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Defining the problem• Infants <60 days old
– T > 38ºC (100.4ºF)– Physical exam findings unreliable– Immunologic status shifting
• Maternal antibodies wane• Infant antibodies still developing
– T cell/B cell function diminished– Immunizations not yet received
• Premature infants at greater disadvantage– Transplacental IgG received in 3rd trimester
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
• 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
– 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• 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– 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– 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 InfantsRochester
criteriaBoston 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
• 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
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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.
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