An Approach to Feverin Infants & Children

DR. Sreeram Reddy M Professor and HOD

Department of peadiatrics ,PIMS

Why Is The Topic Important?

• 20-35% of urban pediatric ED visits: – “Fever Phobia”

• 65% of children visit their pediatrician with complaint of

fever before their 2nd birthday.

• Diagnoses range from minor to life-threatening

• Multiple conflicting recommendations, guidelines, and

algorithms.

To Work Up or Not to Work Up?

• Do all febrile children with no obvious infection site need To be investigated??

Definition

• Fever: elevated body temperature due to change in hypothalamic set point

• Hyperthermia: elevated body temperature due to environmental heat, dehydration, overclothing, excessive internal heat production

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Significant Fever: Definition

Temperature of 38.0 , rectally at rest:– 0-2 months risks increase at 38.0 ,(the occurrence of Serious Bacterial Infection(SBI) increases from < 1% to 5% at 38.0° C)– 3-36 months risks increase at 39.0 ,Fever Without Source: FWS “Fever without source is an acute febrile illness in which the etiology of the fever is not apparent after a careful history and physical exam.”

• In children, fever is generally a sign of infection.

• Fever due to other causes including malignancy is rare. 

• The prognosis for the most common forms of paediatric infections is usually excellent; these infections are much more likely to be viral (rhinitis, pharyngitis, laryngitis, bronchitis, bronchiolitis, gastroenteritis, exanthems) than bacterial (pneumonia, urinary tract infections [UTIs], sinusitis, tonsillitis, otitis).

The medical history, physical examination

when necessary, a few additional complementary tests

 usually lead to a prompt diagnosis

Reassurance Treatment

Neither the medical history, the physical examination, nor complementary tests indicate a bacterial infection that can potentially lead to serious complications.

How can a fever of viral origin be differentiated from one of bacterial origin? Do all febrile children with no obvious infection site need a blood culture? Should antibiotics be administered before the results of the blood culture have been received?

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Reliable Temperature Measurement

• All measurements are estimates of the body’s true core temp—central circulation=aorta and pulmonary artery.

• RECTAL—gold standard• Esophageal—accurate but impractical• Tactile and axillary—inaccurate, varies

considerably with environmental temperature• Tympanic—inaccurate in age <3 years

Benefits of fever

• The hypothalamus will not allow the temp to rise above 41.5ºC(107ºF).

• WBCs work best and kill the most bacteria at 38-40ºC(100.4-104ºF).

• Neutrophils make more superoxide anion, and there is more and increased activity of interferon.

• Coxsackie and polio virus replication is directly inhibited.

Fever Pitfalls

• Bundling:• – Bundling can lead to a rise in skin temperature and eventually rectal

temperature.(Study 1: Cheng, 1993, Study 2: Grover, 1994)

• Route of Measurement: – Tympanic/axillary don’t correlate well with rectal temps (Craig, 2000; Craig, 2002; Jean-Mary, 2002)

• Antipyretics: – No correlation between disease etiology/severity and response to antipyretics (Baker, 1987; numerous others)

• Tactile temperatures: – Sensitivity 83% – Specificity 76% (Hooker, 1996; Graneto, 1996)

• Afebrile on presentation: – 6 of 63 infants 0-3 months with bacteremia/meningitis afebrile in clinic after being febrile at home (pantell, 2004) ( * No comment on whether or not antipyretics were given)

Relevant Age Groupsand development

• 0………4w NEONATES• 0………………..8w• 4w……….……………….12w• 12w………..3y • > 3 years old

• Age stratification of risk for• serious bacterial infections [SBI]

Neonates

• The majority of febrile neonates presenting to the ED have a nonspecific viral illness

• 12% have serious bacterial infections (SBI)• Infected by more virulent bacteria• More likely to develop serious sequelae from viral

infections• GBBS is associated with high rates of

meningitis(39%), non-meningeal foci(10%), and sepsis(7%)

