Study supports ceftolozane-tazobactam over ceftazidime-avibactam for multidrug-resistant Pseudomonas
A multicenter comparative effectiveness study found that treatment with ceftolozane-tazobactam resulted in higher rates of clinical success than ceftazidime-avibactam for invasive infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa, researchers reported yesterday in The Lancet Infectious Diseases.
The study, conducted at 28 US hospitals from 2016 through 2023, compared outcomes in 420 adult patients with microbiologically confirmed MDR P aeruginosa pneumonia or bacteremia who were treated with ceftolozane-tazobactam or ceftazidime-avibactam for more than 48 hours and matched 1:1 by study site, severity of illness, time to treatment initiation, and infection type. Although both drugs are considered first-line therapies for MDR P aeruginosa infections and have been shown to be more effective than older agents, they have not been compared in real-world observational studies.
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.
Clinical success was observed in 168 (61%) of 210 patients treated with ceftolozane-tazobactam and 109 (52%) of 210 patients treated with ceftazidime-avibactam, and the adjusted odds ratio [aOR] of success after treatment with ceftolozane-tazobactam compared with ceftazidime-avibactam was 2.07 (95% confidence interval [CI], 1.16 to 3.70). The results were exclusively driven by higher clinical success in patients with pneumonia (aOR, 2.34; 95% CI, 1.22 to 4.47), as no difference was seen in clinical success rates among patients with bacteremia.
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% of patients treated with ceftolozane-tazobactam and 23% of patients treated with ceftazidime-avibactam.