population pharmacokinetics of anti-infectives in critically ill children

Conditions: Pediatric Intensive Care Unit; Pediatric Immuno-hematology Department

Summary: concentrations and effects of anti-infectives in critically ill children are unpredictable and the risk of under-exposure may be associated with poor clinical outcomes. in addition, between-subject variability (bsv) is known to be substantial in critically ill children. rationalisation of anti-infectives in children is therefore desirable. the investigators aim to investigate, using a population approach, the pharmacokinetics (pk) and pharmacodynamics (pd) of anti-infectives including pk/pd targets (ft(%) \> minimal inhibitory concentration (mic)) and pd endpoints (clinical outcomes) in critically ill children. covariates the effects of covariates on anti-infectives pk and pk/pds are investigated in order to better explain the bsv and to ultimately suggest individualized dosage regimens. it will be a prospective pk study including 11 anti-infectives antibiotics. six blood samples were taken from each patient during dosing interval. the primary pk/ pd targets were anti-infectives concentrations above the mic of the pathogen at both 50% (50% f t\>mic) and 100% (100% f t\>mic) of the dosing interval. the investigators used skewed logistic regression to describe the effect of anti-infectives exposure on patient outcome.

background and aims of the study: recent studies have suggested a risk of under-exposure to anti-infectives in critically ill adults. this under-exposure may be associated with poor clinical outcomes as well as a delay or incomplete clinical resolution of infection; the dosing regimen of anti-infectives in critically ill children is usually based on weight (i.e. mg per kg). however, between-subject variability is known to be substantial in children and even more so in critical illness; as a result, concentrations and effects of anti-infectives are unpredictable and the risk of under- or over-exposure is thus genuine and considerable. rationalisation of anti-infectives in children is therefore desirable. the purpose of the present study is to investigate, using a population approach, the pharmacokinetics (pk) and pharmacodynamics (pd) of intravenous anti-infectives including usual pk/pd targets (ft(%) \> minimal inhibitory concentration (mic)) and pd endpoints (clinical outcomes) in critically ill children. the effects of developmental and other factors related to critical illness on anti-infectives pk and pk/pds are investigated in order to better explain the observed between-subject variabilities and to ultimately suggest individualized dosage regimens. this prospective study will be conducted in six paediatric services of public hospitals in paris, france intervention: patient selection will take place in the 6 paediatric services. the senior physician proposes the study to holders of parental authority whose child receives or will receive anti-infectives during its follow-up or hospitalization. the senior physician will give a briefing note to the holders of parental authority, and if the child is able to understand the information. the non-oral opposition for the retrieval and analysis of data will be collected. no intervention or no charge will be made for this study.

Eligibility criteria:
inclusion criteria: * minor patient requiring the administration of an anti-infective belonging to the following classes : β-lactam antibiotics; aminoglycosides, glycopeptides; fluoroquinolones; other antibiotics (daptomycin, rifampin, trimethoprim, sulfamethoxazole, clarithromycin); fungal; antivirals, during its follow-up or hospitalization exclusion criteria: * patient and parents having notified to the doctor that they refuse data recovery.

Keywords: β-lactam antibiotics children anti-infectives aminoglycosides, glycopeptides fluoroquinolone fungal antiviral