1. Dr. Meenakshi Aggarwal
PGY2 Family Medicine
Emory University
Fever Of Unknown Origin
Dr Meenakshi Aggarwal MD
Emory University Family Medicine

2. Definitions
• Clinically significant fever is
defined as a rectal
temperature of 100.4 degree F
(38C) or higher.
• FUO or FWLS: An acute
febrile illness in which etiology
of the fever is not apparent
after a thorough H&P.

3. Why the “Fever Phobia”?
• Could be a sign of serious infection
• Younger children at higher risk
• Absence of other s/s make diagnosis
difficult
• Antibiotic resistance
Challenge: To identify those kids who have fever due
to a serious illness

4. Incidence
• One in five acutely ill, non toxic
appearing children have an
unidentifiable source of fever.
• Although most of the children have self
limiting viral illness, about 1.6-1.8%
kids < 36 months have occult
bacteremia and serious bacterial
infections (SBI)

5. FUO- Myths Uncovered
• Physiologic response of body to infection
• Usually benign illness
• Serious bacterial infection-SBI and occult
bacteremia is rare due to effective
immunizations. Common occult SBI - UTI,
meningitis, pneumonia
• Symptom, not a disease.
Occult bacteremia is the presence of pathogenic bacteria in the
blood of a febrile child without focus of infection or signs of sepsis.

6. Changing Approach to
FWLS
• 1990’s (H flu common organism with high
risk of complications)
< 3 mnths: screening labs, admission,
empiric abx started
3-36 mnths: temp >39C: CBC, UA. Abx if
WBC>15,000
-Contd…

7. • Early 2000’s (H flu gone,
pneumococcus etiology of OB common)
< 3mnths: Work up and therapy less with
increasing age.
3-36 mnths: temp >= 39.5
 <18mnths- CBC, bld cx, UA and UCx.
Abx for WBC >20,000 (ceftriaxone
50mg/kg)
 >= 18mnths - Bld Cx only

8. Surprise!
• Pneumococcal vaccine introduced(7-
valent conjugate vaccine licensed in
2000). Given at 2,4 and 6 months.
Decrease in rates of S.pneumo:
< 5yrs : Dec by 59%
<2yrs : dec by 69%
24-35 mnths: dec by 44%

9. Current Approach
• Any infant younger than 29 days and
any child that appears toxic should
undergo complete sepsis workup and
get admitted for observation until
culture results are obtained or the
source of the fever is found and
treated.

10. Prerequisites for FWLS
• Temp >=38 degree C
• Well appearing
• No obvious focal infection
• Previously healthy (including birth
history)
• Not on Antibiotics

11. Systemic approach to a
febrile child
• Age
• General appearance
• Past medical history
• Source of fever

12. Evaluation
• A) Thorough history:
Vaccinations
Sick contacts
Recent symptoms
Birth history
Maternal history (GBS, herpes)

13. Physical Exam:
- Vitals, Pulse Oximetry
- Weight
- Cyanosis
- Lethargy
- Poor feeding
- Hypo or hyperventilation
- Poor tone
- Poor perfusion (dec capillary
refill, weak pulses, tachycardia)

14. The Yale Observation Scale
I. Indications: a) Assessment of febrile child ages 3-36 months
b) Predicts serious infection (Occult Bacteremia)
c) Quantifies "Toxic Appearance" in children
II. Scoring: A) Quality of cry - strong, sob or weak
B) Reaction to parents – brief cry, intermittent cry,
persistent cry.
C) State Variation: Awakens quickly, difficult to
awaken, no arousal
D) Color: Pink, acrocyanosis, pale or cyanotic
E) Hydration: moist mucous membranes, slightly dry,
dry
F) Social response: alert, brief smile, no smile

15. Interpretation
d) Score 10; incidence of serious illness
is 2.7%
f) Score 11-15; incidence is 26%
c) Score > 16; incidence of serious
illness is 92.3%

16. Sepsis Evaluation
A) WBC’s and differential:
a) Low risk - Count less than 15,000/mm
and bandemia <1500/mm
b) Count >15,000/mm and ANC>
10,000/mm predictive of SBI (sensitivity
69% and specificity 79%)

17. Urine Analysis
a) UTI common in febrile females
and uncircumcised males
b) Always obtain a culture
c) Urethral catheterization is preferred
method to obtain a specimen

18. Lumbar Puncture:
Cell count
Gram stain
Gluc/prtn
Cx
Stool studies: Consider obtaining a stool
culture to measure fecal WBCs and stool
guaiac for diarrhea.

