Can Population Pharmacokinetics of Antibiotics be Extrapolated? Implications of External Evaluations
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SYSTEMATIC REVIEW
Can Population Pharmacokinetics of Antibiotics be Extrapolated? Implications of External Evaluations Yu Cheng1,2 · Chen‑yu Wang1 · Zi‑ran Li3 · Yan Pan1 · Mao‑bai Liu2 · Zheng Jiao1
© Springer Nature Switzerland AG 2020
Abstract Background and objective External evaluation is an important issue in the population pharmacokinetic analysis of antibiotics. The purpose of this review was to summarize the current approaches and status of external evaluations and discuss the implications of external evaluation results for the future individualization of dosing regimens. Methods We systematically searched the PubMed and EMBASE databases for external evaluation studies of population analysis and extracted the relevant information from these articles. A total of 32 studies were included in this review. Results Vancomycin was investigated in 17 (53.1%) articles and was the most studied drug. Other studied drugs included gentamicin, tobramycin, amikacin, amoxicillin, ceftaroline, meropenem, fluconazole, voriconazole, and rifampicin. Nine (28.1%) studies were prospective, and the sample size varied widely between studies. Thirteen (40.6%) studies evaluated the population pharmacokinetic models by systematically searching for previous studies. Seven (21.9%) studies were multicenter studies, and 27 (84.4%) adopted the sparse sampling strategy. Almost all external evaluation studies of antibiotics (93.8%) used metrics for prediction-based diagnostics, while relatively fewer studies were based on simulations (46.9%) and Bayesian forecasting (25.0%). Conclusion The results of external evaluations in previous studies revealed the poor extrapolation performance of existing models of prediction- and simulation-based diagnostics, whereas the posterior Bayesian method could improve predictive performance. There is an urgent need for the development of standards and guidelines for external evaluation studies.
1 Introduction
Key Points
An intricate and complicated relationship exists between humans and pathogenic microorganisms. Although various antibiotics have been developed as powerful weapons against infection-causing pathogenic microorganisms, treatment outcomes remain poor with high mortality rates in critically ill patients, and the problem of antimicrobial
The number of existing external evaluation studies was limited compared to the booming development of population pharmacokinetic models, especially for antibiotics. The quality of existing external evaluation studies should be assessed and improved. Standards and guidelines needed to be established as soon as possible to clarify key details of external evaluation assessments.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s40262-020-00937-4) contains supplementary material, which is available to authorized users. * Mao‑bai Liu [email protected] * Zheng Jiao [email protected] 1
Department of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 West Huaihai Road, Shanghai 20
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