Variation in antibiotic prescription rates in febrile children presenting to emergency departments across Europe (MOFICHE): A multicentre observational study
Autoři:
Nienke N. Hagedoorn aff001; Dorine M. Borensztajn aff001; Ruud Nijman aff002; Anda Balode aff003; Ulrich von Both aff004; Enitan D. Carrol aff006; Irini Eleftheriou aff008; Marieke Emonts aff009; Michiel van der Flier aff012; Ronald de Groot aff012; Jethro Herberg aff002; Benno Kohlmaier aff015; Emma Lim aff009; Ian Maconochie aff016; Federico Martinon-Torres aff017; Daan Nieboer aff018; Marko Pokorn aff019; Franc Strle aff019; Maria Tsolia aff008; Shunmay Yeung aff020; Dace Zavadska aff003; Werner Zenz aff015; Clementien Vermont aff021; Michael Levin aff002; Henriette A. Moll aff001;
Působiště autorů:
Department of General Paediatrics, Erasmus MC–Sophia Children’s Hospital, Rotterdam, The Netherlands
aff001; Section of Paediatric Infectious Disease, Imperial College London, London, United Kingdom
aff002; Department of Paediatrics, Children’s Clinical University Hospital, Rīgas Stradiņa Universitāte, Riga, Latvia
aff003; Division of Paediatric Infectious Diseases, Dr. von Hauner Children’s Hospital, University Hospital, Ludwig Maximilian University, Munich, Germany
aff004; Partner Site Munich, German Center for Infection Research (DZIF), Munich, Germany
aff005; Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom
aff006; Alder Hey Children’s NHS Foundation Trust, Liverpool, United Kingdom
aff007; Second Department of Paediatrics, P. & A. Kyriakou Children’s Hospital, National and Kapodistrian University of Athens, Athens, Greece
aff008; Paediatric Immunology, Infectious Diseases & Allergy, Great North Children’s Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
aff009; NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Trust and Newcastle University, Newcastle upon Tyne, United Kingdom
aff010; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
aff011; Paediatric Infectious Diseases and Immunology, Amalia Children’s Hospital, Radboud University Medical Center, Nijmegen, the Netherlands
aff012; Section of Paediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands
aff013; Paediatric Infectious Diseases and Immunology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, the Netherlands
aff014; Department of General Paediatrics, Medical University of Graz, Graz, Austria
aff015; Paediatric Emergency Medicine, Imperial College Healthcare NHS Trust, London, United Kingdom
aff016; Genetics, Vaccines, Infections and Paediatrics Research Group (GENVIP), Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
aff017; Department of Public Health, Erasmus University Medical Center, Rotterdam, the Netherlands
aff018; Department of Infectious Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia
aff019; Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom
aff020; Department of Paediatric Infectious Diseases and Immunology, Erasmus MC–Sophia Children’s Hospital, Rotterdam, the Netherlands
aff021
Vyšlo v časopise:
Variation in antibiotic prescription rates in febrile children presenting to emergency departments across Europe (MOFICHE): A multicentre observational study. PLoS Med 17(8): e32767. doi:10.1371/journal.pmed.1003208
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pmed.1003208
Souhrn
Background
The prescription rate of antibiotics is high for febrile children visiting the emergency department (ED), contributing to antimicrobial resistance. Large studies at European EDs covering diversity in antibiotic and broad-spectrum prescriptions in all febrile children are lacking. A better understanding of variability in antibiotic prescriptions in EDs and its relation with viral or bacterial disease is essential for the development and implementation of interventions to optimise antibiotic use. As part of the PERFORM (Personalised Risk assessment in Febrile illness to Optimise Real-life Management across the European Union) project, the MOFICHE (Management and Outcome of Fever in Children in Europe) study aims to investigate variation and appropriateness of antibiotic prescription in febrile children visiting EDs in Europe.
