Bacterial meningitis in febrile young infants acutely assessed for presumed urinary tract infection: a systematic review

Abstract

Urinary tract infections, the most common severe bacterial infections in young infants, may be associated with co-existing meningitis. There is no consensus on when to perform a lumbar puncture in these infants. Our aim was to quantify the frequency of co-existing bacterial meningitis in febrile young infants acutely assessed for presumed urinary tract infections. We systematically reviewed PubMed, EMBASE, and the Cochrane Library for studies including infants ≤ 3 months with suspected/confirmed urinary tract infections, who underwent a lumbar puncture. Two investigators independently reviewed articles for inclusion and extracted relevant data. Our outcomes were culture-confirmed meningitis and identification of low-/high-risk criteria of meningitis. Overall 20/2079 studies, including 4191 infants, met inclusion criteria. A total of 11 infants had bacterial meningitis (frequency between 0 and 2.1% across studies) and were mostly neonates. Of 253 infants meeting the low-risk criteria (well-appearing, age > 21 days, procalcitonin ≤ 0.5 ng/ml, and C reactive protein ≤ 20 mg/L) none developed meningitis, but only 15 underwent lumbar puncture.

Conclusion: Co-existing bacterial meningitis in febrile young infants with urinary tract infection is rare. In those meeting low-risk criteria, a lumbar puncture may not be indicated. A case by case assessment should be made in infants not meeting low-risk criteria.

Trial registration: CRD42018105339

What is known:
When caring for febrile infants ≤ 3 months with urinary tract infections, clinicians may have uncertainty on whether to perform a lumbar puncture (LP) for possible co-existing meningitis
What is new:
An up-to-date systematic review of 20 studies found the frequency of co-existing meningitis in this population to be between 0 and 2.1%
Despite limited data, an LP may not be indicated in infants meeting low-risk criteria (being well-appearing, age > 21 days, procalcitonin ≤ 0.5 ng/ml, C reactive protein ≤ 20 mg/L). Ill-appearance and neonatal age appear to be significant risk factors of co-existing meningitis

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Fig. 1

Abbreviations

CI:

Confidence interval

ED:

Emergency department

LP:

Lumbar puncture

UTI:

Urinary tract infection

References

  1. 1.

    Watt K, Waddle E, Jhaveri R (2010) Changing epidemiology of serious bacterial infections in febrile infants without localizing signs. PLoS One 5(8):e12448. https://doi.org/10.1371/journal.pone.0012448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Byington CL, Rittichier KK, Bassett KE, Castillo H, Glasgow TS, Daly J, Pavia AT (2003) Serious bacterial infections in febrile infants younger than 90 days of age: the importance of ampicillin-resistant pathogens. Pediatrics 111(5 Pt 1):964–968

    Article  PubMed  Google Scholar 

  3. 3.

    Bressan S, Andreola B, Cattelan F, Zangardi T, Perilongo G, Da Dalt L (2010) Predicting severe bacterial infections in well-appearing febrile neonates: laboratory markers accuracy and duration of fever. Pediatr Infect Dis J 29(3):227–232. https://doi.org/10.1097/INF.0b013e3181b9a086

    Article  PubMed  Google Scholar 

  4. 4.

    Olaciregui I, Hernández U, Muñoz JA, Emparanza JI, Landa JJ (2009) Markers that predict serious bacterial infection in infants under 3 months of age presenting with fever of unknown origin. Arch Dis Child 94(7):501–505. https://doi.org/10.1136/adc.2008.146530

    Article  CAS  PubMed  Google Scholar 

  5. 5.

    Tzimenatos L, Mahajan P, Dayan PS, Vitale M, Linakis JG, Blumberg S, Borgialli D, Ruddy RM, Van Buren J, Ramilo O, Kuppermann N, (PECARN) PECARN (2018) Accuracy of the urinalysis for urinary tract infections in febrile infants 60 days and younger. Pediatrics 141(2):e20173068. https://doi.org/10.1542/peds.2017-3068

    Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Velasco R, Benito H, Mozun R, Trujillo JE, Merino PA, de la Torre M, Gomez B, Network GSFIR-S (2015) Using a urine dipstick to identify a positive urine culture in young febrile infants is as effective as in older patients. Acta Paediatr 104(1):e39–e44. https://doi.org/10.1111/apa.12789

    Article  PubMed  Google Scholar 

  7. 7.

