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Infant Fever, What’s Old What’s New

Infant Fever, What’s Old What’s New. Brian R. Moore, M.D., F.A.A.P. PEM Fellowship Director Assistant Professor, Departments of Emergency Medicine and Pediatrics University of New Mexico Health Science Center October 12th, 2011. Disclosures. Disclosures. The 5 Second Rule. Objectives.

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Infant Fever, What’s Old What’s New

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  1. Infant Fever, What’s Old What’s New Brian R. Moore, M.D., F.A.A.P. PEM Fellowship Director Assistant Professor, Departments of Emergency Medicine and Pediatrics University of New Mexico Health Science Center October 12th, 2011

  2. Disclosures

  3. Disclosures

  4. The 5 Second Rule

  5. Objectives • Assessment of Infants and Children <36 months of age with fever • Understand the utility (or lack thereof) of diagnostic tests • Understand the changing epidemiology of pediatric fevers without a clinically evident source (FWS) • Develop an evidence based approach to evaluating and treating pediatric fever without source

  6. Exclusions • What we are NOT talking about • “sick” looking kids • Children with chronic dx • Immunospressed children • What is a “fever” • Temperature taking methods

  7. Case #1 • 21 day old female brought to the ED for fever • Temp 38.1, HR 152, RR 36, O2 Sat 95% RA, Wt 3.8 kg • Term, NSVD, No URI Sxs, nl prenatal care and birth hx, MOC GBS- neg • 2 y.o. sibling at home with URI • Exam- Alert, nonfocal, well appearing, NL exam • WHAT would you do?

  8. Evaluation • CBC/Diff • Blood Cx • LP/CX • UA/CX • Viral NP Swab • CXR • Hospitalize for IV Antibiotics

  9. Predictive Models for FWSTo define Low Risk Infants

  10. Application to Infants < 4 Weeks of Age? • Prospective study of 254 febrile infants < than 1 month • 5 of 32 (15.6%) who had SBI would have been classified to be at low risk of having bacterial disease according to the Philadelphia criteria • would falsely identify as many as 10 per 100 febrile neonates as having low risk of SBI • concluded that febrile infants <1 month of age should include a complete evaluation for bacterial illness and the empiric administration of antibiotics Baker MD, Bell LM, Arch Pediatr Adolesc Med. 1999;153:508-511.

  11. Screening Tests < 28 Days? • 225 infants 1-29 days admitted with T>38.0 • SBI in 31 • 6 missed by Philadelphia criteria (Baker) • 8 missed by Boston criteria (Baskin) Kadish HA, Bolte RG, Tobey J, Loveridge B. Clin Pediatr 2000 Feb;39(2):81-8

  12. Case #2 • 31 day old female brought to the ED for fever • Temp 38.1, HR 152, RR 36, O2 Sat 95% RA Wt 4.3 kg • Term, NSVD, No URI Sxs, nl prenatal care and birth hx, MOC GBS- neg • 2 y.o. sibling at home with URI • Exam- Alert, nonfocal, well appearing, NL exam • WHAT would you do?

  13. Evaluation • CBC/Diff • Blood Cx • LP/CX • UA/CX • Viral NP Swab • CXR • Empiric Antibiotics?

  14. How to differentiate?

  15. Diagnostic tests-CBC • High wbc counts are 2-3X more common in those with bacterial vs. viral illness • Positive predictive value for an elevated wbc count is 8-15% as viral illness far more prevalent than bacterial infection

  16. Diagnostic tests-CBC • 955 infants 3-36 months, T > 39.0ºC had CBC & BC -> 27 had bacteremia • mean wbc in children with bacteremia 20,500 • mean wbc in children without bacteremia 11,800 • Repeatedly shown: wbc >15,000 is 2-3X more common in bacterial than in viral infections • However: • specificity  75% (too many FP) • sensitivity 60% (too many FN) Jaffe DM, Fleisher. Pediatrics. 1991 May;87(5):670-4

  17. Diagnostic tests-CBC • sensitivity: among those with bacteremia, how many are identified by the cutoff point? • positive predictive value: among those identified by the cutoff point, how many have bacteremia? TP TP+FN TP TP+FP

  18. WBC Performance • Retrospective review of febrile infants 0-89 days who had CBC and Bld CX at the same time • 1992-1999 • 38/3810 OB rate (1%) • Tried to find a threshold of WBC that would help predict OB using AUC Bonsu BK Ann Emerg Med. 2003;42:216-225

  19. *Sensitivity is the number of bacteremic infants with test results above the WBC count cutoff. *Specificity is the number of nonbacteremic infants with test results below the WBC count cutoff.

