Fever without focusFever without focus

Dr Rafat MosalliDr Rafat Mosalli

Question 1Question 1• A 3 week old male infant is brought to your ED with a 2 day 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 history of fever. He was born by uncomplicated vaginal delivery at 37 weeks gestation following a normal pregnancy.. His vital at 37 weeks gestation following a normal pregnancy.. His vital signs are: T 38.9signs are: T 38.9C (R), HR 140, RR 40, and BP 90/60. He is C (R), HR 140, RR 40, and BP 90/60. He is sleepy but easily arousable. Physical exam is normal apart from sleepy but easily arousable. Physical exam is normal apart from a slightly dull left tympanic membrane. WBC is 16,000, his UA a slightly dull left tympanic membrane. WBC is 16,000, his UA shows 3 WBC/hpf. BC and UC are sent. Your management at shows 3 WBC/hpf. BC and UC are sent. Your management at this point would consist of:this point would consist of:

a. Discharge on antipyretics with close follow-upa. Discharge on antipyretics with close follow-upb. Discharge on oral amoxicillin with close follow-upb. Discharge on oral amoxicillin with close follow-upc. LP and admission for parenteral antibioticsc. LP and admission for parenteral antibioticsd. CXR to r/o pneumoniad. CXR to r/o pneumoniae. Stool for analysis and culture, and outpatient follow-upe. Stool for analysis and culture, and outpatient follow-up

Question 2Question 2• A 7 week old girl is referred in to ED for evaluation of a A 7 week old girl is referred in to ED for evaluation of a

rectal temperature of 39.2rectal temperature of 39.2C. Her PE is normal. Her UA C. Her PE is normal. Her UA is negative, her WBC is 9,000 (70% neuts, 28% is negative, her WBC is 9,000 (70% neuts, 28% lymphs, 2% bands), and her LP reveals a CSF WBC lymphs, 2% bands), and her LP reveals a CSF WBC count of 8. BC, UC, and CSF cultures are sent. count of 8. BC, UC, and CSF cultures are sent. Acceptable management options for this child would Acceptable management options for this child would include any one of the following except:include any one of the following except:

a.a. IM ceftriaxone in the EDIM ceftriaxone in the EDb.b. Admission to the hospital for IV antibioticsAdmission to the hospital for IV antibioticsc.c. Discharge with follow-up in 24 hoursDischarge with follow-up in 24 hoursd.d. Admission to the hospital for observationAdmission to the hospital for observatione.e. Discharge on amoxicillinDischarge on amoxicillin

Question 3Question 3• A 19 month old boy comes to the ED with a 3 day history A 19 month old boy comes to the ED with a 3 day history

of fever. He appears well but his tympanic T is 39.8of fever. He appears well but his tympanic T is 39.8C. His C. His chest is clear, his abdomen is soft, and he is circumcised. chest is clear, his abdomen is soft, and he is circumcised. No source can be found for his fever. A CBC reveals a No source can be found for his fever. A CBC reveals a WBC of 8200 (60% neuts, 27% bands). BC’s are sent.WBC of 8200 (60% neuts, 27% bands). BC’s are sent.

Appropriate management at this point will be to:Appropriate management at this point will be to:

a. Obtain a urine samplea. Obtain a urine sampleb. Administer IM ceftriaxoneb. Administer IM ceftriaxonec. Perform an LPc. Perform an LPd. Obtain a CXRd. Obtain a CXRe. Discharge on antipyreticse. Discharge on antipyretics

ObjectivesObjectives

• DefinitionsDefinitions• Which patients need in-depth Which patients need in-depth

evaluation and treatment? evaluation and treatment? • What laboratory studies are indicated What laboratory studies are indicated

for various age ranges? for various age ranges? • Which patients need treatment with Which patients need treatment with

antibiotics? antibiotics? • Which patients should be Which patients should be

hospitalized?hospitalized?

DefinitionsDefinitions

• FeverFever• Fever without focusFever without focus• Fever of unknown originFever of unknown origin• Occult bacteremiaOccult bacteremia• Serious bacterial infection (SBI)Serious bacterial infection (SBI)

What is feverWhat is fever??

