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Moises Auron, MD FAAP Pediatric Residency Program Noon Conference 8/21/2009
Fever  <ul><li>20% of pediatric emergency dept visits </li></ul><ul><li>35% of ambulatory visits </li></ul><ul><li>5%-10%-...
Fever  <ul><li>Hypothalamus is the thermoregulatory center for the body </li></ul><ul><li>Fever results when a shift in th...
Fever <ul><li>Fever production begins when an infectious agent, toxin, immune complex, or other inflammatory agent stimula...
Definitions <ul><li>Fever without focus is defined as the acute onset of fever (rectal temp > 38C) in a child in whom no p...
Fever Without Source <ul><li>Age under 36 months old  </li></ul><ul><li>Higher risk in younger infants  </li></ul><ul><li>...
Occult bacteremia <ul><li>Pathogenic bacteria are present in blood culture  </li></ul><ul><li>No apparent focus of infecti...
Data Collection <ul><li>History </li></ul><ul><ul><li>Associated symptoms and behaviors </li></ul></ul><ul><ul><li>Onset a...
Data collection <ul><li>Temperature assessment- rectal temps best assess core temperature </li></ul><ul><li>Bundled infant...
Physical Examination <ul><li>SpO 2  – better predictor of pulmonary infection </li></ul><ul><li>Toxic appearance (irritabi...
Yale Observation Scale <ul><li>Indications   </li></ul><ul><ul><li>Assessment of febrile child ages 3-36 months  </li></ul...
Yale Observation Scale Bang A. Indian J Pediatr 2009; 76 (6) : 599-604.
Yale Observation Scale <ul><li>Scoring   </li></ul><ul><ul><li>Quality of Cry  </li></ul></ul><ul><ul><ul><li>Strong or No...
Yale Observation Scale <ul><li>Color  </li></ul><ul><ul><li>Pink: 1  </li></ul></ul><ul><ul><li>Acrocyanosis: 3  </li></ul...
Laboratory Data And Interpretation <ul><li>WBC </li></ul><ul><li>Neutrophils / Bands / Acute-phase reactants </li></ul><ul...
WBC <ul><li>Direct relationship between the WBC count and the prevalence of bacteremia </li></ul><ul><ul><li>3m to 36m </l...
WBC <ul><li>Limitations </li></ul><ul><ul><li>Up to 50% of children with Hib bacteremia will have WBC 5,000-15,000 </li></...
Neutrophils, Bands, ESR, CRP <ul><li>Have value in identifying children at risk for serious illness </li></ul><ul><li>High...
Antigen Testing <ul><li>Strep pneumoniae </li></ul><ul><li>H. influenzae type b </li></ul><ul><li>PCR methods (HSZ, VZV, e...
Blood cultures <ul><li>Gold standard </li></ul><ul><li>False negatives </li></ul><ul><ul><li>Prior treatment with antibiot...
LP <ul><li>Indicated if the diagnosis of sepsis or meningitis is considered </li></ul><ul><li>Seizures upon presentation <...
UA/Urine culture <ul><li>20% of children with UTI have a normal UA based on a negative reagent strip </li></ul><ul><li>Inf...
CXR <ul><li>Respiratory signs or symptoms are good predictors of clinically significant positive CXR findings in the group...
CXR <ul><li>Children > 3 months </li></ul><ul><li>Oxygen Saturation <95%  </li></ul><ul><li>Respiratory distress  </li></u...
Stool Analysis and Culture <ul><li>Important if diarrhea present </li></ul><ul><li>Can be considered a focus of infection ...
C – Reactive Protein <ul><li>Acute phase reactant released by the liver following inflammation or tissue damage. </li></ul...
Procalcitonin <ul><li>2 observational studies (N=505) cutoff value 0.12 ng/mL to detect SBI </li></ul><ul><ul><li>Sensitiv...
Differential Diagnosis of Fever Without Focus Common 3-36 months 0-3 months Viral Enterovirus, parainflueza, adenovirus, R...
Differential Diagnosis of Fever Without Focus Common 3-36 months 0-3 months Bacterial (UTI) Gram negative organisms (E. co...
Differential Diagnosis of Fever Without Focus Rare 3m-36 months Connective Tissue Diseases Rheumatic fever, SLE, sarcoidos...
Etiology of occult bacteremia <ul><li>S. pneumoniae – 85% </li></ul><ul><li>H. influenzae type b – 10% </li></ul><ul><li>N...
Fever Without Source <ul><li>The purpose of these criteria is to reduce the number of infants hospitalized unnecessarily a...
Fever Without Source <ul><li>Febrile infants and young children have, by tradition, been arbitrarily assigned to different...
Criteria  <ul><li>Rochester  - Jaskiewicz JA, et al. Febrile infants at low risk for serious bacterial infection - an appr...
Philadelphia Rochester Boston Age 29-60d < 60days 28-89d Temp > 38.2C > 38C > 38C History Not specified Term infant No per...
Three Most Common Strategies for Managing Febrile Infants Philadelphia Rochester Boston Higher Risk patients Hospitalize +...
Criteria <ul><li>In the first 2 strategies, the lower risk patients are selected for outpatient therapy without antibiotic...
Criteria <ul><li>Philadelphia protocol and Rochester criteria: </li></ul><ul><ul><li>High NPV - 99.7% and 98.9%, respectiv...
