Pediatric fever of uncertain source

Background

  • Fever accounts for 30% of pediatric visits
  • Children <3 months are immunocompromised (e.g. poor opsonization, poor IgG response to encapsulated bacteria, macrophage and neutrophil dysfunction, bone marrow insufficiency)
  • Concern is for missing a serious bacterial infection (SBI)

Epidemiology and Risk

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
  • Serious bacterial illness (SBI) includes UTI, meningitis, pneumonia, bacteremia
  • 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[1]
  • 4% Prevalence of UTI with common other sources of fever (OM, viral URI, etc)[2]
  • 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[3]

Concomitant Respiratory Viral Infection

  • Relatively high coincidence of RSV, enterovirus, and paraflu with bacteremia (and UTIs), so positive lab test for these viruses should not change testing and management plan[4]
    • RSV+ neonates aged 0-28 days, 3.7% were bactremic (and 6.1% had UTIs)
    • RSV+ infants aged 29-60 days, (5.5% had UTIs)
  • There is a low coincidence of influenza with SBI, so postivie lab test for this virus may change testing and management plan (i.e. lower risk of concurrent bacterial illness)[5]

Clinical Features

  • Febrile
    • Defined as temperature ≥38°C (100.4°F).
    • Peripheral temperature is not clinically accurate and central measurements are the preferred means of determining fever.
    • Parental report of confirmed fever at home (i.e. via thermometer), even with no fever in ED, has rates of SBIs high as 4.7% (0-28 day range)[6]

Differential Diagnosis

Pediatric fever

Evaluation & Management

  • Preemies: Count age by estimated postconception date (not by actual delivery date) for 1st-90d

0-7 Days

For all infants (toxic and well-appearing)

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

8-21 Days[7]

  • For toxic infants, treat for sepsis and admit
  • For well-appearing infants:
8-21 day algorithm
Child Appearance Work Up Treatment Disposition & Follow-up Comments
Temperature ≥38°C

Well-appearing

No evident source of infection

Increased HSV risk

  • Urinalysis, Urine culture
  • Blood culture
  • Inflammatory markers (IMs) - may obtain
  • LP-CSF
  • HSV studies
  • Initiate parenteral antimicrobial(s), including Acyclovir
  • Observe in hospital
  • If pathogen or source identified → Treat infection
  • If all culture results negative at 24-36 hours AND HSV PCR negative → Discontinue antimicrobials; may discharge. Manage for duration of illness.

Consider HSV if:

  • Maternal h/o genital HSV lesions or fever 48 hrs before to 48 hrs after delivery
  • Vesicles, mucous membrane ulcers
  • Seizures
  • Hypothermia
  • CSF pleocytosis + negative gram stain
  • Leukopenia
  • Thrombocytopenia
  • Elevated ALT
Temperature ≥38°C

Well-appearing

No evident source of infection

No increased HSV risk

  • Urinalysis, Urine culture
  • Blood culture
  • Inflammatory markers (IMs) - may obtain
  • LP-CSF
  • Initiate parenteral antimicrobial(s)
  • Observe in hospital
  • If pathogen or source identified → Treat infection
  • If all culture results negative at 24-36 hours → Discontinue antimicrobials; may discharge. Manage for duration of illness.

22-28 Days[8]

  • For toxic infants, treat for sepsis and admit
  • For well-appearing infants:

22-28 day algorithm


Child Appearance Work Up Treatment Disposition & Follow-up Comments
Temperature ≥38°C

Well-appearing No source of infection Abnormal IMs CSF pleocytosis or uninterpretable

  • Urinalysis, Urine culture (bladder catheterization or SPA if UA positive)
  • Blood culture
  • Inflammatory markers (IMs)
  • Perform LP(11b) - CSF
  • Administer IV antibiotics
  • Observe in hospital
  • If pathogen or source identified → Treat infection
  • If all cultures negative at 24-36 hours and HSV PCR negative (if sent) → Discontinue IV antibiotics; may discharge. Follow for duration of illness.
 Abnormal Inflammatory Markers:
  • Temp > 38.5
  • Procalcitonin > 0.5 ng/mL
  • CRP ≥ 20 mg/L
  • ANC > 4500 or 5200
Temperature ≥38°C

Well-appearing No evident source of infection Abnormal IMs No CSF pleocytosis (or CSF not obtained)

