Editor’s note:
Multi-drug resistant organisms (MDRO) are commonly found in bacteria such as Enterobacteriaceae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. In recent years, the emergence and spread of MDRO have posed numerous challenges in clinical practice, with limited treatment options being one of the thorny issues. Beta-lactamase inhibitor combinations are essential in the clinical management of MDRO infections, among which Ceftolozane-Tazobactam (CT) and Ceftazidime-Avibactam (CZA) are frontline drugs for treating Multi-drug Resistant Pseudomonas aeruginosa (MDR-PA) infections. However, there is a lack of sufficient research data comparing the efficacy of these two drugs. At the recent IDWeek 2023 congress held in the United States, researchers presented a multicenter observational study (Abstract No: 1109) that compared the efficacy of CT and CZA in treating MDR-PA-induced bacteremia or pneumonia. We invited Dr. Jun-yan Qu from West China Hospital, Sichuan University, to introduce and comment on this study.
Research Introduction
Ceftolozane-Tazobactam (CT) and Ceftazidime-Avibactam (CZA) are frontline drugs for treating multi-drug-resistant Pseudomonas aeruginosa (MDR-PA). However, there is a lack of real-world efficacy comparison data.
CACTUS is a retrospective, matched-pair, multicenter study aimed at comparing the efficacy of CT and CZA in patients with MDR-PA-induced bacteremia or pneumonia. Patients receiving CT and CZA were matched at each study center in a 1:1 ratio based on the presence of septic shock/severe sepsis, site of infection, and the time of treatment initiation. The primary outcome of the study was clinical success on day 30, defined as survival, resolution of signs/symptoms within the expected course, and no recurrent infection. Patients with cystic fibrosis or COVID-19 infection within 90 days were excluded.
A total of 234 patients from 20 regions were included. The demographic characteristics, disease severity, infection type, and duration of treatment were related to patients receiving CT or CZA. The overall median age was 61 years, 61% were male, and the median Charlson score was 5. At the start of the study drugs, 77% of patients were admitted to the ICU, 67% received mechanical ventilation, and the median SOFA score was 7. 79% of patients received treatment for pneumonia, with 72% occurring in patients receiving mechanical ventilation. In both groups, the median time from culture to starting treatment was 72 hours.
In patients receiving CT and CZA, the clinical success rates were 54.9% and 48.4%, respectively (P=0.30); 30-day all-cause mortality rates were 25.5% and 24.2%, respectively (P=0.89). The respective success rates for treating MDR-PA pneumonia were 56.3% and 48.3% (P=0.26), and the 30-day all-cause mortality rates were 25.6% and 23.4% (P=0.77). Microbiological failures, recurrent infections, and 90-day resistance progression were similar between the two groups. The time to reach the composite endpoint of recurrent infection or death within 90 days was similar in the overall analysis and the pneumonia subgroup.
Dr. Jun-yan Qu’s Commentary
CT is a new generation β-lactam/beta-lactamase inhibitor (BL-BLI) combination. Among them, Ceftolozane is a new third-generation cephalosporin antibiotic that enhances its activity against Pseudomonas aeruginosa (PA) by modifying the structure of the R2 side chain of ceftazidime to increase its inhibition of PBP3 and its affinity for PBP1b and PBP1c. Ceftolozane is not a specific substrate for drug efflux systems and is not affected by OprD deficiency, making it highly active against drug-resistant Pseudomonas aeruginosa (DTR-PA). Both CT and CZA are recommended for the treatment of DTR-PA infections. The mid-term analysis of this real-world clinical study showed that CT and CZA had similar overall clinical treatment success rates, mortality rates, and recurrent infection rates in patients with MDR-PA bacteremia or pneumonia. Future studies will further analyze clinical efficacy, resistance mechanisms, and the treatment outcomes in special populations. Currently, the domestic and international resistance situation is severe, and the choice of antibacterial drugs is limited. No single antibacterial drug can address all clinical infection problems. Real-world clinical research on different antibacterial drugs will provide more data for clinical decision-making.
References
Ryan K. Shields, et al. 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). IDWeek 2023; abstract 1109.
Infectious Diseases Center, West China Hospital, Sichuan University
