Fever without source (FWS) in young kids

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

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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

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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). BCs 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

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Overview

• Definitions
• Frequency of febrile illnesses
• Treatment of fever
• Physical exam
• Rochester and Philadelphia criteria

• Evaluation and management options
• FWS infant lt 28 days
• FWS infant 28-90 days
• FWS gt 90 days to 36 months
• Summary

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Definitions

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

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Where the heck did 98.6ºF come from?

• A.D. 1868!
• Carl Reinhold August Wunderlich
• gt 1 million axillary temps from 25,000 patients
  analyzed

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What constitutes a fever?

• Rectal temperature gt 38?C, either at physicians
  office, ED, or documented at home by a reliable
  parent or other adult

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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

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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 921-12

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Fever of Unknown Origin

• 1. Fever of 38?C 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

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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

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Serious Bacterial Infection

• SBI include meningitis, sepsis, bone and joint
  infections, urinary tract infections, pneumonia
  and enteritis
• Baraff et al, Pediatrics 1993 921-12

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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 lt 39 ?C
• 13 T gt 39.5?C
• 14-20 are FWS

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Epidemiology

• Incidence of bacteremia in febrile infants in
  post-Hib era
• 2-3 if lt 2 months, T gt 38?C
• Avner and Baker, Emerg Med Clin NA 200220(1)
• lt 2 if 3-36 months, T gt39?C
• Klein, Ped Inf Dis J 200221(6)584-8

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Occult bacteremia organisms

• Streptococcus pneumonia gt 85
• Neisseria meningitidis 3-5
• Others
• S. aureus
• S. pyogenes (GAS)
• Salmonella species
• Haemophilus influenzae type B
• (now rare previously 10)

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Outcomes of occult bacteremia without antibiotics

• Persistent fever 56
• Persistent bacteremia 21
• Meningitis 9
• S. pneumonia 6
• H. Influenzae 26 (but no longer see it)

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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 1994124504-12
• Antimicrobial treatment of occult bacteremia a
  multicenter cooperative study.
• Bass e al,PIDJ 199312446-73
• Poor studies
• Suggested ceftriaxone associated with less
  persistent fever, but no difference in outcomes

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Age 3-36 monthsroutine use of antibiotics?

• Risk of meningitis without abx 1500
• 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

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Should fever be treated?

• Pros
• Decrease discomfort
• Calm the folks
• Extreme (gt41?C) may cause permanent brain damage
  rare,rare,rare
• Decrease risk of febrile convulsions in prone
  kids??

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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

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Fever phobia

• Crocetti et al, Pediatrics 2001107
• 91 of caregivers believed a fever could cause
  harmful effects
• 21 listed brain damage 14 said death
• 25 gave antipyretics for T lt 37.8?C
• 85 awaken their child to give antipyretics
• 14 gave acetaminophen too frequently, 44
  gave ibuprofen too frequently

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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

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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 199290851-54

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Can viral infections and bacterial infections be
distinguished based on response to antipyretic
therapy?

• NYET!!
• Traditional theory, but
• no evidence to support it.

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Physical examinationApproach to child

• Gentle, non-threatening
• Parental assistance to comfort
• Observe as much as possible before examining
• Value of a second look

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Physical examinationToxic appearance

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

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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 70802-809

Scores of ? 10 correlate with low likelihood of
serious illness, primarily in infants lt 2 months
old
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Tale of Three CitiesBoston,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 199212022-27
• Baker et al, N Eng J Med19933291437-41
• Jaskiewicz et al, Pediatrics 199494390-96

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Philadelphia Rochester Boston
Age 29-60 d
Temperature 38.2?C
History Not specified
Physical examination Well-appearing (IOS lt 10) Unremarkable exam
Laboratory parameters (defines lower-risk patients) Wbc lt 15,000 BNR lt 0.2 UA lt 10 WBC/hpf Urine gram stain ve CSF lt8 WBC CSF gm stain ve CXR clear Stool no blood, few or no WBCs on smear
High risk patients Hospitalize empiric abx
Low risk patients Home No antibiotics Follow-up required
Reported statistics Sensitivity 98 PPV 14 NPV 99.7
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Philadelphia Rochester Boston
Age 0-60 d
Temperature 38.0?C
History Term infant No perinatal antibiotics No underlying disease No prior hospitalization
Physical examination Well-appearing No ear, soft tissue, or bone infection
Laboratory parameters (defines lower-risk patients) WBC gt 5,000 and lt 15,000 Absolute band count lt1500 UA lt 10 WBC/hpf lt 5 WBC/hpf stool smear
High risk patients Hospitalize empiric antibiotics
Low risk patients Home No antibiotics Follow-up required
Reported statistics Sensitivity 92 PPV 12.3 NPV 98.95 SBI 1.1
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Philadelphia Rochester Boston
Age 28-89 d
Temperature 38.0?C
History No immunizations within preceding 48 h No abx within 48 h Not dehydrated
Physical examination Well-appearing No ear, soft tissue, or bone infection
Laboratory parameters (defines lower-risk patients) CSF lt 10 UA lt 10 WBC/hpf CXR clear WBC lt 20,000
High risk patients Hospitalize empiric abx
Low risk patients Home Empiric abx (IM ceftriaxone) Follow-up required
Reported statistics Sensitivity N/A PPV N/A NPV N/A SBI 5.4
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Philadelphia Rochester Boston
Age 1-2 months 0-2 months 1-3 months
Temperature 38.2?C 38.0?C 38.0?C
History Not specified Term infant Previously well No recent vacc /abx Not dehydrated
Physical examination Well-appearing (IOS lt 10) Well-appearing Well-appearing
Laboratory parameters (defines lower-risk patients) Wbc lt 15,000 BNR lt 0.2 UA lt 10 WBC/hpf Urine gram stain ve CSF lt8 WBC CSF gm stain ve CXR clear Stool no blood, few or no WBCs on smear WBC gt 5,000 lt 15,000 Abs band ct lt1500 UA lt 10 WBC/hpf lt 5 WBC/hpf stool smear No LP required! CSF lt 10 UA lt 10 WBC/hpf CXR clear WBC lt 20,000
Higher risk patients Hospitalize empiric abx Hospitalize empiric abx Hospitalize empiric abx
Lower risk patients Home No antibiotics Follow-up required Home No antibiotics Follow-up required Home Empiric abx (IM ceftriaxone) Follow-up required
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Follow-up good social situation required