  20. *Sensitivity is the number of bacteremic infants with test results above the WBC count cutoff. *Specificity is the number of nonbacteremic infants with test results below the WBC count cutoff.

  21. Results • The odds of bacteremia were not decreased substantially at any cutoff and were increased only modestly at values outside published norms of the test • Conclusion: The total peripheral WBC count is an inaccurate screen for bacteremia in febrile young infants; thus, decisions to obtain blood cultures should not rely on this test

  22. WBC and Bacteremia • Even among TP’s most will have an infection that is likely either • toclear spontaneously (bacteremia) or • to respond to tx withoutserious sequelae even if dx delayed (pneumonia,cellulitis, UTI)

  23. WBC and SBI • PPV for more seriousinfections (meningitis, osteomyelitis, septic arthritis) is much lower • Majority of children with bacterial meningitis have a WBC < 15,000 • Therefore, NEVER use CBC results to determine the need for an LP

  24. Diagnostic test-blood culture • Identify children with OB at risk for more serious sequelae (meningitis) • Consider • most bacteremia clears spontaneously • delayed dx without serious sequelae (pneumonia, UTI, cellulitis) • value of early diagnosis -- ED vs. PCP • sensitivity of single culture 45-70%

  25. Diagnostic test-blood culture • 2-4% false positive rate • 10-20x FP to TP rate • Side effects • Cost • Additional testing • Unnecessary hospitalizations and antibiotics • Side effects of antibiotics

  26. What about UTI’s? • Equal gender incidence under 3 months • Over 3 months, more common in females • Positive urine cultures - FWS • male infants <6 mo: 7% • female infants < 2 years: 8% • Incidence as high as 17.5% of white girls under 24 months T39c

  27. Urine Specimens Acceptable for Culture • Suprapubic aspiration • Cathetererized specimen • Clean mid-stream void

  28. Urine Specimens Unacceptable for Culture • Bagged specimens of any type at any time • Never • Ever • Negative UA does not rule out UTI!

  29. Diagnostic Tests-Urinalysis • Routine urinalysis not sensitive enough to use as a screening tool • pyuria (by LE or micro): 80-85% sensitivity and specificity • nitrite: 85-90% specificity, poor sensitivity • Gram-stained smear of urine sediment is a sensitive screen (>95%) • Can use as a screen, but urine culture is still gold standard

  30. Urine Culture • Clean Catch >100,000 cfu/ml • Straight catheterization > 10,000 cfu/mL • SPA > 1,000 cfu/mL

  31. Question #1 Bag urine specimens have a False Positive Rate of approximately: • 35% • 50% • 85%

  32. Question #1 Bag urine specimens have a False Positive Rate of approximately: • 35% • 50% • 85% ALWAYS COLLECT URINE BY CATH OR SUPRAPUBIC ASPIRATION (U/S GUIDED IS BETTER)

  33. Question # 2 Which of the following has the highest sensitivity for detecting Urinary Tract Infection? • Urine dipstick for LE or Nitrite • Gram stain for bacteria on uncentrifuged urine • Pyuria (>5 WBC) on centrifuged urine.

  34. Question # 2 • Urine dipstick for LE or Nitrite -Sensitivity 0.88 • Gram stain for bacteria on uncentrifuged urine -Sensitivity 0.93, false positive rate .05 • Pyuria (>5 WBC) on centrifuged urine. -Sensitivity 0.67 Gorelick (1999)

  35. That Fever Article • “Expert” panel • Meta-analysis that pooled data from RCT and observational studies + opinion • pre-Hib vaccine data Volume 92(1) July 1993 pp 1-12 Practice Guideline for the Management of Infants and Children 0 to 36 Months of Age With Fever Without Source. Baraff, Larry J.; Bass, James W.; Fleisher, Gary R.; Klein, Jerome O.; McCracken, George H. Jr.; Powell, Keith R.; Schriger, David L.

