Ceftazidime-Avibactam as Salvage Therapy in Pediatric Liver Transplantation Patients with Infections Caused by Carbapenem-Resistant Enterobacterales.

Abstract

ObjectiveThere are few therapeutic options for infections caused by carbapenem-resistant Enterobacterales (CRE) in children following liver transplantation. Ceftazidime-avibactam (CAZ-AVI), a recently licensed antibacterial in China, was utilized as a salvage therapy against CRE in our center, and its efficacy and safety were therefore assessed.MethodsThe retrospective, observational study was conducted at the First Affiliated Hospital of Zhejiang University. Pediatric liver transplantation patients (≤12 years) who received CAZ-AVI as a salvage therapy against CRE infections were included from January 2020 to December 2021. Clinical success and all-cause death during hospitalization were the primary outcomes. Recurrence of infection, drug-related adverse events, and changes in inflammatory biomarkers were collected.ResultsSix children were enrolled, with a median age of 10.1 (interquartile range (IQR) 5.5–13.8) months. Primary intraperitoneal infections occurred in all patients, with five patients developing bloodstream infections. KPC carbapenemases were detected in most isolates, and the susceptibility results showed general sensitivity to tigecycline, polymyxin B, and CAZ-AVI. Tigecycline-based therapy was taken as the initial treatment and withdrawn because of clinical failure (5 cases) or cholestasis (1 case). After CRE infection, the median time to convert to CAZ-AVI was 7.5 (IQR 7.0–8.8) days, and the median CAZ-AVI treatment length was 21.0 (IQR 20.3–28.5) days. Clinical success was achieved in all patients, with a zero percent all-cause death rate. No CRE infections recurred throughout hospitalization, and no resistance to CAZ-AVI was detected. Patients experienced vomiting (1/6), skin rash (1/6), and a transient increase in cystatin C (2/6), γ-glutamyltransferase (2/6), and alkaline phosphatase (3/6).ConclusionCAZ-AVI was shown to be a successful salvage treatment for CRE infection in pediatric liver transplant recipients, with minor and temporary drug-related side effects.