1. health and fitness
2. disease

Febrile Infant
Matthew Steinfeldt MD
Pediatric Hospitalist UVRMC
Objectives
• What I told the CME people:
• What my objectives really are:
1. Confusion
2. Frustration
3. Agitation
Disclosures:
Kenneth B. Roberts, MD Young, Febrile Infants: A 30-Year Odyssey Ends Where It Started, JAMA. 2004;291(10):12611262.doi:10.1001/jama.291.10.1261.
Terminology
• “Rule out Sepsis”
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Work up for serious bacterial infection or SBI.
Sepsis is only one of the SBI we look for.
Sepsis is not the most common SBI
Sepsis is not necessarily the most concerning of the SBI’s (my opinion).
• Fever
• Low grade fever?
• Most common fever associated with teething
• Threshold = or > 38.0
• Infant
• Most studies focus on age 0 to 60 days (some out to 90 days)
The Full Work Up
• What we teach the medical students:
• Age 0-29 days
• Blood
• Urine
• Cerebral Spinal Fluid
• Age 30-60 (or 90) days
• Ill-appearing vs well-appearing
• Ill-appearing (little discussion)
• Well-appearing
• Source vs No Source
• No Source = Consensus recommendation is to do something.
In the beginning…
• 1977 – John’s Hopkins senior residents
• Roberts KB, Borzy MS. Fever in the first eight weeks of life. Johns Hopkins Med J.1977;141:9-13.
• 61 infants with fever
• Emergency department
• 8 month study period
• Results
• 1 well appearing 17 day old infant had GBS bacteremia.
• Conclusion
• Difficult to determine clinically on which febrile infants have a SBI
• More study needs to be done
The “more studies needed to be done.”
• Reaching the same conclusion
• Crain EF, Shelov SP. Febrile infants: predictors of bacteremia. J Pediatr.1982;101:686-689.
• Caspe WB, Chamudes O, Louie B. The evaluation and treatment of the febrile infant. Pediatr Infect Dis.1983;2:131135.
• Leading to the “rules of management” in 1984
(Long SS. Approach to the febrile patient with no obvious focus of infection.
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Pediatr Rev.1984;5:305-315.)
All patients should be admitted to the hospital.
Assessment as ‘ill' predicts the presence of a significant diagnosis.
Assessment as ‘well' does not exclude the presence of a significant diagnosis.
Performance of laboratory tests in an outpatient is inappropriate.
Performance of blood culture in an outpatient is inappropriate.“
Rules were meant to be broken.
• Great in theory… but not well followed.
• Studies showing the unnecessary cost of admitting every febrile
infant.
• DeAngelis C, Joffe A, Wilson M, Willis E. Iatrogenic risks and financial costs of hospitalizing febrile infants. AJDC.1983;137:1146-1149.
• And the frenzy begins.
20 years
2 decades
A score ago
• Varies studies attempting to identify “Low Risk” infants.
• For example…
• Dagan R, Powell KR, Hall CB, Menegus MA. Identification of infants unlikely to have
serious bacterial infection although hospitalized for suspected sepsis. J
Pediatr.1986;107:855-860.
• Baker MD, Bell LM, Avner JR. The efficacy of routine outpatient management without
antibiotics of fever in selected infants. Pediatrics.1999;103:627-631.
• Baskin MN, O'Rourke EJ, Fleisher GR. Outpatient treatment of febrile infants, 28 to 59
days of age with intramuscular ceftriaxone. J Pediatr.1992;120:22-27.
DeAngelis C, Joffe A, Willis E. et al. Hospitalization v outpatient treatment of young,
febrile infants. AJDC.1983;137:1150-1152.
Boston Protocol
Baskin MN, O'Rourke EJ, Fleisher GR Outpatient treatment of febrile infants 28 to 89 days of age with intramuscular administration of ceftriaxone. J Pediatr. 1992;120(1):22
• Criteria of “low risk” infants
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Peripheral white blood cell (WBC) count less than 20,000/microL
CSF with WBC <10/microL
UA <10 WBC per high-powered field
No infiltrate on chest radiograph if one was obtained
• High risk – admission and antibiotics
• Low risk – dose of ceftriaxone and follow up next day
• Stats
• 27 (of 503) patients (5.4 percent) had an SBI identified during follow-up.
• All infants with SBIs received an appropriate course of antimicrobial therapy and
were well at follow-up
• No adverse outcomes
Philadelphia Protocol
Baker MD, Bell LM, Avner JR Outpatient management without antibiotics of fever in selected infants. N Engl J Med. 1993;329(20):1437.
• Criteria for “Low Risk”
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WBC <15,000/microL
Band-neutrophil ratio <0.2
UA <10 WBC/hpf and a negative urine Gram stain
CSF <8 WBC/microL and a negative CSF Gram stain
Chest radiograph lacking an infiltrate if one was obtained
Stool without blood and few or no WBCs on the smear in infants with diarrhea
• High Risk – admitted and treated with antibiotics
• Low Risk – Follow up in 24 hrs and No antibiotics.
