Population Pharmacokinetics of Antibiotics in Critically Ill Children (POPSICLE)

Radboud University Medical Center

Status

Unknown

Conditions

Critical Illness

Children

Infectious Disease

Treatments

Drug: Pharmacokinetics

Study type

Observational

Funder types

Other

Identifiers

NCT03248349

2016-3085

Details and patient eligibility

About

Infections are common on the Intensive Care for both adult and pediatric patients. Adequately dosing antibiotic treatment is of vital importance but both under- and overdosing is frequent due to pathophysiological changes during critical illness. Moreover, the interplay of age and critical illness is even more understudied.

To optimize antibiotic dosing and outcome of infectious disease, personalized dosing guidelines in critically ill patients are highly needed. In this prospective observational population pharmacokinetic study we will evaluate if target attainment for antibiotics is reached in critically ill children with current dosing guidelines. Using these data, individualized dosing guidelines will be developed.

Full description

Approximately one third of all critically ill children develop infectious disease related complications. Mortality due to infections can be as high as 30-45%. In up to 41% of adult critically ill patients antimicrobial dosing recommendations are inadequate, as acute kidney injury, augmented renal clearance, inflammatory response and hypoalbuminaemia all contribute to variation in drug concentrations. This is an important reason for antibiotic treatment failure and emergence of resistance.

Data from adults cannot be directly extrapolated to children, due to developmental changes in the processes involved in drug disposition. Moreover, the interplay of age and critical illness is even more understudied. Hence, to optimize antibiotic dosing and outcome of infectious disease, personalized dosing guidelines in critically ill patients are highly needed.

In this prospective observational population pharmacokinetic study we will evaluate if target attainment for antibiotics is reached in critically ill children with current dosing guidelines. Using these data, individualized dosing guidelines will be developed.

Objectives:

To determine the population pharmacokinetics of antibiotics in critically ill pediatric patients to develop individualized dosing guidelines for antibiotics for this population.

Study design:

Observational study with minimal invasive procedures: population pharmacokinetic study.

Study population:

Critically ill children, admitted on the pediatric intensive care unit (PICU), receiving antibiotics.

Study parameters/endpoints:

Primary:

To estimate population pharmacokinetic parameters for antibiotics

Secondary:

To determine the target attainment rate of antibiotic exposure
To design individualized dosing guidelines for antibiotics

Exploratory:

To describe variability in kidney function
To explore the relationship of genetic variation with disposition of pharmacokinetics.

Enrollment

200 estimated patients

Sex

All

Ages

Under 18 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

0 to 18 years of postnatal age;
>37 weeks of gestational age (in children less than 6 months of postnatal age);
Admitted to pediatric intensive care unit;
Indwelling central line or arterial line in place for clinical purposes, or regular blood work for clinical reasons;
Antibiotic therapy already prescribed by treating physician;
Written informed consent (IC).

Exclusion criteria