Pediatric fever of uncertain source: Difference between revisions

(/* 90dy-36moJaskiewicz, 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....)
 
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==Background==
==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
*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
*Children <3 months are immunocompromised (e.g. poor opsonization, poor IgG response to encapsulated bacteria, macrophage and neutrophil dysfunction, bone marrow insufficiency)
*Serious bacterial illness (SBI) includes UTI, meningitis, pneumonia, bacteremia


===Epidemiology and Risk===
{| class="wikitable"  
{| class="wikitable"  
| align="center" style="background:#f0f0f0;"|'''Age'''
| align="center" style="background:#f0f0f0;"|'''Age'''
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| align="center" style="background:#f0f0f0;"|'''> 90 days'''
| align="center" style="background:#f0f0f0;"|'''> 90 days'''
|-
|-
| Meningitis/SBI Prevalence ||1/10||1/20||1/100||1/1000||1/1000-10,000||> 1/10,000
| [[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<ref>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</ref>
*4% Prevalence of [[UTI]] with common other sources of fever ([[OM]], viral [[URI]], etc)<ref>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</ref>
*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<ref>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</ref>


===Facts and Figures===
===Concomitant Respiratory Viral Infection===
''From  ACEP's Clinical Policy on Pediatric Fevers<ref>Clinical Policy for Children Younger Than Three Years Presenting to the Emergency Department With Fever. Annuals of Emergency Medicine 2003 42. 530-545</ref>
*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<ref>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.</ref>
*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
**[[RSV]]+ neonates aged 0-28 days, 3.7% were bactremic (and 6.1% had [[UTI]]s)  
*4% Prevalence of UTI with common other sources of fever (OM, viral URI, et cetera)
**RSV+ infants aged 29-60 days, (5.5% had [[UTI]]s)
*1.5-2% background prevalence of asymptomatic bacteruria in healthy afebrile controls
*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)<ref>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.</ref>
*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 Infulenza Infection===
==Clinical Features==
*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<ref>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.</ref>
*[[Acute fever|Febrile]]
*RSV+ infants aged 29-60 days, the SBI rate was 5.5%, all of which were UTIs
**Defined as [[Celsius Fahrenheit Temperature Conversion|temperature]] ≥38°C (100.4°F).  
*Influenza+, low risk of bacterial illness
**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)<ref>Serious bacterial infections in neonates presenting afebrile with history of fever Ramgopal S, Walker LW, Tavarez MM, et al. Pediatrics. 2019;144(2):e20183964.</ref>


==Differential Diagnosis==
==Differential Diagnosis==
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==Evaluation & Management==
==Evaluation & Management==
[[File:Pediatric Fever2.png|thumb|Algorithm for the evaluation of pediatric fever]]
*Preemies: Count age by estimated postconception date (not by actual delivery date) for 1st-90d
===0-28dy===
 
*SBI in ill-appearing febrile neonate as high as 20%
===0-7 Days===
*SBI in well-appearing febrile neonate as high as 5%
''For all infants (toxic and well-appearing)''


{| class="wikitable"
{| class="wikitable"
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*Blood cultures  
*Blood cultures  
*[[Urinalysis]], Urine culture  
*[[Urinalysis]], Urine culture  
*LP-CSF  
*[[LP]]-CSF  
*[[CXR]]
*[[CXR]]
*+/- Stool studies (if diarrhea)
*+/- Stool studies (if diarrhea)
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*CXR is optional if no resp sx and another source identified
*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
*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<ref> 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.</ref>===
===8-21 Days<ref>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 </ref>===
{| class="wikitable"
*For toxic infants, treat for sepsis and admit
|-
*For well-appearing infants, see below algorithm
| '''Appearance'''
[[File:Peds fever 8-21 days (2.0).png|8-21 day algorithm]]
| '''Work Up'''
| '''Treatment'''
| '''Disposition & Follow-Up'''
|-
| '''Temp≥38° + Toxic'''
|
*CBC
*Blood cultures
*[[Urinalysis]], Urine culture
*[[LP]]-CSF
*+/- CXR
*+/- Stool studies (if diarrhea)
|
{{Pediatric fever antibiotics 28-90}}
 
| Admit
|-
|
'''Temp≥°38 + Well'''
|
*CBC
*Blood cultures
*[[Urinalysis]], urine culture
*+/- [[LP]]-CSF (must do before giving antibiotics)  
*+/- CXR
|
*+/-[[Ceftriaxone]] (50-100mg/kg IM/IV)
| Workup(+): Antibiotics and admit
Workup(-): ?antibiotics; home with 24 follow-up
|-
|}
^^Can use [[ceftriaxone]] 50-100mg/kg, but concern for bilirubin displacement


