Pediatric fever of uncertain source

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Background

  • Medicine is an art as well as science, practice clinical judgment when using guidelines
  • Preemies: Count age by estimated postconception date (not by actual delivery date) for 1st-90d
  • Fever accounts for 30% of pediatric visits
  • Children <3 mo are immunocompromised- poor opsonization, poor IgG response to encapsulated bacteria, macrophage and neutrophil dysfunction, bone marrow insufficiency
  • Serious bacterial illness (SBI) includes UTI, meningitis, pneumonia, bacteremia
Age 0-14 days 14-28 days 28-60 days (pre vaccine) 28-60 days (post vaccine) 60-90 days > 90 days
Meningitis/SBI Prevalence 1/10 1/20 1/100 1/1000 1/1000-10,000 > 1/10,000

Facts and Figures

From ACEP's Clinical Policy on Pediatric Fevers[1]

  • 7% of patients < 2 years old with fever have pneumonia, however the etiology (viral/bacterial) or even the presence of pneumonia has low inter-observer reliability even among pediatric radiologists
  • 4% Prevalence of UTI with common other sources of fever (OM, viral URI, et cetera)
  • 1.5-2% background prevalence of asymptomatic bacteruria in healthy afebrile controls
  • 0.3% Rate of occult bactremia with healthy, well-appearing child who has a fever 2-24 months
  • 0.3% of previously well children aged 3-36 months who have a fever without a source will develop significant sequelae, 0.03% will develop sepsis or meningitis

Concomitant RSV or Influenza Infection

  • Relatively high coincidence of bronchiolitis w/ UTI, and of enterovirus and paraflu w/ UTI and bacteremia
  • In RSV+ (by PCR) neonates aged 0-28 days, 6.1% had UTIs and 3.7% were bactremic; there was no difference in rates of SBI between RSV+ and RSV- neonates in a large prospective multicenter study entailing 1,248 children[2]
  • RSV+ infants aged 29-60 days, the SBI rate was 5.5%, all of which were UTIs
  • Influenza+, low risk of bacterial illness

Evolving Practices for Febrile Infants 0-60 days (2019 JAMA Peds)[3]

  • Prospective multicenter observational study with 1821 patients split into derivation and validation groups.
  • Inclusion fever >38C in ED or in past 24 hours measured.
  • Exclusion premature < 36 weeks, previously known diagnosis/illness, or severe illness.
  • Incidence of SBI in cohort 9.3% (8.3% UTI)
  • Following elements had 97.7% sensitivity and 60% specificity for SBI
    • ANC of 4090 or less
    • Procalcitonin 1.71 or less
    • Negative urinalysis
  • No cases of bacterial meningitis missed. 3 missed SBI, all of which were > 28 days.
  • May lead to decreased unnecessary LPs, will have variable adoption pending further validated studies/applications.

Differential Diagnosis

Pediatric fever

Evaluation & Management

Algorithm for the evaluation of pediatric fever

0-28dy

  • SBI in ill-appearing febrile neonate as high as 20%
  • SBI in well-appearing febrile neonate as high as 5%
Child Appearance Work Up Treatment Disposition & Follow-up Comments
Temperature ≥38°

Toxic or Well

  • CBC
  • Blood cultures
  • Urinalysis, Urine culture
  • LP-CSF
  • CXR
  • +/- Stool studies (if diarrhea)
Admit SBI incidence
  • Ill appearing: 13%–21%
  • Not ill appearing: <5%

^Acyclovir if:

  • HSV infection in baby or mother
  • CSF pleocytoisis
  • Concerning skin lesions
  • Seizures
  • Abnormal LFTs

Note:

  • CXR is optional if no resp sx and another source identified
  • LP is necessary even if another source identified due to immature blood-brain barrier
  • Do not give ceftriaxone to children <28d as may cause hyperbilirubinemia

28dy-90dy[4]

Appearance Work Up Treatment Disposition & Follow-Up
Temp≥38° + Toxic
  • CBC
  • Blood cultures
  • Urinalysis, Urine culture
  • LP-CSF
  • +/- CXR
  • +/- Stool studies (if diarrhea)
Admit

Temp≥°38 + Well

  • CBC
  • Blood cultures
  • Urinalysis, urine culture
  • +/- LP-CSF (must do before giving antibiotics)
  • +/- CXR
Workup(+): Antibiotics and admit

Workup(-): ?antibiotics; home with 24 follow-up

^^Can use ceftriaxone 50-100mg/kg, but concern for bilirubin displacement

  • Consider CXR for:
    • Respiratory symptoms
    • Fever >48 hrs
    • Tachypnea
    • Hypoxia

^Acyclovir if:

  • HSV infection in baby or mother
  • CSF pleocytoisis
  • Concerning skin lesions
  • Seizures
  • Abnormal LFTs

90dy-36mo[5]

Appearance Work Up Treatment Disposition & Follow-Up
T≥38° + Toxic Admit
T≥39°C + Well + Non-complete Prevnar

