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

Abstract

Lingchun Zhang,1,* Yani Ma,2,* Chenglong Zhao,1 Shujuan Zhao,1 Lulu Zhao,3 Yuxin Yang,4 Yuhan Wang,5 Haiyang Meng,6 Jun Sun1 1Department of Pharmacy, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, People’s Republic of China; 2Department of Pharmacy, the First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Department of Pharmacy, Gongyi People’s Hospital, Zhengzhou, People’s Republic of China; 4Department of Pharmacy, Anyang Ophthalmic Hospital, Anyang, People’s Republic of China; 5Department of Pharmacy, Henan Integrative Medicine Hospital, Zhengzhou, People’s Republic of China; 6Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Sun, Department of Pharmacy, Henan Provincial People’s Hospital, No. 7 Weiwu Road, Zhengzhou, People’s Republic of China, Tel [phone], Email [email protected]: 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.Keywords: carbapenem-resistant Klebsiella pneumoniae, ceftazidime-avibactam, retrospective study, combination therapy

Keywords

• carbapenem-resistant klebsiella pneumoniae
• ceftazidime-avibactam
• retrospective study
• combination therapy