Fever without source (FWS) in young kids Emergency Medicine Core Rounds October 3, 2002 Dr. Edward Les

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. At his two week check-up he was noted to be gaining weight appropriately. His vital signs are: T 38.9  C (R), HR 140, RR 40, and BP 90/60. He is sleepy but easily rousable. Physical exam is normal apart from a slightly dull left tympanic membrane. His peripheral 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: a.IM ceftriaxone in the ED b.Admission to the hospital for IV antibiotics c.Discharge with follow-up in 24 hours d.Admission to the hospital for observation e.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

Overview Definitions Frequency of febrile illnesses Treatment of fever Physical exam Rochester and Philadelphia criteria Evaluation and management options FWS: infant < 28 days FWS: infant days FWS: > 90 days to 36 months Summary

Definitions Fever Fever without source (FWS) Fever without focus Occult bacteremia Serious bacterial infection (SBI)

Where the heck did 98.6ºF come from? A.D. 1868! Carl Reinhold August Wunderlich > 1 million axillary temps from 25,000 patients analyzed

What constitutes a 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 Rectalstandard Oral  lower Axillary  lower Tympanic  lower Documented: –In the absence of antipyretics –Unbundled (“abdomen-toe differential”) –In ED or office or by hx from reliable parents/adults

Fever Without Source “…An acute febrile illness in which the etiology of the fever is not apparent after a careful history and physical examination.” –Baraff et al, Pediatrics 1993; 92:1-12

Fever of Unknown Origin 1. Fever of 38  C or greater which has continued for a two to three week period 2. Absence of localizing clinical signs 3. Failure of simple diagnostic efforts to identify a cause

Occult bacteremia “…a positive blood culture in the setting of well appearance and without focus (e.g. no pneumonia), BUT may bein the presence of URTI, otitis media, diarrhea, or wheezing” –Fleisher et al, J Pediatrics 1994

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

Frequency of febrile illness 35% of unscheduled ambulatory care visits 65% of kids see doc before age 2 c/o fever –Majority (75%) for T < 39  C –13% T > 39.5  C 14-20% are FWS

Epidemiology Incidence of bacteremia in febrile infants in post-Hib era –2-3% if 38  C Avner and Baker, Emerg Med Clin NA 2002;20(1) – 39  C Klein, Ped Inf Dis J 2002;21(6):584-8

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

Outcomes of occult bacteremia without antibiotics Persistent fever56% Persistent bacteremia21% Meningitis9% –S. pneumonia 6% –H. Influenzae 26% (but no longer see it)

Which antibiotics to best treat/prevent occult bacteremia? Two multi-center trials: Ceftriaxone vs amoxil or amoxil/clavulanate »Intramuscular vs oral therapy for the prevention of meningitis and other bacterial sequelae in young febrile children at risk for occult bacteremia. Fleisher et al, J Peds 1994;124: »Antimicrobial treatment of occult bacteremia: a multicenter cooperative study. Bass e al,PIDJ 1993;12: –Poor studies –Suggested ceftriaxone associated with less persistent fever, but no difference in outcomes

Age 3-36 months: routine use of antibiotics? Risk of meningitis without abx = 1:500 Need to treat hundreds to prevent one case HiB virtually eliminated; pneumococcus to follow? Risk of partial treatment, delayed recognition Resistant organisms – selection Risk of drug side effects

Should fever be treated? Pros –Decrease discomfort –Calm the folks –Extreme (>41  C) may cause permanent brain damage –rare,rare,rare –Decrease risk of febrile convulsions in prone kids??

Should fever be treated? Cons –Adverse effect of antipyretic may outweigh benefits –May obscure diagnostic/prognostic signs –Fever usually short-lived and benign –Fever is normal and adaptive physiologic response

Fever phobia Crocetti et al, Pediatrics 2001;107 91% of caregivers believed a fever could cause harmful effects –21% listed brain damage; 14% said death 25% gave antipyretics for T < 37.8  C 85% awaken their child to give antipyretics 14% gave acetaminophen too frequently, 44% gave ibuprofen too frequently

Our fault? Temp is 1 st thing checked at triage Quick to ask about fever on history Instructions often include advice to return if fever is higher or persistent Investigations up the wazoo Little routine info provided to parents about fever

Fever phobia 65% of pediatricians also believe that an elevated body temperature in and of itself could become dangerous to a child –May and Bauchner, Pediatrics 1992;90:851-54

Can viral infections and bacterial infections be distinguished based on response to antipyretic therapy? NYET!! Traditional theory, but…… no evidence to support it.