(No Prevnar or <4 weeks post 1st Prevnar dose)

If WBC(+): Outpatient (24 hour follow-up)
T≥39°C + Well + Prevnar

(2 Prevnar or ≥4 weeks post 1st Prevnar dose)

  • Urine workup (UA, urine culture) for:
    • Circumcised males <6 months
    • Uncircumcised males <12 months
    • All females
  • +/- CXR
Treat cystitis or pneumonia if postitive Outpatient (48hour follow up)
T≥38-38.9°C + Well Consider UA, CXR based on symptoms, etc Treat cystitis or pneumonia if positive Outpatient (48-72 hour follow-up)[6]
  • Consider CXR for:
    • Respiratory symptoms
    • Fever >48 hrs
    • Tachypnea
    • Hypoxia
  • Non-UTI SBI incidence of <.4% in children >6 mo

Low Risk Lab Criteria

If low-risk criteria below not met, then perform the LP (if not done) and admit for inpatient antibiotics[7][8]

CBC

  • WBC 5-15 /mm3
  • Absolute Band count <1500 /mm3

Urinalysis

  • Clear
  • Neg Nitrate and Leukocyte esterase
  • WBC <10/high powered field

CSF

0-28 days

  • WBC: 0-22/mm3
  • Protein: <100mg/dL

>29 days

  • WBC 0-7/mm3
  • Protein: 15-25mg/dL

Low Risk by Step-By-Step Approach[9]

Study validated against Rocheter criteria and Lab-score for identifying low risk for invasive bacterial infections (IBI), with NPV ~98%

  • Well appearing
  • Age > 21 days
  • No leukocyturia
  • Procalcitonin < 0.5 ng/mL
  • ANC < 10,000/mm3
  • CRP < 20 mg/L

Low Risk Management[10]

  • Offer no LP, no antibiotics, 24 hrs observation
  • Plan for prompt follow-up

Symptomatic Managment

Acetaminophen Pediatric Dosing Chart

Weight (kg) Weight (lbs) Age Dosage (mg)
3-4 6-11 0-3 mo 40
5-7 12-17 4-11 mo 80
8-10 18-23 1-2 y 120
11-15 24-35 2-3 y 160
16-21 36-47 4-5 y 240
22-26 48-59 6-8 y 320
27-32 60-71 9-10 y 400
33-43 72-95 11 y 480
Dosage can be given q6hours

See Also

External Links

References

  1. Clinical Policy for Children Younger Than Three Years Presenting to the Emergency Department With Fever. Annuals of Emergency Medicine 2003 42. 530-545
  2. Greenes, D.S.M., & Harper, M. B.M. (1999). Low risk of bacteremia in febrile children with recognizable viral syndromes. Pediatric Infectious Disease Journal, 18(3), 258-261.
  3. Kuppermann N, Dayan PS, Levine DA, et al. A Clinical Prediction Rule to Identify Febrile Infants 60 Days and Younger at Low Risk for Serious Bacterial Infections. JAMA Pediatrics. 2019;173(4):342-351. doi:10.1001/jamapediatrics.2018.5501
  4. Jaskiewicz, J.A., McCarthy, C.A., Richardson, A.C., White, K.C., Fisher, D.J., Powell, K. R., et al. (1994). Febrile infants at low risk for serious bacterial infection-an appraisal of the Rochester criteria and implications for management. Pediatrics 94(3), 390-396.
  5. Jaskiewicz, J.A., McCarthy, C.A., Richardson, A.C., White, K.C., Fisher, D.J., Powell, K. R., et al. (1994). Febrile infants at low risk for serious bacterial infection-an appraisal of the Rochester criteria and implications for management. Pediatrics 94(3), 390-396.
  6. Baker, M.D., Bello, L.M., & Avner, J.R. (1993). Outpatient management without antibiotics of fever in selected infants. New England Jouranl of Medicine, 329(20), 1437-1441.
  7. Smitherman, H.F. & Macias, C.G. (2014). Evaluation and management of fever in the neonate and young infant (less than three months of age) [Electronic Version]. UpToDate,Teach, S.J., Kaplan, SL, Wiley, JF.
  8. Dagan, R. Sofer, S., Phillip, M., & Shachak, E. (1988). Ambulatory care of febrile infants younger than 2 months of age classified as being at low risk for having serous bacterial infections. Journal of Pediatrics, 112(3), 355-360.
  9. Gomez B, Mintegi S, Bressan S, et al. Validation of the “Step-by-Step” Approach in the Management of Young Febrile Infants. Pediatrics. 2016;138(2):e20154381
  10. Mintegi S, Gomez B, Martinez-Virumbrales L, et al. Outpatient management of selected young febrile infants without antibiotics. Arch Dis Child. 2016 Jul 28. pii: archdischild-2016-310600. doi: 10.1136/archdischild-2016-310600.

Authors:

Ross Donaldson