This clinical trial focuses on children with cancer who face infections after receiving chemotherapy. Chemotherapy affects the bone marrow, leading to a decrease in the production of certain white blood cells, particularly those that defend against bacterial infections (neutrophils). One significant concern is febrile neutropenia, where children experience a fever during a period of low white blood cell count. This condition often results from bacterial infections, necessitating prompt wide-spectrum antibiotic treatment. However, some children eliminate antibiotics in the urine too quickly during febrile neutropenia. Their kidneys function more than they normally do (renal hyperfiltration). This can lead to insufficient exposure to antibiotics to control the infection. The current standard antibiotic regimens do not account for this variable elimination rate. In this study we focus on two antibiotics used in this context: piperacillin-tazobactam and meropenem.
The main questions this study aims to answer are, in these children:
* Would higher doses of antibiotics result in better blood levels of antibiotics? * Would they have more sides effects with higher antibiotics dosages? * Would they recover more quickly with higher antibiotic doses? All patients will undergo a blood test upon hospital arrival, including an assessment of renal function. If renal function is normal or diminished, the patient will receive the standard antibiotic dose. Children with increased renal function will be randomly assigned to two groups during each episode of febrile neutropenia. One group will receive standard antibiotic dosages, while the other will receive higher doses to compensate for renal hyperfiltration. Throughout the study, antibiotic levels in the blood will be monitored for all patients. This monitoring will determine if target concentrations can be achieved more quickly with experimental dosages and will allow doctors to readjust the doses if needed.
High probability of febrile neutropenia during the study period
Written informed consent from parents and adolescents older than 14 years
Neutropenia not related to cancer and/or chemotherapy
Refusal to participate
Non-French speaking parents/patients older than 11 years old
Absence of febrile neutropenia or agranulocytosis during the study period (secondary exclusion)
Parallel
Dosage Adjustment Rules for Augmented Renal Clearance (DAR-ARC) for piperacillin-tazobactam and meropenem
DrugMeropenem dosages according to eGFR \[mL/min/1.73 m²\] : eGFR 120-149 : 40 mg/kg q6 h eGFR 150-199 : 30 mg/kg q4h eGFR 200-299 : 40 mg/kg q4h eGFR \>/= 300 : 40 mg/kg q4h Piperacillin-tazobatam dosages according to eGFR \[mL/min/1.73 m²\] : eGFR 120-149 : 150 mg/kg q6 h eGFR 150-199 : 120 mg/kg q4h eGFR 200-299 : 150 mg/kg q4h eGFR \>/= 300 : 180 mg/kg q4h The maximum doses for the antibiotic prescription before the first drug monitoring will be 2gr of MER every 4 hours and 4gr of PIP every 4 hours. The duration of infusion will be set to 2 h.
Standard dosages of piperacillin-tazobactam or meropenem
DrugMeropenem dosages according to eGFR \[mL/min/1.73 m²\] : eGFR\> 50 : 40mg/kg q8h eGFR 25-49 : 40mg/kg q12h eGFR 15-24 : 20mg/kg q12h Piperacillin-tazobactam : eGFR \>50 : 100mg/kg q6h eGFR 20-49 : 50mg/kg q6h eGFR 15-29 : 50 mg/kg q8h
Achievement of antibiotic concentration targets in the intervention group (1i) vs control groupe (1c)
Intervention-drug blood concentration both above the lower limit and below the upper limit of the therapeutic target ranges on the first trough dosage before the fourth dose after treatment initiation.
Achievement of antibiotic concentration targets in control group 2
Intervention-drug blood concentration both above the lower limit and below the upper limit of the therapeutic target ranges on the first trough dosage before the fourth dose after treatment initiation in group 2
Fever duration
Duration of fever (T ≥38°C) after initiation of antibiotherapy (time between first dose of antibiotic and last measurement of T ≥38°C followed by at least 24 hours of T \<38°C)
Side effects of antibiotic therapy
Any relevant adverse event judged to be probably/definitely related to study intervention and all serious adverse events (SAEs)
Number of dosage adjustments required to achieve the target concentration
Readjustment of the intervention drug dosage because of blood concentration either below the lower limit or above the upper limit of the therapeutic target ranges (at any time)
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Centre Hospitalier Universitaire Vaudois
Lead sponsor
Unisanté Centre universitaire de médecine générale et santé publique
Collaborator
FORCE Fondation Recherche sur le Cancer de l'Enfant
Collaborator
