Baby with fever

Fever or a temperature above 100.4 °F (38°C) (taken rectally) in infants and toddlers may indicate a serious infection. If your baby is under three months and has a fever above 100.4 °F (38°C), then you should bring your baby to see a doctor, even if your baby has no other symptoms. 100.4 °F (38°C) fever guideline is based on taking rectal temperature reading. Fever is not an illness in itself, but is the sign of an illness. While fevers can be concerning for parents, doctors will usually be more concerned about what is causing the fever, and not what the child’s temperature is. It is more important for you to monitor any symptoms of the underlying illness, rather than the fever itself.

Young febrile infants (ages 0– 3 months) often present with nonspecific symptoms and it is difficult to distinguish between infants with a viral syndrome and those with early serious bacterial illness (e.g., meningitis, bacteremia (presence of bacteria in the bloodstream), urinary tract infection (UTI), and pneumonia).

Fever is a normal response to many illnesses, the most common being an infection in the body. Fever itself is usually not harmful, in fact, fever is an important part of the body’s defense against infection and helps the body’s immune system fight off infection.

Most fevers are harmless and are caused by mild infections. Many older infants develop high fevers with even minor illnesses.

Overdressing a child may even cause a rise in temperature.

A febrile seizure is a convulsion in a child triggered by a fever. A temperature of 100.4°F (38°C) or above may cause febrile seizures in children. Febrile seizures occur in some children and can be scary to parents. However, most febrile seizures are over quickly and most of the time does not cause any harm. Febrile seizure do not mean your child has epilepsy, and do not cause any lasting harm. The child usually does not have a more serious long-term health problem.

How to take a child’s temperature

Always use a digital thermometer to check your child’s temperature. Mercury thermometers should not be used. The American Academy of Pediatrics encourages parents to remove mercury thermometers from their homes to prevent accidental exposure and poisoning.

There are a number of ways you can take a child’s temperature. Each method measures your child’s temperature in a different way, and the results can vary depending on the type of thermometer you use. Different methods include:

• Digital multiuse thermometer: Reads body temperature when the sensor located on the tip of the thermometer touches that part of the body. Can be used rectally, orally, or axillary.
  • Where to take the temperature:
    • Rectal (in the bottom): Birth to 3 years
    • Oral (in the mouth): 4 to 5 years and older
    • Axillary (under the arm): Least reliable, technique, but useful for screening at any age. Taking an axillary temperature is less reliable. However, this methoid may be used in schools and child care centers to check (screen) a child’s temperature when a child has other signs of illness. the temperature is used as a general guide.
  • Note: Label thermometer “oral” or “rectal”. Don’t use the same thermometer in both places.
• Infrared forehead thermometer: Reads the infared heat waves released by the temporal artery, which runs across the forehead just below the skin.
  • Where to take the temperature: On the side of the forehead over the temporal artery.
  • Age group: 3 months and older. Before 3 months, better as a screening device than armpit temperatures. May be reliable in newborns and infants younger than 3 months according to new research.
• Ear (tympanic) thermometer: Reads the infrared heat waves released by the eardrum.
  • Where to take the temperature: In the ear. When used in older children it needs to be placed correctly in your child’s ear canal to be accurate.
  • Age group: 6 months and older. Not reliable for babies younger than 6 months.
  • Note: Too much earwax can cause the reading to be incorrect.
• Plastic tape thermometers used on the forehead (these are not recommended as they are not reliable).

Some thermometers are more suitable for particular age groups so you should always read and follow the manufacturer’s directions to get an accurate reading.

Figure 1. Digital multi-use thermometer

Figure 2. Infrared forehead thermometer

Figure 3. Ear thermometer

How to use a digital multiuse thermometer

Rectal temperature

If your child is younger than 3 years, taking a rectal temperature gives the best reading. The following is how to take a rectal temperature:

1. Clean the end of the thermometer with rubbing alcohol or soap and water. Rinse it with cool water. Do not rinse it with hot water.
2. Put a small amount of lubricant, such as petroleum jelly, on the end.
3. Place your child belly down across your lap or on a firm surface. Hold him by placing your palm against his lower back, just above his bottom. Or place your child face up and bend his legs to his chest. Rest your free hand against the back of the thighs.
4. With the other hand, turn the thermometer on and insert it 1/2 inch to 1 inch into the anal opening. Do not insert it too far. Hold the thermometer in place loosely with 2 fingers, keeping your hand cupped around your child’s bottom. Keep it there for about 1 minute, until you hear the “beep.” Then remove and check the digital reading.
5. Be sure to label the rectal thermometer so it’s not accidentally used in the mouth.

