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Fever in Infants and Children New Data, New Approaches Kimball Prentiss, MD, FAAP

Fever in Infants and Children New Data, New Approaches Kimball Prentiss, MD, FAAP Pediatric Emergency Medicine November 12, 2010. Objectives. Review the epidemiology of SBI in infants 0-3 months 3+ month Review existing strategies for identifying infants at high risk for SBI

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Fever in Infants and Children New Data, New Approaches Kimball Prentiss, MD, FAAP

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  1. Fever in Infants and Children New Data, New Approaches Kimball Prentiss, MD, FAAP Pediatric Emergency Medicine November 12, 2010

  2. Objectives • Review the epidemiology of SBI in infants • 0-3 months • 3+ month • Review existing strategies for identifying infants at high risk for SBI • Identify clinical conditions that alter risk of SBI • Understand the current epidemiology of bacteremia in children and impact of vaccines • Develop a consensus for the management of fever in infants and children

  3. What was the Old Approach??

  4. Cookbook Approach • Septic work-up for all febrile infants • Admit and treat all febrile infants • CBC, Blood cultures for all febrile children • WBC commonly used to identify “children at risk.” Antibiotics for many febrile children • Very little deviation from these “rules”

  5. Typical Case • A six week old infant presents with a fever of 38.5oC • The child is alert and appears well hydrated • Vital signs are HR of 146, RR of 52 and BP of 80/P • The remainder of the exam is normal • The infant had a normal neonatal course and the pregnancy was uncomplicated • What kind of work up do you complete??

  6. Febrile Infant- Epidemiology • Serious bacterial infection (SBI) occurs in 5 - 12% of infants, (< 3 months of age) with a temp > 100.5o F • SBI • Bacterial pathogen from blood, urine, stool or CSF • Pulmonary infiltrate • Infants with obvious cellulitis, abscess or arthritis • Can YOU identify the child at risk for SBI?

  7. Identifying the infant at risk for SBI • Pregnancy history, especially group B strep status of mother. Early vs. Late Disease • Neonatal course; in-dwelling lines, respiratory support, antibiotic Rx • Post-natal exposures to pathogens • Any known risk factors for immunodeficiency • Use of screening lab tests

  8. Some questions to consider • What diagnostic studies are indicated? • Do you perform an LP? • Is the infant hospitalized? • Do all infants with fever require treatment with antibiotics? • What is the impact of recent immunizations or having a known viral infection?

  9. Question # 1What diagnostic studies are indicated?

  10. Diagnostic Studies • CBC with blood culture • Urinalysis and urine culture • Lumbar puncture • Stool for WBC’s in patients with diarrhea • Chest films only if symptoms, or abnormality on exam

  11. Low Risk Criteria - Philadelphia • History suggests no increased risk for infection • Normal Physical exam • WBC < 15,000 • BNR < 0.2 • UA with < 10 WBC/HPF • If patient has diarrhea, stool gram stain reveals < 5 WBC and no blood • Normal lumbar puncture (< 8 cells)

  12. Performance of Philadelphia Criteria • Sens. 64/65 = 98% (95% CI; 92 – 100%) • PPV: 64/460 = 14% (95% CI; 11-17%) • Spec: 286/682 = 42% (95% CI; 38-46% • NPV: 286/287 > 99% (95% CI; 95-100%) The one patient that was missed was an infant with bacteremia. That infant was well at 24 hours of age when the bacteremia was diagnosed. He was identified by the modified screening criteria. (BNR of <0.2)

  13. Highest Yield?

  14. Most Controversial? • LP • What is done at your institution?

  15. Do you Perform an LP? • Most infants with bacterial meningitis are “ill-appearing” • Bacterial meningitis occurs in 0.3% of well appearing infants • Bacteremia is not a good marker for meningitis • Is viral meningitis important? • The dilemma of pre-treatment

  16. Clinical Correlates of Pleocytosis

  17. Age and LP • 38 (7.6%) of 500 patients < 30 days old had a CSF pleocytosis • 86 (10.4%) of 813 patients 30 – 60 days of age had a CSF pleocytosis • 52 (7.7%) of 680 patients 60 – 90 days of age had a CSF pleocytosis • 98% of patients with pleocytosis were “well appearing” • WBC count not helpful in identifying pleocytosis

  18. Admission? • Ill-appearing or high risk • Uncertain follow up • Well appearing patients can be managed at home, depending on the criteria you use, without antibiotics. • Significant cost and some complications associated with hospitalization

  19. Treatment Options • Patient ill-appearing or high risk for SBI • IV Antibiotics • Ampicillin and gentamicin • Ampicillin and cefotaxime • 3rd generation cephalosporin only will not cover enterococcus and Listeria. • Patient low risk for SBI • No antibiotics • IM ceftriaxone

  20. Screening Criteria for All Ages • Recent data suggest that Philadelphia and Boston criteria are not applicable to infants < 1 month old and could result in 10% of neonates with SBI being categorized as low risk. • “ALL CHILDREN UNDER ONE MONTH MUST BE ADMITTED”

  21. Other Considerations • Recent Vaccination • Confirmed Viral Infection

  22. History of Recent Vaccinations

  23. Serious Bacterial Infection in Recently Immunized Young Febrile Infants Wolf et al. Acad Emerg Med 2009;16(12):1284-1289 • To investigate the prevalence SBI in febrile infants without a source aged 6-12 weeks who have received immunizations in the preceding 72 hours • Hypothesize that a history of recent immunization (RI) decreases the prevalence of SBI • Chart review infants 6-12 weeks with a fever of ≥38.0ºC presenting to PED over 88 months • Primary outcome of an SBI based on culture results

  24. Rates of SBI

  25. Timing of Vaccination and SBI

  26. Conclusion • Among febrile infants, the prevalence of SBI is less in the initial 24 hours following immunizations. However, there is still a substantial risk of UTI. • Infants who present greater than 24 hours after immunizations with fever should be managed similarly to infants without RIs.

