Clinical Outcomes and Risk Factors for Death in Critically Ill Patients with Carbapenem-Resistant Klebsiella pneumoniae Treated with Ceftazidime-Avibactam: A Retrospective Study

Abstract

Purpose Carbapenem-Resistant Klebsiella pneumoniae (CRKP) is a significant public health threat, because it is associated with substantial morbidity and mortality. However, the risk factors associated with treatment failure of ceftazidime-avibactam (CAZ-AVI) and the need for CAZ-AVI-based combination remain unclear. Methods We conducted a retrospective study of critically ill patients (age: > 18 years) diagnosed with CRKP infections and treated with CAZ-AVI for at least 24 h between June 2020 and December 2022 at Henan Provincial People’s Hospital. Results This study included a total of 103 patients who received CAZ-AVI. Of these, 91 (88.3%) patients received the standard dosage of 2.5 g every q8h, while only 20 (19.4%) received monotherapy. The Kaplan–Meier curves showed that the all-cause 30-day mortality was significantly higher among patients who experienced septic shock than those who did not. There was no significant difference in mortality between monotherapy and combination therapy. Dose reduction of CAZ-AVI was associated with a significantly increased mortality rate. Independent risk factors for the 30-day mortality included higher APACHE II score (HR: 1.084, 95% CI: 1.024–1.147, p = 0.005) and lower lymphocyte count (HR: 0.247, 95% CI: 0.093–0.655, p = 0.005). Conversely, a combination therapy regimen containing carbapenems was associated with lower mortality (HR: 0.273, 95% CI: 0.086–0.869, p = 0.028). Conclusion Our study suggests that CAZ-AVI provides clinical benefits in terms of survival and clinical response in critically ill patients with CRKP infection. A higher APACHE II score and lower lymphocyte count were associated with 30-day mortality, while the combination therapy regimen containing carbapenems was the only protective factor. CAZ-AVI dose reduction was associated with an increased mortality rate. Futher large-scale studies are needed to validate these findings.

Clinical outcomes and risk factors for mortality in recipients with carbapenem-resistant gram-negative bacilli infections after kidney transplantation treated with ceftazidime-avibactam: a retrospective study

“…reported 38.1% 30-day mortality in the liver transplant population, which was significantly higher than the 30-day mortality in our study (19.4%), which could be attributed to the difference in patient severity between studies. Our study revealed that 30-day mortality was associated with higher APACHE II scores, consistent with previous reports ( Zhang et al., 2024 ). A meta-analysis conducted by Qian et al ( Qian et al., 2021 ).…”

“…Although some studies have indicated that CAZ-AVI treatment for CR-GNB infections is more effective than polymyxins and tigecycline ( van Duin et al., 2018 ; Fang et al., 2021 ; Shi et al., 2021 ), the risk factors associated with treatment failure of CAZ-AVI remain unclear, especially in this special population of KT recipients. Additionally, previous in vitro studies have demonstrated that CAZ-AVI, when used in combination with other drugs, exhibits high synergistic activity against CR-GNB ( Gaibani et al., 2017 ; Wang et al., 2021 ; Zhang et al., 2024 ). However, it is unclear whether this combination is beneficial.…”