Oral temperature

Once your child is 4 or 5 years of age, you can take his temperature by mouth. The following is how to take an oral temperature:

1. Clean the thermometer with lukewarm soapy water or rubbing alcohol. Rinse with cool water.
2. Turn the thermometer on and place the tip under your child’s tongue toward the back of his mouth. Hold in place for about 1 minute, until you hear the “beep.” Check the digital reading.
3. For a correct reading, wait at least 15 minutes after your child has had a hot or cold drink before putting the thermometer in his mouth.

Normal temperature for babies

Ordinarily, the following are considered normal, while higher readings indicate fever.

• Rectal reading of 100.4 degrees Fahrenheit (38 degrees Celsius) or less
• Oral reading of 99 degrees Fahrenheit (37.2 degrees Celsius) or less

A normal temperature range for children is 97.7 to 100.4 °F (36.5°C to 38°C). A fever is when your child’s rectal thermometer temperature is higher than 100.4 °F (38°C).

Baby with fever causes

Fever in newborns may be due to one of the following:

• Infection: Fevers are normal responses to infection in adults, but only about half of newborns with an infection have fevers. Some, especially premature babies, may have a lowered body temperature with infection or other signs such as a change in behavior, feeding or color.
• Overheating: While it is important to keep a baby from becoming chilled, a baby can also become overheated with many layers of clothing and blankets.
  • This can occur at home, near heaters or near heat vents. It can also occur when a baby is over bundled in a heated car.
  • Avoid placing a baby in direct sunlight, even through a window.
  • Never leave a baby in a hot car even for a minute, since her temperature can rise quickly and cause heat stroke and death.
  • An overheated baby may have a hot, red or flushed face, and may be restless.
  • To prevent overheating, keep rooms at a normal temperature, about 72 to 75 °F, and dress your baby just like you and others in the room.
• Low fluid intake or dehydration: Some babies may not take in enough fluids which causes a rise in body temperature. This may happen around the second or third day after birth. If fluids are not replaced with increased feedings, dehydration (excessive loss of body water) can develop and cause serious complications. Intravenous (IV) fluids may be needed to treat your baby’s dehydration.

The World Health Organization (WHO) categorizes neonatal sepsis into early and late based on the age of onset. Early neonatal sepsis affects infants less than 72 hours of age; whereas, late-onset infections in infants older than 72 hours to 28 days of age.

The cause of early onset neonatal sepsis is predominantly group Beta Streptococcal infection followed by Escherichia coli ¹⁾. Risk factors are maternal group B streptococcal colonization, chorioamnionitis, premature or prolonged (greater than 18 hours) rupture of membranes, preterm birth (less than 37 weeks) and multiple gestations.

The cause of late-onset neonatal sepsis includes pathogens such as group B strep, Escherichia coli (E. coli), Coagulase-negative Staphylococci, Staphylococcus aureus, Klebsiella pneumonia, Enterococci (more common in preterm infants), Pseudomonas, and Candida albicans. Risk factors for late-onset neonatal sepsis are prematurity, low birth weight, prolonged indwelling catheter use, invasive procedures, ventilator-associated pneumonia, and prolonged antibiotic usage ²⁾.

The World Health Organization (WHO) statistics cite over one million neonatal deaths around the world each year result from the neonatal sepsis/pneumonia making it the leading cause of infant mortality, whereas preterm infants are more at risk for neonatal sepsis in the United States. According to the Centers for Disease Control and Prevention (CDC), the estimated incidence of early onset neonatal sepsis in the United States is 0.77 to 1 per 1000 live births. With the establishment of guidelines for universal screening and treatment of maternal group B Streptococcal colonization, the incidence of early onset sepsis in full-term infants has decreased to 0.3 to 0.4/1000 live births ³⁾.

Fever in a newborn

Newborns (≤28 days) with fever may have few clues on history and physical examination to guide therapy; however, 3% have a serious bacterial infection ⁴⁾. Obtaining the pertinent medical history from the mother regarding the pregnancy, delivery, and early neonatal life of the febrile neonate is essential. Typically, infections that occur in the first 7 days of life are secondary to vertical transmission from mother to baby, and those infections occurring after the first 7 days are usually community acquired or hospital acquired.

