Impact of decreasing cerebrospinal fluid enterovirus PCR turnaround time on costs and management of children with suspected enterovirus meningitis

  • Mohammad Alghounaim
  • Chelsea Caya
  • MinGi Cho
  • Marc Beltempo
  • Cedric P. Yansouni
  • Nandini Dendukuri
  • Jesse PapenburgEmail author
Original Article


To estimate the impact of implementing in-hospital enterovirus (EV) polymerase chain reaction (PCR) testing of cerebrospinal fluid (CSF) with same-day turn-around-time (TAT) on length-of-stay (LOS), antibiotic use and on cost per patient with suspected EV meningitis, compared with testing at an outside reference laboratory. A model-based analysis using a retrospective cohort of all hospitalized children with CSF EV PCR testing done between November 2013 and 2017. The primary outcome measured was the potential date of discharge if the EV PCR result had been available on the same day. Patients with positive EV PCR were considered for potential earlier discharge once clinically stable with no reason for hospitalization other than intravenous antibiotics. Descriptive statistics and cost-sensitivity analyses were performed. CSF EV PCR testing was done on 153 patients, of which 44 (29%) had a positive result. Median test TAT was 5.3 days (IQR 3.9–7.6). Median hospital LOS was 5 days (IQR 3–12). Most (86%) patients received intravenous antibiotics with mean duration of 5.72 ± 6.51 days. No patients with positive EV PCR had a serious bacterial infection. We found that same-day test TAT would reduce LOS and duration of intravenous antibiotics by 0.50 days (95%CI 0.33–0.68) and 0.67 days (95%CI 0.42–0.91), respectively. Same-day test TAT was associated with a cost reduction of 342.83CAD (95%CI 178.14–517.00) per patient with suspected EV meningitis. Compared with sending specimens to a reference laboratory, performing CSF EV PCR in-hospital with same-day TAT was associated with decreased LOS, antibiotic therapy, and cost per patient.


Molecular diagnostic techniques Central nervous system Economic evaluation Simulated cohort Pleocytosis Infant Newborn 



Canadian dollar


Central nervous system


Cerebrospinal fluid




Length of stay


McGill University Health Centre


Polymerase chain reaction


Serious bacterial infection




Funding information

This work was supported by the Fonds de recherche Québec santé (to J.P. and C.P.Y.). The funder had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The other authors received no external funding. The authors have no financial disclosures to declare.

Compliance with ethical standards

This study was approved by the McGill University Health Centre research ethics board (2018–4190).

Conflict of interest

J.P. has received consulting/honoraria fees or research grant funding outside of the current work from the following: AbbVie; BD Diagnostics; Cepheid; MedImmune; Hoffmann-La Roche; Jannsen Pharmaceutical; Seegene. C.C. has received honoraria fees outside of the current work from Roche Diagnostics Canada. C.P.Y. has received in-kind support for investigator-initiated research projects from bioMérieux and BD Diagnostics in the last 3 years. The remaining authors declare no conflicts of interest.


