1. Fever without focus
Dr Rafat Mosalli

2. Question 1
A 3 week old male infant is brought to your ED with a 2 day history of fever. He was born by uncomplicated vaginal delivery at 37 weeks gestation following a normal pregnancy.. His vital signs are: T 38.9C (R), HR 140, RR 40, and BP 90/60. He is sleepy but easily arousable. Physical exam is normal apart from a slightly dull left tympanic membrane. WBC is 16,000, his UA shows 3 WBC/hpf. BC and UC are sent. Your management at this point would consist of:
a. Discharge on antipyretics with close follow-up
b. Discharge on oral amoxicillin with close follow-up
c. LP and admission for parenteral antibiotics
d. CXR to r/o pneumonia
e. Stool for analysis and culture, and outpatient follow-up

3. Question 2
A 7 week old girl is referred in to ED for evaluation of a rectal temperature of 39.2C. Her PE is normal. Her UA is negative, her WBC is 9,000 (70% neuts, 28% lymphs, 2% bands), and her LP reveals a CSF WBC count of 8. BC, UC, and CSF cultures are sent. Acceptable management options for this child would include any one of the following except:
IM ceftriaxone in the ED
Admission to the hospital for IV antibiotics
Discharge with follow-up in 24 hours
Admission to the hospital for observation
Discharge on amoxicillin

4. Question 3
A 19 month old boy comes to the ED with a 3 day history of fever. He appears well but his tympanic T is 39.8C. His chest is clear, his abdomen is soft, and he is circumcised. No source can be found for his fever. A CBC reveals a WBC of 8200 (60% neuts, 27% bands). BC’s are sent.
Appropriate management at this point will be to:
a. Obtain a urine sample
b. Administer IM ceftriaxone
c. Perform an LP
d. Obtain a CXR
e. Discharge on antipyretics

5. Objectives Definitions
Which patients need in-depth evaluation and treatment?
What laboratory studies are indicated for various age ranges?
Which patients need treatment with antibiotics?
Which patients should be hospitalized?

6. Definitions Fever Fever without focus Fever of unknown origin
Occult bacteremia
Serious bacterial infection (SBI)

7. What is fever?
Rectal temperature > 38C, either at physician’s office, ED, or documented at home by a reliable parent or other adult

8. Different body sites Rectal standard Oral 0.5-0.6 lower
Axillary  lower
Tympanic  lower
Documented:
In the absence of antipyretics
In ED or office or by hx from reliable parents/adults
Tympanic age and technique specific; long tortuous ear canal in small kids
Rectal preferred in under 3 months of age
Abdomen-toe temperature differential as method of distinguishing overbundling from true fever

9. Frequency of febrile illness
35% of unscheduled ambulatory care visits
65% of kids see doc before age 2y
Majority (75%) for T < 39 C
13% T > 39.5

10. Fever of Unknown Origin
1. Fever of 38C or greater which has continued for a 2 to 3 weeks 2. Absence of localizing clinical signs 3. Negative simple investigations

11. Fever without focus
“An acute febrile illness in which the etiology of the fever is not apparent after a careful history and physical examination.”
20% of childhood fevers have no apparent cause
Baraff et al, Pediatrics 1993; 92:1-12

12. Occult bacteremia
“…a positive blood culture in the setting of well appearance and without focus (e.g. no pneumonia)
Fleisher et al, J Pediatrics 1994

13. Occult bacteremia organisms
Streptococcus pneumonia > 85%
Haemophilus influenzae type B
(now rare – previously 10%)
Neisseria meningitidis 3-5%
Others:
S. aureus
S. pyogenes (GAS)
Salmonella species

14. Outcomes of occult bacteremia without antibiotics
Persistent fever 56%
Persistent bacteremia 21%
Meningitis 9%
S. pneumonia 6%
H. Influenzae 26% (now rare)

15. Age is quite matter
>10 % of well-appearing young infants with a temperature >38°C has a serious bacterial infection or meningitis
Only <2 %of well-appearing older infants and young children with a temperature >39°C (manifest bacteremia

16. Serious Bacterial Infection
“…Include meningitis, sepsis, bone and joint infections, urinary tract infections, pneumonia and enteritis”
Baraff et al, Pediatrics 1993; 92:1-12

17. Fever Practice Guidelines
CPS guidelines: Management of the febrile one-to 36-month-old child with no focus of infection.
Paediatr Child Health 1996;1: *re-affirmed
April 2002
“American” consensus guidelines: Practice guideline for the management of infants and children 0-36 months of age with fever without source.
Baraff et al, Pediatrics 1993;92:1-12

18. Case scenarios - fever By age group: < 1 month of age 1 – 3 months

19. Why according to age
Because in young infants there's a greater probability of serious bacterial infection so more aggressive approach to the evaluation and management of fever is warranted.

20. Febrile infant < 1 month
“American” consensus recommendations
All should have:
Full septic w/u
CSF cultures, gm stain, cell count/diff, gluc/prot
Blood cultures
Urine routine, micro, culture
If diarrhea, stool exam (smear and culture)
If resp sx: CXR
ADMIT, IV antibiotics, or
ADMIT, observe without antibiotics
GBS, E. coli, Listeria

21. Febrile infants 1-3 m of age
According to validated criteria
E.g. Rochester score
Low and high risk

22. Febrile infants < 3 months risk of bacteremia
If meets low risk Rochester 0.2% (1:500)
criteria
If meets low risk criteria %
but < 1 month

23. Febrile infants 1-3 m of age
Hi Risk:
“American” and Canadian Consensus recommendations
ADMIT to hospital with full septic w/u
BC, UC, LP
Broad-spectrum parental antibiotics