The definitions of serious bacterial infection (serious bacterial illness) vary across published literature. Serious bacterial infection typically includes the diagnoses of meningitis, bacteremia, and urinary tract infection (UTI). Some studies have also included pneumonia, bone and joint infections, skin and soft tissue infections, and bacterial enteritis in the definition. Invasive herpes simplex virus (HSV) infections are grouped into meningoencephalitis; disseminated; or skin, eyes, and mouth. There is some overlap in these presentations.

The most common bacterial pathogen for serious bacterial illness in the young infant is Escherichia coli, with group B Streptococcus, Staphylococcus aureus, Listeria monocytogenes, and other gram-negative enteric bacteria being the other likely pathogens in this age group. Although uncommon, herpes simplex virus (HSV) infections are a major cause of morbidity and mortality among neonates (ages 0–28 days) with a case fatality rate of 15.5 percent ⁵⁾. The prevalence of neonatal HSV infection has been reported to be between 25 and 50 per 100,000 live births in the United States ⁶⁾. The prevalence of HSV infection in a febrile neonate is 0.3 percent which is similar
to the prevalence of bacterial meningitis in this age group ⁷⁾.

Definitive identification of a serious bacterial infection requires laboratory investigation; a full sepsis evaluation; and a positive result in blood culture, cerebrospinal fluid (CSF), and/or urine. Bacterial meningitis is more common in the first month of life than at any other time. An estimated 5-10% of neonates with early onset group B streptococcal sepsis have concurrent meningitis ⁸⁾.

Young infants

The general approach to fever in a febrile infant aged 28-60 days includes maintaining a high index of suspicion, because these patients often lack clues on physical examination. The prevalence of a serious bacterial infection in an infant younger than 3 months is approximately 6-10%, most often urinary tract infections (UTIs). Interestingly, infants aged 3 months or younger with a confirmed viral infection are at lower risk for a serious bacterial infection when compared with those in whom a viral infection is not identified ⁹⁾; although a urinary tract infection is still a significant concurrent infection in infants with bronchiolitis.

Infants aged 3 months to children aged 3 years

According to guidelines from the Agency of Health Care Policy and Research published in 2012, in infants younger than 3 months with rectal temperatures of 100.4 °F (38°C) or higher, the prevalence of serious bacterial infection reported in studies conducted in North American emergency departments or primary care practices ranged from 4.1-25.1% ¹⁰⁾.

Historically, children aged 3 months to 3 years with rectal temperatures of 101.3 °F (38.5 °C) or higher had a risk of 2-4% for occult bacteremia ¹¹⁾. The leading cause of bloodstream infection was Streptococcus pneumoniae, followed by Haemophilus influenzae type B. With the introduction of effective vaccines for these pathogens, the incidence and epidemiology of childhood bacteremia in the immunologically normal host has changed considerably; only 1 in 200 (0.5%) febrile children are now found to be bacteremic ¹²⁾.

The incidence of occult bacteremia in this population now ranges from 0.25-0.7%; moreover, 2 of every 3 blood isolates from these children represent an artifact (contamination) and not a true pathogen ¹³⁾. Streptococcus pneumoniae and Escherichia coli are the most common pathogens, accounting for two thirds of cases. In infants with Streptococcus pneumoniae, many isolates are strains not covered by the currently available heptavalent conjugate vaccine.

Children with pneumococcal bacteremia may present with acute otitis media, pneumonia, symptoms of sinusitis, meningitis, febrile seizures, cellulitis (including orbital or facial cellulitis), or nonspecific febrile illnesses. Escherichia coli (E. coli) bacteremia is most common in children younger than 1 year and is usually associated with urinary tract infection (UTI). Staphylococcus aureus accounts for 15% of bloodstream infections and may be associated with skin, soft tissues, or musculoskeletal infections. Salmonella species, Neisseria meningitides, and Streptococcus pyogenes (group A Streptococcus) account for most of the remaining infections.

As with most patients, the approach to the febrile child aged 3 months to 3 years consists of a targeted medical history, a complete physical examination, and the judicious use of the laboratory tests.

Baby with fever signs and symptoms

Your baby has a fever when his/her rectal temperature reads above 100.4 °F (38°C) on a digital multi-use thermometer. Neonatal sepsis has a varied presentation, the infants may have symptoms that are nonspecific (eg, poor feeding, irritability, lethargy) or specific symptoms (eg, diarrhea, cough).. The neonate could have hypo or hyperthermia, irritability or lethargy, apnea or tachypnea, bradycardia or tachycardia, poor feeding, excessive sleepiness or being fussy. Associated symptoms may be system specific (eg, diarrhea, cough) or nonspecific (eg, poor feeding, irritability, lethargy). Seizures have been reported in 20-50% of neonates with meningitis. Necrotizing enterocolitis is common in premature infants. The physical examination could be noncontributory or could show an ill-looking infant with abnormal or unstable vital signs.