Methods and findings
Between January 2017 and April 2018, data were prospectively collected on febrile children aged 0–18 years presenting to 12 EDs in 8 European countries (Austria, Germany, Greece, Latvia, the Netherlands [n = 3], Spain, Slovenia, United Kingdom [n = 3]). These EDs were based in university hospitals (n = 9) or large teaching hospitals (n = 3). Main outcomes were (1) antibiotic prescription rate; (2) the proportion of antibiotics that were broad-spectrum antibiotics; (3) the proportion of antibiotics of appropriate indication (presumed bacterial), inappropriate indication (presumed viral), or inconclusive indication (unknown bacterial/viral or other); (4) the proportion of oral antibiotics of inappropriate duration; and (5) the proportion of antibiotics that were guideline-concordant in uncomplicated urinary and upper and lower respiratory tract infections (RTIs). We determined variation of antibiotic prescription and broad-spectrum prescription by calculating standardised prescription rates using multilevel logistic regression and adjusted for general characteristics (e.g., age, sex, comorbidity, referral), disease severity (e.g., triage level, fever duration, presence of alarming signs), use and result of diagnostics, and focus and cause of infection. In this analysis of 35,650 children (median age 2.8 years, 55% male), overall antibiotic prescription rate was 31.9% (range across EDs: 22.4%–41.6%), and among those prescriptions, the broad-spectrum antibiotic prescription rate was 52.1% (range across EDs: 33.0%–90.3%). After standardisation, differences in antibiotic prescriptions ranged from 0.8 to 1.4, and the ratio between broad-spectrum and narrow-spectrum prescriptions ranged from 0.7 to 1.8 across EDs. Standardised antibiotic prescription rates varied for presumed bacterial infections (0.9 to 1.1), presumed viral infections (0.1 to 3.3), and infections of unknown cause (0.1 to 1.8). In all febrile children, antibiotic prescriptions were appropriate in 65.0% of prescriptions, inappropriate in 12.5% (range across EDs: 0.6%–29.3%), and inconclusive in 22.5% (range across EDs: 0.4%–60.8%). Prescriptions were of inappropriate duration in 20% of oral prescriptions (range across EDs: 4.4%–59.0%). Oral prescriptions were not concordant with the local guideline in 22.3% (range across EDs: 11.8%–47.3%) of prescriptions in uncomplicated RTIs and in 45.1% (range across EDs: 11.1%–100%) of prescriptions in uncomplicated urinary tract infections. A limitation of our study is that the included EDs are not representative of all febrile children attending EDs in that country.
Conclusions
In this study, we observed wide variation between European EDs in prescriptions of antibiotics and broad-spectrum antibiotics in febrile children. Overall, one-third of prescriptions were inappropriate or inconclusive, with marked variation between EDs. Until better diagnostics are available to accurately differentiate between bacterial and viral aetiologies, implementation of antimicrobial stewardship guidelines across Europe is necessary to limit antimicrobial resistance.
Klíčová slova:
Antibiotics – Bacterial diseases – C-reactive proteins – Critical care and emergency medicine – Fevers – Lower respiratory tract infections – Respiratory infections – Viral transmission and infection
Zdroje
1. Poropat F, Heinz P, Barbi E, Ventura A. Comparison of two European paediatric emergency departments: does primary care organisation influence emergency attendance? Ital J Pediatr. 2017;43(1):29. doi: 10.1186/s13052-017-0339-y 28274237
2. Sands R, Shanmugavadivel D, Stephenson T, Wood D. Medical problems presenting to paediatric emergency departments: 10 years on. Emerg Med J. 2012;29(5):379–82. doi: 10.1136/emj.2010.106229 21609944
3. Craig JC, Williams GJ, Jones M, Codarini M, Macaskill P, Hayen A, et al. The accuracy of clinical symptoms and signs for the diagnosis of serious bacterial infection in young febrile children: prospective cohort study of 15 781 febrile illnesses. BMJ. 2010;340:c1594. doi: 10.1136/bmj.c1594 20406860
4. Nijman RG, Vergouwe Y, Thompson M, van Veen M, van Meurs AH, van der Lei J, et al. Clinical prediction model to aid emergency doctors managing febrile children at risk of serious bacterial infections: diagnostic study. BMJ. 2013;346:f1706. doi: 10.1136/bmj.f1706 23550046
5. van de Maat J, van de Voort E, Mintegi S, Gervaix A, Nieboer D, Moll H, et al. Antibiotic prescription for febrile children in European emergency departments: a cross-sectional, observational study. Lancet Infect Dis. 2019;19:382–91. doi: 10.1016/S1473-3099(18)30672-8 30827808
6. Hersh AL, Shapiro DJ, Pavia AT, Shah SS. Antibiotic prescribing in ambulatory pediatrics in the United States. Pediatrics. 2011;128(6):1053–61. doi: 10.1542/peds.2011-1337 22065263
7. Vaz LE, Kleinman KP, Raebel MA, Nordin JD, Lakoma MD, Dutta-Linn MM, et al. Recent trends in outpatient antibiotic use in children. Pediatrics. 2014;133(3):375–85. doi: 10.1542/peds.2013-2903 24488744
8. Goossens H, Ferech M, Vander Stichele R, Elseviers M, ESAC Project Group. Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. Lancet. 2005;365(9459):579–87. doi: 10.1016/S0140-6736(05)17907-0 15708101
9. Costelloe C, Metcalfe C, Lovering A, Mant D, Hay AD. Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis. BMJ. 2010;340:c2096. doi: 10.1136/bmj.c2096 20483949
10. Fleming-Dutra KE, Hersh AL, Shapiro DJ, Bartoces M, Enns EA, File TM Jr, et al. Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010–2011. JAMA. 2016;315(17):1864–73. doi: 10.1001/jama.2016.4151 27139059
11. European Centre for Disease Prevention and Control. Surveillance of antimicrobial resistance in Europe 2017—annual report of the European Antimicrobial Resistance Surveillance Network (EARS-Net). Solna (Sweden): European Centre for Disease Prevention and Control; 2018 [cited 2019 Mar 15]. Available from: https://ecdc.europa.eu/sites/portal/files/documents/EARS-Net-report-2017-update-jan-2019.pdf.
