Clémence Rivaud

and 13 more

Aim: Population pharmacokinetics (PK) models may be effective to improve antibiotic exposure with individualized dosing. The aim of the study is to assess cefazolin exposure using a population PK model in critically ill children. Methods: We conducted a single center observational study including children under 18 years old who had cefazolin plasma monitoring before and after the model implementation. First concentration at steady state of each cefazolin course was analyzed. Optimal exposure was defined by concentrations values ranged from free concentration over 4 times the MIC for 100% of the dosing interval to total trough or plateau concentration under 100 mg/L. Results: Fifty-eight patients were included, of whom 39 and 19 children received conventional dosing or model-informed dosing, respectively. Median [range] age was 2.3 [0.1-17] years old and median weight was 14.2 [2.9-72] kg. There were more continuous infusions (CI) in the model group than in the conventional group (n=19/19 (100%) vs n=23/39 (59%)). Compared to conventional dosing, model-informed dosing provided more optimal exposure (n=17/39 (44%) vs n= 15/19 (79%), p=0.01) and less underexposure (n= 18/39 (46%) vs n= 2/19 (10%), p=0.008), without increasing overexposure (n= 4/39 (10%) vs n= 2/19 (11%), p=1). Moreover, the time to reach a 50% decrease of C Reactive Protein levels was significantly shorter in the model group than the conventional group (3 [0.5-13] vs 4 [1-34]; p=0.045. Conclusions: Use of individualized cefazolin model-informed dosing improves critically ill children’s exposure. Further studies are needed to assess the clinical benefit of cefazolin PK model application.

Michael THY

and 5 more

Background Use of continuous renal replacement therapy (CRRT) in children receiving anti-infective drugs may lead to inappropriate concentrations with risks of treatment failure, toxicity and emergence of multidrug-resistant bacteria. We aimed to describe anti-infective prescribing practices in critically ill children undergoing CRRT. Methods An online survey to assess CRRT, anti-infective prescribing and therapeutic drug monitoring (TDM) practices was sent by e-mail to physicians working in pediatric intensive care units (PICUs) through the French-speaking Group of Pediatric Intensive Care and Emergency medicine (GFRUP). Results From April 1st 2021 to May 1st 2021, 26/40 different PICUs participated in the survey, corresponding to a response rate of 65%. Twenty-one were located in France and five abroad. All PICU practiced CRRT mainly with Prismaflex™ System. Anti-infective prescriptions were adjusted to the presence of CRRT in 23 (88%) PICUs mainly according to the molecular weight in 6 (23%), the molecule protein binding in 6 (23%) and the elimination routes in 15 (58%) including the residual diuresis in 9 (35%), to the CRRT flow in 6 (23%) and to the modality of CRRT used in 15 (58%), PICUs. There was a wide variability noticed between PICUs and between physicians in the same unit. Barriers to TDM were mainly an excessive delay in obtaining results in 11 (42%) and the lack of an on-site laboratory in 8 (31%) PICUs. Conclusions Our survey reported wide variability in anti-infective prescribing practices in children undergoing CRRT highlighting the gap in the knowledge and the need for education and recommendations