management of the febrile infant

Management of the Febrile Infant2001

Theodore C. Sectish, MD

Director, Residency Training Program in Pediatrics

Assistant Professor in Pediatrics

Stanford University School of Medicine

Fever in Infants

Learning Objectives:

Fever in infants and outcomes of fever Evaluation of the febrile infant Modified Clinical Practice Guideline Guidelines and Practice New considerations Management of Fever without Source - 2001

Historical Perspective

1967 Occult bacteremia 1970s Hospitalization of febrile infants 1980s Outpatient management 1985 HIB Vaccine 1993 Clinical Practice Guideline 2000 PCV7 Vaccine

Fever in Practice 4% of 1341 infants <6 mos of age in a family

practice clinic had temperatures >38.30C1

10.5% of 1068 infants 3-24 mos of age in a pediatric practice in New York had temperatures >38.20C2

Fever is a common problem in practice

1-Pantell Clin Pediatr 1980;19:772-Hoekelman AJDC 1979;133:1017

Diagnoses: Febrile Infants < 3 months URI 35.0% Otitis media 16.1% Bronchiolitis 8.4% Gastroenteritis 7.8% Urinary tract infection 4.7% Viral meningitis 2.7% Bacteremia 1.5% Bacterial meningitis 0.3% Cellulitis 0.2% Osteomyelitis 0.04%

Pantell, personal communication, PROS study

Fever without Source (FWS)

20% of all infants <3 years with fever have FWS 3% have occult pneumococcal bacteremia

Of bacteremic infants, 3% have meningitis 1 out of 1000!

Risks of pneumococcal bacteremia in a PCV7 immunized infant is unknown

Risk reduction estimate once immunized: 90%

Definition of Fever

38.00 C Rectal measurement Unbundled infant No recent antipyretics No recent immunizations

Baraff Pediatrics 1993;92:1

Bundling and Fever

Experimental design with controls Bundling = 5 blankets and a hat 20 bundled infants: mean change + 0.560 C 20 infant controls: mean change - 0.040 C 2 infants reached 38.0 C, not higher

Cheng TL Pediatrics 1993;92(2):238

Febrile Infants:Outcomes of Interest

Bacteremia 1.5 - 12% Serious bacterial infection 1.4 - 17.3%

Jaskiewicz Pediatrics 1994;94:390Bass Pediatr Infect Dis J 1993:12:466Fleisher J Pediatr 1994;124:504Jaffe NEJM1987;317:1175Baraff Pediatr Infect Dis J 1992;11:257Pantell, PROS Study, personal communication

Serious Bacterial Infection (SBI)

Urinary tract infection Sepsis or bacteremia Meningitis Bacterial enteritis Bone and joint infections Pneumonia

Probability of Bacterial Infection in

Febrile Infants, <90 Days of Age

0.00%2.00%4.00%6.00%8.00%

10.00%12.00%14.00%16.00%18.00%20.00%

SBI Bacteremia Meningitis

Low Risk

Nontoxic

Toxic

Baraff J Peds 1993;92:1


Lee Arch Pediatr Adolesc Med 1998;152:624

Probability of Occult Bacteremia: Febrile Infants, 3 - 36 months

Era Probability (CI)

Age of Hemophilus 4.3% (2.6-6.5%)

Age of Pneumococcus 1.6% (1.32-1.83%)

Post PCV7 ?

Outcomes of Occult Bacteremia in the Age of Hemophilus

Outcome Untreated Treated

Fever 55.8% 15.6%

Bacteremia 20.9% 3.8%

Meningitis 9.2% 4.5%

Baraff PIDJ 1992;11:146

Occult Bacteremia in the Post-HIB Vaccine Era: 3-36 months

Streptococcus pneumoniae 92% Others: 8%

Salmonella spN meningitidisGroup A StreptococcusGroup B Streptococcus

Lee Arch Pediatr Adolesc Med 1998;152:624

Outcomes of Outpatients with Pneumococcal Bacteremia

548 episodes in an ER population Treatment strategies varied:

No antibiotics (N = 73) Oral antibiotics (N = 239) Parenteral antibiotics (N = 236)

Bachur Pediatrics 2000;105:502

Reevaluation of Outpatients with Pneumococcal Bacteremia

PersistentFever

PersistentBacteremia

FocalInfections

NoAntibiotics 68% 15% 13%

OralAntibiotics 24% 2% 3%ParenteralAntibiotics 21% 0% 5%

Bachur Pediatrics 2000;105:502

Conclusions

Data favor treatment Declining prevalence of

bacteremia demands a change in practice

How Do Clinicians Evaluate Febrile Infants?

Evaluation of the Febrile Infant

Careful history Physical examination Selected laboratory tests


Age Toxicity Decisions to test, to treat, to admit


Evaluate:Vital signsSkin colorBehaviorState of hydration

Document carefully and convey a clear picture of the overall clinical appearance of the patient.