19. Chest X-Ray
A) Chest radiography is indicated when the patient
has tachypnea, retractions, focal auscultatory
findings, or oxygen saturation level (SO2) on room
air of less than 95%.
B) Chest radiographs should also be considered if
WBC is >20,000 and rectal temp > 102.2 degree F.

20. Recommended
Management Strategies
• Treatment approach for each age
group of patients presented here is
consistent with guidelines from the
American College of Emergency
Physicians and Cincinnati Children’s
Hospital.

21. Febrile Neonates (0-28 days)
• Highest risk group
• Admission required
• Complete sepsis workup (CBC, cath
UA and UCx, bld cx, CSF studies)
• HSV PCR needs to be considered if
herpes suspected
• IV antibiotics (ampi and cefotaxime)
• Observe for 48 hrs or until source
found

23. Neonates (29-90 days)
Two management options:
Option One:
a) CBC, bld Cx, CSF, UA and Ucx
b) If WBC’s < 15,000 and ANC < 10,000, then give
ceftriaxone 50mg/kg IM and follow up in 24 hrs
c) Evaluate results of bld Cx,UCx, CSF and re-
examine the child.

24. • Option Two:
c) CBC, UA and Ucx. No bld Cx, CSF
d) No abx
e) Parents carefully observe the child at
home and re-examination within 24 hrs.
f) If laboratory tests are positive,
appropriate action needs to be taken.

25. Age ( 3-36 months)
• Many febrile children do not need testing
• Selective testing based on temp >39 C
• Selective testing based on WBC’s
• Majority have received 3 doses of Prevnar
• LP is rarely needed
• UTI is most common occult bacteremia.

26. Age 3-36 months.
Cont’d
• Rectal temp < 102.2 degree F: No tests, no
abx, follow up if symptoms lasts longer than
48 hrs or worsens.
• Rectal temp > 102.2 degree F: No abx, no
testing OR CBC with diff and UA, Ucx. If WBC
> 15,000 or ANC > 10,000 then obtain bld cx.
Reevaluate in 24-48 hrs and consider
ceftriaxone 50mg/kg IM. CSF should be done
before Abx. No CSF needed if no abx given.

28. Evaluation Summary
• For children who appear ill, conduct a complete evaluation to identify occult
sources of infection. Follow the evaluation with empiric antibiotic treatment
and admit the patient to a hospital for further monitoring and treatment
pending culture results.
• Patients aged 2-36 months may not require admission if they meet the
following criteria:
• Patient was healthy prior to onset of fever.
• Patient has no significant risk factors.
• Patient appears nontoxic and otherwise healthy.
• Patient's laboratory results are within reference ranges defined as low risk.

29. Treatment
• Treatment recommendations for children with fever of unknown etiology are
based upon the child's appearance, age, and temperature.
• For children who do not appear toxic, treatment recommendations are as
follows:
– Consider no antibiotics; however, if ANC is greater than 10,000,
administer ceftriaxone (50 mg/kg/dose).
– Schedule a follow-up appointment within 24-48 hours and instruct
parents to return with the child sooner if the condition worsens.
– Hospital admission is indicated for children whose conditions worsen or
whose evaluation findings suggest a serious infection

30. Treatment Cont’d
• For children who appear toxic, treatment
recommendations are as follows:
– Admit child for further treatment; pending
culture results, administer parenteral antibiotics.
– Initially administer ceftriaxone, cefotaxime, or
ampicillin/sulbactam (50 mg/kg/dose).

32. Medical/Legal Pitfalls
• The biggest pitfall is not considering the possibility that a febrile infant has
a potentially life-threatening illness.
• If not treated promptly, a small percent of febrile infants who have no
obvious source of serious bacterial infection may suffer serious sequelae
or death.
• Physicians who approach their patients as if this is a possibility and who
provide appropriate evaluation and treatment are doing their best to avoid
a poor outcome.
• Stress to parents and caregivers the importance of follow-up care after
patients are discharged.
• Also stress that an infant whose symptoms worsen should be evaluated
prior to the scheduled follow-up appointment or taken to the nearest
emergency department for treatment.