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

Abstract

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.

Funding: Merck Sharp & Dohme.