Model antibiotic use to improve outcomes
| Autor: | Robert Likić, James N. Fullerton, Oscar Della Pasqua |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Pharmacology
medicine.medical_specialty business.industry pharmacocinetic modelling antibiotic prescribing MEDLINE Bacterial Infections Original Articles Anti-Bacterial Agents Text mining Humans Medicine Pharmacology (medical) Practice Patterns Physicians' Antibiotic use business Intensive care medicine |
| Popis: | AIMS: Very little data exist regarding the effect of cardiopulmonary bypass (CPB) on cefuroxime (CXM) pharmacokinetics in children less than one year of age. METHODS: 50 mg kg(−1) CXM i.v. after induction were followed by 75 mg kg(−1) into the CPB circuit. In 42 patients undergoing cardiac surgery, 15–20 samples were obtained between 5 and 360 min after the first dose. Total CXM concentrations were measured by high‐performance liquid chromatography and a pharmacokinetic/pharmacodynamic (PK/PD) modelling was performed. RESULTS: Using a fixed protein binding of 15.6% for CXM, peak plasma concentrations of unbound CXM were 229 ± 52 μg ml(−1) after the first bolus and 341 ± 86 μg ml(−1) on CPB. Nadir concentrations before CPB were 69 ± 20 μg ml(−1) and six hours later decreased to 41 ± 19 μg ml(−1) with and 24 ± 14 μg ml(−1) without CPB. A two‐compartment model was fitted with the main covariates body weight, CPB and postmenstrual age (PMA). PK parameters were as follows: systemic clearance, 5.15 [95% CI 4.5–5.8] l h(−1); central volume of distribution, 11.25 [9.41–13.09] l; intercompartmental clearance, 18.19 [14.79–21.58] l h(−1); and peripheral volume, 17.07 [15.7–18.5] L. ƒT > MIC of 32 μg ml(−1) for an 8‐h time period was between 70 and 100% (2.5–10 kg BW). According to our simulation, 25 mg ml(−1) CXM as a primary bolus and into the prime plus a 5 mg kg(−1) h(−1) infusion maintain CXM concentrations continuously above 32 μg ml(−1). CONCLUSIONS: The routine dosing regimen provided was sufficient for prophylaxis, but continuous dosing can provide a higher percentage of ƒT > MIC. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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