  1. 1.
    Rotbart HA (1995) Enteroviral infections of the central nervous system. Clin Infect Dis 20(4):971–981CrossRefGoogle Scholar
  2. 2.
    Rudolph H, Schroten H, Tenenbaum T (2016) Enterovirus infections of the central nervous system in children: an update. Pediatr Infect Dis J 35(5):567–569CrossRefGoogle Scholar
  3. 3.
    Wallace SS, Lopez MA, Caviness AC (2017) Impact of enterovirus testing on resource use in febrile young infants: a systematic review. Hosp Pediatr 7(2):96–102CrossRefGoogle Scholar
  4. 4.
    King RL, Lorch SA, Cohen DM, Hodinka RL, Cohn KA, Shah SS (2007) Routine cerebrospinal fluid enterovirus polymerase chain reaction testing reduces hospitalization and antibiotic use for infants 90 days of age or younger. Pediatrics 120(3):489–496CrossRefGoogle Scholar
  5. 5.
    Ramers C, Billman G, Hartin M, Ho S, Sawyer MH (2000) Impact of a diagnostic cerebrospinal fluid enterovirus polymerase chain reaction test on patient management. JAMA 283(20):2680–2685CrossRefGoogle Scholar
  6. 6.
    Archimbaud C, Chambon M, Bailly JL, Petit I, Henquell C, Mirand A, Aublet-Cuvelier B, Ughetto S, Beytout J, Clavelou P, Labbe A, Philippe P, Schmidt J, Regagnon C, Traore O, Peigue-Lafeuille H (2009) Impact of rapid enterovirus molecular diagnosis on the management of infants, children, and adults with aseptic meningitis. J Med Virol 81(1):42–48CrossRefGoogle Scholar
  7. 7.
    Leber AL, Everhart K, Balada-Llasat JM, Cullison J, Daly J, Holt S, Lephart P, Salimnia H, Schreckenberger PC, DesJarlais S, Reed SL, Chapin KC, LeBlanc L, Johnson JK, Soliven NL, Carroll KC, Miller JA, Dien Bard J, Mestas J, Bankowski M, Enomoto T, Hemmert AC, Bourzac KM (2016) Multicenter evaluation of BioFire FilmArray meningitis/encephalitis panel for detection of Bacteria, viruses, and yeast in cerebrospinal fluid specimens. J Clin Microbiol 54(9):2251–2261CrossRefGoogle Scholar
  8. 8.
    Giulieri SG, Chapuis-Taillard C, Manuel O, Hugli O, Pinget C, Wasserfallen JB, Sahli R, Jaton K, Marchetti O, Meylan P (2015) Rapid detection of enterovirus in cerebrospinal fluid by a fully-automated PCR assay is associated with improved management of aseptic meningitis in adult patients. J Clin Virol 62:58–62CrossRefGoogle Scholar
  9. 9.
    Panuganti SKN, S. (2018) Acute bacterial meningitis beyond the neonatal period. In: Long SSP, C. G.; Fischer, M. (ed) Principles and Practice of Pediatric Infectious Diseases. Elsevier, pp 278-287.e272Google Scholar
  10. 10.
    Thomson J, Sucharew H, Cruz AT, Nigrovic LE, Freedman SB, Garro AC, Balamuth F, Mistry RD, Arms JL, Ishimine PT, Kulik DM, Neuman MI, Shah SS, Pediatric Emergency Medicine Collaborative Research Committee HSVSG (2018) Cerebrospinal fluid reference values for young infants undergoing lumbar puncture. Pediatrics 141(3):e20173405CrossRefGoogle Scholar
  11. 11.
    Kestenbaum LA, Ebberson J, Zorc JJ, Hodinka RL, Shah SS (2010) Defining cerebrospinal fluid white blood cell count reference values in neonates and young infants. Pediatrics 125(2):257–264CrossRefGoogle Scholar
  12. 12.
    Semret M, Schiller I, Jardin BA, Frenette C, Loo VG, Papenburg J, McNeil SA, Dendukuri N (2017) Multiplex respiratory virus testing for antimicrobial stewardship: a prospective assessment of antimicrobial use and clinical outcomes among hospitalized adults. J Infect Dis 216(8):936–944CrossRefGoogle Scholar
  13. 13.
    AlGhounaim M, Xiao Y, Caya C, Papenburg J (2017) Diagnostic yield and clinical impact of routine cell culture for respiratory viruses among children with a negative multiplex RT-PCR result. J Clin Virol 94:107–109CrossRefGoogle Scholar
  14. 14.