A thorough history is very important for all neonates with fever. Exposures to sick contacts in the household or daycare should be ascertained, as well as a recent history of a previous illness, immunization, or antibiotic use while in the birth hospital or since discharge. History should also include both maternal and infant risk factors. Maternal risk factors are lack of or delayed prenatal care, maternal group B strep colonization, intrapartum antibiotic use, maternal medical history including diabetes, hypertension, thyroid disease and maternal drug abuse. Infant risk factors are prematurity, low birth weight, neonatal course, a detailed history of neonatal intensive care unit (NICU) stay, prolonged rupture of membranes, sick contacts and detailed feeding history ¹⁴⁾.

Your child may also be:

• unwell and hot to touch
• irritable or crying
• more sleepy than usual
• vomiting or refusing to drink
• shivering
• in pain.

If your baby is under three months and has a fever above 38°C, then you should see a doctor, even if they have no other symptoms.

Prenatal history

A review of the prenatal history, including maternal history of sexually transmitted infections (human immunodeficiency virus [HIV], hepatitis B and hepatitis C, syphilis, gonorrhea, chlamydia, herpes simplex), maternal group B Streptococcus status and prophylaxis, mode of delivery, prolonged rupture of membranes, and history of maternal fever should be noted.

A birth weight of less than 2500 g, rupture of membranes before the onset of labor, septic or traumatic delivery, fetal hypoxia, maternal peripartum infection, and galactosemia are all risk factors for a serious bacterial infection in the neonate. Gestational age should be determined, because premature infants are at increased risk for serious bacterial infections.

A family history of a previous death in a young infant from an infectious disease increases the suspicion of congenital anomalies and primary immunodeficiencies.

Nursery course

The neonate’s nursery course should be noted, including the age at which the patient went home from the nursery, whether or not a male neonate has been circumcised, and the use of peripartum or antepartum antibiotics. Any underlying diseases or conditions, as well as the use of medications that may increase the risk of infection, should be ascertained. Diet (ie, quantity and description of milk consumed; breast milk vs formula; and, if pertinent, the method the caregiver uses for preparing and storing the formula) and sleep histories should be obtained, because decreased oral intake or an acute change in sleep patterns may be clues to an invasive infection.

Household contacts

Any ill contacts in the household should also be noted. Exposure to any animals inside the home of the caregiver or outside the home (eg, in daycare facility) should be determined. The vaccination status of household members should be determined. A history of maternal fetal loss or death due to an infectious disease in a previous infant increases the suspicion of congenital anomalies and primary immunodeficiencies.

Identifying who is in the neonate’s household, who is the primary caregiver, contact with recent immigrants, and exposure to homelessness and poverty all impact the care the neonate receives.

Baby with fever diagnosis

Diagnostic studies in infants and toddlers with fever are based on their age groups. Febrile neonates (< 28days) and young infants (28-60 days) may require a full sepsis workup. Young infants are generally assessed for urinary tract and respiratory infections as well as their risk for serious bacterial infections. Febrile children aged 3 months to 3 years are evaluated based on epidemiologic and focal findings revealed during the history taking and physical examination as well as whether or not these children are at low risk for serious bacterial infections.

Historically, febrile infants less than 3 months of age would undergo a complete evaluation for sepsis, including a lumbar puncture and would be admitted to a hospital for intravenous antibiotics for at least 48 hours pending culture results ¹⁵⁾. The rationale for this approach is based on the high prevalence of serious bacterial illness in this group and the difficulty with the clinical assessment for sepsis in the young infant where clinical signs of sepsis are often subtle ¹⁶⁾. Although this approach minimizes the risk of infectious complications, it leads to unnecessary hospitalization and treatment,
resulting in potential iatrogenic harms to infants.

The history and physical examination is the first step in the evaluation of the febrile infant. The initial clinical assessment of the infant involves deciding if the child appears unwell or “toxic.” The clinical features that define toxicity include irritability, lethargy, and decreased social interaction. There may be signs of compromised circulation with poor perfusion and cyanosis or respiratory distress.

