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

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Presentation on theme: "Occult Bacteremia in Infants Current controversies and future developments Denise Watt Dec. 6, 2001."— Presentation transcript:

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) – %, 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 = % 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 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 >15x10 9 : sens 67-80%, spec 69% –ANC best predictor (Kuppermann 1998) >10x10 9 : 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 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 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 : 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 dose Feb 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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