    Roberts KB, Subcommittee on Urinary Tract Infection SeCoQIaM (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(3):595–610. https://doi.org/10.1542/peds.2011-1330

    Article  PubMed  Google Scholar 

  8. 8.

    Tebruegge M, Pantazidou A, Clifford V, Gonis G, Ritz N, Connell T, Curtis N (2011) The age-related risk of co-existing meningitis in children with urinary tract infection. PLoS One 6(11):e26576. https://doi.org/10.1371/journal.pone.0026576

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Schnadower D, Kuppermann N, Macias CG, Freedman SB, Baskin MN, Ishimine P, Scribner C, Okada P, Beach H, Bulloch B, Agrawal D, Saunders M, Sutherland DM, Blackstone MM, Sarnaik A, McManemy J, Brent A, Bennett J, Plymale JM, Solari P, Mann DJ, Dayan PS, Committee AAoPPEMCR (2010) Febrile infants with urinary tract infections at very low risk for adverse events and bacteremia. Pediatrics 126(6):1074–1083. https://doi.org/10.1542/peds.2010-0479

    Article  PubMed  Google Scholar 

  10. 10.

    Thomson J, Cruz AT, Nigrovic LE, Freedman SB, Garro AC, Ishimine PT, Kulik DM, Uspal NG, Grether-Jones KL, Miller AS, Schnadower D, Shah SS, Aronson PL, Balamuth F, Group PEMCRCPCHS (2017) Concomitant bacterial meningitis in infants with urinary tract infection. Pediatr Infect Dis J 36(9):908–910. https://doi.org/10.1097/INF.0000000000001626

    Article  PubMed  Google Scholar 

  11. 11.

    Tebruegge M, Pantazidou A, Curtis N (2011) Question 1. How common is co-existing meningitis in infants with urinary tract infection? Arch Dis Child 96(6):602–606. https://doi.org/10.1136/adc.2011.215277

    Article  PubMed  Google Scholar 

  12. 12.

    Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097. https://doi.org/10.1371/journal.pmed.1000097

    Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Lin DS, Huang SH, Lin CC, Tung YC, Huang TT, Chiu NC, Koa HA, Hung HY, Hsu CH, Hsieh WS, Yang DI, Huang FY (2000) Urinary tract infection in febrile infants younger than eight weeks of age. Pediatrics 105(2):E20

    Article  CAS  PubMed  Google Scholar 

  14. 14.

    Shah SS, Zorc JJ, Levine DA, Platt SL, Kuppermann N (2008) Sterile cerebrospinal fluid pleocytosis in young infants with urinary tract infections. J Pediatr 153(2):290–292. https://doi.org/10.1016/j.jpeds.2008.02.044

    Article  PubMed  Google Scholar 

  15. 15.

    Bonsu BK, Harper MB (2007) Leukocyte counts in urine reflect the risk of concomitant sepsis in bacteriuric infants: a retrospective cohort study. BMC Pediatr 7:24. https://doi.org/10.1186/1471-2431-7-24

    Article  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Dayan PS, Hanson E, Bennett JE, Langsam D, Miller SZ (2004) Clinical course of urinary tract infections in infants younger than 60 days of age. Pediatr Emerg Care 20(2):85–88

    Article  PubMed  Google Scholar 

  17. 17.

    Doby EH, Stockmann C, Korgenski EK, Blaschke AJ, Byington CL (2013) Cerebrospinal fluid pleocytosis in febrile infants 1-90 days with urinary tract infection. Pediatr Infect Dis J 32(9):1024–1026. https://doi.org/10.1097/INF.0b013e31829063cd

    Article  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Meehan WP, Bachur RG (2008) Predictors of cerebrospinal fluid pleocytosis in febrile infants aged 0 to 90 days. Pediatr Emerg Care 24(5):287–293. https://doi.org/10.1097/PEC.0b013e31816ecbb0

    Article  PubMed  Google Scholar 

  19. 19.

    Nosrati A, Ben Tov A, Reif S (2014) Diagnostic markers of serious bacterial infections in febrile infants younger than 90 days old. Pediatr Int 56(1):47–52. https://doi.org/10.1111/ped.12191

    Article  PubMed  Google Scholar 

  20. 20.

