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

Fever in Infants and Children:
Sepsis, Meningitis, and Occult
Bacteremia
Rashmi Srivastava, MD
Department of Child Health
Fever Phobia
• Fever is the most common pediatric complaint, second
•
•
•
•
only to routine care for clinic visits, and the most common
reason kids are brought to the ER.
In the Middle Ages, fever was felt to be a marker of death
or divine punishment.
Some feel true fever is harmful: 1/3 parents thought 3840ºC(100.4-104ºF), 2/3 40-41ºC(104-106ºF), and all
thought brain damage >41ºC(106ºF).
5-20% have no localizing signs on PE with no history to
explain the fever.
The majority of kids with fever do not have a serious
illness, although a small percentage harbor or may develop
a serious bacterial infection.
‘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 3840ºC(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.
Neonatal
• PE is felt to be unreliable in detecting many serious bacterial
infections. Meningitis should always be considered—up to 10%
appear well, only 15% have a bulging fontanelle, and 10-15%
have nuchal rigidity. So, a high index of suspicion is
important!!! ~20% will not have fever initially.
• Hyperthermia or hypothermia
• Lethargy or irritability
• Poor feeding or vomiting
• Apnea
• Dyspnea
• Jaundice
• Hypotension
• Diarrhea or abdominal distension
• Bulging fontanelle
• seizures
Neonates
• The majority of febrile neonates presenting to the ED have
•
•
•
•
•
a nonspecific viral illness
12% have serious bacterial infections (SBI)
Infected by more virulent bacteria
More likely to develop serious sequelae from viral
infections
GBBS is associated with high rates of meningitis(39%),
non-meningeal foci(10%), and sepsis(7%)
The most common bacterial infections are UTI and occult
bacteremia
Neonatal
Early Onset<7 Days
Later Onset>7 Days
Group B Strep
E. Coli
Listeria Monocytogenes
Enterobacteriaceae
Enterococcus
Strep viridans
Strep Pneumoniae
Hemophilus influenza nt
Herpes simplex
Group B Strep
Listeria Monocytogenes
Enterobacteriaceae
Strep Pneumoniae
Neisseria meningitidis
Herpes simplex
Neonatal
• Risk Factors
• Preterm
• Membrane rupture: before labor onset or prolonged>12
•
•
•
•
•
hours
Chorioamnionitis or maternal peripartum fever
UTI
Multiple pregnancy
Hypoxia or Apgar score <6
Poverty or age <20
• 1/3-1/2 neonatal sepsis will have no risk factors!
Neonatal
• Screening tests: WBC<5000 or >20,000, PMN
<4000, I:T>.2, Plt<100,000, CRP>1, LFTs
elevated(suggest HSV)
• So, if <28 days of age and rectal temp> 38ºC
•
•
•
•
Admit
Blood Culture
Urine Culture—cath specimen
Lumbar Puncture
• Cell count, protein, glucose, culture, PCR
• Parenteral Antibiotics
• Ampicillin + Gentamicin(Cefotaxime), consider
Acyclovir(primary maternal infxn, esp if delivered vaginally,
PROM, fetal scalp electrodes, skin eye or mouth lesions,
seizures, CSF pleocytosis)
Infants 1 to 3 months
• Causes
• HSV(17% are 15 days to 6 weeks of age)
• Bacterial sepsis/meningitis
• 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
•
•
•
•
•
•
•
•
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
Heptavalent pneumococcal
conjugate vaccine, PCV7(Prevnar)
• Licensed in February 2000
• Routinely incorporated into the childhood
immunization schedule in mid-2000
• 4, 6B, 9V, 14, 18C, 19F, 23F
• Recommended for all children aged 2 to 23
months
• Invasive pneumococcal disease in children
younger than 2 years has decreased by at least
60%.
Rates of Invasive Pneumococcal Disease by Age Group and Year
Rates of Invasive Pneumococcal Disease Caused by PCV7 and Non-PCV7 Serotypes in
Neonates and Young Infants Aged 0 to 90 Days by Study Year
So what?
• This data is the first to suggest that neonates
and infants too young to receive PCV7 are
benefiting from herd immunity.
• One hypothesis is that vaccinated children
are less likely to have nasal carriage of
pneumococcus.
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.
•
•
•
•
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 to 36 months
• UA with micro, CBC with 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!
•
•
•
•
•
•
•
•
•
•
Oski’s Pediatrics, 3rd edition
Harriet Lane, 16th edition
FWS in Children 0-36 months of age. TCNA 53(2006)167-194
The Febrile Child. Emergency Medicine Reports. September 1995.
Antibiotic Choices: The critical first hour. Pediatric Annals. June 1996.
Evidence based approach to the febrile infant/child. Handout from Dr.
Michael Cooperstock, MD. May 2000.
Advisory Committee on Immunization Practices. Preventing pneumococcal
disease among infants and young children: recommendations of the Advisory
Committee on Immunization Practices. MMWR Recomm Rep. 2000;49(RR9):1-35
AAP; Committee on Infectious Disease. Policy statement: recommendations
for the prevention of pneumococcal infections, including the use of
pneumococcal conjugate vaccine, pneumococcal polysaccharide vaccine, and
antibiotic porphylaxis/ Pediatrics. 2000;106:362-366.
Whitney CG, FarleyMM, Hadler J, et al. Decline in invasive pneumococcal
disease after the introduction of protein-polysaccharide vaccine. NEnglJMed.
2003;348:1737-1746.
Poehling KA etal. Invasive Pneumococcal Disease Among Infants before and
after Introductions of Pneumococcal Conjugate Vaccine. JAMA Apr 12,
2006,295:1668-74.