Evaluation of a clinical decision rule to guide antibiotic prescription in children with suspected lower respiratory tract infection in The Netherlands: A stepped-wedge cluster randomised trial
Autoři:
Josephine S. van de Maat aff001; Daphne Peeters aff002; Daan Nieboer aff003; Anne-Marie van Wermeskerken aff004; Frank J. Smit aff005; Jeroen G. Noordzij aff006; Gerdien Tramper-Stranders aff007; Gertjan J. A. Driessen aff002; Charlie C. Obihara aff008; Jeanine Punt aff009; Johan van der Lei aff010; Suzanne Polinder aff003; Henriette A. Moll aff001; Rianne Oostenbrink aff001
Působiště autorů:
Department of General Paediatrics, Erasmus MC–Sophia Children’s Hospital, Rotterdam, The Netherlands
aff001; Department of Paediatrics, HAGA–Juliana Children’s Hospital, Den Haag, The Netherlands
aff002; Department of Public Health, Erasmus MC, Rotterdam, The Netherlands
aff003; Department of Paediatrics, Flevoziekenhuis, Almere, The Netherlands
aff004; Department of Paediatrics, Maasstad Ziekenhuis, Rotterdam, The Netherlands
aff005; Department of Paediatrics, Reinier de Graaf Gasthuis, Delft, The Netherlands
aff006; Department of Paediatrics, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands
aff007; Department of Paediatrics, Elisabeth–TweeSteden Ziekenhuis, Tilburg, The Netherlands
aff008; Department of Paediatrics, LangeLand Ziekenhuis, Zoetermeer, The Netherlands
aff009; Department of Medical Informatics, Erasmus MC, Rotterdam, The Netherlands
aff010
Vyšlo v časopise:
Evaluation of a clinical decision rule to guide antibiotic prescription in children with suspected lower respiratory tract infection in The Netherlands: A stepped-wedge cluster randomised trial. PLoS Med 17(1): e32767. doi:10.1371/journal.pmed.1003034
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pmed.1003034
Souhrn
Background
Optimising the use of antibiotics is a key component of antibiotic stewardship. Respiratory tract infections (RTIs) are the most common reason for antibiotic prescription in children, even though most of these infections in children under 5 years are viral. This study aims to safely reduce antibiotic prescriptions in children under 5 years with suspected lower RTI at the emergency department (ED), by implementing a clinical decision rule.
Methods and findings
In a stepped-wedge cluster randomised trial, we included children aged 1–60 months presenting with fever and cough or dyspnoea to 8 EDs in The Netherlands. The EDs were of varying sizes, from diverse geographic and demographic regions, and of different hospital types (tertiary versus general). In the pre-intervention phase, children received usual care, according to the Dutch and NICE guidelines for febrile children. During the intervention phase, a validated clinical prediction model (Feverkidstool) including clinical characteristics and C-reactive protein (CRP) was implemented as a decision rule guiding antibiotic prescription. The intervention was that antibiotics were withheld in children with a low or intermediate predicted risk of bacterial pneumonia (≤10%, based on Feverkidstool). Co-primary outcomes were antibiotic prescription rate and strategy failure. Strategy failure was defined as secondary antibiotic prescriptions or hospitalisations, persistence of fever or oxygen dependency up to day 7, or complications. Hospitals were randomly allocated to 1 sequence of treatment each, using computer randomisation. The trial could not be blinded. We used multilevel logistic regression to estimate the effect of the intervention, clustered by hospital and adjusted for time period, age, sex, season, ill appearance, and fever duration; predicted risk was included in exploratory analysis. We included 999 children (61% male, median age 17 months [IQR 9 to 30]) between 1 January 2016 and 30 September 2018: 597 during the pre-intervention phase and 402 during the intervention phase. Most children (77%) were referred by a general practitioner, and half of children were hospitalised. Intention-to-treat analyses showed that overall antibiotic prescription was not reduced (30% to 25%, adjusted odds ratio [aOR] 1.07 [95% CI 0.57 to 2.01, p = 0.75]); strategy failure reduced from 23% to 16% (aOR 0.53 [95% CI 0.32 to 0.88, p = 0.01]). Exploratory analyses showed that the intervention influenced risk groups differently (p < 0.01), resulting in a reduction in antibiotic prescriptions in low/intermediate-risk children (17% to 6%; aOR 0.31 [95% CI 0.12 to 0.81, p = 0.02]) and a non-significant increase in the high-risk group (47% to 59%; aOR 2.28 [95% CI 0.84 to 6.17, p = 0.09]). Two complications occurred during the trial: 1 admission to the intensive care unit during follow-up and 1 pleural empyema at day 10 (both unrelated to the study intervention). Main limitations of the study were missing CRP values in the pre-intervention phase and a prolonged baseline period due to logistical issues, potentially affecting the power of our study.
Conclusions
In this multicentre ED study, we observed that a clinical decision rule for childhood pneumonia did not reduce overall antibiotic prescription, but that it was non-inferior to usual care. Exploratory analyses showed fewer strategy failures and that fewer antibiotics were prescribed in low/intermediate-risk children, suggesting improved targeting of antibiotics by the decision rule.