{{Pediatric fever CXR indications}}
===22-28 Days<ref>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 </ref>===
*For toxic infants, treat for sepsis and admit
*For well-appearing infants, see below algorithm
[[File:Peds fever 22-28 days (2.0).PNG]]


{{Pediatric fever acyclovir indications}}
===29-60 Days<ref>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 </ref>===
*For toxic infants, treat for sepsis and admit
*For well-appearing infants, see below algorithm
[[File:Peds fever 29-60 (2.0).PNG]]


===90dy-36mo<ref>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.</ref>===
===60 Days - 36 Months<ref>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.</ref>===
{| class="wikitable"
{| class="wikitable"
|-
|-
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*WBC 5-15 /mm<sup>3</sup>
*WBC 5-15 /mm<sup>3</sup>
*Absolute Band count <1500 /mm<sup>3</sup>
*Absolute Band count <1500 /mm<sup>3</sup>
*Procalcitonin ≤0.5 ng/mL
*ANC ≤4000/mm<sup>3</sup>
===Urinalysis===
===Urinalysis===
*Clear
*Clear
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*WBC <10/high powered field
*WBC <10/high powered field
===CSF===
===CSF===
*Studies should include WBC, protein, glucose, Gram stain, and culture for bacteria. Consider viral studies (HSV).
====0-28 days====
====0-28 days====
*WBC: 0-22/mm<sup>3</sup>
*WBC: 0-22/mm<sup>3</sup>
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*Protein: 15-25mg/dL
*Protein: 15-25mg/dL


===Low Risk by Step-By-Step Approach<ref>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</ref>===
==Additional Management==
''Study validated against Rocheter criteria and Lab-score for identifying low risk for invasive bacterial infections (IBI), with '''''NPV ~98%'''''
===Initial Empiric Antibiotics for Well-Appearing Infants<ref>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 </ref>===
*Well appearing
{| {{table}}
*Age > 21 days
| align="center" style="background:#f0f0f0;"|'''Suspected Infection Source'''
*No leukocyturia
| align="center" style="background:#f0f0f0;"|'''8-21 Days Old'''
*Procalcitonin < 0.5 ng/mL
| align="center" style="background:#f0f0f0;"|'''22-28 Days Old'''
*ANC < 10,000/mm3
| align="center" style="background:#f0f0f0;"|'''29-60 Days Old'''
*CRP < 20 mg/L
|-
====Low Risk Management<ref>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.</ref>====
| [[UTI]]||
*Offer no LP, no antibiotics, 24 hrs observation
*[[Ampicillin]] IV or IM (150 mg/kg per day divided q8) AND either:
*Plan for prompt follow-up
**[[Ceftazidime]] IV or IM (150 mg/kg per day divided q8) or
**[[Gentamicin]] IV or IM (4 mg/kg per dose q24)
||
*[[Ceftriaxone]] IV or IM (50 mg/kg per dose q24)
||
*[[Ceftriaxone]] IV or IM (50 mg/kg per dose q24)
*Oral options:  
**[[Cephalexin]] 50-100 mg/kg per day QID or
**[[Cefixime]] 8 mg/kg QD
|-
| No source identified
||
*[[Ampicillin]] IV or IM (150 mg/kg per day divided q8) AND either:  
**[[Ceftazidime]] IV or IM (150 mg/kg per day divided q8) or
**[[Gentamicin]] IV or IM (4 mg/kg per dose q24)
||
*[[Ceftriaxone]] IV or IM (50 mg/kg per dose q24)
||
*[[Ceftriaxone]] IV or IM (50 mg/kg per dose q24)
|-
| 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)
||
*Cephalosporin
**[[Ceftriaxone]] IV (100 mg/kg QD) or
**[[Ceftazidime]] IV (150 mg/kg QD)
*AND [[Vancomycin]] IV (60 mg/kg QD)
|}


==Symptomatic Managment==
{{Acetaminophen pediatric dosing chart}}
{{Acetaminophen pediatric dosing chart}}


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*[[Meningitis (peds)]]  
*[[Meningitis (peds)]]  
*[[Febrile seizure]]
*[[Febrile seizure]]
*[[PECARN Febrile Infant]]


==External Links==
==External Links==
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[[Category:Pediatrics]]
[[Category:Pediatrics]]
[[Category:ID]]

Latest revision as of 16:46, 15 March 2023

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)

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, see below algorithm

8-21 day algorithm

22-28 Days[8]

  • For toxic infants, treat for sepsis and admit
  • For well-appearing infants, see below algorithm

Peds fever 22-28 days (2.0).PNG

29-60 Days[9]

  • For toxic infants, treat for sepsis and admit
  • For well-appearing infants, see below algorithm

Peds fever 29-60 (2.0).PNG

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[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)

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

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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