Ceftazidime-Avibactam Versus Polymyxin-Based Combination Therapies: A Study on 30-Day Mortality in Carbapenem-Resistant Enterobacterales Bloodstream Infections in an OXA-48-Endemic Region

Abstract

Background: Ceftazidime-avibactam (CAZ-AVI) is recommended as first-line treatment for Oxacillinase-48 (OXA-48) β-Lactamase-producing carbapenem-resistant Enterobacterales (CRE) infections, while polymyxin-based combination therapies (PBCTs) are used as a last resort when CAZ-AVI is unavailable. Research comparing the effectiveness of CAZ-AVI and PBCT in CRE blood stream infections (CRE-BSIs) is limited, mostly focusing on Klebsiella pneumoniae carbapenemase (KPC)-producing isolates. In Turkey, OXA-48 is endemic and OXA-48-Like is common. Therefore, our study aimed to compare the impact of these treatments on 30-day mortality in patients with CRE-BSIs in endemic regions. Methods: Retrospective data from January 2019 to May 2023 were collected from four tertiary healthcare centers in Istanbul. Demographic, clinical, and outcome data of ICU patients treated with CAZ-AVI monotherapy or PBCT for CRE-BSIs were analyzed. The effect on 30-day survival was evaluated using Cox regression analysis post propensity score matching (PSM). Results: Out of 151 patients, 44.4% (n: 67) received CAZ-AVI and 55.6% (n: 84) received PBCT. All-cause mortality rates were 20% (n: 13) with CAZ-AVI and 36.9% (n: 31) with PBCT. Cox regression analysis post PSM indicated CAZ-AVI monotherapy significantly reduced the mortality risk compared to PBCT (HR: 0.16, 95%CI: 0.07-0.37, p < 0.001), while age increased the risk (HR: 1.02 per year, 95% CI 1.0-1.04, p: 0.01). Conclusions: In OXA-48-predominant areas, CAZ-AVI demonstrated significantly lower mortality in patients with CRE-BSIs compared to PBCT. The results were attributed to the pharmacokinetic and pharmacodynamic disadvantages of polymyxins compared to CAZ-AVI, and the impact of age-related physical conditions. Therefore, CAZ-AVI should be the preferred treatment for CRE-BSIs in OXA-48-endemic regions.

Keywords: OXA-48; blood stream infections; carbapenem-resistant enterobacterales; ceftazidime–avibactam; mortality; polymyxins.

Figure 1

Effect of targeted therapies on outcomes, according to source of infection in total cohort and propensity score-matched groups.

Figure 2

Kaplan–Meier survival analysis for patients receiving Ceftazidime-Avibactam and Polymyxin-based combination therapy for 30 days after treatment initiation.