24. Febrile infants 1-3m of age low risk
Option 2 (“American” and CPS)
No investigation
(or urine culture only )
Careful outpatient observation, without treatment,
close follow-up
Option 1 (“American”):
Blood culture
Urine culture LP
Ceftriaxone 50 mg/kg IM
Return for re-evaluation w/i 24 hours

25. Follow-up of Infants 1-3m old
Within 24 hours
Repeat exam for source, sequelae
Review, repeat labs
Arrange ongoing follow-up

26. Follow-up of 1-3m If blood culture positive If urine culture positive
ADMIT for sepsis evaluation
Parenteral antibiotics pending results
If urine culture positive
Persistent fever: ADMIT for sepsis evaluation and parenteral abx tx pending results
Afebrile and well: outpatient antibiotics

27. Fever Without Source Age 3 – 36 Months

28. Fever Without Source Age 3 – 36 Months
Risk of occult bacteremia
3-11%, mean 4.3% for T>39C
Risk greater with
Higher temperatures
WBC > 15,000 (13% vs 2.6%)
Risk of pneumococcal meningitis (w/o abx tx) % (1:500)

29. How should a child with FWF be evaluated?
Detailed history and thorough physical examination
avoid indiscriminately ordering a large battery of tests.
Laboratory studies should be directed as much as possible toward the most likely diagnostic possibilities.

30. Physical examination: “Toxic appearance”
Lethargy/irritability
Poor/absent eye contact
Poor perfusion
Hypo/hyperventilation
Cyanosis

31. FWS – age 3-36 months: Consensus Recommendations
CHILD NON-TOXIC, T < 39C
No diagnostic tests or antibiotics
Acetaminophen 15 mg/kg prn for fever
Return if fever persists > 48 hours or the followings happened:

32. Return to the Emergency Department if your child
more fussy or won’t stop crying
too sleepy or drowsy
stiff neck
Won’t stop vomiting
new rash
Has a seizure
Gets any other new or worsening symptom(s) that concerns you

33. FWS – age 3-36 months: Recommendations
CHILD NON-TOXIC, T  39C
Urine culture (for M < 6 month, F < 2 yrs age)
BC – 2 options
Option 1: obtain for all children with T  39C
Option 2: obtain if T  39C and WBC >15,000
CXR, stool culture if indicated clinically
Acetaminophen 15 mg/kg q4h for T  39C
Follow-up in hours *no antibiotics
No antibiotics; supported by Baraff in annals of emerg med Dec 2000

34. FWS – age 3-36 months: Consensus Recommendations
CHILD APPEARS TOXIC:
ADMIT to hospital
Sepsis w/u
Parenteral abx

35. Investigation options
[ ] CBC [ ] blood culture [ ] urinalysis [ ] urine culture [ ] CXR [ ] LP [ ] Nothing
Laboratory studies should be directed as much as possible toward the most likely diagnostic possibilities.

36. Choice of antibiotic If decide to treat empirically
ceftriaxone or po Amoxicillin/clavulanate

37. FWS – age 3-36 months: BC returns positive
Pneumococcus:
Persistent fever: ADMIT for sepsis w/u and parenteral abx pending sensitvity
Natural course of pneumococcal bacteremia is resolution

38. FWS – age 3-36 months: BC returns positive
All Other Bacteria:
ADMIT for sepsis w/u and parenteral abx pending sensitivity results

39. FWS – age 3-36 months: Urine culture returns positive
All organisms:
ADMIT if febrile or ill-appearing
Outpatient abx if afebrile and well

40. Summary: FWS Hospitalize +/- abx Infants < 28 days:
-According to risk score hospital Vs home, +/- abx
Home, no antibiotics
+/- labs, home, no antibiotics
Infants < 28 days:
Infants 1-3 months
Non toxic children 3 m- 3 yrs (T < 39C)
Non toxic children 3 m-3 y (T 39C):
close follow-up in all!

41. Regardless of PCV status
Toxic highly Febrile Child Aged 3-36 mos Without Apparent Focus Be Managed ?
Age 3-36 mos
Temp. > 390C
Regardless of PCV status
"ill" , "toxic",
"lethargic" ?
>20,000
WBC/mm3 No ?
 risk for bacteremia
 WBC
 fever
male
age 7-11 mos
Yes ? ?
Hospital/ Antibiotic Rx
Yes
Yes
Consider
AMOX or specify why other

42. “ I think it is clear that the handwriting is on the wall saying that occult bacteremia is dead. It was dying when Hib disappeared and Prevnar has destroyed it.” contribution to Pediatric Emergency Medicine List Serve

43. Heptavalent conjugate pneumococcal vaccine
very efficacious
Likely to make most of the foregoing pneumococcal in 3-36 month group obsolete
Finally become routine by MCH
Given at 2,4,6 month and 12-15m
? Mention C – reactive protein

44. Effect in Target Age Group Invasive Pneumococcal Disease Rates in Children < 3 Years, ABCs,
 77% (<1 yr)
 83% (1 yr)
 64% (2 yr)
2003 vs baseline
PCV7
1 yr
<1 yr
2 yrs
2003 data are preliminary
Farely et al, ICP, Cancun, Mexico, August 2003

45. ~  80% in invasive pneumococcal disease in children < 3 yrs
Effect in Target Age Group Invasive Pneumococcal Disease Rates in Children < 3 Years, ABCs,
 77% (<1 yr)
 83% (1 yr)
 64% (2 yr)
2003 vs baseline
~  80% in invasive
pneumococcal disease
in children < 3 yrs
2003 data are preliminary
Farely et al, ICP, Cancun, Mexico, August 2003