  • Urinalysis, Urine culture (bladder catheterization or SPA if UA positive)
  • Blood culture
  • Inflammatory markers (IMs)
  • Perform LP - CSF (may not be obtained)
  • If observation at home: Administer IV antibiotics
  • If observation in hospital: May administer IV antibiotics
  • If observation at home: Observe at home. Reassess in 24 hours.
  • If observation in hospital: Observe in hospital).
  • If pathogen or source identified → Treat infection
  • If all cultures negative at 24-36 hours and HSV PCR negative (if sent) → Discontinue IV antibiotics; may discharge. Follow for duration of illness.
Temperature ≥38°C

Well-appearing No evident source of infection Normal IMs LP performed, CSF obtained, CSF pleocytosis or traumatic

  • Urinalysis, Urine culture (bladder catheterization or SPA if UA positive)
  • Blood culture
  • Inflammatory markers (IMs)
  • May perform LP - CSF
  • May administer IV antibiotics
  • Observe in hospital
  • If pathogen or source identified → Treat infection
  • If all cultures negative at 24-36 hours and HSV PCR negative (if sent) → Discontinue IV antibiotics; may discharge. Follow for duration of illness.
Temperature ≥38°C

Well-appearing No evident source of infection Normal IMs LP performed, CSF obtained, no CSF pleocytosis/not traumatic OR CSF not obtained OR LP not performed

  • Urinalysis, Urine culture (bladder catheterization or SPA if UA positive)
  • Blood culture
  • Inflammatory markers (IMs)
  • May perform LP
  • If observation at home: Administer IV antibiotics
  • If observation in hospital: May administer IV antibiotics
  • If LP performed but CSF not obtained, or LP not performed: May administer IV antibiotics); Observe in hospital
  • If observation at home: Observe at home. Reassess in 24 hours.
  • If observation in hospital: Observe in hospital.
  • If pathogen or source identified → Treat infection
  • If all cultures negative at 24-36 hours and HSV PCR negative (if sent) → Discontinue IV antibiotics; may discharge. Follow for duration of illness.

29-60 Days[9]

  • For toxic infants, treat for sepsis and admit
  • For well-appearing infants:
29-60 day algorithm
Child Appearance Work Up Treatment Disposition & Follow-up Comments
Temperature ≥38°C

Well-appearing No evident source of infection

Abnormal IMs

  • Urinalysis (obtain for all)
  • Blood culture (obtain for all)
  • Inflammatory markers (IMs) (obtain for all)
  • Send bladder catheterization or SPA urine culture if positive urinalysis (15)
  • May perform LP (18a)
  • If CSF result is positive: Administer parenteral antimicrobial(s) (19a)
  • If CSF result is negative and either urinalysis negative or positive: May administer parenteral or oral antimicrobial(s) (19b)
  • If CSF not available or uninterpretable: Administer parenteral antimicrobial(s) (19a)
  • If CSF result is positive: Observe closely in hospital (20a)
  • If CSF result is negative and either urinalysis negative or positive: May observe closely in hospital or at home (20b,d)
  • If CSF not available or uninterpretable: May observe closely in hospital or at home (20b)
 Abnormal Inflammatory Markers:
  • Temp > 38.5
  • Procalcitonin > 0.5 ng/mL
  • CRP ≥ 20 mg/L
  • ANC > 4500 or 5200
Temperature ≥38°C

Well-appearing No evident source of infection

Normal IMs Positive urinalysis result

  • Urinalysis (obtain for all)
  • Blood culture (obtain for all)
  • Inflammatory markers (IMs) (obtain for all)
  • Send bladder catheterization or SPA urine culture (15)
  • Need not perform LP (18b)
  • Administer oral antimicrobial(s) (19c)
  • May observe closely at home
  • Follow-up in 12 to 24 hours (20d)
Temperature ≥38°C

Well-appearing No evident source of infection

Normal IMs Negative urinalysis result

  • Urinalysis (obtain for all)
  • Blood culture (obtain for all)
  • Inflammatory markers (IMs) (obtain for all)
  • Need not perform LP (18b)
  • Need not administer antimicrobial(s) (19d)
  • Observe closely at home (20c)
  • Follow-up within 24-36 hours (20c)

At 24 to 36 hours follow-up:

  • If pathogen or source identified at 24-36 hours AND source limited to urine → Complete treatment with oral antimicrobials (21c); Discharge hospitalized infants (21b); Manage for duration of illness
  • If pathogen or source identified at 24-36 hours AND source NOT limited to urine → Treat infection (21d)
  • If NO pathogen or source identified at 24-36 hours → Discontinue antimicrobials if administered (21a); Discharge hospitalized infants (21b); Manage for duration of illness

60 Days - 36 Months[10]

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)[11]
  • 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[12][13]

CBC

  • WBC 5-15 /mm3
  • Absolute Band count <1500 /mm3
  • Procalcitonin ≤0.5 ng/mL
  • ANC ≤4000/mm3

Urinalysis

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

CSF

  • Studies should include WBC, protein, glucose, Gram stain, and culture for bacteria. Consider viral studies (HSV).

0-28 days

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

>29 days

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

Additional Management

Initial Empiric Antibiotics for Well-Appearing Infants

Neonatal Antibiotics by Source[14]

Suspected Infection Source 8-21 Days Old 22-28 Days Old 29-60 Days Old
UTI
  • Ampicillin IV or IM (150 mg/kg per day divided q8) AND either:
No source identified
  • Ampicillin IV or IM (150 mg/kg per day divided q8) AND either:
Bacterial meningitis
  • Ampicillin IV or IM (300 mg/kg per day divided q6) AND
  • Ceftazidime IV or IM (150 mg/kg per day divided q8)
  • Ampicillin IV or IM (300 mg/kg per day divided q6) AND
  • Ceftazidime IV or IM (150 mg/kg per day divided q8)

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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 q6 hours

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See Also

External Links

References

  1. ↑ ACEP's Clinical Policy on Pediatric Fever. Clinical Policy for Children Younger Than Three Years Presenting to the Emergency Department With Fever. Annuals of Emergency Medicine 2003 42. 530-545
  2. ↑ ACEP's Clinical Policy on Pediatric Fever. Clinical Policy for Children Younger Than Three Years Presenting to the Emergency Department With Fever. Annuals of Emergency Medicine 2003 42. 530-545
  3. ↑ ACEP's Clinical Policy on Pediatric Fever. Clinical Policy for Children Younger Than Three Years Presenting to the Emergency Department With Fever. Annuals of Emergency Medicine 2003 42. 530-545
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ Serious bacterial infections in neonates presenting afebrile with history of fever Ramgopal S, Walker LW, Tavarez MM, et al. Pediatrics. 2019;144(2):e20183964.
  7. ↑ Evaluation and Management of Well-Appearing Febrile Infants 8 to 60 Days Old Robert H. Pantell, Kenneth B. Roberts, William G. Adams, Benard P. Dreyer, Nathan Kuppermann, Sean T. O'Leary, Kymika Okechukwu and Charles R. Woods; Subcommittee On Febrile Infants Pediatrics July 2021, e2021052228; DOI: https://doi.org/10.1542/peds.2021-052228
  8. ↑ Evaluation and Management of Well-Appearing Febrile Infants 8 to 60 Days Old Robert H. Pantell, Kenneth B. Roberts, William G. Adams, Benard P. Dreyer, Nathan Kuppermann, Sean T. O'Leary, Kymika Okechukwu and Charles R. Woods; Subcommittee On Febrile Infants Pediatrics July 2021, e2021052228; DOI: https://doi.org/10.1542/peds.2021-052228
  9. ↑ Evaluation and Management of Well-Appearing Febrile Infants 8 to 60 Days Old Robert H. Pantell, Kenneth B. Roberts, William G. Adams, Benard P. Dreyer, Nathan Kuppermann, Sean T. O'Leary, Kymika Okechukwu and Charles R. Woods; Subcommittee On Febrile Infants Pediatrics July 2021, e2021052228; DOI: https://doi.org/10.1542/peds.2021-052228
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ Evaluation and Management of Well-Appearing Febrile Infants 8 to 60 Days Old Robert H. Pantell, Kenneth B. Roberts, William G. Adams, Benard P. Dreyer, Nathan Kuppermann, Sean T. O'Leary, Kymika Okechukwu and Charles R. Woods; Subcommittee On Febrile Infants Pediatrics July 2021, e2021052228; DOI: https://doi.org/10.1542/peds.2021-052228
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