Fever without source (FWS) in young kids Emergency Medicine Core Rounds October 3, 2002 Dr. Edward Les.

Fever without source (FWS)in young kids

Emergency Medicine Core Rounds

October 3, 2002

Dr. Edward Les

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. At his two week check-up he was noted to be gaining weight appropriately. His vital signs are: T 38.9C (R), HR 140, RR 40, and BP 90/60. He is sleepy but easily rousable. Physical exam is normal apart from a slightly dull left tympanic membrane. His peripheral 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-upb. Discharge on oral amoxicillin with close follow-upc. LP and admission for parenteral antibioticsd. CXR to r/o pneumoniae. Stool for analysis and culture, and outpatient follow-up

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

rectal temperature of 39.2C. 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:

a. IM ceftriaxone in the EDb. Admission to the hospital for IV antibioticsc. Discharge with follow-up in 24 hoursd. Admission to the hospital for observatione. Discharge on amoxicillin

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 39.8C. 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 sampleb. Administer IM ceftriaxonec. Perform an LPd. Obtain a CXRe. Discharge on antipyretics

Overview

• Definitions• Frequency of

febrile illnesses• Treatment of fever• Physical exam• Rochester and

Philadelphia criteria

• Evaluation and management options

• FWS: infant < 28 days

• FWS: infant 28-90 days

• FWS: > 90 days to 36 months

• Summary

Definitions

• Fever• Fever without source (FWS)• Fever without focus• Occult bacteremia• Serious bacterial infection (SBI)

Where the heck did 98.6ºF come from?

A.D. 1868!

• Carl Reinhold August Wunderlich

• > 1 million axillary temps from 25,000 patients analyzed

What constitutes a fever?

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

Different body sites

• Rectal standard• Oral 0.5-0.6 lower• Axillary 0.8-1.0 lower• Tympanic 0.5-0.6 lower

Documented:– In the absence of antipyretics– Unbundled (“abdomen-toe differential”)– In ED or office or by hx from reliable parents/adults

Fever Without Source

• “…An acute febrile illness in which the etiology of the fever is not apparent after a careful history and physical examination.”– Baraff et al, Pediatrics 1993; 92:1-12

Fever of Unknown Origin

1. Fever of 38C or greater which has continued for a two to three week period

2. Absence of localizing clinical signs

3. Failure of simple diagnostic efforts to identify a cause

Occult bacteremia

• “…a positive blood culture in the setting of well appearance and without focus (e.g. no pneumonia), BUT may bein the presence of URTI, otitis media, diarrhea, or wheezing”– Fleisher et al, J Pediatrics 1994

Serious Bacterial Infection

• “…SBI include meningitis, sepsis, bone and joint infections, urinary tract infections, pneumonia and enteritis”– Baraff et al, Pediatrics 1993; 92:1-12

Frequency of febrile illness

• 35% of unscheduled ambulatory care visits

• 65% of kids see doc before age 2 c/o fever– Majority (75%) for T < 39 C – 13% T > 39.5C

• 14-20% are FWS

Epidemiology

• Incidence of bacteremia in febrile infants in post-Hib era

– 2-3% if < 2 months, T > 38CAvner and Baker, Emerg Med Clin NA 2002;20(1)

– < 2% if 3-36 months, T >39CKlein, Ped Inf Dis J 2002;21(6):584-8

Occult bacteremia organisms

• Streptococcus pneumonia > 85%

• Neisseria meningitidis 3-5%

• Others:– S. aureus– S. pyogenes (GAS)– Salmonella species– Haemophilus influenzae type B

(now rare – previously 10%)

Outcomes of occult bacteremia without

antibiotics

• Persistent fever 56%• Persistent bacteremia 21%• Meningitis 9%

– S. pneumonia 6%– H. Influenzae 26% (but no longer see

Which antibiotics to best treat/prevent occult

bacteremia?Two multi-center trials:• Ceftriaxone vs amoxil or amoxil/clavulanate

» Intramuscular vs oral therapy for the prevention of meningitis and other bacterial sequelae in young febrile children at risk for occult bacteremia.

Fleisher et al, J Peds 1994;124:504-12

» Antimicrobial treatment of occult bacteremia: a multicenter cooperative study.

Bass e al,PIDJ 1993;12:446-73

– Poor studies– Suggested ceftriaxone associated with less persistent fever,

but no difference in outcomes

Age 3-36 months:routine use of antibiotics?

• Risk of meningitis without abx = 1:500• Need to treat hundreds to prevent one case• HiB virtually eliminated; pneumococcus to

follow?• Risk of partial treatment, delayed

recognition• Resistant organisms – selection• Risk of drug side effects

Should fever be treated?

• Pros– Decrease discomfort– Calm the folks– Extreme (>41C) may cause permanent

brain damage –rare,rare,rare– Decrease risk of febrile convulsions in

prone kids??

Should fever be treated?