Rectal temperature > 38Rectal temperature > 38C, either at C, either at physician’s office, ED, or physician’s office, ED, or documented at home by a reliable documented at home by a reliable parent or other adultparent or other adult

Different body sitesDifferent body sites

• RectalRectal standardstandard• OralOral 0.5-0.60.5-0.6 lowerlower• AxillaryAxillary 0.8-1.00.8-1.0 lowerlower• Tympanic 0.5-0.6Tympanic 0.5-0.6 lowerlower

Documented:Documented:• In the absence of antipyreticsIn the absence of antipyretics• In ED or office or by hx from reliable In ED or office or by hx from reliable

parents/adultsparents/adults

Frequency of febrile Frequency of febrile illnessillness

• 35% of unscheduled ambulatory 35% of unscheduled ambulatory care visitscare visits

• 65% of kids see doc before age 2y65% of kids see doc before age 2y• Majority (75%) for T < 39 Majority (75%) for T < 39 C C • 13% T > 39.513% T > 39.5

Fever of Unknown Fever of Unknown OriginOrigin

1. 1. Fever of 38Fever of 38C or greater which C or greater which has has continued for a 2 to 3 weeks continued for a 2 to 3 weeks

2. 2. Absence of localizing clinical Absence of localizing clinical signssigns

3. 3. Negative simple investigationsNegative simple investigations

Fever Fever without focuswithout focus

• ““An acute febrile illness in which the An acute febrile illness in which the etiology of the fever is not apparent after etiology of the fever is not apparent after a careful history and physical a careful history and physical examination.”examination.”

• 20% of childhood fevers have no apparent 20% of childhood fevers have no apparent causecause

Baraff et al, Pediatrics 1993; 92:1-12Baraff et al, Pediatrics 1993; 92:1-12

Occult bacteremiaOccult bacteremia

• “…“…a positive blood culture in the a positive blood culture in the setting of well appearance and setting of well appearance and without focus (e.g. no pneumonia)without focus (e.g. no pneumonia)

• Fleisher et al, J Pediatrics 1994Fleisher et al, J Pediatrics 1994

Occult bacteremia Occult bacteremia organismsorganisms

• Streptococcus pneumoniaStreptococcus pneumonia > 85%> 85%• Haemophilus influenzaeHaemophilus influenzae type B type B

(now (now rarerare – previously 10%) – previously 10%)

• Neisseria meningitidisNeisseria meningitidis 3-5%3-5%• Others:Others:

• S. aureusS. aureus• S. pyogenesS. pyogenes (GAS) (GAS)• SalmonellaSalmonella species species

Outcomes of occult bacteremia Outcomes of occult bacteremia without antibioticswithout antibiotics

• Persistent feverPersistent fever 56%56%• Persistent bacteremiaPersistent bacteremia 21%21%• MeningitisMeningitis 9%9%

• S. pneumoniaS. pneumonia 6% 6%• H. InfluenzaeH. Influenzae 26% (now rare) 26% (now rare)

Age is quite matterAge is quite matter

• >10 % >10 % of well-appearing young of well-appearing young infants with a temperature >38°C infants with a temperature >38°C has a serious bacterial infection or has a serious bacterial infection or meningitismeningitis

• Only <2 %Only <2 %of well-appearing older of well-appearing older infants and young children with a infants and young children with a temperature >39°C (manifest temperature >39°C (manifest bacteremiabacteremia

Serious Bacterial Serious Bacterial InfectionInfection

• “…“…Include meningitis, sepsis, bone Include meningitis, sepsis, bone and joint infections, urinary tract and joint infections, urinary tract infections, pneumonia and enteritis”infections, pneumonia and enteritis”

Baraff et al, Pediatrics 1993; 92:1-Baraff et al, Pediatrics 1993; 92:1-1212

Fever Practice Fever Practice GuidelinesGuidelines

• CPS guidelines: Management of the febrile one-CPS guidelines: Management of the febrile one-to 36-month-old child with no focus of infection. to 36-month-old child with no focus of infection. • Paediatr Child Health 1996;1:41-45 Paediatr Child Health 1996;1:41-45 *re-affirmed*re-affirmed April 2002April 2002

