Fever in children is the most common presenting feature to the pediatrics emergency department. If the infant with fever appears well, a careful systematic approach is advised in order for us to not miss any serious bacterial etiology. Neonates with fever might have a serious bacterial infection such as urinary tract infections or bacterial meningitis despite appearing well, therefore full diagnostic workup including a lumbar puncture is indicated. Older infants who present with a fever should be examined by an experienced emergency pediatrician and they usually do not need to undergo a lumbar puncture routinely.
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child temperature fever

Image: “A young Iraqi girl waits patiently for her temperature to be taken by one of the physicians working at a medical clinic held for the people of Khandari, Iraq. Marines from 1st Battalion, 1st Marine Regiment worked with the Iraqi Army and Iraqi Police to organize the clinic.” by Cpl. William Skelton. License: Public Domain


Definition of Fever in a Well-Appearing Infant

Fever is a common presenting feature that can be seen in young infants who appear well or ill. The distinction between ill and well-appearing is usually based on the clinical evaluation of the infant to exclude severe bacterial infections like meningitis, bacteremia and urinary tract infection.

Fever is defined as a documented rectal temperature of 38° C (100.4 ° F) or more. In this discussion, we also define well-appearing infants as those presenting with fever that do not have a previous medical condition, were not recently admitted to the hospital or have taken antibiotics for any other cause.

Epidemiology of Serious Bacterial Infections and Fever in Infants

Up to 70 % of children’s presentation to the clinic or emergency department are due to fever, hence fever can be considered as perhaps the most common presentation in children who seek medical care.

A very important decision in the evaluation of the well-appearing infant with fever is to exclude the possibility of a serious bacterial infection. Approximately, 7 to 15 % of well-appearing infants who have a fever are eventually diagnosed with a serious bacterial infection.

The most important factor in predicting whether the child has a serious bacterial infection or not, are the child’s age and toxic appearance of the child. Any infant who appears ill should be considered as having a serious condition behind their fever and should not be managed in an outpatient setting.

In a recent study, neonates with fever were far more likely to have a serious bacterial infectious etiology, therefore the authors recommended that all neonates with fever even if appearing well should be considered as sick and should be admitted to the hospital. For instance, the rate of serious bacterial infections in neonates was estimated to be around 20 % in contrast to 12.6 % in infants older than 28 days.

Organisms causing UTI, bacteremia, or meningitis

  • E. coli (vast majority)
  • Group B strep (in GBS positive undertreated mothers)
  • Strep. pneumoniae
  • Neisseria meningitidis
  • Enterococcus
  • Klebsiella
  • Staph. aureus (osteomyelitis of the newborn)

Most Common Diagnoses of Fever in a Well-Appearing Infant

In the majority of the cases, no serious bacterial infection could be identified as the etiology of fever in a well-appearing infant. Approximately, 72 % of infants presenting with fever who appear well are expected to not have a serious bacterial infection.

Klebsiella pneumoniae bacterium

Image: “Colorized scanning electron micrograph showing carbapenem-resistnt Klebsiella pneumoniae interacting with a human neutrophil.” by NIAID. License: CC BY 2.0

Urinary tract infections can present with fever in an otherwise well-appearing infant as they were the final diagnosis in up to 16 % of the cases in one series. On the other hand, meningitis was the final diagnosis in approximately 11.7 % of infants who appear well despite having a fever.

It is important to note that bacterial meningitis was found to be the cause of fever in well-appearing neonates younger than 15 days. Infants of other ages who appear well were unlikely to have bacterial meningitis as the etiology of their fever.

Another possible diagnosis of fever in this group of infants was pneumonia, which was also noticed in neonates but never in older infants. Therefore, it becomes clear that most infants who are older than 28 days and have a fever but appear well are very unlikely to have any serious bacterial infection.

Diagnostic Tests for Fever in a Well-Appearing Infant

It is a challenge to determine which laboratory or invasive tests to perform in a case of fever in a well-appearing infant. Invasive examinations such as lumbar puncture can produce significant discomfort to the infant and carry a risk of localized skin infection.