Rochester Criteria <ul><li>Indications   </li></ul><ul><ul><li>Assessment of febrile child ages 60-90 days  </li></ul></ul...
Rochester Criteria <ul><li>Reassuring if all criteria are present  </li></ul><ul><ul><li>Well appearing infant   </li></ul...
Rochester Criteria <ul><li>Occult bacteremia risk  </li></ul><ul><ul><li>Well-appearing febrile infant risk: 7-9%  </li></...
Management: 0 months to 3 months Baraff LJ. Ann Emerg Med. 2000;36(6):602-614
Management:  0 months to 3 months  <ul><li>Age <1 month old  </li></ul><ul><li>Admit for assessment for Neonatal Sepsis </...
Management:  0 months to 3 months  <ul><ul><li>Management Option 1  </li></ul></ul><ul><ul><ul><li>Ceftriaxone 50 mg/kg IM...
Management:  3m to 36m Baraff LJ. Pediatr Ann. 1993; 22(8): 497-8.
Management: 3m to 36m <ul><li>Toxic appearing febrile child  </li></ul><ul><ul><li>See Yale Observation Scale </li></ul></...
<ul><li>Non-toxic child with fever <39.0 C (<102.2 F)  </li></ul><ul><li>Avoid further diagnostic tests or antibiotics  </...
Non-toxic 3m-36m child with fever >38.9 C (>102.1 F)  <ul><li>Step 1:  Evaluate Urine  </li></ul><ul><li>Obtain Urine LE a...
<ul><li>Step 2: Additional Studies   </li></ul><ul><li>Chest Roentgenogram Indications  </li></ul><ul><ul><li>Oxygen Satur...
<ul><li>Step 2: Additional Studies   </li></ul><ul><li>Stool Culture Indications  </li></ul><ul><ul><li>Stool blood or muc...
<ul><li>Step 3: Consider Antibiotic </li></ul><ul><li>Indications to skip to Step 4 below (no antibiotics)  </li></ul><ul>...
<ul><li>Step 4: Instructions   </li></ul><ul><li>Follow-up  </li></ul><ul><ul><li>Return within 24 hours if antibiotics st...
<ul><li>Step 5: Blood Culture or Urine Culture positive   </li></ul><ul><li>Admit if child febrile or toxic appearance  </...
Antibiotics <ul><li>0-1 month: </li></ul><ul><ul><li>Ampicillin </li></ul></ul><ul><ul><li>Gentamicin or Cefotaxime </li><...
Antivirals <ul><li>Acyclovir </li></ul><ul><ul><li>In patients 0-1 month </li></ul></ul><ul><ul><li>20 mg/kg/dose three ti...
Antipyretics <ul><li>Acetaminophen </li></ul><ul><ul><li>15mg/kg/dose q4hours prn temperature > 39 o C (102.2 F) </li></ul...
Antipyretics <ul><li>In children with baseline temperatures  <  102.2°F - both ibuprofen doses and acetaminophen are equal...
Lumbar Puncture <ul><li>Does my child really need a lumbar puncture? </li></ul><ul><li>Could you wait and see if his WBC c...
 
<ul><li>Logistic regression modeling and ROC  analysis of peripheral blood WBC count and cerebrospinal fluid WBC count for...
Results: P < 0.001
Results: <ul><li>Twenty-two of 5,353 (4.1 per 1,000) infants had acute bacterial meningitis.  </li></ul><ul><li>For diagno...
Conclusions: <ul><li>Decisions to perform or withhold lumbar puncture should not be based on prevailing interpretations of...
Question <ul><li>It is RSV season </li></ul><ul><li>Do we really need to do these work-ups? </li></ul>
Pediatrics. Aug 2003. 112(2): 282-284.
Objective <ul><li>Neonates with fever generally undergo a full, invasive septic evaluation to exclude serious bacterial in...
Objective: <ul><li>Investigate the prevalence of SBI in febrile infants < 8 wk and had documented RSV infection and compar...
Methods <ul><li>Retrospective cohort study  </li></ul><ul><li>Infants  <  8 wk  </li></ul><ul><li>Presented with documente...
Pediatrics. Aug 2003. 112(2): 282-284. RR 0.09 [95% CI 0.02–0.38] P<0.0001
Conclusions: <ul><li>Full septic evaluations are not necessary in nontoxic-appearing infants with a positive RSV test.  </...
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Fever without a source in Pediatrics

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Lecture on fever without a source in the newborn and the infant up to 3 months old.