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

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Case scenarios - fever

• By age group
• lt 1 month of age
• 1 3 months
• 3 36 months

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Evaluation options

• CBC
• blood culture
• urinalysis
• urine culture
• CXR
• LP
• Nothing

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Management options

• Admit
• Treat empirically, or
• Observe, no treatment
• Send home, follow-up within 24 hours
• Treat empirically, or
• No treatment

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Treatment options

• Oral
• Amoxicillin
• Amoxicillin/clavulanate
• Cefaclor
• Other
• Intravenous
• Ceftriaxone
• Other

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Fever Practice Guidelines

• CPS guidelines Management of the febrile one-to
  36-month-old child with no focus of infection.
• Paediatr Child Health 1996141-45
  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 1993921-12

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Febrile infants lt 3 months risk of bacteremia

• If meets low risk Rochester 0.2 (1500)
• criteria
• If meets low risk criteria 0.7-1
• but lt 1 month

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Febrile infant lt 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

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Febrile infants 28-90 days of ageNOT Low Risk

• American and Canadian Consensus recommendations
• ADMIT to hospital with full septic w/u
• BC, UC, LP
• Broad-spectrum parental antibiotics

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Philadelphia Rochester
Age 1-2 months 0-2 months
Temperature 38.2?C 38.0?C
History Not specified Term infant Previously well
Physical examination Well-appearing (IOS lt 10) Well-appearing
Laboratory parameters (defines lower-risk patients) Wbc lt 15,000 BNR lt 0.2 UA lt 10 WBC/hpf Urine gram stain ve CSF lt8 WBC CSF gm stain ve CXR clear Stool no blood, few or no WBCs on smear WBC gt 5,000 lt 15,000 Abs band ct lt1500 UA lt 10 WBC/hpf lt 5 WBC/hpf stool smear No LP required!
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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

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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

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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

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Fever Without SourceAge 3 36 Months

• Risk of occult bacteremia based on old data
• 3-11, mean 4.3 for Tgt39?C
• Risk greater with
• Higher temperatures
• WBC gt 15,000 (13 vs 2.6)
• Risk of pneumococcal meningitis (w/o abx tx)
• 0.21 (1500)

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FWS age 3-36 monthsConsensus Recommendations

• CHILD APPEARS TOXIC
• ADMIT to hospital
• Sepsis w/u
• Parenteral abx

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FWS age 3-36 monthsConsensus Recommendations

• CHILD NON-TOXIC, T lt 39?C
• No diagnostic tests or antibiotics
• Acetaminophen 15 mg/kg q4h for fever
• Return if fever persists gt 48 hours or clinical
  condition deteriorates

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FWS age 3-36 monthsConsensus Recommendations

• CHILD NON-TOXIC, T ? 39?C
• Urine culture (for M lt 6 month, F lt 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 gt15,000
• CXR, stool culture if indicated clinically
• Acetaminophen 15 mg/kg q4h for T ? 39?C
• Follow-up in 24-48 hours no antibiotics

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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

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FWS age 3-36 monthsBC 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

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FWS age 3-36 monthsBC returns positive

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

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FWS age 3-36 monthsUrine culture returns
positive

• All organisms
• ADMIT if febrile or ill-appearing
• Outpatient abx if afebrile and well

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Summary FWS but low risk

• Infants lt 28 days
• Infants 1-3 months
• Infants and children 3 months to 3 yrs (T lt
  39?C)
• Infants and children 3 months to 3 years (T
  ?39?C)

• hospitalize /- abx
• /- labs, home, /- abx
• home, no antibiotics
• /- labs, home, no antibiotics

close follow-up in all!
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• 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

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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

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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
  38.9?C (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-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

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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
  38.9?C (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-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

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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

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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

62
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). BCs 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 CXT
• e. Discharge on antipyretics

63
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). BCs 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 CXT
• e. Discharge on antipyretics

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finis