Fever in the Infant

Gina Lowell

July 5th, 2005

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

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

• 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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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.

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