Effectiveness of ceftazidime–avibactam versus ceftolozane–tazobactam for multidrug-resistant Pseudomonas aeruginosa infections in the USA (CACTUS): a multicentre, retrospective, observational study - 17/12/24

Doi : 10.1016/S1473-3099(24)00648-0

Ryan K Shields, PharmD ^a, Lilian M Abbo, ProfMD ^b,^c, Renee Ackley, PharmD ^e, Samuel L Aitken, PharmD ^f, Benjamin Albrecht, PharmD ^g, Ahmed Babiker, MBBS ^g, Rachel Burgoon, PharmD ^h, Renzo Cifuentes, MD ⁱ, Kimberly C Claeys, PharmD ^j, Brooke N Curry, PharmD ^k, Kathryn E DeSear, PharmD ^l, Jason C Gallagher, ProfPharmD ^m, Esther Y Golnabi, PharmD ⁿ, Alan E Gross, PharmD ^k, Jonathan Hand, MD ^o, Emily L Heil, ProfPharmD ^j, Krutika M Hornback, PharmD ^h, Keith S Kaye, ProfMD ^p, Trieu-Vi Khuu, BS ^q, Megan E Klatt, PharmD ^r, Ellen G Kline, MS ^a,⁎ , Ryan C Kubat, DO ^r, Wesley D Kufel, PharmD ^s, Jae Hyoung Lee, MD ^t, Alexander J Lepak, MD ^u, Ahmi Lim, PharmD ^v, Justin M Ludwig, MA ^w, Conan Macdougall, ProfPharmD ^v, Anjali Majumdar, MD ^p, Amy J Mathers, MD ^x, Erin K McCreary, PharmD ^a, William R Miller, MD ^y, Marguerite L Monogue, PharmD ⁿ, W Justin Moore, PharmD ^z, Shannon Olson, PharmD ^aa, Jessica Oxer, BS ^ab, Jeffrey C Pearson, PharmD ^ac, Christine Pham, PharmD ^ad, Paulette Pinargote, MD ^ae, Christopher Polk, MD ^e, Michael J Satlin, MD ^ab, Sarah W Satola, PhD ^g, Sunish Shah, PharmD ^w, Pranita D Tamma, MD ^t, Truc T Tran, MD ^y, David van Duin, ProfMD ^q, Mollie VanNatta, PharmD ^ae, Ana Vega, PharmD ^d, Veena Venugopalan, PharmD ^ai, Michael P Veve, PharmD ^af,^ag, Walaiporn Wangchinda, MD ^f, Lucy S Witt, MD ^g, Janet Y Wu, PharmD ^ah, Jason M Pogue, ProfPharmD ^f
on behalf of the
PRECEDENT Network^{^†}
Members of the PRECEDENT Network are listed at the end of this Article
Ryan K Shields, Lilian M Abbo, Renee Ackley, Samuel L Aitken, Benjamin Albrecht, Ahmed Babiker, Rachel Burgoon, Renzo Cifuentes, Kimberly C Claeys, Brooke N Curry, Kathryn E DeSear, Jason C Gallagher, Esther Y Golnabi, Alan E Gross, Jonathan Hand, Emily L Heil, Krutika M Hornback, Keith S Kaye, Trieu-Vi Khuu, Megan E Klatt, Ellen G Kline, Ryan C Kubat, Wesley D Kufel, Jae Hyoung Lee, Alexander J Lepak, Ahmi Lim, Justin M Ludwig, Conan Macdougall, Anjali Majumdar, Amy J Mathers, Erin K McCreary, William R Miller, Marguerite L Monogue, W Justin Moore, Shannon Olson, Jessica Oxer, Jeffrey C Pearson, Christine Pham, Paulette Pinargote, Christopher Polk, Michael J Satlin, Sarah W Satola, Sunish Shah, Pranita D Tamma, Truc T Tran, David van Duin, Mollie VanNatta, Ana Vega, Veena Venugopalan, Michael P Veve, Walaiporn Wangchinda, Lucy S Witt, Janet Y Wu, Jason M Pogue