  27. Impact of RSV DiseaseLevine, et.al., Pediatrics 2004;113:1728-1734 • Multi-Center Trial of 1248 patients • 17/244 who were RSV + had an SBI (7%). 14 were UTI’s • 116/925 who were RSV – had an SBI (12.5%) • No child with RSV had meningitis • Rates of bacteremia were lower (1.1%) in RSV + patients compared to 2.3% in RSV - infants

  28. Impact of all Viral InfectionsByington, et.al., Pediatrics 2004;113:1662-1666 • 1385 infants over six year period. • Evaluated infants with fever according to the Rochester Protocol and compared infants with positive viral testing to those who were viral negative • Overall rate of SBI was 9.5%

  29. Rates of Infection • Rate of SBI was 21/491 (4.2%) in infants with a viral infection • Rate of SBI was 110/894 (12.3%) in infants with no viral infection • Five infants (1%) with viral infections had bacteremia compared to 24 (2.7%) of infants with no viral infection • No case of meningitis in infants with viral infections

  30. Influenza Virus Infection and the Risk of Serious Bacterial Infections in Young Febrile InfantsKrief et al. Pediatrics 2009; 124(1):30 • Methods • Multicenter, prospective, cross-sectional study during 3 consecutive influenza seasons • All febrile infants ≤60 days • Influenza virus status by rapid antigen detection • Blood, urine, CSF and stool cultures

  31. Conclusions • Significantly lower risk of SBI than those without influenza • Potential implications for the laboratory evaluation of young febrile infants > 1 month • Clinically important prevalence of UTIs persists

  32. HSV – Maternal Infection • Using type-specific antibodies against HSV 2, about 20% of pregnant women have had HSV 2 infection. • Majority of these women have no evidence of primary or recurrent infections • Viral excretion at time of delivery is 0.01 to 0.39%. It increases to 0.2 to 7.4% with history of known genital herpes

  33. HSV – Maternal Infection • What does it all mean for clinicians?? The most important fact about maternal transmission is that most infants who develop neonatal disease are born to women who are completely asymptomatic during the pregnancy, as well as at the time of delivery

  34. HSV – Newborn Infection • Occurs in 1:2000 to 1:5000 live births • Intrapartum acquisition is most common; in utero and post-partum occur • Neonatal infections are almost invariably symptomatic

  35. HSV – Newborn Infection • Three classifications of infection • Localized to skin, eyes or mouth • CNS infection with or without mucocutaneous lesions • Disseminated infection involving multiple organs • These infections may present after first week of life, and encephalitis may present as late as 4 – 6 weeks of life.

  36. HSV – High Risk • History of active herpes in mother • Unexplained vesicular rash in infants • CNS deterioration, especially seizures • Disseminated disease • Hemorrhagic CNS findings (minority of children with encephalitis) • Send PCR analysis, begin Acyclovir 20 mg/kg/dose TID for 21 days

  37. Conclusion: The Febrile Infant • All infants 0-3 months require a complete laboratory investigation, with several exceptions • Screening criteria can be used to identify “Low-risk” infants who can be managed at home, possibly without antibiotics • Infants 0 –28 days of age still require hospitalization, regardless of screening tests • Recent vaccination and diagnostic testing which yields an alternative diagnosis may alter the approach to febrile infants. • Consider HSV infection in infants up to 4-6 weeks

  38. Bacteremia in Children

  39. Objectives • Review evolving epidemiology of bacteremia in febrile children • Discuss indications for laboratory evaluation of febrile children • Understand the impact of conjugated pneumococcal vaccine in the management of febrile children

  40. Bacteremia: Scope of the Problem • Historically, 3% of febrile children • Age 3 - 36 months • How to identify the at risk child • Significant morbidity from complications • Meningitis • Septic Arthritis

  41. Patient Presentation • An eighteen month old child presents to the ED with a temp of 39.5oC. Upon arrival the child is noted to be irritable but does calm when held by the parents. Vitals are otherwise normal. The child has a runny nose and a red right tympanic membrane. What work-up, if any is indicated in this child?

  42. Which Diagnostic Tests Would You Perform?? • What has impacted your choice of diagnostic testing??

  43. What is Current Rate of Bacteremia?

  44. Rates of Contamination

  45. Prevnar Efficacy • 97% Fully vaccinated • 94% Partial Vaccinated • 89.1% All pneumococcal serotypes • 86% Two dose schedule

  46. Prevnar Efficacy - Massachusetts • 90% Fully vaccinated • 76% Partial Vaccinated • 70% Two dose schedule • <50% Single dose of vaccine

  47. Kaplan – Peds March 2010 • Some suggestion there is an increase in pneumocococcal disease • Seen in non-vaccine serotypes, especially 19A, which has high resistance pattern • Children with bacteremia were more likely to have underlying disease

  48. Will we see a change in pattern of bacteremia?

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