• The most common bacterial infections are UTI and occult bacteremia

Neonatal• Physical examination is felt to be unreliable in detecting

many serious bacterial infections. Meningitis should always be considered—up to 10% appear well, only 15% have a bulging fontanelle, and 10-15% have nuchal rigidity. So, a high index of suspicion is important!!! ~20% will not have fever initially.– Hyperthermia or hypothermia– Lethargy or irritability– Poor feeding or vomiting– Apnea– Dyspnea– Jaundice– Hypotension– Diarrhea or abdominal distension– Bulging fontanelle– seizures

Neonatal

Early Onset<7 DaysGroup B StrepE. ColiListeria MonocytogenesEnterobacteriaceaeEnterococcusStrep viridansStrep PneumoniaeHemophilus influenza ntHerpes simplex

Later Onset>7 DaysGroup B Strep

Listeria MonocytogenesEnterobacteriaceae

Strep PneumoniaeNeisseria meningitidis

Herpes simplex

Neonatal

• Risk Factors– Preterm– Membrane rupture: before labor onset or

prolonged>12 hours– Chorioamnionitis or maternal peripartum fever– UTI– Multiple pregnancy– Hypoxia or Apgar score <6– Poverty or age <20

• 1/3-1/2 neonatal sepsis will have no risk factors!

Neonatal

• Screening tests: WBC<5000 or >20,000, PMN <4000, I:T>.2, Plt<100,000, CRP>1, LFTs elevated(suggest HSV)

• So, if <28 days of age and rectal temp> 38ºC– Admit– Blood Culture– Urine Culture—cath specimen– Lumbar Puncture

• Cell count, protein, glucose, culture, PCR– Parenteral Antibiotics

• Ampicillin + Gentamicin(Cefotaxime), consider Acyclovir(primary maternal infxn, esp if delivered vaginally, PROM, fetal scalp electrodes, skin eye or mouth lesions, seizures, CSF pleocytosis)

Infants 1 to 3 months• Causes

– HSV(17% are 15 days to 6 weeks of age)– Bacterial sepsis/meningitis

• Group B Strep, S. Pneumoniae, H. influenza, N. meningitidis, Enterobacteriaceae

– Bone and joint infections– UTI– Bacterial enteritis(esp Salmonella)– Pneumonia– Enterovirus sepsis/meningitis(July-October)

• The risk of bacteremia/meningitis is 3.3%, pneumonia, bone/joint infections and bacterial enteritis is 13.7%– 30-50% of those who are ultimately diagnosed with bacterial

meningitis have been seen by a physician within the prior week(usually 1-2 days before) and were diagnosed as having a trivial illness and discharged on oral antibiotics.

Pediatric Fever Algorithm

Non toxic appearing, 28 – 90 days and “Low Risk”

No

Blood Culture, Urine Culture, CSF Cx, antibx +/-CXR

Yes

ADMITOutpatient Management

Option 1Blood Cx, Urine Cx, CSF Cx, ceftriaxone 50 mg/kg IV/IM, re-eval in 24 hours

Option 2Blood Cx, Urine Cx, Re-eval in 24 hours

Fever 38°C

BY DR M OSAMA HUSSEIN MD

Rochester Criterias for infants under 3 months

• Term• Previously

healthy• Non-toxic• No focus• No previous ATB

• 15 000 WBC• 1500 bands• 5 WBC/hpf in

stool• 10 WBC/hps in

spun urine

Ron Dagan, Identification of infants unlikely to have serious bacterial infection although hospitalized for suspected sepsis, J Pediatr 1985;107;855-860

Rochester Criterias for infants under 3 months

• Risk of 0.5-1.1% for SBI including meningitis

• NPV 98,5%

Jaskiewicz JA, McCarthy CA, Richardson AC, et al: Febrile infants at low risk for serious bacterial infection-an appraisal of the Rochester criteria and implications for management. Pediatrics

1994;94:390-396

Infants 1 to 3 months

Infants who are toxic and febrile have a much higher risk of serious bacterial infection. They should be admitted, have a full sepsis workup, and given antibiotics/antiviralsAmpicillin and Cefotaxime.

