1 The Febrile Infant SJRH ED Rounds Dec 11 2018 By: Robin Clouston
2 Objectives Discuss the risk of serious bacterial infection (SBI) in the neonate or young infant (<90d) with fever Review current suggestions for the work up, management, disposition, and follow up in the care of neonates and young infants with fever Discuss the role of decision tools (ex: Rochester, Boston, Philadelphia) to aid in decision making for the wellappearing infant with fever
3 Introduction The febrile neonate (<28d) and young infant (<90d) are commonly encountered in the emergency dept. Many will have a self limited, viral illness A small but significant proportion (up to 15% 1 in some series) will have a serious bacterial infection (SBI) How to best assess and manage such infants has long been a matter of debate.
4 Local context No SJRH EM Guideline exists for the management of neonatal fever Local variation in practice regarding: Work up Empiric management Disposition Follow up Recent clinical cases have highlighted this issue Forthcoming SJRH EM Guideline
5 Burning questions What IS the full septic work up? Which kids >30 days need blood work? Which kids >30 days need the LP? Can I avoid antibiotics in any of these kids? Which kids can I send home? Are there any harms to over-investigating and overtreating?
6 Definitions Neonate: 0 to 28d Young Infant <90d Fever = rectal temp >/= 38.0C Serious bacterial infections (SBI) include 2 : Bacterial meningitis, bacteremia, UTI, pneumonia Some series: enteritis, cellulitis, abscess, osteomyelitis, septic joint Invasive Bacterial Infect (IBI) 2 Bacterial meningitis and bacteremia
7 Rates of SBI Many infants with fever have a self-limited viral illness Rates of serious bacterial infection 3 : 3 to 28d: 13% 29 56d: 9% 90 days and younger: 7% *in pre-pneumococcal vaccine era Prevalence is highest <2wk (25%) UTI most common SBI, with prevalence 3 to 11% 1 2 % will have IBI 4
8 Common pathogens In neonates < 28d, most common pathogens are 1 : E. coli Group B streptococcus S. pnuemoniae S. aureus L. monocytogenes Also: Herpes simplex virus Respiratory syncytial virus Enterovirus
9 Work up of the toxic infant Good consensus on management For infants ill appearing / toxic appearing, including 5 : Lethargy Poor perfusion Cyanosis Hypo or hyperventilation Significant abnormalities in vital signs à Full septic work up
10 Work up of toxic infant Full septic work up always includes 1,: CBC Metabolic panel (routines) Blood culture Urinalysis with report of HPF (catheter specimen) Urine culture CSF cell count, glucose, protein CSF fluid culture
11 Work up of toxic infant CXR 2-view only if respiratory symptoms present (tachypnea, hypoxemia, focal findings on exam)t 6 Respiratory panel for RSV if cough, rhinorrhea Stool cultures if diarrhea ALT / AST if considering HSV HSV testing if at risk: < 21d, maternal hx, seizure, vesicles Elevated AST, ALT, thrombocytopenia, CSF pleocytosis CRP? Procalcitonin?
12 Does every kid need the kitchen sink? In the 1970s and 1980s, guidelines recommended a full septic work up for all infants <90d 4,7 In 1980 s various groups derived Low-Risk Criteria for Management of Febrile Young Infants: Rochester Criteria Philadelphia Criteria Boston Criteria
13 Rochester Criteria 8 Includes 0 to 60 days of age Inclusion: Full term Normal prenatal and post natal history No post natal antibiotics Well appearing No focal infection Laboratory parameters defining low risk: WBC 5000 to 15000 Bands < 1500 UA: <10 WBC/HPF Stool < 5 WBC/HPF on smear (of obtained based on sx) Modified Rochester includes normal CRP
14 Rochester Criteria 8 Treatment for high risk: Hospitalize Empiric antibiotics Treatment if low risk: Home 24h follow up required No empiric antibiotics NPV: 98.9% (97.2 99.6) Did not perform as well on series including infants > 60 days
15 Philadelphia Criteria 9 Includes 29 56 days of age Inclusion: Well-appearing No focal infection Lab parameters defining low risk: WBC < 15 000 Band: total neutrophil (I:T) ratio < 0.2 UA < 10 WBC / HPF CSF: gram stain neg CXR: no infiltrate (if obtained) Stool: no blood, few or no WBC on smear (if obtained)
16 Philadelphia Criteria 9 Treatment for high risk: Hospitalize Empiric antibiotics Treatment for low risk: Home, if patient lives within 30 min of hospital 24h follow up required No empiric antibiotics NPV: 99% (99 100)
17 Boston Criteria 10 Includes 28 89 days of age Inclusion: No antibiotics within preceding 48h No immunizations within preceding 48h Well appearing No focal infection Laboratory parameters defining low risk: WBC < 20 000 UA: < 10 WBC / HPF CSF: < 10 WBC/mm 3 CXR: no infiltrate (if performed)
18 Boston Criteria 10 Treatment for high risk patients: Hospitalize Empiric antibiotics Treatment for low risk patients Home if caregiver available by telephone Empiric IM ceftriaxone 50mg/kg Return for 24h follow up for second dose of IM/IV ceftriaxone NPV: 94.6% (92.2 96.4)
19 Comparing the criteria All have high NPVs All have high sensitivity (92 to 97 %) All have low specificity (40 to 55%) à Low Risk Criteria allow approximately 30% of patients to be treated safely without empiric antibiotic therapy à Rochester less invasive but not validated > 60 days
20 Don t forget HSV! Most acquired in peripartum period, 90% < 21d 1 mean age of 14d Three types Skin / Eye Mouth (SEM) Central Nervous System Disseminated Risk factors: Maternal history Seizure at presentation Vesicles CSF with pleocytosis For disseminated disease: transaminitis, DIC, acidosis Treatment: high dose acyclovir (20mg/kg/dose q8h)
21 What about suspected viral infections? Enterovirus positive infants have low rates of cocontaminant bacterial infection 7 Management may consist of supportive care alone Well-appearing, febrile, RSV positive infants are at decreased risk of SBI (7% vs 12.5%) 12 Notable risk for UTI (5.5%) Low risk bacteremia (1.5%) No cases meningitis à Do perform urinalysis and culture,?may avoid Abx and CSF how this applies to suspected viral infections before viral panel results is lest clear...
22 Procalcitonin (PCT) Protein prohormone of calcitonin released by liver and mononuclear cells 4h after tissue injury, peaks 6h after tissue injury, with sustained peak for 8 to 24 h In studies < 90d, favorable test characteristics compared to WBC and CRP Biggest challenge is threshold to define positivity 0.13ng/mL high sensitivity, low specificity 0.5ng/mL high specificity, inadequate sensitivity for SBI detection Most consistent cut off value reported Sensitivity of 60% for SBI and 85% for IBI, specificity 85% for both Up and coming Step-By-Step approach? 17
23 Step By Step Validation of Step by Step Approach in Management of of Young Febrile Infants 17 (Pediatrics Aug 2016) üsuperior sensitivity to Rochester (92% vs 81%) üup to age 90 days Considered low risk if: not ill appearing age > 21d no WBC in urine Procalcitonin <0.5 CRP <20 ANC <10 000 If meeting low risk criteria, infants are admitted x 24h without antibiotics and then discharged if still well-appearing.
24 Antibiotic treatment: If infant toxic or decision to treat: Less than 28d 1 : Consider common pathogens: E. coli, Group B streptococcus, S. pnuemoniae, S. aureus, L. monocytogenes Cefotaxime 50 mg/kg IV OR Gentamicin 4mg/kg IV AND Ampicillin 50mg/kg IV (for L. monocytogenes) Add vancomycin if CSF pleocytosis Add acyclovir 20mg/kg/dose q8h if <21d, toxic or high risk for HSV
25 Antibiotic treatment 29 to 60 days 1 Cefotaxime 50mg/kg OR Ceftriaxone 100mg/kg May defer ampicillin (very low risk of L monocytogenes) Add vanco if CSF Pleocytosis Add acyclovir if high risk for HSV
26 Antibiotic treatment 61 to 90 days 1 Cefotaxime 50mg/kg OR Ceftriaxone 100mg/kg May defer ampicillin (very low risk of L monocytogenes) Add vanco if CSF Pleocytosis
27 Current controversies Many studies done in 1980 s and early 1990s 4 Before HiB (1987) and Pneumococcal vaccine (2000) Before routine GBS prophylaxis in labour Before CRP and procalcitonin available Higher rates of circumcision compared to today
28 Current controversies Significant variation in literature recommendations regarding work up of wellappearing neonate older than > 28d Is CSF > 28 days really necessary? What about suspected viral infections?
29 Current controversies Iatrogenic harms of over testing and over treatment are not well studied 7 Traumatic lumbar puncture Antibiotic pre-treated CSF culture Unnecessary antibiotic exposure Radiation from x-rays Phlebitis due to venipuncture injury Hospitalization during a critical period of family bonding Vulnerable child syndrome
30 Some suggested management Less than 28 days 1 : All get full septic work up regardless of appearance 1,5,14,15, 16 : CBC Metabolic panel (routines) Blood culture Urinalysis with report of HPF (catheter specimen) Urine culture CSF cell count, glucose, protein CSF fluid culture + HSV testing (vesicles, serum, CSF) if <21d or high risk +/- CXR, RSV panel, stool culture only if indicated per sx
31 Some suggested management Less than 28 days 1 : ALL get empiric antibiotics: Ceftaxime or Gentamicin AND Ampicillin AND Acyclovir if < 21d or high risk for HSV AND Vancomycin if CSF pleocytosis or suspect meningitis Admit for IV antibiotics x 48-72h pending culture results
32 Some suggested management 28 to 60 days: Full septic work up if toxic appearing Use corrected age for premature infants 14 May use Rochester Criteria If high risk per criteria àfull septic work up (add CSF) Admit on IV Cefotaxime or Ceftriaxone pending culture results If low risk per criteria: May discharge home without Abx + Follow up in 24h If decision to tx with antibiotics, conensus 1,3,5 to also do LP If well appearing and suspect bronchiolitis, may consider UA only, but many guidelines recommend 5,14,15,16 or strongly consider 1 CBC, routines, blood cultures, +/- CRP
33 Rochester Criteria 8 Includes 0 to 60 days of age Inclusion: Full term Normal prenatal and post natal history No post natal antibiotics Well appearing No focal infection Laboratory parameters defining low risk: WBC 5000 to 15000 Bands < 1500 UA: <10 WBC/HPF Stool < 5 WBC/HPF on smear (of obtained based on sx) Modified Rochester includes normal CRP
34 Some suggested management 61 to 90 days: Full septic work up if toxic appearing Use corrected age for premature infants 14 Rochester Criteria not well validated Many existing guidelines do not include CSF (ex: NICE) Per NICE 13, perform for all infants < 90d: CBC, CRP, blood culture, urinalysis + culture CXR only if resp sx present Stool culture only if diarrhea Add CSF if high WBC??Step-By-Step
35 Some suggested management 61 to 90 days: If sx suggestive of bronchiolitis, some guidelines 1,14 suggest deferring bloods and still do UA Original study endorsed this strategy only for confirmed RSV 12 Admit if work up positive, ex: WBC> 15000 UA with >10 WBC / HPF CRP > 20 mg/l (2mg/dL) Start Abx pending neg cultures (Cefotaxime or Ceftriaxone) If starting Abx, most guidelines recommend lumbar puncture
36 Conclusions Many febrile infants have a viral infection Significant minority (up to 15%) have serious bacterial infection Cannot determine risk for SBI and IBI with Hx & P alone All toxic appearing infants need full septic work up, empiric antibiotics, and admission Several Low Risk Criteria exist to aid in decision making Low specificity, often include recommendation for invasive testing Much variation in existing guidelines for management In absence of an accepting national or society guideline, best approach is a thoughtful departmental guideline for the management of neonatal fever
Questions? 37
38 Resources 1. Aronson, PL. Evaluation of the Febrile Young Infant: An Update. EB medicine: Pediatric Emergency Medicine Practice. February 2013. from www.ebmedicine.net 2. C Woll et al. Management of the Febrile Young Infant: Update for the 21 st Century. Pediatric Emerg Care. 2017 Nov: 33 (11):748-753. 3. ACEP Clinical Policy for Well-Appearing Infants and Children Younger than 2 Years of Age Presenting to the Emergency Dept with Fever. Annals of Emergency Medicine. Vol 67, No. 5. May 2016. 4. Jhaveri R. et al. Management of the Non-Toxic Appearing Acutely Febrile Child: A 21 st Cetury Approach. The Journal of Pediatrics. August 2011. www.jpeds.com. 5. Clinical Practice Guidelines for Febrile Infants. University of Iowa Stead Family Children s Hospital. Updated 06/06/2017. Retrieved fr www.trekk.ca on Dec 2 2018. 6. Mintegi S et al. Occult pneumonia in Infants with High Fever Without Source: A prospective multicentre study. Pediatric Emergency Care 2010;26: 470 474. 7. Deporre AG et al. Facing the ongoing challenge of the febrile young infant. Critical Care (2017) 21:68. 8. Jaskiewicz JA et al. Febrile Infants at low risk for Serious Bacterial Infection An Appraisal of the Rochester Criteria and Implications on Management. Pediatrics Vol 94. NO 3. Sept 1994. 9. Baker MD et al. Outpatient Management without antibiotics of fever in selected infants. New England Journal of Medicine. 1993; 329(20):1437-1441.
39 Resources 10. Baskin MN et al. Outpatient treatment of febrile infants 28 to 89 days of age with intramuscular administration of ceftriaxone, Journal of Pedicatrics 1992:120(1):22-27. 11. Huppler et al. Performance of Low risk criteria in the evaluation of young infants with fever: review of the literature. Pediatrics 2010: 125(2):228-233. 12. Lavine DA et al. 2004 Risk of Serious Bacterial Infection in Young Febrile Infants with Respiratory Syncytial Virus Infections. Pediatrics Vol. 113. No 6. June 2004. 13. NICE Guideline. Fever in under 5 Years: Asessment and Initial Management. Published 22 May 2013. nice.org.uk/guideance/cg160. 14. Smitherman Hf et al. UpToDate: Febrile Infant Younger than 90 days of age: Outpatient evaluation. Retrieved Dec 6 2018 from www.uptodate.com. 15. BC Children s Hospital Febrile Infant Guideline. Retrieved Dec 2 2018 from www.trekk.ca. 16. Fever in Infants Less than 60 days Algorithm.. Children s Hospital of Colorado. Updated February 2018. Retreived Dec 2 2018 from www.trekk.ca 17. Gomez B et al. Validation of the Step By Step Approach in the Management of Young Febrile Infants. Pediatrics. Vol 138. Number 2. August 2016.