12. Van Boeckel TP, Gandra S, Ashok A, Caudron Q, Grenfell BT, Levin SA, et al. Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data. Lancet Infect Dis. 2014;14(8):742–50. doi: 10.1016/S1473-3099(14)70780-7 25022435
13. Zanichelli V, Monnier AA, Gyssens IC, Adriaenssens N, Versporten A, Pulcini C, et al. Variation in antibiotic use among and within different settings: a systematic review. J Antimicrob Chemother. 2018;73(Suppl 6):vi17–29.
14. Hsia Y, Sharland M, Jackson C, Wong ICK, Magrini N, Bielicki JA. Consumption of oral antibiotic formulations for young children according to the WHO Access, Watch, Reserve (AWaRe) antibiotic groups: an analysis of sales data from 70 middle-income and high-income countries. Lancet Infect Dis. 2019;19(1):67–75. doi: 10.1016/S1473-3099(18)30547-4 30522834
15. Sarpong EM, Miller GE. Narrow- and broad-spectrum antibiotic use among U.S. children. Health Serv Res. 2015;50(3):830–46. doi: 10.1111/1475-6773.12260 25424240
16. van de Voort EMF, Mintegi S, Gervaix A, Moll HA, Oostenbrink R. Antibiotic use in febrile children presenting to the emergency department: a systematic review. Front Pediatr. 2018;6:260. doi: 10.3389/fped.2018.00260 30349814
17. Hicks LA, Bartoces MG, Roberts RM, Suda KJ, Hunkler RJ, Taylor TH Jr, et al. US outpatient antibiotic prescribing variation according to geography, patient population, and provider specialty in 2011. Clin Infect Dis. 2015;60(9):1308–16. doi: 10.1093/cid/civ076 25747410
18. PERFORM. About PERFORM: Personalised Risk assessment in Febrile illness to Optimise Real-life Management London: PERFORM; 2019 [cited 2019 Sep 10]. Available from: https://www.perform2020.org/.
19. Borensztajn D, Yeung S, Hagedoorn NN, Balode A, von Both U, Carrol ED, et al. Diversity in the emergency care for febrile children in Europe: a questionnaire study. BMJ Paediatr Open. 2019;3(1):e000456. doi: 10.1136/bmjpo-2019-000456 31338429
20. Peduzzi P, Concato J, Kemper E, Holford TR, Feinstein AR. A simulation study of the number of events per variable in logistic regression analysis. J Clin Epidemiol. 1996;49(12):1373–9. doi: 10.1016/s0895-4356(96)00236-3 8970487
21. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377–81. doi: 10.1016/j.jbi.2008.08.010 18929686
22. Simon TD, Cawthon ML, Stanford S, Popalisky J, Lyons D, Woodcox P, et al. Pediatric medical complexity algorithm: a new method to stratify children by medical complexity. Pediatrics. 2014;133(6):e1647–54. doi: 10.1542/peds.2013-3875 24819580
23. National Institute for Health and Care Excellence. Fever in under 5s: assessment and initial management. Clinical guideline CG160. London: National Institute for Health and Care Excellence; 2013 [cited 2020 Jul 30]. Available from: https://www.nice.org.uk/guidance/cg160.