• Stats:
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Sensitivity 98 percent (95% CI 92-100 percent)
Specificity was 42 percent (95% CI 38-46 percent)
Positive predictive value was 14 percent (95% CI 11-17 percent)
Negative predictive value was 99.7 percent (95% CI 98-100 percent)
Did not miss many infants with SBI.
Many well infants underwent excessive laboratory testing, and admissions.
No adverse outcomes.
Rochester Protocol
Jaskiewicz JA, McCarthy CA, Richardson AC, White KC, Fisher DJ, Dagan R, Powell KR Febrile infants at low risk for serious bacterial infection--an
appraisal of the Rochester criteria and implications for management. Febrile Infant Collaborative Study Group. diatrics. 1994;94(3):390.
• Criteria for “Low Risk”
• WBC 5,000 to 15,000/microL with an absolute band count <1,500/microL
• Urinalysis with <10 WBC/hpf and no bacteria seen
• Stool with <5 WBC/hpf if obtained
• High Risk – admitted and treated with antibiotics
• Low Risk – discharged if “follow up was reliable.”
• Stats:
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931 well-appearing infants
437 (47%) were classified as low risk.
5 low-risk infants had an SBI
Negative predictive value of 98.9 percent (95% CI 97-100 percent).
No adverse outcomes
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McCarthy CA, Powell KR, Jaskiewicz JA, Carbrey CL, Hylton JW, Monroe DJ, Meyer H, Outpatient management of selected infants younger than two months of age evaluated for possible
sepsis. Pediatr Infect Dis J. 1990;9(6):385
Meanwhile back at the ranch
• Vaccines
• Various other markers
• Viral studies
• Cost cutting
Immunizations
• Hib
• Introduced 1988
• Incidence of disease decreased by 99% from 1987 to 2007 (age <5 yrs)
• PCV 7
• Introduced 2000
• Incidence of disease decreased by 64% (age < 2 yrs)
• PCV 13 (2010) and PCV 27 (not for everyone)
• ???????????
• GBS prophylaxis
• Introduced 1996
• Decrease of early onset GBS by 80%
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Progress toward elimination of Haemophilus influenzae type B disease among infants and children—United States, 1987–1995. MMWR Morb Mortal Wkly Rep
1996;45:901-6.
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Invasive pneumococcal disease in children 5 years after conjugate vaccine introduction—eight states, 1998–2005. MMWR Morb Mortal Wkly Rep 2008;57:144-8.
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Licensure of a 13-valent pneumococcal conjugate vaccine (PCV13) and recommendations for use among children—Advisory Committee on Immunization Practices
(ACIP), 2010. MMWR Morb Mortal Wkly Rep 2010;59:258-61.
CRP and PCT
• Both show elevations in infants with SBI.
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Andreola B, Bressan S, Callegaro S, Liverani A, Plebani M, Da Dalt L. Procalcitonin and C-reactive protein as diagnostic markers of severe bacterial infections
in febrile infants and children in the emergency department. Pediatr Infect Dis J 2007;26:672-7.
• Superior Sensitivity and Specificity to WBC.
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Fernandez Lopez A, Luaces Cubells C, Garcia Garcia JJ, Fernandez Pou J. Procalcitonin in pediatric emergency departments for the early diagnosis of invasive
bacterial infections in febrile infants: results of a multicenter study and utility of a rapid qualitative test for this marker. Pediatr Infect Dis J 2003;22:895-903.
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Andreola B, Bressan S, Callegaro S, Liverani A, Plebani M, Da Dalt L. Procalcitonin and C-reactive protein as diagnostic markers of severe bacterial infections
in febrile infants and children in the emergency department. Pediatr Infect Dis J 2007;26:672-7.
DFA and/or PCR
You can pick your friends. You can pick your nose. You can NOT pick your friends nose.
• Viral testing has become fast, reliable, sensitive, and specific.
• SBI’s are less common is febrile infants with RSV, Enterovirus, and Influenza
• Many hospitals have adopted these tests and have altered their management of the febrile
neonate
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Byington CL, Enriquez FR, Hoff C, Tuohy R, Taggart EW, Hillyard DR,et al. Serious bacterial infections in febrile infants 1 to 90 days old with and without viral infections. Pediatrics
2004;113:1662-6.
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Bender JM, Ampofo K, Gesteland P, Sheng X, Korgenski K, Raines B, et al. Influenza virus infection in infants less than three months of age. Pediatr Infect Dis J 2010;29:6-9.
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Krief WI, Levine DA, Platt SL, Macias CG, Dayan PS, Zorc JJ, et al. Influenza virus infection and the risk of serious bacterial infections in young febrile infants. Pediatrics
2009;124:30-9.
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Rittichier KR, Bryan PA, Bassett KE, Taggart EW, Enriquez FR, Hillyard DR, et al. Diagnosis and outcomes of enterovirus infections in young infants. Pediatr Infect Dis J 2005;24:54650.