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Fever without a source in Pediatrics

  1. 1. Moises Auron, MD FAAP Pediatric Residency Program Noon Conference 8/21/2009
  2. 2. Fever <ul><li>20% of pediatric emergency dept visits </li></ul><ul><li>35% of ambulatory visits </li></ul><ul><li>5%-10%-20% percent of febrile children have fever without an apparent source of infection after history and physical examination. </li></ul>
  3. 3. Fever <ul><li>Hypothalamus is the thermoregulatory center for the body </li></ul><ul><li>Fever results when a shift in the hypothalamic set point causes a controlled elevation of body temperature above the normal range </li></ul><ul><li>Normal set point for humans has a daily circadian rhythm ranging 36C-37.8C with peak occurring in the afternoon </li></ul>Current Opinion in Pediatrics 2009, 21:139–144
  4. 4. Fever <ul><li>Fever production begins when an infectious agent, toxin, immune complex, or other inflammatory agent stimulates macrophages or endothelial cells to produce endogenous pyrogens, such as interlukin-1 and tumor necrosis factor </li></ul><ul><li>Pyrogens  hypothalamus  PGE 2 and AA metabolites </li></ul><ul><li> raise thermostat set point (thermoregulatory neurons) </li></ul>Current Opinion in Pediatrics 2009, 21:139–144
  5. 5. Definitions <ul><li>Fever without focus is defined as the acute onset of fever (rectal temp > 38C) in a child in whom no probable cause for the fever is evident after a careful history and physical examination </li></ul><ul><li>Other terms </li></ul><ul><ul><li>Fever without source </li></ul></ul><ul><ul><li>Fever without localizing signs </li></ul></ul>Current Opinion in Pediatrics 2009, 21:139–144
  6. 6. Fever Without Source <ul><li>Age under 36 months old </li></ul><ul><li>Higher risk in younger infants </li></ul><ul><li>Fever (38 C or 100.4 F) without localizing signs </li></ul><ul><li>Acute onset of fever persisting <1 week </li></ul><ul><li>Assess for occult bacteremia </li></ul>
  7. 7. Occult bacteremia <ul><li>Pathogenic bacteria are present in blood culture </li></ul><ul><li>No apparent focus of infection and no signs of sepsis </li></ul><ul><li>Cause serious bacterial illnesses (SBIs): </li></ul><ul><ul><li>Meningitis </li></ul></ul><ul><ul><li>Sepsis </li></ul></ul><ul><ul><li>Bone and joint infections </li></ul></ul><ul><ul><li>Urinary tract infections </li></ul></ul><ul><ul><li>Pneumonia </li></ul></ul><ul><ul><li>Enteritis </li></ul></ul>
  8. 8. Data Collection <ul><li>History </li></ul><ul><ul><li>Associated symptoms and behaviors </li></ul></ul><ul><ul><li>Onset and duration of fever </li></ul></ul><ul><ul><li>Degree of temperature-method and anatomic site </li></ul></ul><ul><ul><li>Medications </li></ul></ul><ul><ul><li>Environmental exposures </li></ul></ul><ul><ul><li>Similar symptoms in siblings </li></ul></ul><ul><ul><li>Birth and nursery history (STD, TORCH, GBS, ROM) </li></ul></ul><ul><ul><li>Date of last immunizations (MMR-fever and rash 7-10 days afterwards) </li></ul></ul>
  9. 9. Data collection <ul><li>Temperature assessment- rectal temps best assess core temperature </li></ul><ul><li>Bundled infants- rectal temp >38C may not attributable to bundling </li></ul><ul><li>Fever by History at home who is afebrile on presentation: manage as fever documented in acute care setting </li></ul><ul><li>General appearance-acute illness observation scale </li></ul><ul><li>Response to antipyretics-may hinder ability to assess the child </li></ul>
  10. 10. Physical Examination <ul><li>SpO 2 – better predictor of pulmonary infection </li></ul><ul><li>Toxic appearance (irritability, poor perfusion, lethargy) </li></ul><ul><li>Signs of infection (omphalitis, arthritis, cellulitis, herpes lesions) </li></ul><ul><li>Meningitis – change in sleep pattern, decreased po, paradoxical irritability, bulging fontanelle (late sign). </li></ul><ul><li>Use of Yale Observation Scale (McCarthy, 1980-1987). </li></ul>
  11. 11. Yale Observation Scale <ul><li>Indications </li></ul><ul><ul><li>Assessment of febrile child ages 3-36 months </li></ul></ul><ul><ul><li>Predicts serious infection (Occult bacteremia) </li></ul></ul><ul><ul><li>Quantifies &quot;Toxic Appearance&quot; in children </li></ul></ul><ul><li>Interpretation </li></ul><ul><ul><li>Score = 10 </li></ul></ul><ul><ul><ul><li>Incidence of serious illness: 2.7% </li></ul></ul></ul><ul><ul><li>Score = 11-15 </li></ul></ul><ul><ul><ul><li>Incidence of serious illness: 26% </li></ul></ul></ul><ul><ul><li>Score >16 </li></ul></ul><ul><ul><ul><li>Incidence of serious illness: 92.3% </li></ul></ul></ul><ul><ul><ul><li>McCarthy. J Pediatrics. 1987. 110:36-30 </li></ul></ul></ul>
  12. 12. Yale Observation Scale Bang A. Indian J Pediatr 2009; 76 (6) : 599-604.