Trial registration
Netherlands Trial Register NTR5326.
Klíčová slova:
Antibiotics – Critical care and emergency medicine – Fevers – Forecasting – Netherlands – Oxygen – Physicians – Bacterial pneumonia
Zdroje
1. 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(4):382–91. doi: 10.1016/S1473-3099(18)30672-8 30827808
2. Tramper-Stranders GA. Childhood community-acquired pneumonia: a review of etiology- and antimicrobial treatment studies. Paediatr Respir Rev. 2018;26:41–8. doi: 10.1016/j.prrv.2017.06.013 28844414
3. GBD 2016 Lower Respiratory Infections Collaborators. Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory infections in 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Infect Dis. 2018;18(11):1191–210. doi: 10.1016/S1473-3099(18)30310-4 30243584
4. Cassini A, Hogberg LD, Plachouras D, Quattrocchi A, Hoxha A, Simonsen GS, et al. Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis. Lancet Infect Dis. 2019;19(1):56–66. doi: 10.1016/S1473-3099(18)30605-4 30409683
5. van Houten CB, Cohen A, Engelhard D, Hays JP, Karlsson R, Moore E, et al. Antibiotic misuse in respiratory tract infections in children and adults-a prospective, multicentre study (TAILORED Treatment). Eur J Clin Microbiol Infect Dis. 2019;38(3):505–14. doi: 10.1007/s10096-018-03454-2 30707378
6. Kronman MP, Zhou C, Mangione-Smith R. Bacterial prevalence and antimicrobial prescribing trends for acute respiratory tract infections. Pediatrics. 2014;134(4):e956–65. doi: 10.1542/peds.2014-0605 25225144
7. Bradley JS, Byington CL, Shah SS, Alverson B, Carter ER, Harrison C, et al. The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis. 2011;53(7):e25–76. doi: 10.1093/cid/cir531 21880587
8. Harris M, Clark J, Coote N, Fletcher P, Harnden A, McKean M, et al. British Thoracic Society guidelines for the management of community acquired pneumonia in children: update 2011. Thorax. 2011;66(Suppl 2):ii1–23.
9. Kapasi AJ, Dittrich S, Gonzalez IJ, Rodwell TC. Host biomarkers for distinguishing bacterial from non-bacterial causes of acute febrile illness: a comprehensive review. PLoS ONE. 2016;11(8):e0160278. doi: 10.1371/journal.pone.0160278 27486746
10. van Houten CB, de Groot JAH, Klein A, Srugo I, Chistyakov I, de Waal W, et al. A host-protein based assay to differentiate between bacterial and viral infections in preschool children (OPPORTUNITY): a double-blind, multicentre, validation study. Lancet Infect Dis. 2017;17(4):431–40. doi: 10.1016/S1473-3099(16)30519-9 28012942
11. Engelmann I, Dubos F, Lobert PE, Houssin C, Degas V, Sardet A, et al. Diagnosis of viral infections using myxovirus resistance protein A (MxA). Pediatrics. 2015;135(4):e985–93. doi: 10.1542/peds.2014-1946 25802344
12. 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
13. Irwin AD, Grant A, Williams R, Kolamunnage-Dona R, Drew RJ, Paulus S, et al. Predicting risk of serious bacterial infections in febrile children in the emergency department. Pediatrics. 2017;140(2):e20162853. doi: 10.1542/peds.2016-2853 28679639
14. de Vos-Kerkhof E, Nijman RG, Vergouwe Y, Polinder S, Steyerberg EW, van der Lei J, et al. Impact of a clinical decision model for febrile children at risk for serious bacterial infections at the emergency department: a randomized controlled trial. PLoS ONE. 2015;10(5):e0127620. doi: 10.1371/journal.pone.0127620 26024532
15. Reilly BM, Evans AT. Translating clinical research into clinical practice: impact of using prediction rules to make decisions. Ann Intern Med. 2006;144(3):201–9. doi: 10.7326/0003-4819-144-3-200602070-00009 16461965
16. Hussey MA, Hughes JP. Design and analysis of stepped wedge cluster randomized trials. Contemp Clin Trials. 2007;28(2):182–91. doi: 10.1016/j.cct.2006.05.007 16829207
17. 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 2019 Mar 11]. Available from: https://www.nice.org.uk/guidance/cg160.
18. Nederlandse Vereniging voor Kindergeneeskunde. Richtlijn Koorts in de tweede lijn bij kinderen van 0–16 jaar. Utrecht: Nederlandse Vereniging voor Kindergeneeskunde; 2013 [cited 2019 Jul 1]. Available from: https://www.nvk.nl/Portals/0/richtlijnen/koorts/koortsrichtlijn.pdf.