• ““American” consensus guidelines: Practice American” consensus guidelines: Practice guideline for the management of infants and guideline for the management of infants and children 0-36 months of age with fever without children 0-36 months of age with fever without source. source. • Baraff et al, Pediatrics 1993;92:1-12Baraff et al, Pediatrics 1993;92:1-12

Case scenarios - feverCase scenarios - fever

• By age groupBy age group::

• < 1 month of age< 1 month of age• 1 – 3 months1 – 3 months• 3 – 36 months3 – 36 months

Why according to ageWhy according to age

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

Febrile infant < 1 Febrile infant < 1 monthmonth

““American” consensus recommendationsAmerican” consensus recommendations• All should have:All should have:

• Full septic w/uFull septic w/u• CSF cultures, gm stain, cell count/diff, gluc/protCSF cultures, gm stain, cell count/diff, gluc/prot• Blood culturesBlood cultures• Urine routine, micro, cultureUrine routine, micro, culture• If diarrhea, stool exam (smear and culture)If diarrhea, stool exam (smear and culture)• If resp sx: CXRIf resp sx: CXR

• ADMIT, IV antibiotics, orADMIT, IV antibiotics, or• ADMIT, observe without antibioticsADMIT, observe without antibiotics

Febrile infants 1-3 m of Febrile infants 1-3 m of ageage

According to validated criteriaAccording to validated criteria

E.g. Rochester scoreE.g. Rochester score• Low and high riskLow and high risk

Febrile infants < 3 Febrile infants < 3 monthsmonthsrisk of bacteremiarisk of bacteremia• If meets low risk Rochester If meets low risk Rochester

0.2% (1:500)0.2% (1:500)

criteriacriteria

• If meets low risk criteria If meets low risk criteria 0.7-1% 0.7-1%

but < 1 monthbut < 1 month

Febrile infants 1-3 m of Febrile infants 1-3 m of ageage

Hi Risk:Hi Risk:

““American” and Canadian Consensus American” and Canadian Consensus recommendationsrecommendations

• ADMIT to hospital with full septic ADMIT to hospital with full septic w/uw/u• BC, UC, LPBC, UC, LP

• Broad-spectrum parental antibioticsBroad-spectrum parental antibiotics

Febrile infants 1-3m of Febrile infants 1-3m of age age low risklow risk

•Option 1 Option 1 (“American”)(“American”)::

Blood cultureBlood culture

Urine cultureUrine culture

LPLP

Ceftriaxone 50 mg/kg IMCeftriaxone 50 mg/kg IM

Return for re-evaluation Return for re-evaluation w/i 24 hoursw/i 24 hours

•Option 2 (“American” Option 2 (“American” and CPS)and CPS)

No investigationNo investigation((or or urine culture only urine culture only) )

Careful outpatient Careful outpatient observation, without observation, without treatmenttreatment , ,

close follow-upclose follow-up

Follow-up of Infants 1-Follow-up of Infants 1-3m old3m old

• Within 24 hoursWithin 24 hours• Repeat exam for source, sequelaeRepeat exam for source, sequelae• Review, repeat labsReview, repeat labs• Arrange ongoing follow-upArrange ongoing follow-up

Follow-up of 1-3mFollow-up of 1-3m

• If blood culture positiveIf blood culture positive• ADMIT for sepsis evaluationADMIT for sepsis evaluation• Parenteral antibiotics pending resultsParenteral antibiotics pending results

• If urine culture positiveIf urine culture positive• Persistent fever:Persistent fever: ADMIT for sepsis ADMIT for sepsis

evaluation and parenteral abx tx pending evaluation and parenteral abx tx pending resultsresults

• Afebrile and well:Afebrile and well: outpatient antibiotics outpatient antibiotics

Fever Without SourceFever Without SourceAge 3 – 36 MonthsAge 3 – 36 Months

Fever Without SourceFever Without SourceAge 3 – 36 MonthsAge 3 – 36 Months

• Risk of occult bacteremia Risk of occult bacteremia

• 3-11%, mean 3-11%, mean 4.3%4.3% for T>39 for T>39CC

• Risk greater withRisk greater with• Higher temperaturesHigher temperatures• WBC > 15,000 (WBC > 15,000 (13%13% vs vs 2.6%2.6%))

• Risk of pneumococcal meningitis (w/o Risk of pneumococcal meningitis (w/o abx tx) abx tx) 0.21% (1:500)0.21% (1:500)

How should a child with How should a child with FWF be evaluatedFWF be evaluated??