  13. 13. Yale Observation Scale <ul><li>Scoring </li></ul><ul><ul><li>Quality of Cry </li></ul></ul><ul><ul><ul><li>Strong or No cry: 1 </li></ul></ul></ul><ul><ul><ul><li>Whimper or Sob: 3 </li></ul></ul></ul><ul><ul><ul><li>Weak cry, Moan, or high pitched cry: 5 </li></ul></ul></ul><ul><ul><li>Reaction to parents </li></ul></ul><ul><ul><ul><li>Brief Cry or Content: 1 </li></ul></ul></ul><ul><ul><ul><li>Cries off and on: 3 </li></ul></ul></ul><ul><ul><ul><li>Persistent cry: 5 </li></ul></ul></ul><ul><ul><li>State variation </li></ul></ul><ul><ul><ul><li>Awakens quickly: 1 </li></ul></ul></ul><ul><ul><ul><li>Difficult to awaken: 3 </li></ul></ul></ul><ul><ul><ul><li>No arousal or falls asleep: 5 </li></ul></ul></ul><ul><ul><ul><li>McCarthy. J Pediatrics. 1987. 110:36-30 </li></ul></ul></ul>
  14. 14. Yale Observation Scale <ul><li>Color </li></ul><ul><ul><li>Pink: 1 </li></ul></ul><ul><ul><li>Acrocyanosis: 3 </li></ul></ul><ul><ul><li>Pale, Cyanotic, or Mottled: 5 </li></ul></ul><ul><li>Hydration </li></ul><ul><ul><li>Eyes, skin, and mucus membranes moist: 1 </li></ul></ul><ul><ul><li>Mouth slightly dry: 3 </li></ul></ul><ul><ul><li>Mucus Membranes dry, eyes sunken: 5 </li></ul></ul><ul><li>Social Response </li></ul><ul><ul><li>Alert or Smiles: 1 </li></ul></ul><ul><ul><li>Alert or brief smile: 3 </li></ul></ul><ul><ul><li>No smile, anxious, or dull: 5 </li></ul></ul><ul><ul><ul><li>McCarthy. J Pediatrics. 1987. 110:36-30 </li></ul></ul></ul>
  15. 15. Laboratory Data And Interpretation <ul><li>WBC </li></ul><ul><li>Neutrophils / Bands / Acute-phase reactants </li></ul><ul><li>Antigen testing </li></ul><ul><li>Blood cultures </li></ul><ul><li>Lumbar puncture </li></ul><ul><li>UA/Urine culture </li></ul><ul><li>CXR </li></ul><ul><li>Stool Analysis and Culture </li></ul>
  16. 16. WBC <ul><li>Direct relationship between the WBC count and the prevalence of bacteremia </li></ul><ul><ul><li>3m to 36m </li></ul></ul><ul><ul><ul><li>WBC >30,000 42.9% </li></ul></ul></ul><ul><ul><ul><li>WBC 15,000-30,000 16.6% </li></ul></ul></ul><ul><ul><ul><li>WBC 10,000-15,000 2.8% </li></ul></ul></ul><ul><ul><ul><li>Below 10,000 no bacteremia </li></ul></ul></ul><ul><ul><li>Temperature curve – not useful </li></ul></ul><ul><ul><li>Combination of temperature curve and WBC curve offered no advantage over the WBC curve alone </li></ul></ul><ul><ul><ul><ul><ul><li>Jaffe et al. Pediatrics 1991; 87:670 </li></ul></ul></ul></ul></ul>
  17. 17. WBC <ul><li>Limitations </li></ul><ul><ul><li>Up to 50% of children with Hib bacteremia will have WBC 5,000-15,000 </li></ul></ul><ul><ul><li>Children with Neisseria meningitidis may be leukopenic </li></ul></ul><ul><ul><li>Not predictive of bacteremia in infants < 8 weeks of age </li></ul></ul><ul><ul><ul><ul><ul><li>Jaffe et al. Pediatrics 1991; 87:670 </li></ul></ul></ul></ul></ul>
  18. 18. Neutrophils, Bands, ESR, CRP <ul><li>Have value in identifying children at risk for serious illness </li></ul><ul><li>Higher the values, the greater the risk of bacteremia </li></ul><ul><li>No clearly demonstrated advantage over the WBC </li></ul>
  19. 19. Antigen Testing <ul><li>Strep pneumoniae </li></ul><ul><li>H. influenzae type b </li></ul><ul><li>PCR methods (HSZ, VZV, enterovirus) </li></ul>
  20. 20. Blood cultures <ul><li>Gold standard </li></ul><ul><li>False negatives </li></ul><ul><ul><li>Prior treatment with antibiotics </li></ul></ul><ul><ul><li>Missing an episode of bacteremia </li></ul></ul><ul><ul><li>Inoculation of too little blood (<1ml) into the media; too much blood may yield false negative due to ongoing killing of bacteria by neutrophils </li></ul></ul><ul><li>False positives </li></ul><ul><ul><li>Improperly cleaning the skin, resulting in contamination with skin flora </li></ul></ul>
  21. 21. LP <ul><li>Indicated if the diagnosis of sepsis or meningitis is considered </li></ul><ul><li>Seizures upon presentation </li></ul><ul><li>If empiric antibiotics are administered </li></ul>
  22. 22. UA/Urine culture <ul><li>20% of children with UTI have a normal UA based on a negative reagent strip </li></ul><ul><li>Infants < 8w with UTI – 50% will have normal UA </li></ul><ul><li>Best method if not toilet trained </li></ul><ul><ul><li>Bladder catheterization or supra-pubic aspiration </li></ul></ul><ul><ul><li>NOT BAG COLLECTION </li></ul></ul><ul><li>OBTAIN IN ALL CHILDREN ON EMPIRIC ANTIBIOTICS </li></ul>
  23. 23. CXR <ul><li>Respiratory signs or symptoms are good predictors of clinically significant positive CXR findings in the group under 2 months of age </li></ul><ul><ul><li>Sensitivity 93% </li></ul></ul><ul><ul><li>Specificity 73% </li></ul></ul><ul><ul><ul><ul><ul><li>Crain et al. Pediatrics 1991; 88:821 </li></ul></ul></ul></ul></ul>
  24. 24. CXR <ul><li>Children > 3 months </li></ul><ul><li>Oxygen Saturation <95% </li></ul><ul><li>Respiratory distress </li></ul><ul><li>Tachypnea </li></ul><ul><li>Rales on lung auscultation </li></ul><ul><li>Fever 39.5 C (103.1 F) or higher </li></ul><ul><li>Asymptomatic with WBC >20,000 </li></ul>
  25. 25. Stool Analysis and Culture <ul><li>Important if diarrhea present </li></ul><ul><li>Can be considered a focus of infection </li></ul><ul><li>If parent or guardian unsure of bowel habits, obtain stool sample for guaiac and proceed if positive </li></ul>
  26. 26. C – Reactive Protein <ul><li>Acute phase reactant released by the liver following inflammation or tissue damage. </li></ul><ul><li>Wide range of sensitivity and specificity that vary by cutoff levels. </li></ul><ul><li>Increase until 12 hours after the onset of fever and can rise in both viral and bacterial infections. </li></ul>Pulliam PN. Pediatrics. 2001 Dec; 108(6):1275-9.
