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0406 marmorfws

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  • Black S, Shinefield H, Fireman B, et al. Efficacy, safety and immunogenicity of heptavalent conjugate pneumococcal vaccine in children. Pediatric Infect Dis Journal 2000; 19:187-195
  • Transcript

    • 1. Advanced Cases in Pediatric Fever Without a Source Andi Marmor June, 2004
    • 2. Key Questions What are the risk factors for SBI and UTI in febrile infants? How effective is the pneumococcal vaccine?  Partial vaccination Technical difficulties: when the best laid plans go awry How do you collect urine? Do viruses count as a fever source?
    • 3. Fever Without a Source – A QuickReview For nearly 20% of febrile children, no source of infection can be identified after thorough history and physical exam A small proportion of these children, although well-appearing, will have a serious bacterial infection (SBI) or occult urinary tract infection (UTI) Guidelines have been developed to help physicians identify and treat those children at high risk for these conditions
    • 4. Age Groups for Estimating Risk of SBI inWell-Appearing Infants Guidelines for management of infants with fever without a source are based on groupings of infants into 3 age groups based on both their risk of SBI/UTI and the most likely bacterial causes of SBI Neonate (0-28 days) Infant 1-3 mo Infant 3-36 mo
    • 5. Neonates (<28 days) Causes of SBI/UTI:  E. Coli, GBS, Listeria, Salmonella What counts as a fever source?  Clinical exam is unreliable, and even infants with viral symptoms may be at risk for SBI Prevalence of SBI in well-appearing infants <28 days with T>38  4-12% UTI  Prevalance of UTI is high for boys and girls  Associated with a 15-20% risk of bacteremia
    • 6. Recommendations:Neonates, T >38 CBC, blood cultures Cath UA and urine culture LP Antibiotics  Ampicillin and gentamicin IV, or ampicillin and cefotaxime IM Admission
    • 7. Infants 1-3 months of age Causes of SBI/UTI  E. Coli (UTI), GBS, S. pneumonia, N. meningitidis, Hib What counts as a fever source?  Named viral syndrome  Otitis media  Other viruses? Prevalence of UTI in this age group is about 9% overall, (highest in uncirc boys, but only 2% in circumcised boys)
    • 8. Infants 1-3 months of age:Predictors of SBI Studies in the early 90’s established criteria for dividing well-appearing febrile infants this age into groups at high or low risk for SBI based on WBC count  WBC 5-15: Risk of SBI (NOT including UTI) is ~1-3%  High risk: ~10-20%
    • 9. Recommendations: 1-3 months, T>38 Cath urinalysis and urine culture on all infants  If UA is positive, begin treatment for pyelonephritis and consider admission CBC and blood culture  If WBC>15K, antibiotics (ceftriaxone IM/IV) Lumbar puncture  If signs of CNS irritability, and strongly consider if giving antibiotics Follow up  The next day (2nd dose if antibiotics were given)  Admit if unable to follow up
    • 10. Infants 3-36 months, T>38.5 Causes of SBI:  S. pneumonia>>>N. meningitidis, Hib Causes of UTI:  E. Coli>>>Klebsiella, Proteus, Strep spp  Risk highest in girls and in uncirc boys up to 6-12 mo Risk for SBI…before pneumococcal vax  Overall risk of SBI in these infants estimated 2-6%  WBC count useful to stratify infants into “high risk” (~10%) and “low risk” (~1%)
    • 11. Hooray for the pneumococcal vaccine! 7-valent polysaccharide conjugate vaccine Approximately 97% of pneumococcal isolates that cause IPD are represented in PCV-7 Recommended since August, 2000  2,4 and 6 months with booster at 12-15 mo
    • 12. Vaccine Efficacy PCV-7 tested in a large NC Kaiser-based randomized controlled trial of 37,868 children Efficacy against IPD from vaccine serotypes  Fully vaccinated children (4 doses): 97.4%  Those receiving one or more dose of vaccine: 94%. Efficacy against IPD from any pneumococcal serotype,  Those receiving one or more doses: 89.1%
    • 13. Vaccine Efficacy – Post-licensure Multiple post-licensure studies have supported the expected reduction in invasive pneumococcal disease (IPD) 78-85% drop in rates of IPD in children <2 years of age. Rates of disease from non-vaccine serotypes have not increased However, IPD and SBI are still possible, even in vaccinated children.
    • 14. How should vaccine change ourmanagement? Since IPD is responsible for the majority of SBI in infants >3 months of age And the vaccine is at least 90% effective against IPD The risk of SBI in vaccinated children is <1%, regardless of WBC count. Therefore, a CBC is unlikely to significantly impact the assessment or management of vaccinated children.
    • 15. Is this change in management cost-effective? Lee et al (2001) conducted a cost- effectiveness analysis of various management strategies for infants with FWS Conclusion: empiric CBC/blood cx NOT cost effective if rates of SBI <0.5%  Costs >300,000$ per life saved  Rates of SBI <0.5% in vaccinated infants, based on current data
    • 16. Recommendations for vaccinatedchildren 3-36 mo of age Is the child effectively immunized?  At least two doses (3 is better!)  2 weeks from 2nd dose Screen for UTI as for the unvaccinated child Well-appearing, vaccinated children are low risk, so blood tests not likely to change management!
    • 17. Case 1 Rutabaga is a 9 week old male infant with fever at home to 103, parents gave Tylenol. In clinic, T is 37.6, vitals otherwise normal for age, baby is well-appearing Exam/hx: hint of a cough, mild papular rash onchest, feeding well, older sibs with colds Received 1st dose of Prevnar 3 weeks ago Uncircumcised
    • 18. What are the key parts of Rutabaga’s Hx/PE in estimating his risk of SBI/UTI? Age: 1-3 mo Appearance: Non-toxic Fever source:  Possible viral source? Sick contacts? Uncircumcised Immunization status:  *One dose of PCV-7 – is he protected?
    • 19. Partial Vaccination – Evidence Efficacy of the vaccine after < 3 doses is unclear at the moment due to lack of sufficient data. Kaiser study results suggest that immunity against invasive disease is good in partially immunized infants  Herd immunity protective Two recent studies have demonstrated good serotype-specific antibody responses after 2 doses of the vaccine (Goldblatt, 2006; Huebner 2002) Vaccination against pneumococcus DOES NOT protect against UTI, primarily caused by E. Coli
    • 20. What’s your plan? Cath U/A  Negative for LE, nitrites, + small blood CBC  WBC 18.7, 75% lymphs Blood culture  Can’t obtain blood culture after multiple sticks What are your options?  Try again for blood cultures  Treat without cx: commit to full course of antibiotics  No antibiotics, admit for obs  No antibiotics, home for obs
    • 21. Another version… In a similar case, you obtain blood cultures, but are unable to obtain spinal fluid after 3 tries… What are your options? Treat without tap:  Commit to full course for presumed meningitis  Try again tomorrow for cell count Don’t treat:  Admit for obs without tap (plan to tap and treat if ill- appearing)
    • 22. Case 2 Cheyote is 6 month old girl who just received 3rd dose of PCV-7 2 days ago She has had a fever for 3 days, has a temp of 39.8 in clinic, no source for fever on exam or history, and is well-appearing What studies, if any, would you do on this infant? How do you obtain urine?
    • 23. Bag vs Cath Catheter specimens  Current gold standard  For culture: Sens 95%, spec 99% Bag  Less invasive (?)  BUT results difficult to interpret  Culture: Sens/spec ~85%
    • 24. Can a bag specimen be used for UA? Bottom line: No published data compares sensitivity and specificity of UA on bag specimens to other types of specimens! UA from bag may have slightly decreased specificity compared to cath specimen  False positives may result from contamination from distal urethra, diaper  Avoid in patients in whom false positives are unacceptable
    • 25. Predictive value of UA “Predictive value” refers to the posterior probability of disease, given a positive or negative test Depends on sensitivity, specificity, and prior probability Example: For a UA positive for LE only: Prior prob PPV NPV 5% 20% <1% 10% 33% 1% 20% 53% 3% Which patient is most likely to be impacted?
    • 26. Predictive value of UA “Predictive value” refers to the posterior probability of disease, given a positive or negative test Depends on sensitivity, specificity, and prior probability Example: For a UA positive for LE only: Prior prob PPV NPV 5% 20% <1% 10% 33% 1% 20% 53% 3% Which patient is most likely to be impacted?
    • 27. Predictive Value: The Bottom Line PPV is maximized when PP is high NPV is maximized when PP is low Best use of UA for  Low prior prob patient: Rule OUT UTI  High prior prob patient: start empiric treatment
    • 28. Can a bag specimen be sent for culture? False positives are the major concern:  Contamination rate depends on the population, technique, and positive threshold  Very low in circ boys  As high as 20% in other populations However, false negatives also occur, depending on the threshold chosen for positive test…  For >100,000 org, sens and spec ~85%
    • 29. Predictive value of bag culture NPV of bag cx best in low prior prob patient, PPV best in high prior prob pt Example: Prior prob PPV NPV 5% 23% 1% 10% 40% 2% 20% 60% 4% The only clinically meaningful use of the bag culture is to rule OUT UTI in the low prior probability patient
    • 30. Predictive value of bag culture NPV of bag cx best in low prior prob patient, PPV best in high prior prob pt Example: Prior prob PPV NPV 5% 23% 1% 10% 40% 2% 20% 60% 4% The only clinically meaningful use of the bag culture is to rule OUT UTI in the low prior probability patient
    • 31. Summary: Bag specimen Characteristics of UA from bag specimen make it most useful to rule out UTI in low probability patients  Can also be used to start treatment in high risk patient Bag culture  False positive/negative results are a significant risk  Neg results helpful in low-prob patients  Must weigh the implications of false pos/false neg for the patient, against the discomfort of a cath
    • 32. Recommendations: Collection of UrineSpecimen High risk infants, or a child who looks sick enough to require IV antibiotics/admission:  Obtain a catheter specimen for UA and culture  Positive UA: empiric treatment, confirm with culture Lower risk patients:  If desired, collect bag specimen for screening UA:  Negative UA: UTI is unlikely  Positive UA: consider empiric treatment, but confirm with a culture  If you send the bag for culture – consider the clinical implications before you send the test!
    • 33. Case Three Daikon is a 6 week old boy, temp of 101 at home, 38.7 in clinic It’s winter, influenza and RSV are rampant He is well-appearing, without any URI symptoms on exam or history, mom says she has had the “flu” and is wondering if he might have the same thing No immunizations yet
    • 34. Key Question: Would viral testing change your management?
    • 35. Viral Testing - Evidence The advent of rapid viral testing has added a new option for identifying infants at low risk for SBI Rapid tests exist for RSV, adeno, paraflu, influenza, entero and rotaviruses In general, these tests are more specific than they are sensitive, which makes false positives extremely rare
    • 36. Viral Testing - Evidence A number of recent studies, mostly retrospective, have evaluated the risk of SBI in infants found to have a positive viral test Example: recent prospective trial (Byington, et al 2004) of 1385 febrile infants <90 days, tested for multiple viruses  Stratified infants into HR/LR by Rochester criteria  Among LR infants, risk of SBI low (1-3%) regardless of viral test  Among HR infants, those with + viral tests had a significantly reduced chance of SBI (16.7% -> 5.5)  Risk of UTI still clinically significant in HR+ infants (4%), while bacteremia occurred in <1%, and none had meningitis
    • 37. Recommendations Bottom Line:The negative predictive value of a rapid viral test is best in low probability patients! Therefore, viral testing is most likely to change management in those infants with a low-mod prior probability of SBI In very young infants or those at high risk, an appreciable risk of UTI remains  Consider testing for UTI in infants at high risk of UTI, regardless of viral diagnosis
    • 38. Case 3 - Continued You decide to get a CBC and blood culture, a cath UA and a rapid viral test for RSV and influenza Results:  WBC 18, with 67% lymphs  Rapid viral test positive for influenza  Cath U/A negative What do you want to do?  Treat with antibiotics? Admit? Tap?
    • 39. Summary of Recommendations5 questions to ask about child with FWS 1. Is this child toxic? 2. Is there a source for the fever? 3. Has this child been vaccinated against pneumococcus? 4. If it’s a boy, is he circumcised? 5. Will this child come back if he/she gets sick?
    • 40. My Silly Mnemonic… If the baby’s smiling at me And has had Prevnar X 3 Skip the CBC But don’t forget to collect the pee!