Infants who are nontoxic and febrile who meet all Rochester criteria can ‘safely’ be treated as an outpatient. Generally, 1-2.9% of children meeting these criteria will develop a serious bacterial infection, 0.7% bacteremia, 0.14% meningitis.

Infants 1 to 3 months

• If all of the criteria are met, then there are 2 options for outpatient management:– 1) Blood, Urine Cultures, LP, Ceftriaxone 50mg/kg IM

(to 1g), and return for reevaluation within 24 hours.– 2) Blood, Urine Cultures and careful observation.

• Parents should have mature judgement, can return within 30 minutes and have a thermometer and a phone.

• IF NO LP IS DONE, DO NOT GIVE CEFTRIAXONE AS IT WILL COMPROMISE F/U IF THE PATIENT IS STILL FEBRILE

Management of children under 3 months by a paediatric specialist

· Assess: look for life-threatening, traffic light and specific diseases symptoms and signs

· Observe and monitor:· temperature· heart rate· respiratory rate.

· Perform:· full blood count· C-reactive protein· blood culture· urine test for urinary tract infection· chest X-ray if respiratory signs are present· stool culture if diarrhoea is present.

· Admit, perform lumbar puncture and start parenteral antibiotics if the child is:· younger than 1-month old· 1–3 months old appearing unwell · 1–3 months old and with a white blood cell count of less than 5 or greater than 15 x 109/litre

· Whenever possible, perform lumbar puncture before the administration of antibiotics

Infants 1 to 3 months

• Follow-up of low risk infants– If all cultures negative: afebrile, well

appearingCareful observation– Blood cultures negative: well appearing,

febrileCareful observation, may consider second dose of Ceftriaxone

– Blood culture positiveadmit for sepsis workup and parenteral antibiotics pending results

– Urine culture positive: if persistent feveradmit for sepsis workup, parenteral antibiotics pending results. If afebrile and welloutpatient antibiotics

Occult Bacteremia

5% of children with FWS have OCCULT BACTEREMIA– The presence of a positive blood culture in

kids who look well enough to be treated as outpatients and in whom the positive results are not anticipated.

Occult Bacteremia

• Streptococcus pneumonia is responsible for 2/3 to ¾ of all cases.– Peak prevalence between 6 and 24 months– Association with high fever(39.4ºC or 103ºF)– High WBC count(>15,000)– Absence of evident focal soft tissue infection.

• Neisseria meningitidis, Haemophilus influenzae type b, and salmonellae account for most of the remaining cases.

Risk of Occult Bacteremia

OB has a low prevalence, so even though WBC is a sensitive and specific screening test, it has a low PPV. So the test does not discriminate between children who have FWS who are bacteremic and those who are not.

Therefore, blood culture is the gold standardstill has a high number of false positives, take 24-48hrs, and most cases of occult pneumococcal bacteremia clear without treatment.

Low RiskAge >3yrTemp <39.4ºCWBC >5000 and

<15,000

High Risk<2yr>40ºC(104ºF)<5000 or >15,000

Hx of contact with H. Flu or N. meningitidis

Occult Bacteremia

• Empiric antibiotics should be targeted against S. pneumoniae, N. meningitidis, and H. influenza– Amoxicillin– Augmentin, Bactrim, 2nd or 3rd gen

Cephalosporins– Single dose Ceftriaxone 50-75mg/kg

• Followup is essential!