• Detailed history and thorough Detailed history and thorough physical examinationphysical examination

• avoid indiscriminately ordering a avoid indiscriminately ordering a large battery of tests. large battery of tests.

Physical examination:Physical examination:“Toxic appearance“Toxic appearance””

• Lethargy/irritabilityLethargy/irritability• Poor/absent eye contactPoor/absent eye contact• Poor perfusionPoor perfusion• Hypo/hyperventilationHypo/hyperventilation• Cyanosis Cyanosis

FWS – age 3-36 months:FWS – age 3-36 months:Consensus RecommendationsConsensus Recommendations

• CHILD NON-TOXIC, T < 39CHILD NON-TOXIC, T < 39CC

• No diagnostic tests or antibioticsNo diagnostic tests or antibiotics• Acetaminophen 15 mg/kg prn for Acetaminophen 15 mg/kg prn for

feverfever• Return if fever persists > 48 hours or Return if fever persists > 48 hours or

the followings happened:the followings happened:

Return to the Return to the Emergency Department Emergency Department

if your childif your child• more fussy or won’t stop cryingmore fussy or won’t stop crying• too sleepy or drowsytoo sleepy or drowsy• stiff neckstiff neck• Won’t stop vomitingWon’t stop vomiting• new rashnew rash• Has a seizureHas a seizure• Gets any other new or worsening Gets any other new or worsening

symptom(s) that concerns yousymptom(s) that concerns you

FWS – age 3-36 FWS – age 3-36 months:months:

RecommendationsRecommendations• CHILD NON-TOXIC, T CHILD NON-TOXIC, T 39 39CC

• Urine culture (for M < 6 month, F < 2 yrs age)Urine culture (for M < 6 month, F < 2 yrs age)• BC – 2 optionsBC – 2 options

• Option 1: obtain for all children with T Option 1: obtain for all children with T 39 39CC• Option 2: obtain if T Option 2: obtain if T 39 39C and WBC >15,000C and WBC >15,000

• CXR, stool culture if indicated clinicallyCXR, stool culture if indicated clinically• Acetaminophen 15 mg/kg q4h for T Acetaminophen 15 mg/kg q4h for T 39 39C C • Follow-up in 24-48 hours *no antibioticsFollow-up in 24-48 hours *no antibiotics

FWS – age 3-36 months:FWS – age 3-36 months:Consensus RecommendationsConsensus Recommendations

• CHILD APPEARS TCHILD APPEARS TOXIC:OXIC:

• ADMIT to hospitalADMIT to hospital• Sepsis w/uSepsis w/u• Parenteral abxParenteral abx

Investigation optionsInvestigation options

[ ] CBC[ ] CBC[ ] blood culture[ ] blood culture[ ] urinalysis [ ] urinalysis [ ] urine culture[ ] urine culture[ ] CXR[ ] CXR[ ] LP[ ] LP[ ] Nothing[ ] Nothing

Choice of antibioticChoice of antibiotic

• If decide to treat empiricallyIf decide to treat empiricallyceftriaxone or po ceftriaxone or po

Amoxicillin/clavulanateAmoxicillin/clavulanate

FWS – age 3-36 FWS – age 3-36 months:months:

BC returns positiveBC returns positive• Pneumococcus:Pneumococcus:

• Persistent fever: ADMIT for sepsis Persistent fever: ADMIT for sepsis w/u and parenteral abx pending w/u and parenteral abx pending sensitvitysensitvity

FWS – age 3-36 FWS – age 3-36 months:months:

BC returns positiveBC returns positive• All Other Bacteria:All Other Bacteria:

• ADMIT for sepsis w/u and ADMIT for sepsis w/u and parenteral abx pending sensitivity parenteral abx pending sensitivity resultsresults

FWS – age 3-36 FWS – age 3-36 months:months:

Urine culture returns Urine culture returns positivepositive• All organisms:All organisms:

• ADMIT if febrile or ill-appearingADMIT if febrile or ill-appearing• Outpatient abx if afebrile and wellOutpatient abx if afebrile and well

