Transcript Fever in the Infant - University of Chicago

Fever in the Infant
Gina Lowell
July 5th, 2005
Defining the problem
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Infants <60 days old
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T > 38ºC (100.4ºF)
Physical exam findings unreliable
Immunologic status shifting
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Maternal antibodies wane
Infant antibodies still developing
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T cell/B cell function diminished
Immunizations not yet received
Premature infants at greater disadvantage
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Transplacental IgG received in 3rd trimester
Serum IgG levels in the first five years of life
©2005 UpToDate®
Etiology
• Viral causes
– Most common (presumed vs. confirmed)
– Adenoviruses, Enteroviruses, Influenza, RSV,
Parainfluenza, etc.
– HSV: uncommon but worrisome
• Bacterial causes
– Less common
• 7.2-8.5% of febrile infants <90 days old will have
a serious bacterial infection (SBI)
• A greater proportion of these occur during the
first month of life
Serious Bacterial Infection
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Bacteremia
Meningitis
Urinary tract infection
Soft tissue infection
Bone/joint infection
Endocarditis
Pneumonia
Gastroenteritis
Pathogens
• The first month
– GBS (Streptococcus agalactiae)
– E. coli
– Listeria monocytogenes
• The second month: All of the above, plus…
– Streptococcus pneumoniae
– Hemophilus influenza type b
• Incidence has decreased to fewer than 1 case
per 100,000 children less than 5 years old
Group B Streptococcus (GBS)
• Gram positive diplococcus; 9 serotypes
• Range of infection: EOD versus LOD
– EOD: Presents 1st week after birth
• Vertical transmission
• Risk factors
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Delivery <37wks gestation
Maternal chorioamnionitis (T>38°C)
Prolonged rupture of membranes (>18 hours)
Previous infant with invasive GBS disease
• Prevented by appropriate intrapartum antibiotics (IPA)
– 2 doses of Ampicillin prior to delivery
– LOD: Presents 1-4 weeks after birth
• Can present up to 3-6 months after birth
• Horizontal transmission
• IPA does not prevent LOD
GBS: Treatment
• Empiric treatment for suspected GBS
– EOD: Ampicillin and an aminoglycoside (Gentamicin)
– LOD: Ampicillin and a 3rd generation cephalosporin
(Cefotaxime or Ceftriaxone)
• Await culture and sensitivities
– Uniformly sensitive to penicillin
– While GBS are susceptible to cephalosporins and other
antibiotics, none of these are superior to ampicillin or
penicillin
• Length of treatment
– Bacteremia: 10 days
– Meningitis: 14-21 days
– Osteomyelitis or Endocarditis: 4 weeks
Escherichia coli
• Gram negative bacillus
• Lengthy range of infection: from birth to several weeks old
• Risk factors
– Intrapartum
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Delivery <37wks gestation
Maternal chorioamnionitis (T>38°C)
Prolonged rupture of membranes (>18 hours)
Low birth weight
Traumatic delivery
– Metabolic
• Galactosemia
• Acidosis
– Skin defects
• Myelomeningocele
E. coli: Treatment
• Empiric treatment for suspected E. coli
– Ampicillin and an aminoglycoside (Gentamicin) or
– Ampicillin and a 3rd generation cephalosporin
(Cefotaxime or Ceftriaxone)
• CAUTION! Emergence of gram negative bacilli with ESBL
can occur with routine use of cephalosporins (Klebsiella,
Enterobacter, Serratia sp.)
