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Occult Bacteremia in Infants

Occult Bacteremia in Infants. Current controversies and future developments Denise Watt Dec. 6, 2001. Outline. background and epidemiology management algorithms evidence for Abx oral vs. parenteral antibiotic resistance pneumococcal conjugate vaccine. Case.

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Occult Bacteremia in Infants

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  1. Occult Bacteremia in Infants Current controversies and future developments Denise Watt Dec. 6, 2001

  2. Outline • background and epidemiology • management algorithms • evidence for Abx • oral vs. parenteral • antibiotic resistance • pneumococcal conjugate vaccine

  3. Case • 10 month old girl, previously well • URI symptoms x 10 days • drinking well, wetting diapers, no N/V/D • 2hr hx fever, lethargy, irritability • O/E: 180, 42, T39.2, 95% • looks unwell, moaning/crying, HEENT normal, clear BS, some indrawing, CVS normal, abd benign, no rash

  4. Occult Bacteremia: definitions • FWS: rectal temp  38C, no focus, no obvious virus, ‘non-toxic’, no significant underlying illness/immunocompromise • OB: FWS and +ve BC • 10-20% PED visits for febrile illness • 20% febrile children <3yr: no source

  5. Epidemiology: pre-HIB • prior to early 1990’s • OB incidence 3-12% of FWS • 60-85% S.pneumo • 5-20% HIB • 40% complication rate

  6. Epidemiology: post-HIB • incidence of OB (FWS, 3-36 mos, T39°C) • 1.6-2.8%, highest age 1-2 yr (Kupperman 1998, Lee 1998) • 90-95% S.pneumo • 96%  invasive HIB <5 yr (Alpern 2000) • 5% non-typhoid Salmonella • others: Neisseria, GAS, GBS, Moraxella, E.coli, S. aureus

  7. Implications of OB • 10% SBI if untreated, 17% persistent bacteremia (Harper, Baraff) • meningitis: 1% (Baraff), 2.7% (Rothrock) • 7.7% mort, 25-30% neuro sequelae • overall risk of meningitis in untreated FWS = 0.02-0.05% • natural course of OPB? • 96% resolve without Abx(Alpern 2000)

  8. Occult Bacteremia:Subsequent development of focus Dashefsky, J Pediatr 1983., Shapiro, J Pediatr 1986., Woods, AJDC 1990., Baraff, Pediatr Infect Dis J 1992.

  9. Local Microbiology • S. pneumo bacteremia rates vary widely across Canada • related to rates of BC drawn • rate in Calgary unknown • 30 OPB/yr, 10 SBI/yr, 4-5 meningitis/yr • 20 cases invasive HIB/yr (most adults) • 139 +BC last year age 1-15 (all comers) • 27% contaminants

  10. Predicting OB • Hx and PE unreliable • may appear well • subjective vs. objective ‘toxicity’ • YOS >10: sensitivity 77%, specificity 88% • age • fever • OPB rare if temp <39.0 (<1%); 3.7% if >40 • similar response to defervescence ± OB (Baker 1989, Bonadio 1993)

  11. Predicting OB • lab tests insensitive • U/A: most common occult bacterial infection (2% febrile <5yr) • WBC >15x109: sens 67-80%, spec 69% • ANC best predictor (Kuppermann 1998) • >10x109: sens 76%, spec 78% • band count unhelpful • one poke most practical (CBC + hold BC)

  12. Blood Cultures • 12% +ves return for F/U before BC result, 50% called back (Joffe 1992) • time to +ve = 36hr, time to F/U = 43hr • most pathogens +ve < 18hr • F/U more important than BC • 76% SBI or PB called back (Bachur 2000) • BC allow earlier F/U and Rx • faster lab techniques coming?

  13. Approach to FWS • <2-3 mos, 3-36mos, >3 yr treated differently • <1980s, all pt <3mos admitted for septic W/U and empiric Abx • low risk criteria developed to avoid hospital admission

  14. Low-risk criteria • Rochester criteria 1985 (<2 mos) • NPV 98.9%, PPV 12% • Boston criteria 1992 (<3 mos) • NPV 95% • Philadelphia criteria 1993 (1-2 mos) • NPV 99.7%, PPV 14%

  15. Baraff • “expert consensus” (Pediatrics 1993) • 1-3 mos, ‘low risk’ • option 1: septic W/U and Abx • option 2: urine C&S and observe • 3-36 mos, non-toxic: septic W/U if T>39.0 • update (Annals Emerg Med 2000) • 3-36 mos • T39.0: U/A; T39.5: WBC  BC (send if >15) • if empiric Abx, do LP!