Physical examination: Approach to child Gentle, non-threatening Parental assistance to comfort Observe as much as possible before examining Value of a second look

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

Yale Observation Scale 6 items of observation and physical signs Normal (1 point), moderate impairment (3 points), and severe impairment (5 points) scores are given for: –Quality of cry –Reaction to parental stimulation –State of alertness –Color –Hydration –Response to social overtures McCarthy, PL, et al, Pediatrics 1982; 70: Scores of  10 correlate with low likelihood of serious illness, primarily in infants < 2 months old

Tale of Three Cities: Boston,Philadelphia, and Rochester Guides developed to identify febrile infants at low or neglible risk of a serious bacterial infection Goal was to reduce the number of infants hospitalized unnecessarily and to identify infants who may be managed as outpatients Consist of clinical and laboratory procedures Baskin et al, J Pediatr 1992;120:22-27 Baker et al, N Eng J Med1993;329: Jaskiewicz et al, Pediatrics 1994;94:390-96

PhiladelphiaRochesterBoston Age29-60 d Temperature38.2  C HistoryNot specified Physical examinationWell-appearing (IOS < 10) Unremarkable exam Laboratory parameters (defines lower-risk patients) Wbc < 15,000 BNR < 0.2 UA < 10 WBC/hpf Urine gram stain –ve CSF <8 WBC CSF gm stain –ve CXR clear Stool: no blood, few or no WBC’s on smear High risk patientsHospitalize + empiric abx Low risk patientsHome No antibiotics Follow-up required Reported statisticsSensitivity 98% PPV 14% NPV 99.7%

PhiladelphiaRochesterBoston Age0-60 d Temperature38.0  C HistoryTerm infant No perinatal antibiotics No underlying disease No prior hospitalization Physical examinationWell-appearing No ear, soft tissue, or bone infection Laboratory parameters (defines lower-risk patients) WBC > 5,000 and < 15,000 Absolute band count <1500 UA < 10 WBC/hpf < 5 WBC/hpf stool smear High risk patientsHospitalize + empiric antibiotics Low risk patientsHome No antibiotics Follow-up required Reported statisticsSensitivity 92% PPV 12.3% NPV *SBI 1.1%

PhiladelphiaRochesterBoston Age28-89 d Temperature38.0  C HistoryNo immunizations within preceding 48 h No abx within 48 h Not dehydrated Physical examinationWell-appearing No ear, soft tissue, or bone infection Laboratory parameters (defines lower-risk patients) CSF < 10 UA < 10 WBC/hpf CXR clear WBC < 20,000 High risk patientsHospitalize + empiric abx Low risk patientsHome Empiric abx (IM ceftriaxone) Follow-up required Reported statisticsSensitivity – N/A PPV – N/A NPV – N/A *SBI 5.4%

PhiladelphiaRochesterBoston Age1-2 months0-2 months1-3 months Temperature38.2  C38.0  C HistoryNot specifiedTerm infant Previously well No recent vacc /abx Not dehydrated Physical examinationWell-appearing (IOS < 10) Well-appearing Laboratory parameters (defines lower-risk patients) Wbc < 15,000 BNR < 0.2 UA < 10 WBC/hpf Urine gram stain –ve CSF <8 WBC CSF gm stain –ve CXR clear Stool: no blood, few or no WBC’s on smear WBC > 5,000; < 15,000 Abs band ct <1500 UA < 10 WBC/hpf < 5 WBC/hpf stool smear * No LP required! CSF < 10 UA < 10 WBC/hpf CXR clear WBC < 20,000 Higher risk patientsHospitalize + empiric abx Lower risk patientsHome No antibiotics Follow-up required Home No antibiotics Follow-up required Home Empiric abx (IM ceftriaxone) Follow-up required

Follow-up: “good social situation” required: Telephone at home Availability of vehicle Parental maturity Thermometer ED or office travel < 30 min