  27. 27. Procalcitonin <ul><li>2 observational studies (N=505) cutoff value 0.12 ng/mL to detect SBI </li></ul><ul><ul><li>Sensitivity 95-96% (95% CI 83-99 percent) </li></ul></ul><ul><ul><li>Specificity 23-26% (95% CI 20-32 percent) </li></ul></ul><ul><ul><li>NPV 96% (95% CI 85-99 percent) </li></ul></ul><ul><li>Caveats: limited availability </li></ul><ul><ul><li>Variation in results by age, type of infection, and pathogen </li></ul></ul>Maniaci, et al. Pediatrics. 2008 Oct;122(4):701-10.   Dauber, et al. Pediatrics. 2008 No5;122(4):e1119-22.
  28. 28. Differential Diagnosis of Fever Without Focus Common 3-36 months 0-3 months Viral Enterovirus, parainflueza, adenovirus, RSV, CMV, roseola, PV, influenza Same + HSV Bacterial (occult bacteremia) Strep pneumoniae, H.influenza, N. meningitidis, Salmonella Same + GBS Gram negative (E. coli, Kebsiella, Enterobacter cloacae, Salmonella) Listeria
  29. 29. Differential Diagnosis of Fever Without Focus Common 3-36 months 0-3 months Bacterial (UTI) Gram negative organisms (E. coli, Klebsiella) Same (other) Unlikely without signs meningitis
  30. 30. Differential Diagnosis of Fever Without Focus Rare 3m-36 months Connective Tissue Diseases Rheumatic fever, SLE, sarcoidosis, JRA Malignancies Leukemia, Lymphoma, neuroblastoma, Ewing sarcoma Poisoning Atropine, salicylates, cocaine, anticholinergics
  31. 31. Etiology of occult bacteremia <ul><li>S. pneumoniae – 85% </li></ul><ul><li>H. influenzae type b – 10% </li></ul><ul><li>N. meningitidis – 3% </li></ul><ul><li>Salmonella – 2% </li></ul>
  32. 32. Fever Without Source <ul><li>The purpose of these criteria is to reduce the number of infants hospitalized unnecessarily and to identify infants who may be managed as outpatients by using clinical and laboratory criteria. </li></ul>
  33. 33. Fever Without Source <ul><li>Febrile infants and young children have, by tradition, been arbitrarily assigned to different management strategies by age group: </li></ul><ul><ul><li>neonates (birth to 28 days) </li></ul></ul><ul><ul><li>young infants (29 to 90 days) </li></ul></ul><ul><ul><li>older infants and young children (3 to 36 months). </li></ul></ul>
  34. 34. Criteria <ul><li>Rochester - Jaskiewicz JA, et al. Febrile infants at low risk for serious bacterial infection - an appraisal of the Rochester criteria and implications for management. Febrile Infant Collaborative Study Group. Pediatrics 1994 Sep;94(3):390-6 </li></ul><ul><li>Philadelphia - Baker MD, et al. Outpatient management without antibiotics of fever in selected infants. N Engl J Med 1993 Nov 11;329(20):1437-41. </li></ul><ul><li>Boston - Baskin MN, et al. Outpatient treatment of febrile infants 28 to 89 days of age with intramuscular administration of ceftriaxone. J Pediatr 1992 Jan; 120(1): 22-7. </li></ul>
  35. 35. Philadelphia Rochester Boston Age 29-60d < 60days 28-89d Temp > 38.2C > 38C > 38C History Not specified Term infant No perinatal Abx No underlying disease Not hospitalized longer than the mother No immunizations < 48h No antimicrobial < 48h Not dehydrated Physical Exam Well-appearing Unremarkable exam Well-appearing No ear, soft tissue or bone infection Well-appearing No ear, soft tissue, or bone infection Labs (define Lower risk) WBC<15,000 Band-neutrophil ratio<0.2 UA <10wbc/hpf Urine gm stain: negative CSF<8wbc CSF gm stain: negative CXR: no infiltrate Stool: no RBC, no WBC WBC 5,000-15,000 Absolute band <1500/mm3 UA < 10wbc/hpf Stool smeal <5WBC/hpf WBC <20,000 CSF<10/mm3 UA<10wbc/hpf CXR: no infiltrate
  36. 36. Three Most Common Strategies for Managing Febrile Infants Philadelphia Rochester Boston Higher Risk patients Hospitalize + Empiric antibiotics Hospitalize+ Empiric antibiotics Hospitalize+ Empiric antibiotics Lower risk patients Home No antibiotics Follow-up required Home No antibiotics Follow-up required Home Empiric antibiotics Follow-up required Reported Stats Sensitivity 98% Specificity 42% PPV 14% NPV 99.7% Sensitivity 92% Specificity 50% PPV 12.3% NPV 98.9% Sensitivity-not available Specificity 94.6% PPV-not available NPV-not available
