Transcript Fever in Infants and Children: Sepsis, Meningitis, and Occult

Rashmi Srivastava, MD
Department of Child Health
‘True’ Fever
 Occurs when IL-1, IL-6, TNF-ά or other cytokines
are released from monocytes and macrophages in
response to infection, tissue injury, drugs, and
other inflammatory processes, increasing the
body’s set point. The anterior hypothalamus
maintains an inherent set point near 36ºC(98.6ºF).
 Normal circadian rhythm, which is highest(up to
2ºC, 3ºF) ~6pm and lowest at 6am. This accounts
for increased volume of ER visits that peaks in the
evening. Most true fevers follow this diurnal
pattern.
‘False’
fever,
aka
hyperthermia
 Does not directly increase the body’s set point.
 CNS disease that directly affects the hypothalamus--ICH,
infection.
 Diseases that increase the body’s production of heat-hyperthyroidism, malignant hyperthermia, salicylate
overdose.
 Excess heat load--child left in a car or left next to a heater
for too long.
 Defective heat loss mechanisms--burns, heat stroke,
drugs that compromise blood flow and sweating
mechanisms.
 Normal causes of temperature elevation include
physical activity, ovulation, and environmental
temperature.
Reliable Temperature
Measurement
 All measurements are estimates of the body’s true
core temp—central circulation=aorta and
pulmonary artery.
 RECTAL—gold standard
 Esophageal—accurate but impractical
 Tactile and axillary—inaccurate, varies
considerably with environmental temperature
 Tympanic—inaccurate in age <3 years
Benefits of fever
 The hypothalamus will not allow the temp to rise
above 41.5ºC(107ºF).
 WBCs work best and kill the most bacteria at 38-
40ºC(100.4-104ºF).
 Neutrophils make more superoxide anion, and
there is more and increased activity of interferon.
 Coxsackie and polio virus replication is directly
inhibited.
Fever without a source(FWS)
 5 to 20% of febrile children have no localizing
signs on PE and nothing in the history to explain
the fever. By definition, less than 7 days.
 FWS(like fever) is most common in children
younger than age 5, with a peak prevalence
between 6 and 24 months of age.
 Those <6 months retain protective maternal antibodies
against common organisms, while those 18-24 months
old are more immune competent, and are at a lower risk
of developing bacteremia
Diagnostic Assessment in Children
 Age is important as 1) etiologic pathogens, 2) clinical
exam, and 3) immune system capacity changes as the
newborn ages.
 Most break them into the first 2-4 weeks of
life(neonatal), 1-3 months, and 3 to 36 months.
Infants 1 to 3 months
 Causes
 HSV(17% are 15 days to 6 weeks of age)
 Bacterial sepsis/meningitis
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Group B Strep, S. Pneumoniae, H. influenza, N. meningitidis,
Enterobacteriaceae
Bone and joint infections
UTI
Bacterial enteritis(esp Salmonella)
Pneumonia
Enterovirus sepsis/meningitis(July-October)
 The risk of bacteremia/meningitis is 3.3%, pneumonia,
bone/joint infections and bacterial enteritis is 13.7%
 30-50% of those who are ultimately diagnosed with bacterial
meningitis have been seen by a physician within the prior
week(usually 1-2 days before) and were diagnosed as having a
trivial illness and discharged on oral antibiotics.
Infants 1 to 3 months
Infants who are toxic and febrile have a much higher
risk of serious bacterial infection. They should be
admitted, have a full sepsis workup, and given
antibiotics/antiviralsAmpicillin and Cefotaxime.
Infants who are nontoxic and febrile who meet all
Rochester criteria can ‘safely’ be treated as an
outpatient. Generally, 1-2.9% of children meeting
these criteria will develop a serious bacterial
infection, 0.7% bacteremia, 0.14% meningitis.
Infants 1 to 3 months
 Rochester Criteria/Low Risk Criteria
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Nontoxic—most critical and difficult
Previously healthy, not low birth weight
No focal bacterial infection on PE except Otitis Media
WBC 5,000-15,000/mm3 (normal)
Bands<1500/mm3 (normal)
Normal urinalysis, including gram stain
If diarrhea, must be non-bloody and WBC<5/hpf.