Case scenarios - fever By age group: – < 1 month of age – 1 – 3 months – 3 – 36 months

Evaluation options [ ] CBC [ ] blood culture [ ] urinalysis [ ] urine culture [ ] CXR [ ] LP [ ] Nothing

Management options [ ] Admit [ ]Treat empirically, or [ ]Observe, no treatment [ ] Send home, follow-up within 24 hours [ ]Treat empirically, or [ ]No treatment

Treatment options [ ] Oral [ ]Amoxicillin [ ]Amoxicillin/clavulanate [ ]Cefaclor [ ]Other [ ] Intravenous [ ]Ceftriaxone [ ]Other

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

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 infant < 28 days “ American” consensus recommendations Whether or not low risk –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

Febrile infants days of age NOT Low Risk “American” and Canadian Consensus recommendations ADMIT to hospital with full septic w/u –BC, UC, LP Broad-spectrum parental antibiotics

PhiladelphiaRochester Age1-2 months0-2 months Temperature38.2  C38.0  C HistoryNot specifiedTerm infant Previously well Physical examinationWell-appearing (IOS < 10) Well-appearing Laboratory parameters (defines lower-risk patients) Wbc < 15,000 BNR < 0.2 UA < 10 WBC/hpf Urine gram stain –ve CSF <8 WBC CSF gm stain –ve CXR clear Stool: no blood, few or no WBC’s on smear WBC > 5,000; < 15,000 Abs band ct <1500 UA < 10 WBC/hpf < 5 WBC/hpf stool smear * No LP required!

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

Follow-up of “Low Risk” Infants days old Within 24 hours Repeat exam for source, sequelae Review, repeat labs/xrays if performed Repeat antibiotics? Arrange ongoing follow-up

Follow-up of “Low Risk” Infants days old If blood 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 Risk of occult bacteremia – based on “old data” –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)

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

FWS – age 3-36 months: Consensus Recommendations CHILD NON-TOXIC, T < 39  C –No diagnostic tests or antibiotics –Acetaminophen 15 mg/kg q4h for fever –Return if fever persists > 48 hours or clinical condition deteriorates

FWS – age 3-36 months: Consensus 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 hours *no antibiotics

Choice of antibiotic If decide to treat empirically (follow-up not assured, not low risk) –“American” guidelines: ceftriaxone – CPS: ceftriaxone or po amoxicillin 60 mg/kg/day

FWS – age 3-36 months: BC returns positive Pneumococcus: –Persistent fever: ADMIT for sepsis w/u and parenteral abx pending results –If no fever and looks well: repeat cultures, no treatment

FWS – age 3-36 months: BC returns positive All Other Bacteria: ADMIT for sepsis w/u and parenteral abx pending 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 but “low risk” Infants < 28 days: Infants 1-3 months Infants and children 3 months to 3 yrs (T < 39  C): Infants and children 3 months to 3 years (T  39  C): hospitalize +/- abx +/- labs, home, +/- abx home, no antibiotics +/- labs, home, no antibiotics close follow-up in all!

“ 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 90% efficacious Likely to make most of the foregoing discussion in 3-36 month group obsolete Need more evidence first Also, still be alert for: –Unimmunized, under-immunized, vaccine failures, infection with serotypes not included in vaccine

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. At his two week check-up he was noted to be gaining weight appropriately. His vital signs are: T 38.9  C (R), HR 140, RR 40, and BP 90/60. He is sleepy but easily rousable. Physical exam is normal apart from a slightly dull left tympanic membrane. His peripheral 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 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. At his two week check-up he was noted to be gaining weight appropriately. His vital signs are: T 38.9  C (R), HR 140, RR 40, and BP 90/60. He is sleepy but easily rousable. Physical exam is normal apart from a slightly dull left tympanic membrane. His peripheral 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: a.IM ceftriaxone in the ED b.Admission to the hospital for IV antibiotics c.Discharge with follow-up in 24 hours d.Admission to the hospital for observation e.Discharge on amoxicillin

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: a.IM ceftriaxone in the ED b.Admission to the hospital for IV antibiotics c.Discharge with follow-up in 24 hours d.Admission to the hospital for observation e.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 CXT e. Discharge on antipyretics

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 CXT e. Discharge on antipyretics

finis