  37. 37. Criteria <ul><li>In the first 2 strategies, the lower risk patients are selected for outpatient therapy without antibiotics, whereas the Boston strategy treats all patients with empiric antibiotics but selects a smaller high-risk population for hospitalization. </li></ul>
  38. 38. Criteria <ul><li>Philadelphia protocol and Rochester criteria: </li></ul><ul><ul><li>High NPV - 99.7% and 98.9%, respectively. </li></ul></ul><ul><ul><li>Low PPV - 14% and 12% - large numbers of patients considered higher risk and therefore hospitalized for antibiotics. </li></ul></ul><ul><li>Boston criteria - more cost-effective strategy </li></ul><ul><ul><li>Treating all with antibiotics </li></ul></ul><ul><ul><li>Fewer patients require admission. </li></ul></ul>
  39. 39. Rochester Criteria <ul><li>Indications </li></ul><ul><ul><li>Assessment of febrile child ages 60-90 days </li></ul></ul><ul><ul><li>Reassures against serious infection </li></ul></ul>Jaskiewicz JA, Pediatrics 1994 Sep;94(3):390-6
  40. 40. Rochester Criteria <ul><li>Reassuring if all criteria are present </li></ul><ul><ul><li>Well appearing infant </li></ul></ul><ul><ul><li>No skeletal, soft tissue, skin or ear infections </li></ul></ul><ul><ul><li>Full term birth </li></ul></ul><ul><ul><li>No prior illness </li></ul></ul><ul><ul><ul><li>No prior hospitalizations </li></ul></ul></ul><ul><ul><ul><li>Not hospitalized longer than mother after delivery </li></ul></ul></ul><ul><ul><ul><li>No prior antibiotics </li></ul></ul></ul><ul><ul><ul><li>No Hyperbilirubinemia </li></ul></ul></ul><ul><ul><ul><li>No chronic or underlying illness </li></ul></ul></ul><ul><ul><li>CBC normal </li></ul></ul><ul><ul><ul><li>WBC normal (5000 to 15,000/mm3) </li></ul></ul></ul><ul><ul><ul><li>Band Neutrophils < 1,500/mm3 </li></ul></ul></ul><ul><ul><li>Other Lab Findings </li></ul></ul><ul><ul><ul><li>If Diarrhea is present, Fecal WBC <5 per hpf </li></ul></ul></ul><ul><ul><ul><li>Urine WBC <10 per hpf </li></ul></ul></ul>Jaskiewicz JA, Pediatrics 1994 Sep;94(3):390-6
  41. 41. Rochester Criteria <ul><li>Occult bacteremia risk </li></ul><ul><ul><li>Well-appearing febrile infant risk: 7-9% </li></ul></ul><ul><ul><li>All Rochester criteria present: <1% </li></ul></ul>Jaskiewicz JA, Pediatrics 1994 Sep;94(3):390-6
  42. 42. Management: 0 months to 3 months Baraff LJ. Ann Emerg Med. 2000;36(6):602-614
  43. 43. Management: 0 months to 3 months <ul><li>Age <1 month old </li></ul><ul><li>Admit for assessment for Neonatal Sepsis </li></ul><ul><li>Age >1 month old </li></ul><ul><li>Evaluate Rochester Criteria for Febrile Infants </li></ul><ul><li>Rochester Criteria suggests low risk patient </li></ul><ul><ul><li>Evaluation </li></ul></ul><ul><ul><ul><li>Blood Culture </li></ul></ul></ul><ul><ul><ul><li>Urine Culture </li></ul></ul></ul><ul><ul><ul><li>Consider Lumbar Puncture </li></ul></ul></ul><ul><ul><ul><ul><li>Normal WBC Count does not rule-out Meningitis </li></ul></ul></ul></ul>Bonsu. Ann Emerg Med. 1993, 41:206-14
  44. 44. Management: 0 months to 3 months <ul><ul><li>Management Option 1 </li></ul></ul><ul><ul><ul><li>Ceftriaxone 50 mg/kg IM x1 dose </li></ul></ul></ul><ul><ul><ul><li>Re-evaluate infant within 24 hours </li></ul></ul></ul><ul><ul><li>Management Option 2 </li></ul></ul><ul><ul><ul><li>Observe inpatient without antibiotics </li></ul></ul></ul><ul><li>Rochester Criteria suggests high risk patient </li></ul><ul><ul><li>Admit for assessment for Neonatal Sepsis </li></ul></ul>
  45. 45. Management: 3m to 36m Baraff LJ. Pediatr Ann. 1993; 22(8): 497-8.
