Editor’s Note: Ceftolozane-tazobactam is a new BL-BLI combination drug, and ceftolozane is a third-generation cephalosporin antibiotic, and tazobactam is a beta-lactamase inhibitor. At the recent 2023 IDWeek in the United States, Dr. Ryan K. Shields from the University of Pittsburgh presented a real-world observational study assessing the effectiveness of ceftolozane-tazobactam compared to ceftazidime-avibactam in treating multidrug-resistant Pseudomonas aeruginosa (MDR-PA). He shared his insights in an interview with “ Infectious Disease Frontline”.
Dr. Ryan K. Shields
Infectious Diseases pharmacist, Associate Professor
University of Pittsburgh Medical Center (UPMC)
Study Introduction
A multicenter, observational study to compare the effectiveness of eftazidim vibactam versus eftolozane azobactam for multidrug-resistant Pseudomonas aeruginosa infections in the United States (CACTUS) (Abstract No: 1109)
Background: Ceftolozane-tazobactam (CT) and ceftazidime-avibactam (CZA) are first-line drugs for the treatment of multidrug-resistant (MDR) Pseudomonas aeruginosa, but there is a lack of real-world comparative efficacy data.
Methods: CACTUS is a retrospective, matched, multicenter study aimed at comparing the efficacy of CT and CZA in patients with bacteremia or pneumonia caused by MDR-PA. Patients receiving CT and CZA were matched at a 1:1 ratio at each study center based on the presence of septic shock/severe sepsis, site of infection, and time of initiating treatment. The primary outcome of the study was clinical success at day 30, defined as survival, resolution of signs/symptoms within the expected course, and no recurrence of infection. Patients with cystic fibrosis or COVID-19 infection within 90 days were excluded.
Results: A total of 234 patients from 20 regions were included. Demographic characteristics, disease severity, infection type, and treatment duration were similar between patients receiving CT and CZA. The overall median age was 61 years, 61% were male, and the median Charlson score was 5. At the initiation of the study drugs, 77% of patients were admitted to the ICU, 67% received mechanical ventilation, and the median SOFA score was 7. A total of 79% of patients received treatment for pneumonia, with 72% occurring in patients receiving mechanical ventilation. The median time from culture to initiating 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% (P=0.89). The corresponding success rates for treating MDR-PA pneumonia were 56.3% and 48.3% (P=0.26), with 30-day all-cause mortality rates of 25.6% and 23.4% (P=0.77). Microbiological failure, recurrent infection, and 90-day resistance progression were similar between the two groups. Time to the composite endpoint of recurrent infection or death within 90 days was similar in the overall analysis and in the pneumonia subgroup.
Conclusion: In the mid-term analysis of the CACTUS study, patients receiving CT and CZA treatment had similar clinical outcomes. We plan to recruit up to 420 patients to evaluate whether there are any differences in the efficacy of CT and CZA in the treatment of MDR Pseudomonas aeruginosa infection.
Researchers Speak
IDF: Good afternoon. Your presentation was excellent, and we appreciate you granting us this interview. You have conducted extensive research in the field of multi-drug resistance infections. Could you give us an overview of your recent work and how it deepens our understanding of the diagnosis and treatment of infectious diseases?
Dr. Shields: Yes, I think one of the biggest challenges in the management of antibiotic resistance and infections caused by resistant gram-negative bacteria is the lack of real-world data. This is particularly true for comparing real-world data of new treatment regimens. We don’t have a lot of data, so our focus has been on comparing new treatment options and conducting comparative effectiveness studies, designing them to achieve meaningful clinical outcomes that impact real-world patients while controlling for many of the residual confounding factors that have limited previous research. Therefore, we conducted the CACTUS study comparing ceftolozane-tazobactam to ceftazidime-avibactam in the treatment of multidrug-resistant Pseudomonas aeruginosa, and we presented preliminary results at this year’s IDWeek.
IDF: Your research is of great value in addressing antibiotic resistance. How do you view the practical applications of your research findings in helping physicians formulate treatment strategies for drug-resistant infections, especially in the case of multi-drug resistance infections?
Dr. Shields: We have learned from the literature that infections caused by multi-drug-resistant organisms lead to worse patient outcomes, including higher morbidity and mortality rates. Therefore, as clinical service providers, we have a responsibility to select the best therapy for these patients who are at high risk of adverse outcomes. We don’t have many large randomized clinical trials to tell us what might be the best treatment, so we must rely on real-world effectiveness studies to understand these issues. I believe that through these real-world studies, we will eventually be able to answer these questions and select the optimal treatment for patients.
IDF: Looking ahead to the future, what progress and innovations do you see in the field of infectious diseases? How should professionals prepare to address these changes?
Dr. Shields: I think we are continually seeing new advancements and innovations, including the discovery of new molecules and the application of rapid diagnostic tests. Many of these new technologies are advancing our clinical practice. Therefore, by continuing to develop new antibiotics to overcome known resistance mechanisms and being able to detect them in clinical microbiology laboratories, this will ultimately have a significant impact on patient care.
