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. 2020 Feb;59(2):173-205.
doi: 10.1007/s40262-019-00813-w.

Pharmacokinetics and Target Attainment of Antibiotics in Critically Ill Children: A Systematic Review of Current Literature

Stan J F Hartman  1 , Roger J Brüggemann  2 , Lynn Orriëns  3 , Nada Dia  3 , Michiel F Schreuder  4 , Saskia N de Wildt  3   5   6
Affiliations

Pharmacokinetics and Target Attainment of Antibiotics in Critically Ill Children: A Systematic Review of Current Literature

Stan J F Hartman et al. Clin Pharmacokinet. 2020 Feb.

Abstract

Background: Pharmacokinetics (PK) are severely altered in critically ill patients due to changes in volume of distribution (Vd) and/or drug clearance (Cl). This affects the target attainment of antibiotics in critically ill children. We aimed to identify gaps in current knowledge and to compare published PK parameters and target attainment of antibiotics in critically ill children to healthy children and critically ill adults.

Methods: Systematic literature search in PubMed, EMBASE and Web of Science. Articles were labelled as relevant when they included information on PK of antibiotics in critically ill, non-neonatal, pediatric patients. Extracted PK-parameters included Vd, Cl, (trough) concentrations, AUC, probability of target attainment, and elimination half-life.

Results: 50 relevant articles were identified. Studies focusing on vancomycin were most prevalent (17/50). Other studies included data on penicillins, cephalosporins, carbapenems and aminoglycosides, but data on ceftriaxone, ceftazidime, penicillin and metronidazole could not be found. Critically ill children generally show a higher Cl and larger Vd than healthy children and critically ill adults. Reduced target-attainment was described in critically ill children for multiple antibiotics, including amoxicillin, piperacillin, cefotaxime, vancomycin, gentamicin, teicoplanin, amikacin and daptomycin. 38/50 articles included information on both Vd and Cl, but a dosing advice was given in only 22 articles.

Conclusion: The majority of studies focus on agents where TDM is applied, while other antibiotics lack data altogether. The larger Vd and higher Cl in critically ill children might warrant a higher dose or extended infusions of antibiotics in this patient population to increase target-attainment. Studies frequently fail to provide a dosing advice for this patient population, even if the necessary information is available. Our study shows gaps in current knowledge and encourages future researchers to provide dosing advice for special populations whenever possible.

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Conflict of interest statement

Stan J. F. Hartman, Roger J. Brüggemann, Lynn Orriëns, Nada Dia, Michiel F. Schreuder and Saskia N. de Wildt declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
A total of 1742 articles were screened from the 3 databases. After excluding duplicates and non-eligible articles and including articles from references a total of 48 eligible articles were analyzed for data extraction. RRT renal replacement therapy, ECMO extracorporeal membrane oxygenation, ICU intensive care unit
See this image and copyright information in PMC

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