Perform a complete physical exam with particular attention to:Skin: for petechiae / purpura, rashesOropharynx: for signs of gingivostomatitis/herpanginaPulmonary examination: for occult pneumoniaBones, joints and soft tissues: for infection

Consider the history of fever as correct in all reported measured temperatures

What is “Toxic”?

It is a very difficult task to define “toxic”; the closest I can come to a definition is to say that if to an experienced physician he looks and acts damned sick, he’s toxic.

Sidney Gellis

Pediatric Notes, 1979

Definition: “Toxic” Infant

Lethargy poor or absent eye contact failure to recognize parents poor interaction with persons / environment

Signs of poor perfusion Marked hypoventilation / apnea Hyperventilation Cyanosis

1993 Clinical Practice Guideline

Review of literature Evidence based Outcomes driven Consensus opinion


Clinical Practice Guideline

Th e g u id e lin e is s tra tified b y ag e g rou p s :

0 - 2 8 d ays 2 9 - 9 0 d ays 3 - 3 6 m on th s

F ever w ith ou t sou rce

Clinical Practice Guideline

. . .an d b y c lin ica l ap p earan ce :

Toxic in fan t N on -toxic in fan t


Important Clinical Questions

Which young infants are at low risk for serious bacterial infection?

Which older infants deserve empiric antibiotic therapy?

Clinical Practice GuidelineLow Risk Criteria: Clinical Appearance

Nontoxic appearance Previously healthy No focal bacterial infection on exam

Otitis media is not considered a focal infection

Clinical Practice GuidelineLow Risk Criteria: Laboratory Tests

WBC: 5,000-15,000 / mm3

< 1500 bands Normal urinalysis or Gram stained smear If diarrhea is present:

< 5 WBCs per hpf on stool examination

Guideline: 0 - 28 days

S ep s is w ork -u pA n tib io tic s

S ep s is w ork -u pO b serva tion

A d m it


Guideline: 0 - 28 days Sepsis Evaluation including:

CBC, Blood Culture Urinalysis, Urine Culture CSF Exam and Culture

Hospitalization Options:

#1 Parenteral antibiotics #2 Observation

Guideline: 29 - 90 days

A d m itS e p s is w o rk -up

A n tib io tics

T o x ic in fa n t


A n tib io tics

N o t lo w ris k(L a b c rite ria )

O u tp t M g m t #1B lo od ,u rin e ,

C S F cu ltu resA n tib io tics

O u tp t M g m t #2B lo od cu ltu reU rin e C u ltu reO b se rva tion

L o w ris k(L a b c rite ria )

N o n -to x ic in fa n t

F e ver w itho u t so u rce

Guideline: 29 - 90 daysFollow-up

Blood culture is positive: Admit Sepsis work-up Antibiotics

Urine culture is positive: Febrile: admit for sepsis work-up, treat Afebrile: outpatient antibiotics

Modified Guideline: 3 - 36 months


A n tib io tics

T o x ic in fa n t

O b se rve

T e m p < 39 .5 C

O p tio ns

T e m p > 39 .4 C

N o n -to x ic in fa n t

F e ver w itho u t so u rce

Modifications to the Guideline

Higher temperature threshold in view of Pneumococcal bacteremia prevalance T > 39.50 C + WBC > 15,000: 10% T > 39.50 C + WBC < 15,000: 1%

Guideline applies to those 3-36 month olds who have not yet received 3 doses of PCV7

Baraff LJ Annals of Emerg Med 2000;36(6):602

Fleischer GR J Pediatrics 1994;124:504

Bass JW PIDJ 1993;12:466

Modified Guideline: 3 - 36 monthsOptions

Urinalysis or Urine leukocyte esterase + nitrite Send urine culture:

All males <6 months + uncircumcised males <1yr Females <1 yr

Send urine culture if positive urine screening Circumcised males 6-12 months Females 1-2 yrs



Infants and children who have not yet received 3 doses of PCV7 Vaccine

Temp > 39.50 C (103.10 F) WBC and hold Blood Culture

If WBC > 15,000 (ANC > 10,000) Send Blood Culture Give Ceftriaxone 50 mg / kg



CXR to rule out pneumonia if: SaO2 < 95%

Tachypnea, rales, respiratory distress T > 39.50 C and WBC > 20,000


Guideline: 3 - 36 monthsFollow-up

Blood culture is positive: S. pneumo: if febrile, admit for sepsis

work-up and antibiotics; if afebrile, treat as outpatient

All other pathogens: admit for sepsis work-up and antibiotics

Urine culture is positive: Febrile / ill: inpatient antibiotics Afebrile / well: outpatient antibiotics

Guidelines and Practice

Quotable Quote:

“I don’t consider these ‘rules.’ They are kind of…..like….‘guidelines’”

John Prober, speaking about tournament rules at the 50th Birthday Golf Tournament for brother