  46. 46. Management: 3m to 36m <ul><li>Toxic appearing febrile child </li></ul><ul><ul><li>See Yale Observation Scale </li></ul></ul><ul><ul><li>Admit to hospital </li></ul></ul><ul><ul><li>Full rule-out sepsis workup </li></ul></ul><ul><ul><li>Parenteral antibiotics </li></ul></ul>
  47. 47. <ul><li>Non-toxic child with fever <39.0 C (<102.2 F) </li></ul><ul><li>Avoid further diagnostic tests or antibiotics </li></ul><ul><li>Fever Symptomatic Treatment </li></ul><ul><li>Careful examination to rule out serious infection </li></ul><ul><ul><li>Pneumonia </li></ul></ul><ul><ul><li>Abscess </li></ul></ul><ul><ul><li>Cellulitis or Impetigo </li></ul></ul><ul><ul><li>Acute Sinusitis </li></ul></ul><ul><ul><li>Otitis Media </li></ul></ul><ul><ul><li>Osteomyelitis </li></ul></ul><ul><ul><li>Lymphadenitis </li></ul></ul><ul><ul><li>Streptococcal Pharyngitis or Scarlet Fever </li></ul></ul><ul><li>Re-evaluation criteria </li></ul><ul><ul><li>Fever persists longer than 48 hours </li></ul></ul><ul><ul><li>Condition deteriorates </li></ul></ul>Management: 3m to 36m
  48. 48. Non-toxic 3m-36m child with fever >38.9 C (>102.1 F) <ul><li>Step 1: Evaluate Urine </li></ul><ul><li>Obtain Urine LE and Nitrite or Urinalysis </li></ul><ul><li>Urine Culture in all patients on empiric antibiotics (2001) </li></ul><ul><li>Urine screening positive (LE and nitrite on UA) </li></ul><ul><ul><li>Outpatient oral 3 rd generation Cephalosporin </li></ul></ul>
  49. 49. <ul><li>Step 2: Additional Studies </li></ul><ul><li>Chest Roentgenogram Indications </li></ul><ul><ul><li>Oxygen Saturation <95% </li></ul></ul><ul><ul><li>Respiratory distress </li></ul></ul><ul><ul><li>Tachypnea </li></ul></ul><ul><ul><li>Rales on lung auscultation </li></ul></ul><ul><ul><li>Fever 39.5 C (103.1 F) or higher </li></ul></ul><ul><ul><li>Asymptomatic with WBC >20,000 </li></ul></ul>Non-toxic 3m-36m child with fever >38.9 C (>102.1 F)
  50. 50. <ul><li>Step 2: Additional Studies </li></ul><ul><li>Stool Culture Indications </li></ul><ul><ul><li>Stool blood or mucus present </li></ul></ul><ul><ul><li>Fecal WBC > 5/hpf </li></ul></ul>Non-toxic 3m-36m child with fever >38.9 C (>102.1 F)
  51. 51. <ul><li>Step 3: Consider Antibiotic </li></ul><ul><li>Indications to skip to Step 4 below (no antibiotics) </li></ul><ul><ul><li>Pneumococcal Conjugate Vaccine received </li></ul></ul><ul><ul><li>Temperature under 39.5 C (103.1 F) </li></ul></ul><ul><li>Obtain Complete Blood Count (and hold Blood Culture) </li></ul><ul><li>Antibiotics </li></ul><ul><ul><li>Indications </li></ul></ul><ul><ul><ul><li>White Blood Cell Count >15,000 </li></ul></ul></ul><ul><ul><ul><li>Consider for White Blood Cell Count <5000 </li></ul></ul></ul><ul><ul><ul><li>Absolute Neutrophil Count (ANC) > 10,600 </li></ul></ul></ul><ul><ul><li>Protocol </li></ul></ul><ul><ul><ul><li>Send Blood Culture </li></ul></ul></ul><ul><ul><ul><li>Ceftriaxone 50 mg/kg/day (max: 1 g) </li></ul></ul></ul><ul><ul><ul><li>Re-evaluate within 24 to 48 hours </li></ul></ul></ul>Non-toxic 3m-36m child with fever >38.9 C (>102.1 F)
  52. 52. <ul><li>Step 4: Instructions </li></ul><ul><li>Follow-up </li></ul><ul><ul><li>Return within 24 hours if antibiotics started </li></ul></ul><ul><ul><li>Return in 48 hours indication </li></ul></ul><ul><ul><ul><li>Fever persists </li></ul></ul></ul><ul><ul><ul><li>Condition deteriorates </li></ul></ul></ul><ul><li>Home management </li></ul><ul><ul><li>Observe for toxic appearance </li></ul></ul><ul><ul><li>Fever Symptomatic Treatment </li></ul></ul>Non-toxic 3m-36m child with fever >38.9 C (>102.1 F)
  53. 53. <ul><li>Step 5: Blood Culture or Urine Culture positive </li></ul><ul><li>Admit if child febrile or toxic appearance </li></ul><ul><li>Outpatient antibiotics if afebrile and well-appearing </li></ul>Non-toxic 3m-36m child with fever >38.9 C (>102.1 F)
  54. 54. Antibiotics <ul><li>0-1 month: </li></ul><ul><ul><li>Ampicillin </li></ul></ul><ul><ul><li>Gentamicin or Cefotaxime </li></ul></ul><ul><li>1-2 months: </li></ul><ul><ul><li>Ampicillin and Cefotaxime </li></ul></ul><ul><ul><li>Ceftriaxone (100mg/kg/day) </li></ul></ul><ul><li>2m-36 months: </li></ul><ul><ul><li>Ceftriaxone </li></ul></ul>