LOW AND HIGH-RISK CRITERIA COMMONLY USED IN STUDIES OF FEVER WITHOUT SOURCE

• Low-risk Criteria High-risk Criteria

• Term gestation (37 weeks) Recurrent febrile illnesses

• Uncomplicated prenatal course Prematurity

• No recent (7d) antibiotic Congenital immune disease

• No recent surgery Sickle cell disease

• No chronic illness Asplenia

• No perinatal ATB Malignancy/chemotherapyRecent steroid therapy

• Hospitalized = to mother HIV disease

Yale Observation Scale Score

• Quality of cry• Alertness• Color• Hydration• Response to parents• Response to others

• Score 6-10 well• Score 11-15 mod• Score > 15 toxic

McCarthy PL, Sharpe MR, Spiesel SZ, et al: Observation scales to identify serious illness in febrile children. Pediatrics 1982; 70:802

Yale Observation Scale Score

• 6-10 well• 11-15 mod• > 15 toxic

• OB• 2,5%• 4,7%• 5,7%

Management of children 3 months to 5 years by a paediatric specialist

· Perform test for urinary tract infection.

· Assess for pneumonia.

· Do not perform routine blood tests or chest X-ray.

Perform (unless deemed unnecessary)· urine test for urinary tract infection· full blood count· blood culture· C-reactive protein.

Perform chest x-ray if fever higher than 39°C and white blood cell count greater than 20 x 109/litre.

Consider lumbar puncture if child is younger than 1-year old.

Perform:· blood culture· full blood count· urine test for urinary tract infection· C-reactive protein.

Consider the following, as guided by clinical assessment:· lumbar puncture in children

of all ages· chest X-ray· serum electrolytes· blood gas.

Consider admission. If admission is not necessary but no diagnosis has been reached, provide a safety net for the

parents/carers.

· If no diagnosis is reached, manage the

child at home with appropriate care advice.

Assess: look for life-threatening, traffic light and specific diseases symptoms and signs

Bacteremia

Prevalence of Serious Bacterial Infection (SBI) Infants 0-2 Months Old• Febrile neonates: SBI = 13%• Febrile infants 1 to 2 months of age: SBI = 10%

• Febrile infants younger than 3 months of age Urinary Tract Infections account for 1/3 all bacterial diseases

Management of Fever In Infants and Children

Jeffrey R. Avner MD, M. Douglas Baker MD

Emergency Medicine Clinics of North America

Volume 20 • Number 1 • February 20

Predictors of bacteremia

• History• Physical exam• Gender• Height of fever

• WBC• ANC• Bands• Band/Neutrophils

ratio• PMN% • ESR-CRP-cytokines

Daniel Isaacman, Predictors of bacteremia in febrile children 3-36 Mo of age, Pediatrics;106;5;Nov 2000

Nathan Kupperman, Predictors of occult bacteremia in young febrile children, Ann Emerg Med June 98;31;679-687

Bacteremia

• In a study performed in children between three and 36 months with a rectal or tympanic temperature of 39°C or higher, the incidence of various types of bacteremia was 1.6% . 

• H influenzae was not among the isolated germs.

• Over 90% of all bacteremias are caused by pneumococcus .

• The remaining 10% are caused by various bacterial germs, such as Neisseria meningitidis, nontyphoidal salmonella, group A streptococcus, group B streptococcus, Escherichia coli, Staphylococcus aureus and other more unusual germs . Meningococcus is the most dangerous of them. 

Bacteremia

• In the absence of treatment, bacteremias either resolve spontaneously, persist or are complicated by other symptoms.

• The most serious complications arising from occult bacteremia include septicemia, meningitis, pneumonia, arthritis, osteomyelitis and cellulitis.

• The usual prognosis for pneumococcus bacteremia is excellent. Most cases (90.3%) resolve completely without treatment.#

• Meningococcus bacteremia is rare but high risk. In the absence of prompt treatment, the speed at which it develops can be rapid. Any delay in treatment can be catastrophic for the child and have serious legal repercussions for the physician . The immediate danger arising from meningococcus bacteremia is that it may lead to purpura fulminans, with irreversible septic shock and death. 

AGE

• Bacteremia appears at all ages; however, it is more frequent in infants between the ages of three and 36 months.

• • Before the age of three months, the incidence of bacterial disease in

febrile infants is about 10% and that of bacteremia is between 2% and 3%.

• As a rule, bacterial infections are more serious and insidious in infants less than three months.

