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

Abstract

Objective 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 Tigecycline-based therapy was taken as the initial treatment and withdrawn because of clinical failure (5 cases) or cholestasis (1 case).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.

Ceftazidime-Avibactam Use in a Cohort of Children with Complex Chronic Conditions: Effectiveness and Absence of Resistance Development Following Difficult-to-Treat or Recurrent Infections

“…This discrepancy may be attributed to notable differences in baseline characteristics [15,22,23] and infection types [17,21,22]. While the patient demographics and types of infections in our study could be somewhat comparable to the previously mentioned study by Wang et al, unlike our approach, where we investigated the recurrence of infections caused by CR Enterobacterales beyond the hospitalization period, Wang et al's study solely concentrated on assessing recurrence during the hospital stay [16]. Therefore, drawing conclusive comparisons between the two studies may be limited.…”

“…This scenario likely offers a more accurate reflection of the clinical context wherein the utilization of CZA is necessary. Recently, Wang et al published a notable series comprising 6 cases of pediatric patients who underwent liver transplantation and presented with cIAI, all of which were effectively managed using CZA [16]. Furthermore, data on the off-label utilization of CZA in pediatric patients for conditions such as respiratory tract and bloodstream infections, accounting for 5 treatment courses, as well as its application in critically ill pediatric cases (comprising 10 admissions to the PICU), remain limited [17][18][19][20][21][22].…”

New Antibiotics Against Multidrug-Resistant Gram-Negative Bacteria in Liver Transplantation: Clinical Perspectives, Toxicity, and PK/PD Properties

“…Of note, three patients (3/21, 14.3%) developed acute kidney injury, and no other significant adverse event was reported. A similar study on six paediatric LTR [ 37 ] evaluated the efficacy and safety of CZA as salvage therapy for cIAI and bloodstream infections (BSI) caused by CRE, mostly KPC-E, and showed clinical success in all patients, without recurrence or development of resistance. CZA was mainly used as monotherapy (66%), and there were no serious adverse events.…”

Rationale and evidence for the use of new beta-lactam/beta-lactamase inhibitor combinations and cefiderocol in critically ill patients

“…Two large retrospective multicentre cohort studies including patients with infections due to KPC-producing K. pneumoniae and published after the above-mentioned meta-analyses yielded similar results [ 128 , 129 ]; of note, one of them reported a trend toward improved survival with combination therapy in the subgroup of patients with hospital-acquired pneumonia [ 128 ]. Clinical evidence related to the potential benefit of combining ceftazidime–avibactam with colistin is limited to case-reports or small case-series, precluding any conclusion to be drawn [ 95 , 130 ].…”