On the other hand, withholding such investigations might put the infant at risk of suffering from significant sequelae. Because of these hazards and benefits, one should follow a systematic approach in determining which investigations should be performed in a given patient.

As we have noted before, bacterial meningitis is very unlikely to present with fever alone in an otherwise well-appearing infant who is older than 28 days. Additionally, while lumbar puncture was performed in up to 20 % of infants older than 28 days, the diagnosis of bacterial meningitis in well-appearing infants was not made.

On the other hand, the diagnosis of bacterial meningitis was made in 2 out of 81 cerebrospinal fluid examinations in neonates with fever who appeared well. Therefore, despite the low risk, this condition is very significant and a lumbar puncture should be performed in neonates who present with fever even if they appear well.

While a complete blood count can show leukocytosis or leukopenia, they rarely point towards a single etiology in infants presenting with fever despite appearing well. Regardless, a complete blood count with differentials should be performed in all infants presenting with fever because it can reliably differentiate between infants who are likely to have a serious bacterial infection and those who are not. A white blood cell count above 15,000 cells/mL or less than 5,000 cell/mL is highly suggestive of a severe bacterial infection even if the infant looks well.

Urinalysis

Perhaps, the most important investigation in a well-appearing infant with fever is a urinalysis. Up to 15 % of infants who appear well despite having a fever were eventually diagnosed with a urinary tract infection.

Interpreting the UA

Result on UA Sensitivity Specificity
WBC count 0.74 0.86
Bacteria present 0.88 0.92
Leuko esterase 0.79 0.87
Nitrite 0.46 0.98
Entire UA 0.97 0.70

If the urinalysis is inconclusive, a urine culture might be a reasonable diagnostic test to reliably exclude the diagnosis of urinary tract infections. Again, the decision to go for a urine culture might be skewed towards neonates who are more likely to have atypical presentations of febrile illnesses.

Special imaging studies such as chest x-rays are most likely not indicated in well-appearing infants with fever, unless they are younger than 28 days. Even though only 1 % of well-appearing neonates with fever might have a pneumonia, the condition can still be considered as severe enough to warrant the performance of a chest x-ray in this group. A chest x-ray should be reserved to infants who present with fever associated with cough or tachypnea but appear well otherwise.

Finally, the most important diagnostic method to determine whether invasive investigations such as lumbar puncture are needed or not in a febrile infant is perhaps the consultation of an emergency pediatrician. If an experienced emergency pediatrician is not available and the patient is less than one month of age, a complete blood count, urinalysis and a lumbar puncture should be routinely included in your evaluation of the feverish child even if appearing relatively well.

HSV Disease in the Neonate

What tests to get (in addition to febrile infant testing):

  • HSV PCR of blood (best test)
  • HSV culture: eyes, nose, mouth, rectum 
  • HSV PCR of CSF (only 90 % sensitive!)
  • LFTs
Critical: Don’t start acyclovir until AFTER you get the cultures!

When to worry about HSV in a newborn?

Management of Well-Appearing Infants With Fever

Younger than 28 days

Admitted infants should be watched 24-36 hours, discharge if cultures are negative.

  • Urinalysis
  • Urine culture
  • CBC/CRP/Procalc
  • Blood culture
  • Lumbar puncture (almost all)

Abnormal labs?

NO → Admit +/- antibiotics

YES → Admit Amp/Gent or Amp/Cefotax

29-60 days old

If only CBC is abnormal, consider d/c (on oral antibiotics?), watch closely at home. Admitted infants should be watched for 24-36 hours, discharge if cultures are negative.

  • Urinalysis
  • Urine culture
  • CBC/CRP/Procalc
  • Blood culture

Abnormal labs?

NO → Discharge, close follow-up

YES → LP, admit BUT: If only +UA, consider discharge on oral abx

61-90 days old

  • Urinalysis
  • Urine culture

Abnormal labs?

NO → Discharge, close follow-up

YES → Oral antibiotics, follow up closely

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