    Paquette K, Cheng MP, McGillivray D, Lam C, Quach C (2011) Is a lumbar puncture necessary when evaluating febrile infants (30 to 90 days of age) with an abnormal urinalysis? Pediatr Emerg Care 27(11):1057–1061. https://doi.org/10.1097/PEC.0b013e318235ea18

    Article  PubMed  Google Scholar 

  21. 21.

    Syrogiannopoulos GA, Grivea IN, Anastassiou ED, Triga MG, Dimitracopoulos GO, Beratis NG (2001) Sterile cerebrospinal fluid pleocytosis in young infants with urinary tract infection. Pediatr Infect Dis J 20(10):927–930

    Article  CAS  PubMed  Google Scholar 

  22. 22.

    Velasco R, Benito H, Mozún R, Trujillo JE, Merino PA, Mintegi S, Tiago S, Network GftSoFIotR-S (2015) Febrile young infants with altered urinalysis at low risk for invasive bacterial infection. A Spanish Pediatric Emergency Research Network's Study. Pediatr Infect Dis J 34(1):17–21. https://doi.org/10.1097/INF.0000000000000482

    Article  PubMed  Google Scholar 

  23. 23.

    Velasco R, Gómez B, Hernández-Bou S, Olaciregui I, de la Torre M, González A, Rivas A, Durán I, Rubio A (2016) Validation of a predictive model for identifying febrile young infants with altered urinalysis at low risk of invasive bacterial infection. Eur J Clin Microbiol Infect Dis 36(2):281–284. https://doi.org/10.1007/s10096-016-2798-2

    Article  CAS  PubMed  Google Scholar 

  24. 24.

    Vuillermin PJ, Starr M (2007) Investigation of the rate of meningitis in association with urinary tract infection in infants 90 days of age or younger. Emerg Med Australas 19(5):464–469. https://doi.org/10.1111/j.1742-6723.2007.01001.x

    Article  PubMed  Google Scholar 

  25. 25.

    Yam AO, Andresen D, Kesson AM, Isaacs D (2009) Incidence of sterile cerebrospinal fluid pleocytosis in infants with urinary tract infection. J Paediatr Child Health 45(6):364–367. https://doi.org/10.1111/j.1440-1754.2009.01502.x

    Article  PubMed  Google Scholar 

  26. 26.

    Adler-Shohet FC, Cheung MM, Hill M, Lieberman JM (2003) Aseptic meningitis in infants younger than six months of age hospitalized with urinary tract infections. Pediatr Infect Dis J 22(12):1039–1042. https://doi.org/10.1097/01.inf.0000100576.99266.07

    Article  PubMed  Google Scholar 

  27. 27.

    Bonadio W, Maida G (2014) Urinary tract infection in outpatient febrile infants younger than 30 days of age: a 10-year evaluation. Pediatr Infect Dis J 33(4):342–344. https://doi.org/10.1097/inf.0000000000000110

    Article  PubMed  Google Scholar 

  28. 28.

    Wallace SS, Brown DN, Cruz AT (2017) Prevalence of concomitant acute bacterial meningitis in neonates with febrile urinary tract infection: a retrospective cross-sectional study. J Pediatr 184:199–203. https://doi.org/10.1016/j.jpeds.2017.01.022

    Article  PubMed  Google Scholar 

  29. 29.

    Magín EC, García-García JJ, Sert SZ, Giralt AG, Cubells CL (2007) Efficacy of short-term intravenous antibiotic in neonates with urinary tract infection. Pediatr Emerg Care 23(2):83–86. https://doi.org/10.1097/PEC.0b013e3180302c47

    Article  PubMed  Google Scholar 

  30. 30.

    Goldman RD, Matlow A, Linett L, Scolnik D (2003) What is the risk of bacterial meningitis in infants who present to the emergency department with fever and pyuria? CJEM 5(6):394–399

    Article  PubMed  Google Scholar 

  31. 31.

    Mintegi S, Gomez B, Carro A, Diaz H, Benito J (2018) Invasive bacterial infections in young afebrile infants with a history of fever. Arch Dis Child 103(7):665–669. https://doi.org/10.1136/archdischild-2017-313578

    Article  PubMed  Google Scholar 

  32. 32.

