Ceftazidime-Avibactam for the Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infections in Patients With Liver Cirrhosis

Shani Feldman; Alessandro Russo; Giancarlo Ceccarelli; Cristian Borrazzo; Chiara Madge; Mario Venditti; Manuela Merli

doi:10.1016/j.jceh.2022.04.016

Ceftazidime-Avibactam for the Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infections in Patients With Liver Cirrhosis

J Clin Exp Hepatol. 2022 Sep-Oct;12(5):1293-1300. doi: 10.1016/j.jceh.2022.04.016. Epub 2022 Apr 21.

Authors

Shani Feldman¹, Alessandro Russo², Giancarlo Ceccarelli², Cristian Borrazzo², Chiara Madge¹, Mario Venditti², Manuela Merli¹

Affiliations

¹ Division of Gastroenterology, Department of Translational and Precision Medicine, "Sapienza" University of Rome, Viale Dell'Università 37, 00185 Rome, Italy.
² Department of Public Health and Infectious Diseases, "Sapienza" University of Rome, Viale Dell'Università 37, 00185, Rome, Italy.

Abstract

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in patients with cirrhosis represent a significant therapeutic challenge as they are associated with poor outcomes due to high rates of treatment failure, and frequently induce liver decompensation.

Aims: To evaluate treatment failure and in-hospital mortality in two cohorts of patients with cirrhosis and with CRKP infections treated with antibiotic regimens including or excluding Ceftazidime-avibactam.

Methods: Data from hospitalized patients with liver cirrhosis and CRKP infections were extracted and retrospectively analyzed.

Results: During the study period, 39 cirrhotic patients with confirmed invasive CRKP infections were enrolled. Overall, the median age was 60 years with a median MELD score of 16 points. Urinary tract infections were diagnosed in 46%, followed by pneumonia in 23%, and primary bacteremia in 18% of patients. Treatment failure was reported in 10 patients (26%), while in-hospital mortality in 15 patients (38%). A monotherapy was used in 8 patients (20.5%), while a combination therapy was required in 31 patients (79.5%). Ceftazidime-avibactam therapy was associated with lower rates of treatment failure (7% vs. 38%, P = 0.032) independent of severity of liver disease (Child Class) and mono or combination antibiotic therapy. Acute kidney injury, hepatorenal syndrome, and acute-on-chronic liver failure were the consequences more frequently observed in patients with treatment failure. In-hospital mortality was associated with treatment failure, and Ceftazidime-avibactam therapy improved in-hospital survival (log rank test: P = 0.035) adjusted for Child class and mono or combination therapy.

Conclusion: Treatment including ceftazidime-avibactam was associated with a lower rate of treatment failure in cirrhotic patients with CRKP infections. Considering the favorable efficacy and outcomes of ceftazidime-avibactam, this drug should be considered for the treatment of these severe infections in patients with liver cirrhosis, though further investigation is required.

Keywords: ACLF, Acute-on-Chronic Liver Failure; AKI, Acute Kidney Injury; CAZ-AVI, Ceftazidime-Avibactam; COPD, Chronic Obstructive Pulmonary Disease; CRKP, Carbapenem-Resistant Klebsiella Pneumoniae; DCT, Double-Carbapenem Therapy; EASL-CLIF, European Association for the Study of the Liver- Chronic Liver Failure; EUCAST, EUropean Committee for Antimicrobial Susceptibility Testing; Ecdc, European Centre for Disease Prevention and Control; HCC, Hepatocellular Carcinoma; HRS, Hepatorenal Syndrome; MDR, Multi-Drug Resistant; MELD, Model for End-stage Liver Disease; MIC, Minimum Inhibitory Concentration; NASH, Non-Alcoholic Steatohepatitis; TIPS, Transjugular Intrahepatic Portosystemic Shunt; antibiotic therapy; bacterial infections; carbapenem-resistant strains; liver cirrhosis.