Impact of the lab-score on antibiotic prescription rate in children with fever without source: a randomized controlled trial

Laurence Lacroix, Sergio Manzano, Lynda Vandertuin, Florence Hugon, Annick Galetto-Lacour, Alain Gervaix, Laurence Lacroix, Sergio Manzano, Lynda Vandertuin, Florence Hugon, Annick Galetto-Lacour, Alain Gervaix

Abstract

Background: The Lab-score, based on the combined determination of procalcitonin, C-reactive protein and urinary dipstick results, has been shown accurate in detecting serious bacterial infections (SBI) in children with fever without source (FWS) on retrospective cohorts. We aimed to prospectively assess the utility of the Lab-score in safely decreasing antibiotic prescriptions in children with FWS and to determine its diagnostic characteristics compared to common SBI biomarkers.

Methods: Randomized controlled trial in children 7 days to 36 months old with FWS, allocated either to the Lab-score group (Lab-score reported, blinded WBC count) or to the control group (WBC, bands and C-reactive protein determined, blinded procalcitonin and Lab-score), followed up until recovery. Demographic data, antibiotic prescription rate, admission rate and diagnostic properties of the Lab-score were analyzed.

Results: 271 children were analyzed. No statistically significant difference concerning antibiotic prescription rate was observed: 41.2% (54 of 131) in the Lab-score group and 42.1% (59 of 140) in the control group (p = 1.000). If recommendations based on the Lab-score had been strictly applied, a hypothetical 30.6% treatment rate would have been encountered, compared to the overall 41.7% observed rate (p = 0.0095). A Lab-score ≥3 showed the following characteristics: sensitivity 85.1% (95% CI: 76.5-93.6%), specificity 87.3% (95% CI: 82.7-91.8%), positive predictive value 68.7% (95% CI: 58.7-78.7%), negative predictive value 94.1% (95% CI: 91.5-97.9%), positive and negative likelihood ratios: 6.68 and 0.17 respectively. Area under the receiver operating characteristic curve was best for the Lab-score (0.911, 95% CI: 0.871-0.950).

Discussion: No difference regarding antibiotic treatment rate was observed when using the Lab-score, due to lack of adherence to the related recommendations. However, if strictly followed, a significant 26.5% reduction of antibiotic prescriptions would have been encountered. Medical education needs to be reinforced in order to observe rather than treat low-risk well-appearing children with FWS.

Trial registration: ClinicalTrials.gov NCT02179398.

Conflict of interest statement

Competing Interests: The authors have thus provided an amended statement of competing interests that explicitly states that this commercial funder has no relationship relating to employment, consultancy, patents, products in development, marketed products, etc. with any of the authors. This does not alter the authors' adherence to all PLOS ONE policies on sharing data and materials, as detailed in the guide for authors (page 20, line 9-12).

Figures

Figure 1. Search results on CONSORT Flow…
Figure 1. Search results on CONSORT Flow Diagram (Consolidated Standards of Reporting Trials).
Figure 2. Receiver operating characteristic curve for…
Figure 2. Receiver operating characteristic curve for Lab-score, PCT, CRP, WBC and band counts for SBI detection in children 0-3 years (A) and in children