  16. Bachur 2001 • Recursive partitioning model • U/A first step • WBC <4 or >20 • T > 39.6 • age < 13d • 82% sensitive • admit 28% (vs. 53% with Rochester)

  17. Cost-Effectiveness of FWS strategies • 1990’s: BC and empiric Abx for all • Lee (Pediatrics 2001) • FWS, age 3-36 mos, OPB (1.5%) • meningitis 1° outcome • incl. health care and societal costs • CE: CBC + selective BC + Rx if WBC 15 • $30,800 / life-year saved • if rate OPB, less aggressive aproach

  18. Why guidelines need re-evaluation • controversy among ‘experts’ • lower incidence of OB • elimination of HIB • cost and complications of tests and Rx • pen-resistant S. pneumo • not followed anyway (Finklestein 2000) • vaccine…..

  19. Antibiotics and FWS • Only 2 prospective RCTs with placebo • both small, pre-HIB • Jaffe 1987: • no change in SBI • Abx  fever, improved appearance • large, retrospective study (Harpur 1995) • more focal infection, admissions w/o Abx • Abx and meningitis (meta-analysis Baraff) • no Abx 5.8%; oral or parenteral Abx 0.4%

  20. Rothrock 1997: Meta-analysis • not all RCTs, underpowered • no significant  meningitis • significant  SBI (OR 0.35 p=0.003) • NNT to prevent 1 meningitis = 651 • NNT to prevent 1 SBI = 2190 • NNH with Abx for every meningitis prevented = 567 • no prospective studies post-HIB

  21. Oral vs. Parenteral Antibiotics • Fleisher (1994) • no sign difference in focal infections •  persistent fever with Ctx • not blinded, not intention-to-treat, pre-HIB • Rothrock (1997); meta-analysis • meningitis OR=0.67 (oral vs. parenteral) • SBI OR=1.48 • closer F/U with parenteral

  22. Risks of Empiric Antibiotics • cost (tests, Rx, F/U, hospitalization) • side effects • discomfort of tests, treatment • altered presentation (Rothrock 1992) • development of resistant strains • missed/partially Rx focal infections • parental preference? • will accept small risk of SBI vs. discomfort of tests & Rx (Kramer, Oppenheim)

  23. Penicillin-resistant Pneumococcus • Castillo • San Diego 1991-8: 18% pen resistance • 14% int. resistance 1991, 42% in 1998 • no difference in mortality • NS increased resistance with prior Abx use

  24. Pen and Cephalosporin resistance • Silverstein • 11 year review: 8% resistance • no diff in outcome, LOS in pen-resistant • Ceftriaxone-resistant: more focal infection, more LPs, more febrile at F/U, more admitted (NS),  HR and temp at presentation

  25. Antibiotic resistant Pneumococcus in Calgary • 15% pen resistance • <2% amoxicillin resistance • 10% Cefuroxime resistance • 3-4% Ceftriaxone resistance • need higher MIC for CNS • clinically, has not been an issue

  26. Conjugate Pneumococcal Vaccine • heptavalent, 4 doses: 2,4,6,12-15 mos • FDA approval Feb 2000 (Prevnar) • 3 RCTs of safety and immunogenicity • Rennels (1998) • Shinefield (1999) • Black (2000) • efficacy 97%, intention-to-treat 94% • including ALL S.pneumo serotypes: 89% • similar SE as DPTP/HIB, none severe

  27. Pneumococcal Vaccine • significantly  OM • Black: ongoing trial on herd immunity • long-term efficacy? • strain selection? Bottom line: • will significantly decrease burden of S.pneumo disease • likely lag time to change practices

  28. Impact Of Prevnar in N. California~33,000 with ≥1 doseFeb 2000-Mar 2001 Shinefield et al. 3rd Int’l PID Conference Monterey, 2001

  29. Pneumococcal Vaccine:Cost Effectiveness • Lieu (JAMA 2000) • cost < savings if each dose <$46 (US) • present: $56 (US) = $278,000/life-yr saved • >2x savings for society vs. health payer •  $760 million/3.8M infants/yr in US • most from parental work loss,  productivity • Calgary: $110/dose ($84 at ACH) • current immunization budget: $17M/yr • cost of SP vaccine: $13M/yr

  30. Occult Bacteremia: Summary • age, temp, appearance important • don’t forget U/A • save labs for ‘unwell’ • faster BC techniques in distant future • F/U most important tool • empiric Abx have very limited role • no clear evidence favouring parenteral

  31. Occult Bacteremia: Summary II • antibiotic-resistance is rising; impact small in Calgary • vaccine WILL change the face of FWS • ‘It’s viral!’ • until then, the controversy continues! • “Are you a risk-minimizer or test-minimizer?” (Green, Rothrock. Annals Emerg Med. 1999)

  32. Case revisited • WBC 14.9 • ANC 8.3 • BC +ve S.pneumo in 24hr (pen I) • R/A: looks well, T 38.5 • Mgt?

  33. Case cont. • Ceftriaxone IV • F/U ID clinic: • well-looking • Ctx IV x 3 days, then Amoxil x 7 days

  34. QUESTIONS?

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