24. van Houten CB, Oved K, Eden E, Cohen A, Engelhard D, Boers S, et al. Observational multi-centre, prospective study to characterize novel pathogen-and host-related factors in hospitalized patients with lower respiratory tract infections and/or sepsis—the “TAILORED-Treatment” study. BMC Infect Dis. 2018;18(1):377. doi: 10.1186/s12879-018-3300-9 30086729
25. Herberg JA, Kaforou M, Wright VJ, Shailes H, Eleftherohorinou H, Hoggart CJ, et al. Diagnostic test accuracy of a 2-transcript host RNA signature for discriminating bacterial vs viral infection in febrile children. JAMA. 2016;316(8):835–45. doi: 10.1001/jama.2016.11236 27552617
26. Martinon-Torres F, Salas A, Rivero-Calle I, Cebey-Lopez M, Pardo-Seco J, Herberg JA, et al. Life-threatening infections in children in Europe (the EUCLIDS Project): a prospective cohort study. Lancet Child Adolesc Health. 2018;2(6):404–14. doi: 10.1016/S2352-4642(18)30113-5 30169282
27. Aabenhus R, Siersma V, Hansen MP, Bjerrum L. Antibiotic prescribing in Danish general practice 2004–13. J Antimicrob Chemother. 2016;71(8):2286–94. doi: 10.1093/jac/dkw117 27107098
28. Gerber JS, Ross RK, Bryan M, Localio AR, Szymczak JE, Wasserman R, et al. Association of broad- vs narrow-spectrum antibiotics with treatment failure, adverse events, and quality of life in children with acute respiratory tract infections. JAMA. 2017;318(23):2325–36. doi: 10.1001/jama.2017.18715 29260224
29. National Institute for Health and Care Excellence. Antimicrobial prescribing guidelines. London: National Institute for Health and Care Excellence; 2020 [cited 2020 Feb 17]. Available from: https://www.nice.org.uk/about/what-we-do/our-programmes/nice-guidance/antimicrobial-prescribing-guidelines.
30. Public Health England, National Institute for Health and Care Excellence. Managing common infections: guidance for primary care. London: Public Health England; 2019 [cited 2020 Feb 17]. Available from: https://www.gov.uk/government/publications/managing-common-infections-guidance-for-primary-care.
31. Pouwels KB, Hopkins S, Llewelyn MJ, Walker AS, McNulty CA, Robotham JV. Duration of antibiotic treatment for common infections in English primary care: cross sectional analysis and comparison with guidelines. BMJ. 2019;364:l440. doi: 10.1136/bmj.l440 30814052
32. von Hippel PT. 4. Regression with missing Ys: an improved strategy for analyzing multiply imputed data. Sociol Methodol. 2007;37(1):83–117. doi: 10.1111/j.1467-9531.2007.00180.x
33. Bates D, Maechler M, Bolker B, Walker S. Fitting linear mixed-effects models using lme4. J Stat Softw. 2015;67:1–48. doi: 10.18637/jss.v067.i01
34. Van den Bruel A, Haj-Hassan T, Thompson M, Buntinx F, Mant D, European Research Network on Recognising Serious Infection investigators. Diagnostic value of clinical features at presentation to identify serious infection in children in developed countries: a systematic review. Lancet. 2010;375(9717):834–45. doi: 10.1016/S0140-6736(09)62000-6 20132979
35. Galetto-Lacour A, Zamora SA, Andreola B, Bressan S, Lacroix L, Da Dalt L, et al. Validation of a laboratory risk index score for the identification of severe bacterial infection in children with fever without source. Arch Dis Child. 2010;95(12):968–73. doi: 10.1136/adc.2009.176800 20515973
36. Van den Bruel A, Thompson MJ, Haj-Hassan T, Stevens R, Moll H, Lakhanpaul M, et al. Diagnostic value of laboratory tests in identifying serious infections in febrile children: systematic review. BMJ. 2011;342:d3082. doi: 10.1136/bmj.d3082 21653621
37. Gidengil CA, Linder JA, Hunter G, Setodji C, Mehrotra A. The volume-quality relationship in antibiotic prescribing: when more isn’t better. Inquiry. 2015;52:0046958015571130. doi: 10.1177/0046958015571130 25672338
38. Khine H, Goldman DL, Avner JR. Management of fever in postpneumococcal vaccine era: comparison of management practices by pediatric emergency medicine and general emergency medicine physicians. Emerg Med Int. 2014;2014:702053. doi: 10.1155/2014/702053 24982807
39. Bird C, Winzor G, Lemon K, Moffat A, Newton T, Gray J. A pragmatic study to evaluate the use of a rapid diagnostic test to detect group A streptococcal pharyngitis in children with the aim of reducing antibiotic use in a UK emergency department. Pediatr Emerg Care. 2018 Jul 24. doi: 10.1097/PEC.0000000000001560 30045356
40. Lemiengre MB, Verbakel JY, Colman R, De Burghgraeve T, Buntinx F, Aertgeerts B, et al. Reducing inappropriate antibiotic prescribing for children in primary care: a cluster randomised controlled trial of two interventions. Br J Gen Pract. 2018;68(668):e204–10. doi: 10.3399/bjgp18X695033 29440016
41. Sanagou M, Wolfe R, Forbes A, Reid CM. Hospital-level associations with 30-day patient mortality after cardiac surgery: a tutorial on the application and interpretation of marginal and multilevel logistic regression. BMC Med Res Methodol. 2012;12:28. doi: 10.1186/1471-2288-12-28 22409732
42. Di Martino M, Lallo A, Kirchmayer U, Davoli M, Fusco D. Prevalence of antibiotic prescription in pediatric outpatients in Italy: the role of local health districts and primary care physicians in determining variation. A multilevel design for healthcare decision support. BMC Public Health. 2017;17(1):886. doi: 10.1186/s12889-017-4905-4 29149875
43. World Health Organization. Prioritization of pathogens to guide discovery, research and development of new antibiotics for drug-resistant bacterial infections, including tuberculosis. Geneva: World Health Organization; 2017 [cited 2019 Mar 25]. Available from: https://www.who.int/medicines/areas/rational_use/PPLreport_2017_09_19.pdf?ua=1.