If respiratory symptoms present, normal CXR
 Negative predictive value 98.9%
Infants 1 to 3 months
 If all of the criteria are met, then there are 2
options for outpatient management:
 1) Blood, Urine Cultures, LP, Ceftriaxone 50mg/kg IM
(to 1g), and return for reevaluation within 24 hours.
 2) Blood, Urine Cultures and careful observation.
 Parents should have mature judgement, can return
within 30 minutes and have a thermometer and a
phone.
 IF NO LP IS DONE, DO NOT GIVE
CEFTRIAXONE AS IT WILL COMPROMISE F/U
IF THE PATIENT IS STILL FEBRILE
Infants 1 to 3 months
 Follow-up of low risk infants
 If all cultures negative: afebrile, well
appearingCareful observation
 Blood cultures negative: well appearing,
febrileCareful observation, may consider second dose
of Ceftriaxone
 Blood culture positiveadmit for sepsis workup and
parenteral antibiotics pending results
 Urine culture positive: if persistent feveradmit for
sepsis workup, parenteral antibiotics pending results. If
afebrile and welloutpatient antibiotics
Infants
3
to
36
months
 Infant sepsis syndrome:
 Age 3-36 months
 Fever>39ºC
 ANC>10,000
 If a child meets all 3 criteria, he has a 3% risk for
pneumococcemia. If untreated, 3% will progress to
meningitis.
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Bacteremia risk peaks at 8-12 months
Pneumococcal sepsis peaks at 1 year, then drops off
Pneumococcal meningitis peaks at 3-5 months
OM, sinusitis, pneumonia, response to antipyretics, and social
status do not significantly alter risk.
 Other causes: HHV6(15%), UTI(girls 3%, boys 0.6%),
menigococcemia(0.1%), Salmonella(0.2%), H.
influenza(0.05%), Enterovirus(JulyOctober).
Infants
3 toCBC
36withmonths
 UA with micro,
differential, Blood
Cultures
 LP if meningeal signs, not wanting to be held or moved,
petechiae, purpura or toxic.
 Antimicrobials:
 OM or pneumonia: cover for pneumococcus, non-typable H.
flu and Moraxella: amoxicillin+augmentin, ceftriaxone
 URI or no focus: cover for pneumococcus and menigococcus:
amoxicillin(80-100mg/dg/day), ceftriaxone
 Pneumococcemia: promptly reassess, if well, should at least
treat with 1 dose ceftriaxone.
 PCV-7 >97% protection, thus all pneumococcal sepsis
will decrease by 90%. So CBC and antimicrobials for
this age group is becoming less critical.
Occult Bacteremia
5% of children with FWS have OCCULT
BACTEREMIA
 The presence of a positive blood culture in kids who
look well enough to be treated as outpatients and in
whom the positive results are not anticipated.
Occult Bacteremia
 Streptococcus pneumonia is responsible for 2/3 to
¾ of all cases.
 Peak prevalence between 6 and 24 months
 Association with high fever(39.4ºC or 103ºF)
 High WBC count(>15,000)
 Absence of evident focal soft tissue infection.
 Neisseria meningitidis, Haemophilus influenzae
type b, and salmonellae account for most of the
remaining cases.
Risk of Occult Bacteremia
Age
Temp
WBC
Low Risk
>3yr
<39.4ºC
>5000 and
<15,000
High Risk
<2yr
>40ºC(104ºF)
<5000 or >15,000
Hx of contact with H. Flu
or N. meningitidis
OB has a low prevalence, so even though WBC is a sensitive and
specific screening test, it has a low PPV. So the test does not
discriminate between children who have FWS who are bacteremic
and those who are not.
Therefore, blood culture is the gold standardstill has a high
number of false positives, take 24-48hrs, and most cases of occult
pneumococcal bacteremia clear without treatment.
Occult Bacteremia
 Empiric antibiotics should be targeted against S.
pneumoniae, N. meningitidis, and H. influenza
 Amoxicillin
 Augmentin, Bactrim, 2nd or 3rd gen Cephalosporins
 Single dose Ceftriaxone 50-75mg/kg
 Followup is essential!