Charles. August 1999

Data Support Departures from the Guideline

Jaskiewicz Pediatrics 1994;94:390 437 low risk febrile infants < 60 days < 1% risk of bacteremia 1% risk of SBI

Chiu Pediatr Infect Dis J 1994;13:946 254 low risk febrile infants < 31 days 0.7% risk of bacteremia 5.3% had UTI, no other SBI

Adherence Rates with Guideline

194 Utah primary care pediatricians’ adherence with the practice guideline 0 - 28 days: 39% 29 - 90 days: 9.6% 3 - 36 months: 75% all three ages:0%

Young, Pediatrics 1995;95:623

Otitis Media Influences Management

194 Utah pediatricians surveyed in 1994 Scenario of a 2 month old with a temp of 38.70 C

and otitis media 82% would treat with oral antibiotics if

screening tests were negative

Young Pediatrics 1995;95:623

Data from Pediatric Practice:the PROS Fever Study

• White 73.7%• Hispanic 13.8%• African-Amer 7.2%• Asian/PacIsle 2.5%• Other 2.8%

Personal communication, Pantell, PROS Study

• Medicaid 37%• HMO 35%• Private 22%• Self Pay 3%• Other 3%

3093 infants, < 3 months of age

PROS Fever Study: Laboratory Tests

0.0%

10.0%

20.0%

30.0%

40.0%

50.0%

60.0%

70.0%

80.0%

90.0%

100.0%

No Labs WBC BldCult UA LP


PROS Fever Study: Management

0.0%10.0%20.0%30.0%40.0%50.0%60.0%70.0%80.0%90.0%

100.0%

0 to 2weeks

2 to 4weeks

4 to 8weeks

8 to 12weeks

AntibioticsHospitalization


Outcomes in PROS Fever Study

Observed rates of:

Bacteremia 1.5 %

Bacterial meningitis 0.3%

Of these:

Treated at initial contact 96%

Hospitalized at initial contact 84%

Preventable bad outcomes 0%Personal communication, Pantell, PROS Study

PROS Fever Study:Adherence Rates to Guideline

Age Rate

0-1 month 44%

1-3 months

– Appears sick 32%

– Appears well 44%


New Considerations

Automated Blood Culture Systems Band counts - out? Importance of UTI Fever with Source

Recognizable Viral Syndromes

Automated Blood Culture Systems

More rapid detection of bacterial pathogens Direct plating techniques: 36 hours Automated systems: < 24 hours

Facilitates outpatient management

McGowan KL Pediatrics 2000;106(2):251

Alpern ER Pediatrics 106(3):505

Band Count: Not Discriminatory

100 infants less than 2 years of age 31 with bacterial infections 69 with respiratory viral infections

No difference in: Absolute band count Percentage band count Band-to-neutrophil ratio

Kuppermann Arch Pediatr Adolesc Med 1999;153:261

Importance of UTI UTI is the most common SBI Prevalence varies by age and gender:

Females < 1: 6.5% 1-2: 8.1% Males < 1: 3.3% 1-2: 1.9%

Uncircumcised boys under 1 year have a rate of UTI 5-20 times greater than circumcised boys

Infants are at greater risk for renal injury: Reflux is more likely and more severe

AAP Committee on Quality Improvement Pediatrics 1999;103:843

Recognizable Viral Syndromes

21,216 patients, 3-36 months of age 6% had a recognizable viral syndrome (RVS)

RVS Bacteremia (%)

Croup 0%

Bronchiolitis 0.2%

Varicella 1.1%

Stomatitis 0%

Greenes Pediatr Infect Dis 1999;18:258

Why Do Clinicians not Adhere to the Clinical Practice Guideline?

Many clinicians disagree with: Definition of fever Age thresholds Applying study data to their practices in

which there is better compliance and follow-up

Why Do Clinicians not Adhere to the Clinical Practice Guideline?

Clinical decisions are driven by: Desire to detect serious bacterial infection

early rather than to treat “occult” bacteremia Low probability of bacteremia and SBI Preferences of parents Personal experience

Caveat

Experience is worth any amount of evidence... ...clinical experience….can be defined as “making the same mistakes with increasing confidence over an impressive number of years”

BMJ 1999;319:18

Management of Fever Without Source

Guideline is a place to start Need to know IZ status UTI: most frequent infection Recognize the “toxic” infant If you treat, obtain cultures Document carefully Arrange follow-up

Charles Prober’s Golden Rules The younger the infant, the greater

the uncertainty A toxic appearance demands

immediate action A non-toxic appearance fuels

controversy Careful follow-up must be assured Recommendations continue to

evolve No rules are golden

Keep up with the literature..

..managing febrile infants is an ever changing topic

management of the febrile infant

Health & Medicine

pediatric practice

low risk febrile infants

antibiotics urine culture

outpatient antibiotics

outcomes of fever evaluation

months followup blood

s outpatient management

months uri