An exploratory pharmacokinetics and pharmacodynamics study of beta-lactam antibiotics in pediatric intensive care patients: is there a need for more precision? (EXPAT-Kids)
- Conditions
- critically ill patientsinfections10019815
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 145
All patients admitted to the pediatric intensive care unit wards and given
standard of care intravenous therapy of target antibiotic are screened for
participating trial.
Antibiotic initiation based on clinical suspicion of infection and/or cultured
pathogens susceptible to the target drugs, initial dosage prescription, and
duration of therapy are at the discretion of the attending physician. In order
to be eligible to participate in this study a subject must also meet all the
followinng criteria:
• Written informed consent has been obtained from the patient or their legally
authorized representative.
• Recruitment within 36 hours after start of antibiotic therapy
• Intravenous antibiotic therapy of the target antibiotic should be aimed for
at least 2 days.
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
• Premature infants
• History of anaphylaxis for the study antibiotics
• Consent not obtained
• Study antibiotic cessation before blood collection
• Prophylactic use of the study antibiotics
Study & Design
- Study Type
- Observational invasive
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The PK/PD endpoints are the unbound concentration above the MIC at 100% (PICU<br /><br>target) of the dosing interval (*T*>*MICECOFF and *T*>*4 x MICECOFF). The<br /><br>percentage *T*>*MIC is determined by calculating the intercept of the MIC<br /><br>values with the concentration-time curve.<br /><br><br /><br>The following PK/PD indices are calculated:<br /><br>• %*T>MICECOFF for each individual patient<br /><br>• % of patients that achieved the target of 100% *T>MICECOFF and 100%<br /><br>*T>4×MICECOFF<br /><br>• Target attainment for the study antibiotics and dosing regimens to reach the<br /><br>target of 100% *T*>*MIC and 100% *T*>*4×MIC for a range of MICs (0.03125 to 128*<br /><br>mg/L)</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary endpoints are estimated multivariate binomial and binary logistic<br /><br>regression models, to examining the association of target attainment with<br /><br>patient characteristics and clinical outcomes. We defined ICU length of stay<br /><br>(LOS) from the start of therapy (enrollment) as a secondary endpoint. Factors<br /><br>likely to contribute to these two outcomes were analyzed for association based<br /><br>on clinical relevancy and previously described relationships (11). These<br /><br>included patient characteristics (age, gender, body mass index (BMI)), organ<br /><br>dysfunction score (PELOD), serum albumin, serum urea, sepsis, estimated<br /><br>glomerular filtration rate (eGFR >= 90 mL/min/1.73 m2), and presence of<br /><br>extracorporeal circuits (CRRT (continuous renal replacement therapy), ECMO<br /><br>(extracorporeal membrane oxygenation)).</p><br>