19. van de Maat J, Nieboer D, Thompson M, Lakhanpaul M, Moll H, Oostenbrink R. Can clinical prediction models assess antibiotic need in childhood pneumonia? A validation study in paediatric emergency care. PLoS ONE. 2019;14(6):e0217570. doi: 10.1371/journal.pone.0217570 31194750
20. Cordoba G, Schwartz L, Woloshin S, Bae H, Gotzsche PC. Definition, reporting, and interpretation of composite outcomes in clinical trials: systematic review. BMJ. 2010;341:c3920. doi: 10.1136/bmj.c3920 20719825
21. European Medicines Agency. ICH topic E9: statistical principles for clinical trials. Amsterdam: European Medicines Agency; 1998 [cited 2019 Nov 15]. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/ich-e-9-statistical-principles-clinical-trials-step-5_en.pdf.
22. Hemming K, Haines TP, Chilton PJ, Girling AJ, Lilford RJ. The stepped wedge cluster randomised trial: rationale, design, analysis, and reporting. BMJ. 2015;350:h391. doi: 10.1136/bmj.h391 25662947
23. Lacroix L, Manzano S, Vandertuin L, Hugon F, Galetto-Lacour A, Gervaix A. Impact of the lab-score on antibiotic prescription rate in children with fever without source: a randomized controlled trial. PLoS ONE. 2014;9(12):e115061. doi: 10.1371/journal.pone.0115061 25503770
24. Torres FA, Pasarelli I, Cutri A, Ossorio MF, Ferrero F. Impact assessment of a decision rule for using antibiotics in pneumonia: a randomized trial. Pediatr Pulmonol. 2014;49(7):701–6. doi: 10.1002/ppul.22849 24039234
25. Keitel K, Kagoro F, Samaka J, Masimba J, Said Z, Temba H, et al. A novel electronic algorithm using host biomarker point-of-care tests for the management of febrile illnesses in Tanzanian children (e-POCT): a randomized, controlled non-inferiority trial. PLoS Med. 2017;14(10):e1002411. doi: 10.1371/journal.pmed.1002411 29059253
26. Do NT, Ta NT, Tran NT, Than HM, Vu BT, Hoang LB, et al. Point-of-care C-reactive protein testing to reduce inappropriate use of antibiotics for non-severe acute respiratory infections in Vietnamese primary health care: a randomised controlled trial. Lancet Glob Health. 2016;4(9):e633–41. doi: 10.1016/S2214-109X(16)30142-5 27495137
27. Lemiengre MB, Verbakel JY, Colman R, Van Roy K, De Burghgraeve T, Buntinx F, et al. Point-of-care CRP matters: normal CRP levels reduce immediate antibiotic prescribing for acutely ill children in primary care: a cluster randomized controlled trial. Scand J Prim Health Care. 2018;36(4):423–36. doi: 10.1080/02813432.2018.1529900 30354904
28. Verbakel JY, Lee JJ, Goyder C, Tan PS, Ananthakumar T, Turner PJ, et al. Impact of point-of-care C reactive protein in ambulatory care: a systematic review and meta-analysis. BMJ Open. 2019;9(1):e025036. doi: 10.1136/bmjopen-2018-025036 30782747
29. Baer G, Baumann P, Buettcher M, Heininger U, Berthet G, Schafer J, et al. Procalcitonin guidance to reduce antibiotic treatment of lower respiratory tract infection in children and adolescents (ProPAED): a randomized controlled trial. PLoS ONE. 2013;8(8):e68419. doi: 10.1371/journal.pone.0068419 23936304
30. Verbakel JY, Lemiengre MB, De Burghgraeve T, De Sutter A, Aertgeerts B, Bullens DMA, et al. Point-of-care C reactive protein to identify serious infection in acutely ill children presenting to hospital: prospective cohort study. Arch Dis Child. 2018;103(5):420–6. doi: 10.1136/archdischild-2016-312384 29269559
31. van de Maat JS, van Klink D, den Hartogh-Griffioen A, Schmidt-Cnossen E, Rippen H, Hoek A, et al. Development and evaluation of a hospital discharge information package to empower parents in caring for a child with a fever. BMJ Open. 2018;8(8):e021697. doi: 10.1136/bmjopen-2018-021697 30166298
32. Srugo I, Klein A, Stein M, Golan-Shany O, Kerem N, Chistyakov I, et al. Validation of a novel assay to distinguish bacterial and viral infections. Pediatrics. 2017;140(4):e20163453. doi: 10.1542/peds.2016-3453 28904072
Článek vyšel v časopise
PLOS Medicine
2020 Číslo 1
- Proč jsou nemocnice nepřítelem spánku? A jak to změnit?
- Dlouhodobá ketodieta může poškozovat naše orgány
- „Jednohubky“ z klinického výzkumu – 2024/42
- Metamizol jako analgetikum první volby: kdy, pro koho, jak a proč?
- Distribuce a lokalizace speciálně upravených exosomů může zefektivnit léčbu svalových dystrofií
Nejčtenější v tomto čísle
- Association of puberty timing with type 2 diabetes: A systematic review and meta-analysis
- Advances in cervical cancer prevention: Efficacy, effectiveness, elimination?
- Infectious disease pandemic planning and response: Incorporating decision analysis
- Projected costs of single-payer healthcare financing in the United States: A systematic review of economic analyses