• Cons– Adverse effect of antipyretic may

outweigh benefits– May obscure diagnostic/prognostic signs– Fever usually short-lived and benign– Fever is normal and adaptive

physiologic response

Fever phobiaCrocetti et al, Pediatrics 2001;107

• 91% of caregivers believed a fever could cause harmful effects– 21% listed brain damage; 14% said death

• 25% gave antipyretics for T < 37.8C

• 85% awaken their child to give antipyretics

• 14% gave acetaminophen too frequently, 44% gave ibuprofen too frequently

Our fault?

• Temp is 1st thing checked at triage• Quick to ask about fever on history• Instructions often include advice to

return if fever is higher or persistent• Investigations up the wazoo• Little routine info provided to

parents about fever

Fever phobia

• 65% of pediatricians also believe that an elevated body temperature in and of itself could become dangerous to a child– May and Bauchner, Pediatrics

1992;90:851-54

Can viral infections and bacterial infections be distinguished

based on response to antipyretic therapy?

• NYET!!Traditional theory, but……

no evidence to support it.

Physical examination:Approach to child

• Gentle, non-threatening• Parental assistance to comfort• Observe as much as possible

before examining• Value of a second look

Physical examination:“Toxic appearance”

• Lethargy/irritability• Poor/absent eye contact• Poor perfusion• Hypo/hyperventilation• Cyanosis

Yale Observation Scale

• 6 items of observation and physical signs

• Normal (1 point), moderate impairment (3 points), and severe impairment (5 points) scores are given for:

– Quality of cry– Reaction to parental stimulation– State of alertness– Color– Hydration– Response to social overtures

McCarthy, PL, et al, Pediatrics 1982; 70:802-809

Scores of 10 correlate with low likelihood of serious illness, primarily in infants < 2 months old

Tale of Three Cities:Boston,Philadelphia, and

Rochester

• Guides developed to identify febrile infants at low or neglible risk of a serious bacterial infection

• Goal was to reduce the number of infants hospitalized unnecessarily and to identify infants who may be managed as outpatients

• Consist of clinical and laboratory procedures

Baskin et al, J Pediatr 1992;120:22-27Baker et al, N Eng J Med1993;329:1437-41Jaskiewicz et al, Pediatrics 1994;94:390-96

Philadelphia Rochester Boston

Age 29-60 d

Temperature 38.2C

History Not specified

Physical examination Well-appearing (IOS < 10)Unremarkable exam

Laboratory parameters (defines lower-risk patients)

Wbc < 15,000BNR < 0.2UA < 10 WBC/hpfUrine gram stain –veCSF <8 WBCCSF gm stain –veCXR clearStool: no blood, few or no WBC’s on smear

High risk patients Hospitalize + empiric abx

Low risk patients HomeNo antibioticsFollow-up required

Reported statistics Sensitivity 98%PPV 14%NPV 99.7%

Age 0-60 d

Temperature 38.0C

History Term infantNo perinatal antibioticsNo underlying diseaseNo prior hospitalization

Physical examination Well-appearingNo ear, soft tissue, or bone infection

WBC > 5,000 and < 15,000Absolute band count <1500UA < 10 WBC/hpf< 5 WBC/hpf stool smear

High risk patients Hospitalize + empiric antibiotics

Low risk patients HomeNo antibioticsFollow-up required

Reported statistics Sensitivity 92%PPV 12.3%NPV 98.95 *SBI 1.1%

Age 28-89 d

Temperature 38.0C

History No immunizations within preceding 48 hNo abx within 48 hNot dehydrated

Physical examination Well-appearingNo ear, soft tissue, or bone infection

CSF < 10UA < 10 WBC/hpfCXR clearWBC < 20,000

High risk patients Hospitalize + empiric abx

Low risk patients HomeEmpiric abx (IM ceftriaxone)Follow-up required

Reported statistics Sensitivity – N/APPV – N/ANPV – N/A *SBI 5.4%

Age 1-2 months 0-2 months 1-3 months

Temperature 38.2C 38.0C 38.0C

History Not specified Term infantPreviously well

No recent vacc /abxNot dehydrated

Physical examination Well-appearing (IOS < 10)

Well-appearing Well-appearing

WBC > 5,000; < 15,000Abs band ct <1500UA < 10 WBC/hpf< 5 WBC/hpf stool smear

* No LP required!

CSF < 10UA < 10 WBC/hpfCXR clearWBC < 20,000

Higher risk patients Hospitalize + empiric abx

Hospitalize + empiric abx

Lower risk patients HomeNo antibioticsFollow-up required

HomeNo antibioticsFollow-up required

HomeEmpiric abx (IM ceftriaxone)Follow-up required

Follow-up: “good social situation” required:

• Telephone at home• Availability of vehicle• Parental maturity• Thermometer• ED or office travel < 30 min

Case scenarios - fever

• By age group:

– < 1 month of age– 1 – 3 months– 3 – 36 months

Evaluation options

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

Management options

[ ] Admit[ ]Treat empirically, or[ ]Observe, no treatment

[ ] Send home, follow-up within 24 hours

[ ]Treat empirically, or[ ]No treatment

Treatment options

[ ] Oral

[ ]Amoxicillin[ ]Amoxicillin/clavulanate[ ]Cefaclor[ ]Other

[ ] Intravenous

[ ]Ceftriaxone[ ]Other

Fever Practice Guidelines

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

Febrile infants < 3 monthsrisk of bacteremia

• If meets low risk Rochester 0.2% (1:500)

criteria

• If meets low risk criteria 0.7-1% but < 1 month

Febrile infant < 28 days

“American” consensus recommendations

• Whether or not low risk– 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

Febrile infants 28-90 days of age

NOT Low Risk

“American” and Canadian Consensus recommendations

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

• Broad-spectrum parental antibiotics

Philadelphia Rochester

Age 1-2 months 0-2 months

Temperature 38.2C 38.0C

History Not specified Term infantPreviously well

Physical examination Well-appearing (IOS < 10)

Well-appearing

WBC > 5,000; < 15,000Abs band ct <1500UA < 10 WBC/hpf< 5 WBC/hpf stool smear

* No LP required!

Febrile infants 28-90 days of age

“Low Risk”

• Option 1 (“American”):

– Blood culture– Urine culture– LP– Ceftriaxone 50 mg/kg

IM– Return for re-

evaluation w/i 24 hours

• Option 2 (“American” and CPS)

– No investigations(or urine culture only )

– Careful outpatient observation, without treatment, close follow-up

Follow-up of “Low Risk” Infants 28-90 days old

• Within 24 hours• Repeat exam for source, sequelae• Review, repeat labs/xrays if

performed• Repeat antibiotics?• Arrange ongoing follow-up

Follow-up of “Low Risk” Infants 28-90 days old

• If blood 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

Fever Without SourceAge 3 – 36 Months

• Risk of occult bacteremia – based on “old data”– 3-11%, mean 4.3% for T>39C

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

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

FWS – age 3-36 months:Consensus

Recommendations

• CHILD APPEARS TOXIC:

– ADMIT to hospital– Sepsis w/u– Parenteral abx

Recommendations

• CHILD NON-TOXIC, T < 39C

– No diagnostic tests or antibiotics– Acetaminophen 15 mg/kg q4h for

fever– Return if fever persists > 48 hours or

clinical condition deteriorates

Recommendations

• CHILD NON-TOXIC, T 39C

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

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

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

Choice of antibiotic

• If decide to treat empirically (follow-up not assured, not low risk)

– “American” guidelines: ceftriaxone– CPS: ceftriaxone or po amoxicillin

60 mg/kg/day

FWS – age 3-36 months:BC returns positive

• Pneumococcus:

– Persistent fever: ADMIT for sepsis w/u and parenteral abx pending results

– If no fever and looks well: repeat cultures, no treatment

FWS – age 3-36 months:BC returns positive

• All Other Bacteria:

• ADMIT for sepsis w/u and parenteral abx pending results

FWS – age 3-36 months:Urine culture returns

positive

• All organisms:

– ADMIT if febrile or ill-appearing– Outpatient abx if afebrile and well

Summary: FWS but “low risk”

• Infants < 28 days:

• Infants 1-3 months

• Infants and children 3 months to 3 yrs (T < 39C):

• Infants and children 3 months to 3 years (T 39C):

hospitalize +/- abx

+/- labs, home, +/- abx

home, no antibiotics

+/- labs, home, no antibiotics

close follow-up in all!

“ 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

Heptavalent conjugate pneumococcal vaccine

• 90% efficacious• Likely to make most of the foregoing

discussion in 3-36 month group obsolete• Need more evidence first• Also, still be alert for:

– Unimmunized, under-immunized, vaccine failures, infection with serotypes not included in vaccine

Question 1A 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. At his two week check-up he was noted to be gaining weight appropriately. His vital signs are: T 38.9C (R), HR 140, RR 40, and BP 90/60. He is sleepy but easily rousable. Physical exam is normal apart from a slightly dull left tympanic membrane. His peripheral WBC is 16,000, his UA shows 3 WBC/hpf. BC and UC are sent. Your management at this point would consist of:

Question 1A 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. At his two week check-up he was noted to be gaining weight appropriately. His vital signs are: T 38.9C (R), HR 140, RR 40, and BP 90/60. He is sleepy but easily rousable. Physical exam is normal apart from a slightly dull left tympanic membrane. His peripheral WBC is 16,000, his UA shows 3 WBC/hpf. BC and UC are sent. Your management at this point would consist of:

rectal temperature of 39.2C ®. 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:

of fever. He appears well but his tympanic T is 39.8C. 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.

a. Obtain a urine sampleb. Administer IM ceftriaxonec. Perform an LPd. Obtain a CXTe. Discharge on antipyretics

of fever. He appears well but his tympanic T is 39.8C. 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.

a. Obtain a urine sampleb. Administer IM ceftriaxonec. Perform an LPd. Obtain a CXTe. Discharge on antipyretics

Fever without source (FWS) in young kids Emergency Medicine Core Rounds October 3, 2002 Dr. Edward Les.

definitions fever fever

source fws fever

amoxicillin slide

adult slide

day history of fever

outpatient followup

fever of unknown origin

reliable parentsadults

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