

University of California ( email )

Justin M. Ludwig

University of Pittsburgh Medical Center ( email )

Conan Macdougall

University of California ( email )

Anjali Majumdar

Rutgers University, Piscataway - Robert Wood Johnson Medical School ( email )

Amy J. Mathers

University of Virginia ( email )

Erin K. McCreary

University of Pittsburgh ( email )

135 N Bellefield Ave
Pittsburgh, PA 15260
United States

William R. Miller

Houston Methodist Hospital ( email )

6621 Fannin St
Houston, TX 77030
United States

Marguerite L. Monogue

University of Texas at Dallas - The University of Texas Southwestern Medical Center ( email )

W. Justin Moore

Northwest School of Medicine ( email )

Shannon Olson

Detroit Médica Center Sinai-Grace Hospital ( email )

Jessica Oxer

Cornell University - Weill Cornell Medicine ( email )

1300 York Avenue
New York, NY 10065
United States

Jeffrey C. Pearson

Brigham and Women’s Hospital ( email )

Christine Pham

University of California ( email )

Paulette Pinargote

Ochsner Health ( email )

Christopher Polk

Wake Forest University - Section on Infectious Diseases ( email )

Michael J. Satlin

Cornell University - Department of Medicine ( email )

1300 York Avenue
P.O. Box 24144
New York, NY 10065
United States

Sarah W. Satola

Emory University School of Medicine ( email )

Sunish Shah

University of Pittsburgh Medical Center ( email )

Pranita D. Tamma

Johns Hopkins University School of Medicine ( email )

Truc T. Tran

Houston Methodist Hospital ( email )

6621 Fannin St
Houston, TX 77030
United States

David Van Duin

University of North Carolina (UNC) at Chapel Hill - Institute for Global Health and Infectious Diseases ( email )

Mollie VanNatta

Ochsner Health ( email )

Ana Vega

Jackson Memorial Hospital ( email )

USA

Veena Venugopalan

University of Florida ( email )

PO Box 117165, 201 Stuzin Hall
Gainesville, FL 32610-0496
United States

Michael P. Veve

Henry Ford Health System - Henry Ford Hospital ( email )

Detroit
United States

Walaiporn Wangchinda

University of Michigan at Ann Arbor - College of Pharmacy ( email )

Lucy S. Witt

Emory University School of Medicine ( email )

Janet Y. Wu

Cleveland Clinic ( email )

9500 Euclid Ave.
Cleveland, OH 44195
United States

Jason M. Pogue

University of Michigan at Ann Arbor - College of Pharmacy ( email )

PRECEDENT Network

Independent

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