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

Weili Wang,1,2,* Rongrong Wang,3,* Yuntao Zhang,1,2 Lei Zeng,1,2 Haisen Kong,4 Xueli Bai,1,2 Wei Zhang,1,2 Tingbo Liang1,2,5,6 1Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Liver Transplant Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Department of Laboratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 5Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 6Key Laboratory of Combined Multi-organ Transplantation of the Ministry of Health, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tingbo Liang, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China, Email liangtingbo@zju.edu.cnObjective: There 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.Methods: The 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.Results: Six 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).Conclusion: CAZ-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.Keywords: ceftazidime-avibactam, carbapenem-resistant Enterobacterales, pediatric liver transplantation, salvage treatment, effectiveness, safety