• Await culture and sensitivities
– Ampicillin or 3rd generation cephalosporin with an
aminoglycoside
• Length of treatment
– Bacteremia: 10-14 days
– Meningitis: 21 days
Listeria monocytogenes
• Gram positive bacillus
• Rare: 124/10^6 births
• Foodborne transmission
– Unpasteurized milk, soft cheeses, prepared meats,
unwashed raw vegetables
• Similar range of infection to GBS
– EOD: days after birth
• Moms may have flu-like illness days prior to delivery
• In utero transmission (while mom bacteremic)
– LOD: several days to weeks after birth
• Mom asymptomatic
• Postpartum transmission
Listeria: Treatment
• Empiric treatment for suspected Listeria
– Ampicillin and Gentamicin
• Await culture and sensitivities
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Ampicillin: bacteriostatic
Gentamicin: bactericidal
Bactrim is preferred in PCN allergic patients
Cephalosporins are not active against Listeria
• Length of treatment
– Bacteremia: 10-14 days
– Meningitis: 14-21 days
Streptococcus pneumoniae
• Gram positive diplococcus; 90 serotypes
• SPIN: S. pneumoniae infections in the neonate
– Accounts for 1-11% of septicemia in the infant <30
days old
– 2-3 weeks old at presentation
– Patients were ill with bacteremia, meningitis,
pneumonia, and otitis media
• Incidence rises during the second month of life
• Predominates from the 3rd month of life onward
S. pneumoniae: Treatment
• Empiric treatment for suspected S. pneumoniae
– 3rd generation cephalosporin
• 50% of isolates are resistant to penicillin
• 50% of PCN-resistant strains are also resistant to
cephalosporins
– If bacterial meningitis is suspected, add Vancomycin
• Await culture and sensitivities
– 3rd generation cephalosporins
– If resistant to cephalosporins, consult ID
• Length of treatment
– Bacteremia: 10-14 days
– Meningitis: 14-21 days
Herpes Simplex Virus
• Two serotypes: HSV-1 and HSV-2
– 75% of neonatal infections are due to HSV-2
• Incidence: 1 in 3,000-20,000 live births
– Infection occurs in 33-50% of infants born vaginally to
mothers with primary HSV infection
– More than 75% of these moms had no signs or
symptoms of infection before or during pregnancy
• Range of presentation: Birth to 4 weeks old
• Pattern of presentation
– SEM: 40%
– CNS: 35%
– Disseminated: 25%
HSV: Treatment
• Empiric treatment for suspected HSV
– Acyclovir IV
• Await diagnostic results
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Tzanck preparation (skin scraping)
Culture (eyes, nasopharynx, skin, rectal)
PCR (CSF)
EEG, MRI (temporal lobe abnormalities)
• Length of treatment
– 14 days for SEM
– 21 days for CNS and disseminated disease
Lab investigation of the febrile infant
• Blood
– CBC, culture
– LFT’s if suspicious for HSV
• Urine
– UA, culture
• CSF
– Cell count, protein, glucose, culture, HSV PCR when
suspicious
• Stool
– Culture if suspicious for bacterial gastroenteritis
• CXR
– If patient has one or more respiratory symptoms
Empiric treatment of the febrile infant
• Ampicillin: 1st and 2nd month
– GBS
– E. coli
– Listeria
• Gentamicin: 1st month
– E. coli
– Listeria
• Ceftriaxone/Cefotaxime: 2nd month
– S. pneumoniae
– E. coli
• Vancomycin: 2nd month
– Only if strongly suspicious of bacterial meningitis
• Acyclovir: 1st month
– Only if strongly suspicious of HSV
Admission and Antibiotics:
Who needs it?
Defining
Low Risk Infants
Rochester
criteria
Boston criteria
Philadelphia
criteria
Age
Gestation
0-60 days
>37 wks
28-89 days
N/S
29-60 days
N/S
Temp
Appearance
>38°C
Well
>38°C
Well
>38.2°C
Well
Labs
(Not complete)
WBC 5-15
Bands<1.5
WBC<20
CSF WBC<10
WBC<15
CSF WBC<8
Treatment
Follow up
Not defined
Reliable
CTX IM
24 hours
None
24 hours
Low risk infants
Outcome
47%
NPV 98.9%
Not defined
5.4% of low risk
infants had SBI
19%
NPV 99.7%
Troubleshooting
• LP
– Dry
– Traumatic
• Confirmed viral infection: Risk of concomitant SBI
– Infants with confirmed viral infection (e.g. RSV+) are at lower risk
for SBI than those without an identified viral infection
• Predisposition to SBI can vary among viruses
• Preterm infants or infants<30 days generally should receive the full
sepsis evaluation and treatment even if viral infection is confirmed
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ABX received prior to lab evaluation
– At risk for partially treated meningitis
– Full sepsis evaluation and treatment
– If negative, close observation off of antibiotics is warranted
• In all of these scenarios, follow your clinical judgement
Sources
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and children 0 to 36 months of age with fever without source. Agency for Health Care
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Baskin, MN. The prevalence of serious bacterial infection by age in febrile infants during
the first 3 months of life. Pediatr Ann. 1993;22:462.
Behrman RE, Kliegman RM. Nelson Essentials of Pediatrics, 3rd Edition. Immunology and
Allergy: Physiologic Immunodeficiency in the Neonate. 1998;8:269
Byington CL et al. Serious bacterial infections in febrile infants 1 to 90 days old with and
without viral infections. Pediatrics. 2004;113(6):1662-1666
Byington CL et al. Ampicillin-resistant pathogens in febrile infants. Pediatrics.
2003;111(5):964-968.
Durbin WJ. Pneumococcal Infections. Pediatrics in Review. 2004;25(12):418-423.
Gotoff SP. Group B Streptococcal Infections. Pediatrics in Review. 2002;23(11):381-385.
Hoffman JA et al. Streptococcus pneumoniae infections in the neonate. Pediatrics.
2003;112(5):1095-1102.
Posfay-Barbe KM, Wald ER. Listeriosis. Pediatrics in Review. 2004;25(5):151-156.
Waggoner-Fountain LA, Grossman LB. Herpes Simplex Virus. Pediatrics in Review.
2004;25(3):86-92.