44. World Health Organization. WHO model list of essential medicines for children. Geneva: World Health Organization; 2017.
45. Hsia Y, Lee BR, Versporten A, Yang Y, Bielicki J, Jackson C, et al. Use of the WHO Access, Watch, and Reserve classification to define patterns of hospital antibiotic use (AWaRe): an analysis of paediatric survey data from 56 countries. Lancet Glob Health. 2019;7(7):e861–71. doi: 10.1016/S2214-109X(19)30071-3 31200888
46. Poole NM, Shapiro DJ, Fleming-Dutra KE, Hicks LA, Hersh AL, Kronman MP. Antibiotic prescribing for children in United States emergency departments: 2009–2014. Pediatrics. 2019;143(2):e20181056. doi: 10.1542/peds.2018-1056 30622156
47. Hersh AL, Fleming-Dutra KE, Shapiro DJ, Hyun DY, Hicks LA, Outpatient Antibiotic Use Target-Setting Workgroup. Frequency of first-line antibiotic selection among US ambulatory care visits for otitis media, sinusitis, and pharyngitis. JAMA Intern Med. 2016;176(12):1870–2. doi: 10.1001/jamainternmed.2016.6625 27775770
48. Palms DL, Hicks LA, Bartoces M, Hersh AL, Zetts R, Hyun DY, et al. First-line antibiotic selection in outpatient settings. Antimicrob Agents Chemother. 2019;63(11):e01060–19. doi: 10.1128/AAC.01060-19 31548186
49. Frost HM, McLean HQ, Chow BDW. Variability in antibiotic prescribing for upper respiratory illnesses by provider specialty. J Pediatr. 2018;203:76–85.e8. doi: 10.1016/j.jpeds.2018.07.044 30195553
50. Agiro A, Gautam S, Wall E, Hackell J, Helm M, Barron J, et al. Variation in outpatient antibiotic dispensing for respiratory infections in children by clinician specialty and treatment setting. Pediatr Infect Dis J. 2018;37(12):1248–54. doi: 10.1097/INF.0000000000002004 30408006
51. World Health Organization. WHO UNICEF review of national immunization coverage, 1980–2017. Geneva: World Health Organization; 2019 [cited 2019 Mar 22]. Available from: http://apps.who.int/immunization_monitoring/globalsummary/wucoveragecountrylist.html.
52. Williams DJ, Hall M, Shah SS, Parikh K, Tyler A, Neuman MI, et al. Narrow vs broad-spectrum antimicrobial therapy for children hospitalized with pneumonia. Pediatrics. 2013;132(5):e1141–8. doi: 10.1542/peds.2013-1614 24167170
Článek vyšel v časopise
PLOS Medicine
2020 Číslo 8
- Případ Bulovka: Jak postupují jiné nemocnice, aby podobným tragédiím zabránily?
- FDA varuje před selfmonitoringem cukru pomocí chytrých hodinek. Jak je to v Česku?
- Státní zdravotní ústav: Čeká nás „pertusový rok“
- Vědci vytvořili první funkční mozkovou tkáň pomocí 3D tisku
- Jak souvisí postcovidový syndrom s poškozením mozku?
Nejčtenější v tomto čísle
- Social distancing to slow the US COVID-19 epidemic: Longitudinal pretest–posttest comparison group study
- Coming together to improve access to medicines: The genesis of the East African Community’s Medicines Regulatory Harmonization initiative
- Age and the association between apolipoprotein E genotype and Alzheimer disease: A cerebrospinal fluid biomarker–based case–control study
- A clinical algorithm for same-day HIV treatment initiation in settings with high TB symptom prevalence in South Africa: The SLATE II individually randomized clinical trial