• This group, particularly the neonates, is more vulnerable and is exposed to a greater variety of causal agents; group B streptococcus and E coli being the two main ones.

• The main danger during the neonatal period is for UTI or meningitis 

Temperature

•  the physician’s clinical judgement is usually based on the temperature and the general appearance at the time of the examination, not the temperature taken at home. This applies to all children except those younger than three months. In the case of normal temperature at the time of the examination but a history of fever, a sepsis examination is indicated for neonates and possibly some infants between the ages of one and three months or if there is the slightest appearance of toxicity

• The degree of temperature is an important but misleading indicator.

• Bacteremia is more frequent in children with a temperature of 39°C or high .

• The absence of fever or the presence of a low grade fever does not preclude the possibility of a serious infection .

Leucocytosis

• Bacterial infections are more likely than viral infections to have a leukocytosis count of 15,000/mm3 or more, but because viral infections are much more frequent than bacterial infections, the majority of febrile children with a high leukocytosis count have a viral infection.

• In healthy children from one to three years of age, the normal white cell count varies between 6000 and 17,500/mm3;

• in children one month of age it varies between 5000 and 19,500/mm3 (36).

• It is rightly possible to wonder why the risk level for bacteremia has been set at 15,000/mm3 

leucocytosis

• The percentage and absolute number of total neutrophils are more precise and useful than those of unsegmented neutrophils (bands) ------- why ?

• Children between three and 36 months of age with an absolute neutrophil count greater than 10,000 cells/m3 are at higher risk of occult pneumococcal bacteremia: 8% compared with 0.8% for those with an absolute neutrophil count less than 10,000 cells/m3.

• Conclusion : White blood cell count results can be confusing for physicians when there is an obvious discrepancy between the number of leukocytes and the child’s general condition. 

OTHER MARKERS OF INFECTION

ESRCRPIL8PROCALCITONIN CRP AND ESR NON SPECIFIC  PCT has the greatest sensitivity (85%) and specificity (91%) for differentiating patients with systemic inflammatory response syndrome (SIRS) from those with sepsis, when compared with IL-2, IL-6, IL-8, CRP and TNF-alpha.[3] Evidence is emerging that procalcitonin levels can reduce unnecessary antibiotic prescribing to people withlower respiratory tract infections

Conclusion: It is likely to make the decision more confusing when there is a discrepancy between the general appearance of the child and the C-reactive protein result and/or white blood cell count.

CHEST X-RAYS

• An unexplained and persistent fever can be the only manifestation of pneumonia.

• When faced with high fever and leukocytosis greater than 20,000/mm3, the physician should suspect pneumonia .

• Up to 26% of children younger than five years old with an unexplained fever of 39°C or higher and leukocytosis 20,000/mm3 or higher, who have no respiratory symptoms, may have a pneumonia that can only be detected by a chest x-ray.

•  In the absence of respiratory symptoms, chest x-rays are usually normal. 

UTIs

• Repeated spells of fever or normal tympanic membranes following several alleged bouts of otitis media should lead the physician to suspect UTI .

• The diagnosis of a UTI must be confirmed by a culture;• Thus, febrile infants less than three months of age should either be

catheterized or have a bladder tap.

• Older febrile children who are not toilet-trained and who have a risk factor for a UTI, such as UTI symptoms, UTI past history, known renal anomalies, toxic appearance or who have positive urine analysis by bag specimen should be catheterized .

•  Febrile infants older than three months of age who are not toilet-trained and are at low risk of UTI should have a bag specimen taken initially

Antipyretics• Antipyretics do not prevent febrile

convulsions and should not be used specifically for this purpose.

• Do not routinely give antipyretic drugs to a child with fever with the sole aim of reducing body temperature

• Do not administer paracetamol and ibuprofen at the same time but consider using the alternative agent if the child does not respond to the first drug.