  36. Harriet Lane Baraff LJ Ann Emerg Med 2000;36[6]:602–614

  37. > View this image in its location within the book Harriet Lane Baraff LJ Pediatr Ann 1993;22[8]:497–498, 501–504

  38. 1993 Strep. Pneumo 70% H Flu 15% N. Meningitidis 3% 4. Salmonella 1-2% Baraff and Lee 1992 2002 Strep. Pneumo 84% Group A Strept. 5% N. Meningitidis 3% Salmonella 3% Bandyopadhay 2002 Main Sources of Occult Bacteremia

  39. H. influenzae type b bacteremia • Routine use of the vaccine in infants: 1990 • 1989-1995: Hib invasive disease in US children <5 yr declined 95% • CA surveillance: • 1990: 13.9/105 • 1996: 0.1/105

  40. Streptococcus pneumoniae • 65-85% of occult bacteremia in children • usually cleared by host • most common cause of bacterial meningitis in children • PCV7 FDA approved 2001 • Prevnar was expected to eliminate (< 6 yr olds) • 86% of bacteremia • 83% of meningitis • 65% of OM

  41. The Future Guidelines? • “The widespread use of this vaccine (PCV7) will make the use of WBC counts and blood cultures and empiric antibiotic treatment of children with fever without source who have received this vaccine obsolete.” • Baraff, 2000

  42. D’OH WAKE UP!!!!!! • YOU IN THE BACK ROW WAKE UP!!!!! YOU ARE MISSING A VERY GOOD LECTURE

  43. PROS • 3066 infants > 3 months old in Primary Care with T >38.0 • Feb 95 to April 98 • Bacteremia in 1.8% of infants • Bacterial meningitis on 0.5% • Well appearing infants with fever >38.6 had a rate of OB/BM 0.4% • Practitioners followed current guideline 42% of episodes JAMA. 2004;291(10):1203-1212

  44. PROS • They tx’ed 61/63 BM initially • Conclusions- Pediatric clinicians use individualized judgment in tx febrile infants • Relying on current clinical guidelines would not have improved care but would have resulted in more hospitalization, lab testing, and antibiotic use.

  45. Peds ED Adherence • TCH Denver 2004-06 • 167 patients total, 79 29-59d, 88 60-90d • 19 ‘SBI’ (11%) • OB 3/1 • UTI 11 • BM 0 • Complete SBI W/U as by ‘guideline’ • Age 29-59 day old 49% • Age 60-90 day old 8%

  46. Study Conclusions • We found that pediatric emergency medicine physicians in our institution do not follow existing practice guidelines for the workup of fever in young infants. • Whether this reflects a lack of awareness of the guidelines or more likely, a culture that favors test minimization over risk minimization, could not be determined from this study. • We also found that these physicians obtained fewer CBCs, blood cultures, urine cultures, CSF cultures, and viral studies in the infants aged 60 to 90 days than in those infants aged 28-59 days.

  47. SBI in post PCV7 • 985 children, 0-24 months • Dec 2002- Dec 2003 • Tertiary care military hospital in San Diego • SBI defined at PNA, UTI, OB, BM • 79% had received at least one PCV7 Rudinsky SL Acad Emerg Med 2009; 16:585–590

  48. SBI in post PCV7 • OB 0.7% • No statistical difference in the WBC count between the SBI and Non-SBI groups (p=0.055) • No WBC cutoff on the ROC curve proved to be an accurate predictor of SBI • No statistical difference in mean temp between SBI and Non-SBI groups

  49. “SBI” • 82 PNA • 45 UTIs (33F, 12M) • 5 OB (690 pts had bld cx, 70%) • Contaminated Blood culture rate- 4.9%! • Enterococcus 2, E. Coli, GBS, S. pneumo • S. pneumo OB 0.14% • 0 meningitis

  50. Herd Immunity? • OB 0.14% - 0.17% but vaccination rate 50-86% (79% in this study) • Herd immunity for invasive pneumoccocial disease has also been suggested • Serotyping in both studies were unavailable

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