^a Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, PA, USA
^b Division of Infectious Diseases, University of Miami Miller School of Medicine, Miami, FL, USA
^c Department of Infection Control and Antimicrobial Stewardship, Jackson Memorial Hospital, Miami, FL, USA
^d Department of Pharmacy and Antimicrobial Stewardship, Jackson Memorial Hospital, Miami, FL, USA
^e Atrium Health, Charlotte, NC, USA
^f University of Michigan College of Pharmacy, Ann Arbor, MI, USA
^g Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA, USA
^h Department of Pharmacy, Medical University of South Carolina (MUSC) Health, Charleston, SC, USA
ⁱ University of Miami, Miller School of Medicine, Miami, FL, USA
^j University of Maryland School of Pharmacy, Baltimore, MD, USA
^k University of Illinois Chicago College of Pharmacy, Chicago, IL, USA
^l University of Florida Health Shands Hospital, Gainesville, FL, USA
^m Temple University School of Pharmacy, Philadelphia, PA, USA
ⁿ University of Texas Southwestern Medical Center, Dallas, TX, USA
^o Ochsner Health, New Orleans, LA, USA
^p Division of Allergy, Immunology, and Infectious Diseases, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA
^q Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC, USA
^r The University of Kansas Health System, Kansas City, KS, USA
^s Binghamton University School of Pharmacy and Pharmaceutical Sciences, Binghamton, NY, USA
^t Johns Hopkins University School of Medicine, Baltimore, MD, USA
^u University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
^v Department of Clinical Pharmacy, University of California, San Francisco, CA, USA
^w University of Pittsburgh Medical Center, Pittsburgh, PA, USA
^x University of Virginia, Charlottesville, VA, USA
^y Division of Infectious Diseases, Houston Methodist Hospital, Houston, TX, USA
^z Department of Antimicrobial Stewardship, Northwestern Medicine, Chicago, IL, USA
^aa Sinai-Grace Hospital Detroit Medical Center, Detroit, MI, USA
^ab Division of Infectious Diseases, Weill Cornell Medicine, New York, NY, USA
^ac Department of Pharmacy, Brigham and Women’s Hospital, Boston, MA, USA
^ad Division of Infectious Diseases, Department of Medicine, and Department of Pharmaceutical Services, University of California, Los Angeles, CA, USA
^ae Ochsner Louisiana State University Health, Shreveport, LA, USA
^af Department of Pharmacy, Henry Ford Hospital, Detroit, MI, USA
^ag Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA
^ah Department of Pharmacy, Cleveland Clinic, Cleveland, OH, USA
^ai University of Florida College of Pharmacy, Gainesville, FL, USA

^*Correspondence to: Ms Ellen G Kline, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, PA 15213, USADivision of Infectious DiseasesUniversity of PittsburghPittsburghPA5213USA

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Summary

Background

Ceftolozane–tazobactam and ceftazidime–avibactam are preferred treatment options for multidrug-resistant Pseudomonas aeruginosa infections; however, real-world comparative effectiveness studies are scarce. Pharmacokinetic and pharmacodynamic differences between the agents might affect clinical response rates. We aimed to compare the effectiveness of ceftolozane–tazobactam and ceftazidime–avibactam for treatment of invasive multidrug-resistant P aeruginosa infections.

Methods

This multicentre, retrospective, observational study was conducted at 28 hospitals in the USA between Jan 1, 2016, and Dec 31, 2023. Eligible patients were adults (age ≥18 years old) with microbiologically confirmed multidrug-resistant P aeruginosa pneumonia or bacteraemia treated with ceftolozane–tazobactam or ceftazidime–avibactam for more than 48 h. Patients were matched (1:1) by study site, severity of illness, time to treatment initiation (≤72 h or >72 h), and infection type. The primary outcome was clinical success at day 30, which was defined as survival, resolution of signs and symptoms of infection with the intended treatment course, and the absence of recurrent infection due to P aeruginosa. Secondary outcomes included all-cause mortality and development of resistance to study drug.

Findings

420 eligible patients were included (210 in each treatment group), of whom 350 (83%) had pneumonia and 70 (17%) had bacteraemia. Baseline demographics, comorbidities, and severity of illness indicators were similar between groups. On treatment initiation, 336 (80%) patients were in the intensive care unit, 296 (70%) were receiving mechanical ventilation, and 168 (40%) required vasopressor support. Clinical success was observed in 128 (61%) of 210 patients treated with ceftolozane–tazobactam and 109 (52%) of 210 patients treated with ceftazidime–avibactam. By conditional logistic regression analysis, the adjusted odds ratio (aOR) of success after treatment with ceftolozane–tazobactam compared with ceftazidime–avibactam was 2·07 (95% CI 1·16–3·70). For patients with pneumonia, clinical success was observed in 110 (63%) of 175 patients in the ceftolozane–tazobactam group and 89 (51%) of 175 patients in the ceftazidime–avibactam group (aOR 2·34 [95% CI 1·22–4·47]). Among patients with bacteraemia, rates of clinical success were 51% (18 of 35 patients) for patients treated with ceftolozane–tazobactam and 57% (20 of 35 patients) for those treated with ceftazidime–avibactam (0·76 [0·23–2·57]). There were no significant differences between groups in 30-day or 90-day mortality. Among patients whose baseline isolates were tested for susceptibility, resistance developed in 22% (38 of 173) of patients treated with ceftolozane–tazobactam and 23% (40 of 177) of patients treated with ceftazidime–avibactam.

Interpretation

Treatment with ceftolozane–tazobactam resulted in higher rates of clinical success compared with ceftazidime–avibactam for invasive infections due to multidrug-resistant P aeruginosa. Differences were driven by improved response rates for patients with pneumonia who were treated with ceftolozane–tazobactam. There were no significant differences between study groups with respect to all-cause mortality; treatment-emergent resistance was common with both agents.