Antibiotic dosing in children in Europe: can we grade the evidence from pharmacokinetic/pharmacodynamic studies - and when is enough data enough?

被引:27
作者
Barker, Charlotte I. S. [1 ,2 ]
Standing, Joseph F. [3 ]
Turner, Mark A. [4 ]
McElnay, James C. [5 ]
Sharland, Mike [1 ]
机构
[1] Univ London, Div Clin Sci, Paediat Infect Dis Res Grp, London SW17 0QT, England
[2] Univ Oxford, John Radcliffe Hosp, Div Med Sci, Oxford Univ Clin Acad Grad Sch, Oxford OX3 9DU, England
[3] UCL, Inst Child Hlth, Infect Dis & Microbiol Unit, London, England
[4] Univ Liverpool, Dept Womens & Childrens Hlth, Liverpool L69 3BX, Merseyside, England
[5] Queens Univ Belfast, Ctr Med Biol, Sch Pharm, Clin & Practice Res Grp, Belfast BT7 1NN, Antrim, North Ireland
基金
英国医学研究理事会;
关键词
antimicrobials; children; pharmacodynamics; pharmacokinetics; PHARMACOKINETICS; INFANTS; PHARMACODYNAMICS; FORMULARY; THERAPY; DRUGS;
D O I
10.1097/QCO.0b013e328353105c
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Purpose of review Antibiotics are prescribed more frequently to children than any other class of medication. Analysis of the evidence behind antimicrobial dosing regimes is imperative to improve clinical outcomes, minimize antimicrobial resistance development, and to identify priority research areas for the future. This review aims to promote debate amongst paediatricians, pharmacologists, and pharmacists about how to improve antimicrobial prescribing by considering methods to develop and disseminate optimal dosage information. Recent findings There has been increasing use of population analyses to understand pharmacokinetic/pharmacodynamic (PK/PD) parameters in children. Nonlinear mixed effects modelling is widely accepted to be the method of choice for analyses of PK/PD data. However, communicating the quality of PK/PD studies is an equally important factor to allow clinicians to gauge the robustness of the evidence. The possibility of grading PK/PD studies is discussed, along with using systematic reviews and PK/PD meta-analysis for generating high-quality evidence. Many doses in existing formularies (including the British National Formulary for Children) are based on outdated evidence. The need to update formularies to account for new evidence, population changes (e. g. obesity), and changing patterns of resistance requires a more systematic evaluation of antimicrobial PK/PD relationships in children. The possibility of e-formularies with links directly to the evidence should be considered and regulators must also play a role in supporting the re-evaluation of off-patent dosing guidelines. Summary Advancing our understanding of the evidence behind paediatric antimicrobial therapeutic regimens is essential to improve both clinical outcomes and patient safety. Using a combination of international collaboration, electronic communication, and PK/PD modelling techniques, we can now define the gaps in our knowledge base and develop the techniques to answer them.
引用
收藏
页码:235 / 242
页数:8
相关论文
共 40 条
[1]   CHRISTMAS 2011: ORAL TRADITIONS Dosing of oral penicillins in children: is big child=half an adult, small child=half a big child, baby=half a small child still the best we can do? [J].
Ahmed, Umar ;
Spyridis, Nikos ;
Wong, Ian C. K. ;
Sharland, Mike ;
Long, Paul F. .
BRITISH MEDICAL JOURNAL, 2011, 343
[2]   Mechanism-based concepts of size and maturity in pharmacokinetics [J].
Anderson, B. J. ;
Holford, N. H. G. .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 2008, 48 :303-332
[3]   Data sharing for pharmacokinetic studies [J].
Anderson, Brian J. ;
Merry, Alan F. .
PEDIATRIC ANESTHESIA, 2009, 19 (10) :1005-1010
[4]  
[Anonymous], WHO model lists of essential medicines
[5]  
[Anonymous], OXFORD CTR EVIDENCE
[6]  
[Anonymous], EMA987172012
[7]   Is it time for a European formulary of paediatric medicines? [J].
Bonati, M ;
Pandolfini, C .
ARCHIVES OF DISEASE IN CHILDHOOD, 2004, 89 (09) :890-891
[8]  
Bradley JS, 2010, NELSONS POCKET BOOK
[9]   The role of population PK-PD modelling in paediatric clinical research [J].
De Cock, Roosmarijn F. W. ;
Piana, Chiara ;
Krekels, Elke H. J. ;
Danhof, Meindert ;
Allegaert, Karel ;
Knibbe, Catherijne A. J. .
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 2011, 67 :S5-S16
[10]  
Drug Formulary for Children, 2003, DRUG FORM CHILDR GEN