EMPIRICAL ANTIBIOTIC THERAPY

• may reduce the number of serious bacterial complications • it does not prevent meningitis•  It has not been formally proven that the absence of treatment

has ever been the direct cause of a serious accident• The scientific data are contradictory and unclear.• The choice of antibiotics can also be debated.• Oral antibiotic therapy cannot prevent the risk of meningitis, but

it can delay its diagnosis • Too liberal a use of ceftriaxone will most likely lead to an

increase in the number of resistant strains of bacteria • Ceftriaxone is not a panacea, nor is it total risk insurance. It is

an expensive drug that is administered intravenously or intramuscularly in a painful way.

EMPIRICAL ANTIBIOTIC THERAPY

• The widespread use of pneumococcal immunization in the near future will likely reduce the morbidity and mortality associated with pneumococcal bacteremias . This will decrease the difference in outcome between the different approaches: observation in comparison to the approach of empirical treatment for all patients or based on an elevated white blood cell count 

• Efficacious and widespread use of pneumococcal immunization will likely favour the observational approach based on clinical judgement

Home care instructions

Educate parent about appropriate wt-based med dose with return demonstration

When discharged from ED follow up with primary care provider within 24 hrs

When discharged from inpatient follow up with primary care provider in 1-2 days

Reasons to call provider or return to ED

CONCLUSIONS

• There are no sufficiently reliable markers of bacterial infection.

• The physician must therefore practice medicine that is fraught with empiricism, but also based on sound scientific arguments and on his or her own personal experience.

• The child’s general appearance, temperature and leukocyte count are the best evaluation criteria.

• Practice guidelines never entirely compensate for a lack of clinical judgement.

Let us practise

• 1. In infants younger than 3 months of age, the most commonly occurring bacterial infection is:

• A. Group B Streptococcal infection• B. Meningitis• C. Neonatal sepsis• D. Urinary tract infection

Q2

• 2. Which statement about temperature measurement in infants less than 3 months of age is accurate?

• A. Bundling (swaddling) causes elevation in skin temperature, but not in rectal temperature

• B. Fever that lowers quickly after antipyretic medication indicates a less severe infection than a fever that is less responsive to medication

• C. Temperature of 38.0°C (100.4°F) is defined as fever

• D. Tympanic measurement is closely correlated with rectal measurement

Q3

• 3. The following asymptomatic infants come to the emergency department with fever of unknown source. Who will definitely have a lumbar puncture?

• A. 1 month old

• B. 5 month old

• C. 7 month old

• D. All of them

Q5

• A 3 week old infant presents with fever and cough. He has no signs of respiratory distress and has been healthy since birth. The nurse anticipates which of the following orders?

• A. Blood culture

• B. Chest x-ray

• C. Lumber puncture

• D. All of the above

Q6

• A fully immunized 6 month old uncircumcised male infant presents with cough, decreased feeding, temperature of 39.0°C (102.2°F) and a diagnosis of clinical bronchiolitis. , the nurse anticipates which of the following orders?

• A. Blood culture

• B. Cath UA and culture

• C. Lumbar puncture

• D. RSV viral study

Q7

• A 2 year old presents with a fever of 39.1°C, is difficult to arouse, and eating poorly. Based on the Pediatric Fever Clinical Practice, the nurse anticipates which of the following orders?

• A. Blood culture

• B. Cath UA and culture

• C. Lumbar puncture

• D. All of the above

Q8

• A 3 month old is discharged from the ED after work up for fever of unknown source. The nurse’s parent teaching should include the importance of a follow up appointment with the baby’s primary care provider at:

• A. 24 hours

• B. 2-3 days

• C. 1 week

• D. Next well baby check at 4

Q9

• Fever of unknown origin is most dangerous in the following age groups:

• A. 0-3 years

• B. 5-7 years

• C. 10-12 years

• D. 15-17 years

Finally

•Evaluation & management of fever of unknown source in infants andyoung children is challenging History & physical exam may provide few clues to guide

therapy Findings may be nonspecific Social interaction skill is limited Clinical scoring systems identifying those at low risk of SBI

have varying degrees of reliability in the very young. (Avner & Baker, 2002)

Thank you