  55. 55. Antivirals <ul><li>Acyclovir </li></ul><ul><ul><li>In patients 0-1 month </li></ul></ul><ul><ul><li>20 mg/kg/dose three times daily </li></ul></ul><ul><ul><li>Ill appearing </li></ul></ul><ul><ul><li>Mucocutaneous vesicles </li></ul></ul><ul><ul><li>Seizures </li></ul></ul><ul><ul><li>Elevated LFT (disseminated infection) </li></ul></ul><ul><ul><li>Send HSV antigen DFA (vesicles) </li></ul></ul><ul><ul><li>HSV DNA PCR (CSF). </li></ul></ul>
  56. 56. Antipyretics <ul><li>Acetaminophen </li></ul><ul><ul><li>15mg/kg/dose q4hours prn temperature > 39 o C (102.2 F) </li></ul></ul><ul><li>Ibuprofen </li></ul><ul><ul><li>10mg/kg/dose q6hours prn temperature > 39 o C (102.2 F) </li></ul></ul><ul><ul><li>Use in children 6 months or older </li></ul></ul>
  57. 57. Antipyretics <ul><li>In children with baseline temperatures < 102.2°F - both ibuprofen doses and acetaminophen are equally effective. </li></ul><ul><li>In those children with temperatures > 102.2°F, the ibuprofen 10 mg/kg dose is more effective. </li></ul><ul><ul><li>It is superior in efficacy and length of anti-pyretic effect that 5 mg/kg dose. </li></ul></ul><ul><li>Infants: Safety and efficacy of ibuprofen in < 6 months has not been established </li></ul>
  58. 58. Lumbar Puncture <ul><li>Does my child really need a lumbar puncture? </li></ul><ul><li>Could you wait and see if his WBC count is high? </li></ul><ul><li>I really don’t want my child to have a LP. </li></ul>
  59. 60. <ul><li>Logistic regression modeling and ROC analysis of peripheral blood WBC count and cerebrospinal fluid WBC count for results obtained from 3- to 89-day-old infants undergoing a full sepsis evaluation. </li></ul>Methods:
  60. 61. Results: P < 0.001
  61. 62. Results: <ul><li>Twenty-two of 5,353 (4.1 per 1,000) infants had acute bacterial meningitis. </li></ul><ul><li>For diagnosing acute bacterial meningitis, the peripheral blood WBC count was poorly discriminating and significantly inferior to the cerebrospinal fluid WBC count. </li></ul><ul><li>This was true both when the odds of meningitis were modeled to vary linearly and as a U-shaped function of the peripheral blood WBC count. </li></ul><ul><li>When relying on single and interval-based high-risk thresholds of peripheral blood WBC counts alone, the majority of infants with acute bacterial meningitis would have been missed. </li></ul>
  62. 63. Conclusions: <ul><li>Decisions to perform or withhold lumbar puncture should not be based on prevailing interpretations of the total peripheral blood WBC counts to maximize detection of bacterial meningitis in young infants. </li></ul>
  63. 64. Question <ul><li>It is RSV season </li></ul><ul><li>Do we really need to do these work-ups? </li></ul>
  64. 65. Pediatrics. Aug 2003. 112(2): 282-284.
  65. 66. Objective <ul><li>Neonates with fever generally undergo a full, invasive septic evaluation to exclude serious bacterial infection (SBI). </li></ul><ul><li>The risk of SBI in febrile older infants and children with documented respiratory syncytial virus (RSV) infection has been found to be negligible. </li></ul>Pediatrics. Aug 2003. 112(2): 282-284.
  66. 67. Objective: <ul><li>Investigate the prevalence of SBI in febrile infants < 8 wk and had documented RSV infection and compare the risk of SBI with control subjects who were febrile and RSV-negative </li></ul>Pediatrics. Aug 2003. 112(2): 282-284.
  67. 68. Methods <ul><li>Retrospective cohort study </li></ul><ul><li>Infants < 8 wk </li></ul><ul><li>Presented with documented fever to the ER </li></ul><ul><li>October - April x 4-year period. </li></ul><ul><li>RSV-positive cases were gender- and age-matched to febrile RSV-negative control subjects (N=174 each) </li></ul><ul><li>Clinical characteristics and the rate of SBI were compared between the 2 groups. </li></ul>Pediatrics. Aug 2003. 112(2): 282-284.
  68. 69. Pediatrics. Aug 2003. 112(2): 282-284. RR 0.09 [95% CI 0.02–0.38] P<0.0001
  69. 70. Conclusions: <ul><li>Full septic evaluations are not necessary in nontoxic-appearing infants with a positive RSV test. </li></ul><ul><li>It seems prudent to examine the urine in these infants, as there is a clinically relevant rate of urinary tract infection. </li></ul>Pediatrics. Aug 2003. 112(2): 282-284.

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