References

    1. Baraff LJ (2000) Management of fever without source in infants and children. Ann Emerg Med 36:602–614.
    1. Simon AE, Lukacs SL, Mendola P (2013) National trends in emergency department use of urinalysis, complete blood count, and blood culture for fever without a source among children aged 2 to 24 months in the pneumococcal conjugate vaccine 7 era. Pediatr Emerg Care 29:560–567.
    1. Craig JC, Williams GJ, Jones M, Codarini M, Macaskill P, et al. (2010) 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 340:c1594.
    1. McCarthy PL, Sharpe MR, Spiesel SZ, Dolan TF, Forsyth BW, et al. (1982) Observation scales to identify serious illness in febrile children. Pediatrics 70:802–809.
    1. McCarthy PL, Lembo RM, Baron MA, Fink HD, Cicchetti DV (1985) Predictive value of abnormal physical examination findings in ill-appearing and well-appearing febrile children. Pediatrics 76:167–171.
    1. Baraff LJ, Bass JW, Fleisher GR, Klein JO, McCracken GH Jr, et al. (1993) Practice guideline for the management of infants and children 0 to 36 months of age with fever without source. Agency for Health Care Policy and Research. Ann Emerg Med 22:1198–1210.
    1. Baraff LJ (2008) Management of infants and young children with fever without source. Pediatr Ann 37:673–679.
    1. Manzano S, Bailey B, Gervaix A, Cousineau J, Delvin E, et al. Markers for bacterial infection in children with fever without source. Arch Dis Child 96:440–446.
    1. Andreola B, Bressan S, Callegaro S, Liverani A, Plebani M, et al. (2007) Procalcitonin and C-reactive protein as diagnostic markers of severe bacterial infections in febrile infants and children in the emergency department. Pediatr Infect Dis J 26:672–677.
    1. Lacour AG, Gervaix A, Zamora SA, Vadas L, Lombard PR, et al. (2001) Procalcitonin, IL-6, IL-8, IL-1 receptor antagonist and C-reactive protein as identificators of serious bacterial infections in children with fever without localising signs. Eur J Pediatr 160:95–100.
    1. Manzano S, Bailey B, Girodias JB, Galetto-Lacour A, Cousineau J, et al. Impact of procalcitonin on the management of children aged 1 to 36 months presenting with fever without source: a randomized controlled trial. Am J Emerg Med 28:647–653.
    1. Irwin AD, Carrol ED (2011) Procalcitonin. Arch Dis Child Educ Pract Ed 96:228–233.
    1. Maniaci V, Dauber A, Weiss S, Nylen E, Becker KL, et al. (2008) Procalcitonin in young febrile infants for the detection of serious bacterial infections. Pediatrics 122:701–710.
    1. Mahajan P, Grzybowski M, Chen X, Kannikeswaran N, Stanley R, et al. (2014) Procalcitonin as a marker of serious bacterial infections in febrile children younger than 3 years old. Acad Emerg Med 21:171–179.
    1. Galetto-Lacour A, Gervaix A. Identifying severe bacterial infection in children with fever without source. Expert Rev Anti Infect Ther 8:1231–1237.
    1. Lacour AG, Zamora SA, Gervaix A (2008) A score identifying serious bacterial infections in children with fever without source. Pediatr Infect Dis J 27:654–656.
    1. Galetto-Lacour A, Zamora SA, Andreola B, Bressan S, Lacroix L, et al. (2010) Validation of a laboratory risk index score for the identification of severe bacterial infection in children with fever without source. Arch Dis Child 95:968–973.
    1. Lacroix L, Manzano S, Galetto A, Gervaix A (2012) Procalcitonin measurement for detection of serious bacterial infection in febrile children: comparison between two automated immunoassays. Clin Biochem 45:593–595.
    1. Subcommittee on Urinary Tract Infection SCoQI, Management Roberts KB (2011) Urinary tract infection: clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics 128:595–610.
    1. Benador N, Siegrist CA, Gendrel D, Greder C, Benador D, et al. (1998) Procalcitonin is a marker of severity of renal lesions in pyelonephritis. Pediatrics 102:1422–1425.
    1. Luthander J, Bennet R, Giske CG, Nilsson A, Eriksson M (2013) Age and risk factors influence the microbial aetiology of bloodstream infection in children. Acta Paediatr 102:182–186.
    1. Herz AM, Greenhow TL, Alcantara J, Hansen J, Baxter RP, et al. (2006) Changing epidemiology of outpatient bacteremia in 3- to 36-month-old children after the introduction of the heptavalent-conjugated pneumococcal vaccine. Pediatr Infect Dis J 25:293–300.
    1. Sard B, Bailey MC, Vinci R (2006) An analysis of pediatric blood cultures in the postpneumococcal conjugate vaccine era in a community hospital emergency department. Pediatr Emerg Care 22:295–300.
    1. Basmaci R, Mariani P, Delacroix G, Azib S, Faye A, et al. (2011) Enteroviral meningitis does not exclude concurrent bacterial meningitis. J Clin Microbiol 49:3442–3443.
    1. Massin MM, Montesanti J, Lepage P (2006) Management of fever without source in young children presenting to an emergency room. Acta Paediatr 95:1446–1450.
    1. Holstiege J, Garbe E (2013) Systemic antibiotic use among children and adolescents in Germany: a population-based study. Eur J Pediatr 172:787–795.
    1. Belfer RA, Gittelman MA, Muniz AE (2001) Management of febrile infants and children by pediatric emergency medicine and emergency medicine: comparison with practice guidelines. Pediatr Emerg Care 17:83–87.
    1. Bressan S, Berlese P, Mion T, Masiero S, Cavallaro A, et al. (2012) Bacteremia in feverish children presenting to the emergency department: a retrospective study and literature review. Acta Paediatr 101:271–277.
    1. Hsu HE, Shutt KA, Moore MR, Beall BW, Bennett NM, et al. (2009) Effect of pneumococcal conjugate vaccine on pneumococcal meningitis. N Engl J Med 360:244–256.
    1. Chiappini E, Galli L, Bonsignori F, Venturini E, Principi N, et al. (2009) Self-reported pediatricians' management of the well-appearing young child with fever without a source: first survey in an European country in the anti-pneumococcal vaccine era. BMC Public Health 9:300.
    1. Gabriel ME, Aiuto L, Kohn N, Barone SR (2004) Management of febrile children in the conjugate pneumococcal vaccine era. Clin Pediatr (Phila) 43:75–82.
    1. Arora R, Mahajan P (2013) Evaluation of child with fever without source: review of literature and update. Pediatr Clin North Am 60:1049–1062.
    1. Guyatt GH, Haynes RB, Jaeschke RZ, Cook DJ, Green L, et al. (2000) Users' Guides to the Medical Literature: XXV. Evidence-based medicine: principles for applying the Users' Guides to patient care. Evidence-Based Medicine Working Group. JAMA 284:1290–1296.
    1. Mintegi S, Bressan S, Gomez B, Da Dalt L, Blazquez D, et al.. (2013) Accuracy of a sequential approach to identify young febrile infants at low risk for invasive bacterial infection. Emerg Med J.
    1. Bressan S, Gomez B, Mintegi S, Da Dalt L, Blazquez D, et al. (2012) Diagnostic performance of the lab-score in predicting severe and invasive bacterial infections in well-appearing young febrile infants. Pediatr Infect Dis J 31:1239–1244.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera