Fever without focus Dr Rafat Mosalli

Question 1 A 3 week old male infant is brought to your ED with a 2 day history of fever. He was born by uncomplicated vaginal delivery at 37 weeks gestation following a normal pregnancy.. His vital signs are: T 38.9C (R), HR 140, RR 40, and BP 90/60. He is sleepy but easily arousable. Physical exam is normal apart from a slightly dull left tympanic membrane. WBC is 16,000, his UA shows 3 WBC/hpf. BC and UC are sent. Your management at this point would consist of: a. Discharge on antipyretics with close follow-up b. Discharge on oral amoxicillin with close follow-up c. LP and admission for parenteral antibiotics d. CXR to r/o pneumonia e. Stool for analysis and culture, and outpatient follow-up

Question 2 A 7 week old girl is referred in to ED for evaluation of a rectal temperature of 39.2C. Her PE is normal. Her UA is negative, her WBC is 9,000 (70% neuts, 28% lymphs, 2% bands), and her LP reveals a CSF WBC count of 8. BC, UC, and CSF cultures are sent. Acceptable management options for this child would include any one of the following except: IM ceftriaxone in the ED Admission to the hospital for IV antibiotics Discharge with follow-up in 24 hours Admission to the hospital for observation Discharge on amoxicillin

Question 3 A 19 month old boy comes to the ED with a 3 day history of fever. He appears well but his tympanic T is 39.8C. His chest is clear, his abdomen is soft, and he is circumcised. No source can be found for his fever. A CBC reveals a WBC of 8200 (60% neuts, 27% bands). BC’s are sent. Appropriate management at this point will be to: a. Obtain a urine sample b. Administer IM ceftriaxone c. Perform an LP d. Obtain a CXR e. Discharge on antipyretics

Objectives Definitions Which patients need in-depth evaluation and treatment? What laboratory studies are indicated for various age ranges? Which patients need treatment with antibiotics? Which patients should be hospitalized?

Definitions Fever Fever without focus Fever of unknown origin Occult bacteremia Serious bacterial infection (SBI)

What is fever? Rectal temperature > 38C, either at physician’s office, ED, or documented at home by a reliable parent or other adult

Different body sites Rectal standard Oral 0.5-0.6 lower Axillary 0.8-1.0 lower Tympanic 0.5-0.6 lower Documented: In the absence of antipyretics In ED or office or by hx from reliable parents/adults Tympanic age and technique specific; long tortuous ear canal in small kids Rectal preferred in under 3 months of age Abdomen-toe temperature differential as method of distinguishing overbundling from true fever

Frequency of febrile illness 35% of unscheduled ambulatory care visits 65% of kids see doc before age 2y Majority (75%) for T < 39 C 13% T > 39.5

Fever of Unknown Origin 1. Fever of 38C or greater which has continued for a 2 to 3 weeks 2. Absence of localizing clinical signs 3. Negative simple investigations

Fever without focus “An acute febrile illness in which the etiology of the fever is not apparent after a careful history and physical examination.” 20% of childhood fevers have no apparent cause Baraff et al, Pediatrics 1993; 92:1-12

Occult bacteremia “…a positive blood culture in the setting of well appearance and without focus (e.g. no pneumonia) Fleisher et al, J Pediatrics 1994

Occult bacteremia organisms Streptococcus pneumonia > 85% Haemophilus influenzae type B (now rare – previously 10%) Neisseria meningitidis 3-5% Others: S. aureus S. pyogenes (GAS) Salmonella species

Outcomes of occult bacteremia without antibiotics Persistent fever 56% Persistent bacteremia 21% Meningitis 9% S. pneumonia 6% H. Influenzae 26% (now rare)

Age is quite matter >10 % of well-appearing young infants with a temperature >38°C has a serious bacterial infection or meningitis Only <2 %of well-appearing older infants and young children with a temperature >39°C (manifest bacteremia

Serious Bacterial Infection “…Include meningitis, sepsis, bone and joint infections, urinary tract infections, pneumonia and enteritis” Baraff et al, Pediatrics 1993; 92:1-12

Fever Practice Guidelines CPS guidelines: Management of the febrile one-to 36-month-old child with no focus of infection. Paediatr Child Health 1996;1:41-45 *re-affirmed April 2002 “American” consensus guidelines: Practice guideline for the management of infants and children 0-36 months of age with fever without source. Baraff et al, Pediatrics 1993;92:1-12

Case scenarios - fever By age group: < 1 month of age 1 – 3 months

Why according to age Because in young infants there's a greater probability of serious bacterial infection so more aggressive approach to the evaluation and management of fever is warranted.

Febrile infant < 1 month “American” consensus recommendations All should have: Full septic w/u CSF cultures, gm stain, cell count/diff, gluc/prot Blood cultures Urine routine, micro, culture If diarrhea, stool exam (smear and culture) If resp sx: CXR ADMIT, IV antibiotics, or ADMIT, observe without antibiotics GBS, E. coli, Listeria

Febrile infants 1-3 m of age According to validated criteria E.g. Rochester score Low and high risk

Febrile infants < 3 months risk of bacteremia If meets low risk Rochester 0.2% (1:500) criteria If meets low risk criteria 0.7-1% but < 1 month

Febrile infants 1-3 m of age Hi Risk: “American” and Canadian Consensus recommendations ADMIT to hospital with full septic w/u BC, UC, LP Broad-spectrum parental antibiotics

Febrile infants 1-3m of age low risk Option 2 (“American” and CPS) No investigation (or urine culture only ) Careful outpatient observation, without treatment, close follow-up Option 1 (“American”): Blood culture Urine culture LP Ceftriaxone 50 mg/kg IM Return for re-evaluation w/i 24 hours

Follow-up of Infants 1-3m old Within 24 hours Repeat exam for source, sequelae Review, repeat labs Arrange ongoing follow-up

Follow-up of 1-3m If blood culture positive If urine culture positive ADMIT for sepsis evaluation Parenteral antibiotics pending results If urine culture positive Persistent fever: ADMIT for sepsis evaluation and parenteral abx tx pending results Afebrile and well: outpatient antibiotics

Fever Without Source Age 3 – 36 Months

Fever Without Source Age 3 – 36 Months Risk of occult bacteremia 3-11%, mean 4.3% for T>39C Risk greater with Higher temperatures WBC > 15,000 (13% vs 2.6%) Risk of pneumococcal meningitis (w/o abx tx) 0.21% (1:500)

How should a child with FWF be evaluated? Detailed history and thorough physical examination avoid indiscriminately ordering a large battery of tests. Laboratory studies should be directed as much as possible toward the most likely diagnostic possibilities.

Physical examination: “Toxic appearance” Lethargy/irritability Poor/absent eye contact Poor perfusion Hypo/hyperventilation Cyanosis

FWS – age 3-36 months: Consensus Recommendations CHILD NON-TOXIC, T < 39C No diagnostic tests or antibiotics Acetaminophen 15 mg/kg prn for fever Return if fever persists > 48 hours or the followings happened:

Return to the Emergency Department if your child more fussy or won’t stop crying too sleepy or drowsy stiff neck Won’t stop vomiting new rash Has a seizure Gets any other new or worsening symptom(s) that concerns you

FWS – age 3-36 months: Recommendations CHILD NON-TOXIC, T  39C Urine culture (for M < 6 month, F < 2 yrs age) BC – 2 options Option 1: obtain for all children with T  39C Option 2: obtain if T  39C and WBC >15,000 CXR, stool culture if indicated clinically Acetaminophen 15 mg/kg q4h for T  39C Follow-up in 24-48 hours *no antibiotics No antibiotics; supported by Baraff in annals of emerg med Dec 2000

FWS – age 3-36 months: Consensus Recommendations CHILD APPEARS TOXIC: ADMIT to hospital Sepsis w/u Parenteral abx

Investigation options [ ] CBC [ ] blood culture [ ] urinalysis [ ] urine culture [ ] CXR [ ] LP [ ] Nothing Laboratory studies should be directed as much as possible toward the most likely diagnostic possibilities.

Choice of antibiotic If decide to treat empirically ceftriaxone or po Amoxicillin/clavulanate

FWS – age 3-36 months: BC returns positive Pneumococcus: Persistent fever: ADMIT for sepsis w/u and parenteral abx pending sensitvity Natural course of pneumococcal bacteremia is resolution

FWS – age 3-36 months: BC returns positive All Other Bacteria: ADMIT for sepsis w/u and parenteral abx pending sensitivity results

FWS – age 3-36 months: Urine culture returns positive All organisms: ADMIT if febrile or ill-appearing Outpatient abx if afebrile and well

Summary: FWS Hospitalize +/- abx Infants < 28 days: -According to risk score hospital Vs home, +/- abx Home, no antibiotics +/- labs, home, no antibiotics Infants < 28 days: Infants 1-3 months Non toxic children 3 m- 3 yrs (T < 39C) Non toxic children 3 m-3 y (T 39C): close follow-up in all!

Regardless of PCV status Toxic highly Febrile Child Aged 3-36 mos Without Apparent Focus Be Managed ? Age 3-36 mos Temp. > 390C Regardless of PCV status "ill" , "toxic", "lethargic" ? >20,000 WBC/mm3 No ?  risk for bacteremia  WBC  fever male age 7-11 mos Yes ? ? Hospital/ Antibiotic Rx Yes Yes Consider AMOX or specify why other

“ I think it is clear that the handwriting is on the wall saying that occult bacteremia is dead. It was dying when Hib disappeared and Prevnar has destroyed it.” contribution to Pediatric Emergency Medicine List Serve

Heptavalent conjugate pneumococcal vaccine very efficacious Likely to make most of the foregoing pneumococcal in 3-36 month group obsolete Finally become routine by MCH Given at 2,4,6 month and 12-15m ? Mention C – reactive protein

Effect in Target Age Group Invasive Pneumococcal Disease Rates in Children < 3 Years, ABCs, 1998-2003  77% (<1 yr)  83% (1 yr)  64% (2 yr) 2003 vs baseline PCV7 1 yr <1 yr 2 yrs 2003 data are preliminary Farely et al, ICP, Cancun, Mexico, August 2003

~  80% in invasive pneumococcal disease in children < 3 yrs Effect in Target Age Group Invasive Pneumococcal Disease Rates in Children < 3 Years, ABCs, 1998-2003  77% (<1 yr)  83% (1 yr)  64% (2 yr) 2003 vs baseline ~  80% in invasive pneumococcal disease in children < 3 yrs 2003 data are preliminary Farely et al, ICP, Cancun, Mexico, August 2003