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.

Keywords:

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

Abbreviations

CLSI, Clinical and Laboratory Standards Institute; CRE, Carbapenem-resistant Enterobacteriaceae; CRKP, Carbapenem-Resistant Klebsiella pneumoniae; HAP, Hospital-acquired pneumonia; HR, Hazard ratios; MIC, Minimum inhibitory concentration; ROC, Receiver operating characteristic; APACHE, Acute Physiology and Chronic Health Evaluation; IQR, Interquartile range.

Data Sharing Statement

The authors confirm that the data supporting the findings of this study are available within the article.

Ethics Approval and Informed Consent

This study was conducted following the Declaration of Helsinki and obtained approval from the clinical research ethics committee of Henan Provincial People’s Hospital, and the need for obtaining written informed consent was waived due to the retrospective nature of this study.

Author Contributions

All authors made a significant contribution to the work reported in the conception, study design, execution, acquisition of data, analysis, and interpretation. All authors took part in drafting, revising, or critically reviewing the article, gave final approval of the version to be published, and have agreed on the journal to which the article has been submitted. All authors agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.