Ceftazidime/Avibactam-Based Versus Polymyxin B-Based Therapeutic Regimens for the Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infection in Critically Ill Patients: A Retrospective Cohort Study

Abstract

Introduction: Considering the importance of ceftazidime/avibactam (CAZ/AVI) and polymyxin B (PMB) in treating carbapenem-resistant Klebsiella pneumoniae (CRKP) infection, it is essential to evaluate the efficacy and safety of these agents and provide appropriate medical advice to clinical specialists. Methods: We conducted a retrospective cohort study in two Chinese tertiary hospitals for critically ill patients with CRKP infection who received at least 24-h CAZ/AVI-based or PMB-based treatment. A binary logistic model and a Cox proportional hazards regression model were constructed to analyze variables that could potentially affect 30-day microbiological eradication and all-cause mortality, respectively. Results: From January 2019 to December 2021, 164 eligible patients were divided into CAZ/AVI and PMB cohorts. A notably lower 30-day mortality rate (35.4% vs 69.5%, P < 0.001) and a higher 30-day microbiological eradication rate (80.5% vs 32.9%, P < 0.001) were observed for patients receiving CAZ/AVI-based treatment, compared with cases in the PMB group. A longer antimicrobial treatment duration (> 7 days) could also significantly decrease the mortality rate and increase the microbiological eradication rate. Female patients had a higher survival rate than male patients. Age over 65 years, sepsis, continuous renal replacement therapy, and organ transplantation were identified as negative factors for survival. In the subgroup analysis, CAZ/AVI combined with tigecycline or amikacin could effectively lower mortality. According to safety evaluation results, potential elevation of hepatic enzymes was associated with CAZ/AVI-based treatment, while renal impairment was probably related to PMB-based treatment. Conclusions: CAZ/AVI was more effective than PMB in treating CRKP-infected patients. Tigecycline and amikacin were proven to be beneficial as concomitant agents in combination with CAZ/AVI. A treatment period lasting over 7 days was recommended. Hepatoxicity of CAZ/AVI and nephrotoxicity of PMB should be monitored carefully. Further well-designed studies should be performed to verify our conclusion.