Ceftazidime/Avibactam versus Polymyxin B in the Challenge of Carbapenem-Resistant Pseudomonas aeruginosa Infection

Abstract

Purpose

Ceftazidime/avibactam (CAZ/AVI) monotherapy and polymyxin B-based combination therapy are currently two treatment options for patients with carbapenem-resistant Pseudomonas aeruginosa (CRPA) infection; however, few studies have contrasted the relative efficacy of the two antibiotic regimens. The purpose of this study was to compare the effectiveness of CAZ/AVI and polymyxin B against CRPA infection and analyze the independent predictors of 30-day mortality or survival.

Patients and Methods

This single-center retrospective observational study included patients with CRPA infection treated with CAZ/AVI or polymyxin B between January 2018 and December 2020. The primary outcomes were the 14-day and 30-day mortality. The secondary outcomes were in-hospital mortality and bacterial clearance. Baseline characteristics and outcomes were compared between the two groups, and COX regression analysis was used to identify predictors of 30-day mortality.

Results

A total of 136 patients with CRPA infection were enrolled, including 51 patients in the CAZ/AVI group and 85 patients in the polymyxin B group. The 14-day mortality (5.9% vs 27.1%, p=0.002), 30-day mortality (13.7% vs 47.1%, p<0.001) and in-hospital mortality (29.4% vs 60.0%, p=0.001) in the CAZ/AVI group were significantly lower than the polymyxin B group. The bacterial clearance rate (45.1% vs 12.9%, p<0.001) in the CAZ/AVI group were higher than in the polymyxin B group. After adjustment by propensity score matching, the CAV/AVI group still had lower 30-day mortality (14.3% vs 42.9%, p=0.018) and higher bacterial clearance rate (42.9% vs 14.3%, p=0.018) than the polymyxin B group. The multivariate COX analysis showed that the age was identified as independent predictor of 30-day mortality while CAZ/AVI therapy and central venous catheterization emerged as independent predictors of 30-day survival.

Conclusion

CAZ/AVI therapy was superior to polymyxin B therapy for patients with CRPA infection, and provided significant survival benefits, but further larger studies were needed to substantiate our findings.

Keywords:

• carbapenem-resistant Pseudomonas aeruginosa
• ceftazidime/avibactam
• polymyxin B
• effectiveness
• mortality

Abbreviations

CAZ/AVI, Ceftazidime/avibactam; CRPA, Carbapenem-resistant Pseudomonas aeruginosa; PSM, Propensity score matching; CRGNB, Carbapenem-resistant gram-negative bacteria; HAI, Healthcare associated infections; ECDC, European Centers for Disease Control and Prevention; CHINET, China Antimicrobial Surveillance Network; CRRT, Continuous renal replacement therapy; PICCO, Pulse indicator continuous cardiac output; ECMO, Extracorporeal membrane oxygenation; CCI, Charlson comorbidity index; aCCI, age-adjusted Charlson comorbidity index; IDSA, Infectious Diseases Society of America; CLSI, Clinical and Laboratory Standards Institute; MIC, Minimum inhibitory concentration; IQR, Interquartile range; MDR, Multidrug-resistant; XDR, Extensively drug-resistant; SOT, solid organ transplantation; HSCT, Hematopoietic stem cell transplantation; CDI, Clostridium difficile infection; FDA, Food and Drug Administration; CRE, Carbapenem-resistant Enterobacteriaceae.

Data Sharing Statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Ethics Approval

This study was approved by the Research Ethics Committee of Second Affiliated Hospital of Zhejiang University. In addition, for organ transplantation, all organs were donated voluntarily with written informed consent, and the organ donations and transplants were conducted in accordance with the Declaration of Istanbul.

Acknowledgments

We wish to thank the staff of the general intensive care unit of the Second Affiliated Hospital of Zhejiang University for their support and cooperation in data access and analysis.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no conflicts of interest.

Additional information

Funding

None funding.