Summary: FWSSummary: FWS

Infants < 28 daysInfants < 28 days::

Infants 1-3 monthsInfants 1-3 months

Non toxic children 3 m- 3 Non toxic children 3 m- 3 yrs (T <yrs (T < 3939C)C)

Non toxic children 3 m-3 yNon toxic children 3 m-3 y (T (T 3939C)C)::

Hospitalize +/- abxHospitalize +/- abx

--According to risk score According to risk score hospital Vs home, +/- hospital Vs home, +/- abxabx

Home, no antibioticsHome, no antibiotics

-/+ -/+labs, home, no labs, home, no antibioticsantibiotics

close follow-up in all!

4141

Toxic highly Febrile Child Aged 3-36 Toxic highly Febrile Child Aged 3-36 mos Without Apparent Focus Be mos Without Apparent Focus Be

ManagedManaged? ?

Regardless of PCV statusRegardless of PCV statusRegardless of PCV statusRegardless of PCV status

Hospital/ Antibiotic RxHospital/ Antibiotic Rx

YesYesYesYes

"ill" , "toxic,""lethargic""ill" , "toxic,"

"lethargic"

????>20,000

WBC/mm3 >20,000

WBC/mm3

NoNoNoNo

???? risk for bacteremia WBC fever•male•age 7-11 mos

risk for bacteremia WBC fever•male•age 7-11 mos

YesYesYesYes????

YesYesYesYesConsiderConsiderConsiderConsider

•Age 3-36 mos•Temp. > 390C•Age 3-36 mos•Temp. > 390C

AMOX or specify why otherAMOX or specify why otherAMOX or specify why otherAMOX or specify why other

????

“ “ I think it is clear that the I think it is clear that the handwriting is on the wall saying handwriting is on the wall saying that occult bacteremia is dead. It that occult bacteremia is dead. It was dying when Hib disappeared was dying when Hib disappeared and Prevnar has destroyed it.”and Prevnar has destroyed it.”

contribution to Pediatric Emergency contribution to Pediatric Emergency Medicine List ServeMedicine List Serve

Heptavalent conjugate Heptavalent conjugate pneumococcal vaccinepneumococcal vaccine

• very efficaciousvery efficacious• Likely to make most of the foregoing Likely to make most of the foregoing

pneumococcal in 3-36 month group pneumococcal in 3-36 month group obsoleteobsolete

• Finally become routine by MCHFinally become routine by MCH

Given at 2,4,6 month and 12-15mGiven at 2,4,6 month and 12-15m

4444

Effect in Target Age Group Invasive Effect in Target Age Group Invasive Pneumococcal Disease Rates in Children > 3 Pneumococcal Disease Rates in Children > 3

Years, ABCs, 1998-2003Years, ABCs, 1998-2003

0

50

100

150

200

250

1998 1999 2000 2001 2002 2003

Cas

es/1

00,0

00 p

op

ula

tio

n

>>11 yryr

22 yrsyrs

11 yryr 77% (>1 yr)77% (>1 yr)

83% (1 yr)83% (1 yr)

64% (2 yr)64% (2 yr)

20032003 vs baselinevs baseline

20032003 data are preliminarydata are preliminary

PCV7PCV7

Farely et al, ICP, Cancun, Mexico, August 2003Farely et al, ICP, Cancun, Mexico, August 2003

4545

Effect in Target Age Group Invasive Effect in Target Age Group Invasive Pneumococcal Disease Rates in Children > 3 Pneumococcal Disease Rates in Children > 3

Years, ABCs, 1998-2003Years, ABCs, 1998-2003

20032003 data are preliminarydata are preliminaryFarely et al, ICP, Cancun, Mexico, August 2003Farely et al, ICP, Cancun, Mexico, August 2003

~ ~in invasive 80% in invasive 80% pneumococcal diseasepneumococcal disease

in children > 3 yrsin children > 3 yrs

~ ~ 80% in invasive 80% in invasive pneumococcal diseasepneumococcal disease

in children > 3 yrsin children > 3 yrs

77% (>1 yr)77% (>1 yr)

83% (1 yr)83% (1 yr)

64% (2 yr)64% (2 yr)

20032003 vs baselinevs baseline