    Biondi EA, McCulloh R, Staggs VS, Garber M, Hall M, Arana J, Barsotti B, Natt BC, Schroeder AR, Schroeder L, Wylie T, Ralston SL (2019) Reducing variability in the infant sepsis evaluation (REVISE): a National Quality Initiative. Pediatrics 144(3)CrossRefGoogle Scholar
  15. 15.
    McCulloh RJ, Fouquet SD, Herigon J, Biondi EA, Kennedy B, Kerns E, DePorre A, Markham JL, Chan YR, Nelson K, Newland JG (2018) Development and implementation of a mobile device-based pediatric electronic decision support tool as part of a national practice standardization project. J Am Med Inform Assoc 25(9):1175–1182CrossRefGoogle Scholar
  16. 16.
    Byington CL, Reynolds CC, Korgenski K, Sheng X, Valentine KJ, Nelson RE, Daly JA, Osguthorpe RJ, James B, Savitz L, Pavia AT, Clark EB (2012) Costs and infant outcomes after implementation of a care process model for febrile infants. Pediatrics 130(1):e16–e24CrossRefGoogle Scholar
  17. 17.
    Timurkan MO, Aydin H, Sait A (2019) Identification and molecular characterisation of bovine parainfluenza virus-3 and bovine respiratory syncytial virus - first report from Turkey. J 63(2):167–173Google Scholar
  18. 18.
    Otto MP, Toyer AL, Poggi C, Janvier F (2019) Influenza B false-positive results by rapid molecular tests AlereTM i influenza a&B 2 in France. Diagn Microbiol Infect Dis 94(4):342–343CrossRefGoogle Scholar
  19. 19.
    Robinson CC, Willis M, Meagher A, Gieseker KE, Rotbart H, Glode MP (2002) Impact of rapid polymerase chain reaction results on management of pediatric patients with enteroviral meningitis. Pediatr Infect Dis J 21(4):283–286CrossRefGoogle Scholar
  20. 20.
    Aronson PL, Lyons TW, Cruz AT, Freedman SB, Okada PJ, Fleming AH, Arms JL, Thompson AD, Schmidt SM, Louie J, Alfonzo MJ, Monuteaux MC, Nigrovic LE, Pediatric Emergency Medicine Clinical Research Network Herpes Simplex Virus Study G (2017) Impact of enteroviral polymerase chain reaction testing on length of stay for infants 60 days old or younger. J Pediatr 189(169–174):e162Google Scholar
  21. 21.
    Nigrovic LE, Chiang VW (2000) Cost analysis of enteroviral polymerase chain reaction in infants with fever and cerebrospinal fluid pleocytosis. Arch Pediatr Adolesc Med 154(8):817–821CrossRefGoogle Scholar
  22. 22.
    Basmaci R, Mariani P, Delacroix G, Azib S, Faye A, Taha MK, Bingen E, Bonacorsi S, Romero JR, Rotbart HA, Nyquist AC, Nolte FS (2011) Enteroviral meningitis does not exclude concurrent bacterial meningitis. J Clin Microbiol 49(9):3442–3443CrossRefGoogle Scholar
  23. 23.
    Asner SA, Petrich A, Hamid JS, Mertz D, Richardson SE, Smieja M (2014) Clinical severity of rhinovirus/enterovirus compared to other respiratory viruses in children. Influenza Other Respir Viruses 8(4):436–442CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Division of Pediatric Infectious Diseases, Department of PediatricsMontreal Children’s Hospital, McGill University Health CentreMontrealCanada
  2. 2.Division of Microbiology, Department of Clinical Laboratory MedicineMcGill University Health CentreMontrealCanada
  3. 3.Centre for Outcomes Research and Evaluation, McGill University Health Centre – Research Institute, Montreal, Quebec, CanadaMcGill UniversityMontrealCanada
  4. 4.Division of Neonatology, Department PediatricsMontreal Children’s Hospital, McGill University Health CentreMontrealCanada
  5. 5.Division of Infectious Diseases, Department of MedicineMcGill University Health CentreMontrealCanada
  6. 6.Department of Epidemiology, Biostatistics and Occupational HealthMcGill UniversityMontrealCanada
  7. 7.The Montreal Children’s HospitalMontréalCanada

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