    Davis T (2013) NICE guideline: feverish illness in children--assessment and initial management in children younger than 5 years. Arch Dis Child Educ Pract Ed 98(6):232–235. https://doi.org/10.1136/archdischild-2013-304792

    Article  PubMed  Google Scholar 

  33. 33.

    Biondi EA, Lee B, Ralston SL, Winikor JM, Lynn JF, Dixon A, McCulloh R (2019) Prevalence of bacteremia and bacterial meningitis in febrile neonates and infants in the second month of life: a systematic review and meta-analysis. JAMA Netw Open 2(3):e190874. https://doi.org/10.1001/jamanetworkopen.2019.0874

    Article  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Jaskiewicz JA, McCarthy CA, Richardson AC, White KC, Fisher DJ, Dagan R, Powell KR (1994) Febrile infants at low risk for serious bacterial infection--an appraisal of the Rochester criteria and implications for management. Febrile Infant Collaborative Study Group. Pediatrics 94(3):390–396

    CAS  PubMed  Google Scholar 

  35. 35.

    Greenhow TL, Hung YY, Herz AM (2012) Changing epidemiology of bacteremia in infants aged 1 week to 3 months. Pediatrics 129(3):e590–e596. https://doi.org/10.1542/peds.2011-1546

    Article  PubMed  Google Scholar 

  36. 36.

    Lacour AG, Zamora SA, Gervaix A (2008) A score identifying serious bacterial infections in children with fever without source. Pediatr Infect Dis J 27(7):654–656. https://doi.org/10.1097/INF.0b013e318168d2b4

    Article  PubMed  Google Scholar 

  37. 37.

    Mintegi S, Bressan S, Gomez B, Da Dalt L, Blázquez D, Olaciregui I, de la Torre M, Palacios M, Berlese P, Benito J (2014) Accuracy of a sequential approach to identify young febrile infants at low risk for invasive bacterial infection. Emerg Med J 31(e1):e19–e24. https://doi.org/10.1136/emermed-2013-202449

    Article  Google Scholar 

  38. 38.

    Tosif S, Baker A, Oakley E, Donath S, Babl FE (2012) Contamination rates of different urine collection methods for the diagnosis of urinary tract infections in young children: an observational cohort study. J Paediatr Child Health 48(8):659–664. https://doi.org/10.1111/j.1440-1754.2012.02449.x

    Article  Google Scholar 

  39. 39.

    Glissmeyer EW, Korgenski EK, Wilkes J, Schunk JE, Sheng X, Blaschke AJ, Byington CL (2014) Dipstick screening for urinary tract infection in febrile infants. Pediatrics 133(5):e1121–e1127. https://doi.org/10.1542/peds.2013-3291

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We would like to thank medical librarian Lisa Dainese, M.Ed., University of Padova (Padova, Italy), for her help in building and executing the literature search strategy.

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Authors

Contributions

Elisa Poletto and Lorenzo Zanetto designed the study protocol and built the search strategy, searched the literature and undertook selection of retrieved articles, performed data extraction and quality assessment of selected studies, drafted the initial manuscript, and reviewed and revised the manuscript.

Roberto Velasco reviewed the study protocol, contributed to drafting the manuscript, and critically reviewed and revised the manuscript for important intellectual content.

Liviana Da Dalt reviewed the study protocol, co-supervised the study conduct, and critically reviewed and revised the manuscript for important intellectual content.

Silvia Bressan conceptualized the study and designed the study protocol, supervised study selection, data extraction, and quality assessment of selected studies, drafted the initial manuscript, and reviewed and revised the manuscript.

All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Silvia Bressan.

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Elisa Poletto and Lorenzo Zanetto are joint first authors

Communicated by Nicole Ritz

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Poletto, E., Zanetto, L., Velasco, R. et al. Bacterial meningitis in febrile young infants acutely assessed for presumed urinary tract infection: a systematic review. Eur J Pediatr 178, 1577–1587 (2019). https://doi.org/10.1007/s00431-019-03442-4

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Keywords

  • Children
  • Emergency department
  • Meningitis
  • Urinary tract infection
  • Infants
  • Lumbar puncture