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Levine DA, Platt SL, Dayan PS, Macias CG, Zorc JJ, Krief W, et al. Risk of serious bacterial infection in young febrile infants with respiratory syncytial virus infections. Pediatrics
2004;113:1728-34.
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Ramers C, Billman G, Hartin M, Ho S, Sawyer MH. Impact of a diagnostic cerebrospinal fluid enterovirus polymerase chain reaction test on patient management. JAMA
2000;283:2680-5.
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Benito-Fernandez J, Vazquez-Ronco MA, Morteruel-Aizkuren E, Mintegui- Raso S, Sanchez-Etxaniz J, Fernandez-Landaluce A. Impact of rapid viral testing for influenza A and B
viruses on management of febrile infants without signs of focal infection. Pediatr Infect Dis J 2006;25:1153-7.
GBS
• Since 1970 one of the leading causes of neonatal morbidly and
mortality.
• Universal screen and treatment recommended in 2002.
• Estimated decrease in early onset GBS disease by 80%.
• Van Dyke MK, Phares CR, Lynfield R, et al. Evaluation of universal antenatal screening for group B Streptococcus. N Engl J
Med. 2009;360(25):2626 –2636
• www.pediatrics.org/cgi/doi/10.1542/peds.2011-1466
Herding Cats
• Pantell RH, Newman TB, Bernzweig J. et al. Management and outcomes of
care of fever in early infancy. JAMA.2004;291:1203-1212.
• Prospective cohort study
• Involved clinics in the American Academy of Pediatrics Pediatric Research in Office
Settings (PROS) network
• Offices of 573 practitioners
• 44 states, the District of Columbia, and Puerto Rico
• Patients:
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3066 infants
3 months or younger
Temperatures of at least 38°C
3 years - from February 28, 1995, through April 25, 1998. (Remember Hib, PCV, and GBS?)
Cats… are not a herding animal
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Hospitalized 36% of the infants
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Performed laboratory testing in 75%
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Treated 57% with antibiotics.
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Majority (64%) were treated exclusively outside of the hospital.
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Bacteremia was detected in 1.8% of infants (2.4% of those tested)
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Bacterial meningitis in 0.5%.
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Well-appearing infants aged 25 days or older with fever of less than 38.6°C had a rate of 0.4% for bacteremia/bacterial meningitis.
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Frequency of other illnesses:
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Urinary tract infection, 5.4%
Otitis media, 12.2%
Upper respiratory tract infection, 25.6%
Bronchiolitis, 7.8%
Gastroenteritis, 7.2%.
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Practitioners followed current guidelines in 42% of episodes.
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In the initial visit, they treated 61 of the 63 cases of bacteremia/bacterial meningitis with antibiotics.
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Neither current guidelines nor the model developed in this study performed with greater accuracy than observed practitioner management.
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No change in outcome regardless of management.
Arguments
• Not in an ER setting
• Patients presenting to clinics tend to have better socioeconomic
status
• Follow up is more reliable
• Sicker patients go to the ER
• Low incidence of illness
• PROS physicians are not a accurate sample of physicians.
In honor of Bill Nye… Consider the following.
• First study done at John’s Hopkins
• 1977 – found work up for febrile infants is highly variable
• Boston Protocol – no adverse outcomes
• Philadelphia Protocol – no adverse outcomes
• Rochester Protocol – no adverse outcomes
• PROS study
• Found work up for febrile infants is highly variable
• No adverse outcomes.
Meanwhile back at the ranch
• Vaccines – Hib and PCV(insert number here)
• Antepartum prophylaxis for GBS
• CRP and/or PCT
• DFA
• PCR
• Listeria… what’s that again?
The Complaint Box
• In essence: No changes to the work up for febrile infants have been
made to reflect the changes in infection rates, infection types, new
tests, or taken into account the modern era of cost savings.
My recommendations.
Talk to someone smarter than me!
What I Do (context… I’m a Hospitalist).
• 0-29 days
• Nearly always:
• Blood, Urine, CSF – start antibiotics.
• Ampicillin, cefotaxime.
• Add gentamicin and/or vancomycin if suspicion of meningitis is high.
• Admit for about 36 hrs.
• Not nearly always – if source.
• If starting antibiotics will always obtain CSF prior.
• Age 30-60 (or 90) days
• Ill-appearing vs well-appearing
• Ill-appearing (little discussion)
• Well-appearing
• Source vs No Source
• No Source = Consensus recommendation is to do something.
The something
• Well appearing:
• Blood, Urine, CSF, Antibiotics
• If follow up – discharge home if labs reassuring after antibiotics.
• If no follow up – admit for 24 hrs.
• If concerned parents – admit for 24 hrs.
• Blood, Urine
• Admit for 24 hours and observe patient
• No antibiotics without CSF
• If they are “sick” enough to be admitted and “need” antibiotics they are sick enough to need
CSF.