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

Background: 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-hour 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 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. Age over 65 years, sepsis, Continuous Renal Replacement Therapy (CRRT) and organ transplantation were identified as negative factors on survival. In the subgroup analysis, we found that CAZ/AVI combined with tigecycline (Hazard ratio, 0.267; 95% Confidence Interval, 0.077-0.921; P = 0.037) or amikacin (Hazard ratio, 0.105; 95% Confidence Interval, 0.014-0.766; P = 0.026) could effectively lower mortality. According to safety evaluation results, potential hepatic enzymes elevation 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 proved to be beneficial as concomitant agents in combination with CAZ/AVI. A treatment period lasting over 7 days was recommended. Although clinical safety of these two agents could be ensured because the severity level and incidence of adverse effects were relatively low, hepatoxicity of CAZ/AVI and nephrotoxicity of PMB should be monitored carefully. Further well-designed studies should be performed to verify our conclusion.