The clinical diagnosis of serious bacterial illness in young infants is difficult; infants at this age may have serious bacterial illness in the absence of signs of toxicity. There is a limited range of behavior in the young infant and signs of serious bacterial infection may be subtle. In addition, in the young infant with meningitis, there are often nonspecific symptoms with no meningeal signs.

Several studies have used observation scales to help predict serious bacterial illness. In young infants, clinical observation scales have low sensitivity for the diagnosis of serious bacterial illness. Although clinical assessment cannot adequately predict serious bacterial illness, it may help define a group of infants who are at low risk for serious bacterial illness due to their high sensitivity in identifying serious bacterial illness ¹⁷⁾.

There are several published protocols which combine clinical and laboratory criteria in an attempt to identify young infants at low risk of serious bacterial illness who can be safely managed as outpatients. Laboratory testing includes blood testing with white blood cell count, absolute band count or band to neutrophil ratio and blood culture. Urine testing is performed by catheterization or suprapubic aspiration with urinalysis and urine culture obtained. If the infant has diarrhea, stool microscopic testing and cultures are added. Some of the protocols include cerebrospinal fluid testing. Although this is the only test that will diagnose meningitis, lumbar puncture is the most invasive test.

The most commonly used criteria in practice are the Rochester criteria. Two modified versions of the Rochester criteria have been subsequently developed with the addition of either stool white blood cell (in presence of diarrhea) or normal inflammatory markers (erythrocyte sedimentation rate [ESR] or C-reactive protein levels [CRP]) ¹⁸⁾. The Rochester criteria aims to identify a low-risk group of infants who are well appearing, previously healthy, with no evidence of bacterial illness on examination, and with normal laboratory testing. In the Rochester criteria, if the infant is considered low risk, no lumbar puncture is performed and antibiotics are not routinely used.

Other commonly used low risk criteria are the Boston criteria ¹⁹⁾ and the Philadelphia protocol (original and modified versions) ²⁰⁾. For these criteria, all infants require to have an analysis of cerebrospinal fluid as part of the laboratory criteria. Low risk infants identified with these criteria receive intramuscular ceftriaxone and are treated as outpatients. Other criteria- the Milwaukee ²¹⁾ also include lumbar puncture as part of the assessment but no antibiotics are given.

The use of above-mentioned criteria are recommended for different age groups of infants (Philadelphia: 29–60 days; Rochester: 60 days or younger; Boston: 28–89 days) ²²⁾.

Infants who present with a recognizable viral illness or who have a confirmed viral infection by laboratory testing may have a different rate of serious bacterial illness than those with no viral symptoms. The various low risk protocols do not include viral testing in the assessment of the febrile infant.

Large studies have not been performed on the diagnostic accuracy of clinical assessment for invasive HSV infection in an infant who presents with fever. The literature has been focused on patients with confirmed infections, thereby not allowing better understanding of the diagnostic accuracy of clinical and/or laboratory assessments.

Review of systems and physical examination

A thorough review of systems must be obtained to identify any other symptoms associated with the fever. A complete physical examination including vital signs (temperature 38°C = 100.4°F), pulse oximetry, and growth parameters with percentiles is necessary. General appearance should be noted for activity level, color, tone, and irritability. Signs of localized infection should be identified via a thorough examination of the skin, mucous membrane, ear, and extremities.

The presence of an umbilical stump after age 4 weeks should be noted, because it is a potential clue to leukocyte adhesion deficiency, and the lack of a circumcision in males should be noted, because it increases the risk for a urinary tract infection (UTI). In addition to fever, the most common clinical features of a UTI in a neonate include failure to thrive, jaundice (typically secondary to conjugated hyperbilirubinemia from cholestasis), and vomiting. Irritability, inconsolability, poor perfusion, poor tone, decreased activity, and lethargy can be signs of a serious infection in this age group.

Most neonates with bacterial meningitis have a full fontanelle with normal neck flexion at the time of presentation. Remember that neonates younger than 28 days with significant bacterial infections can appear to be at low risk when analyzing history, physical examination findings, and laboratory values; thus, a high index of suspicion must be maintained.

Diagnostic tests

The management of well looking previously healthy febrile infants from age 7-90 days is changing from the traditional teaching. Infants from 7 to 28 days of age received full septic work up in 58% of the cases. That number dropped to 25% in infants aged 29 days-60 days, further dropped to 5% in infants aged 61 days to 90 days ²³⁾.

Initial workup of neonates with suspected sepsis should include complete blood count (CBC), chemistry panel, and cultures of the blood, urine and cerebrospinal fluid (CSF). Some centers use a microscopic analysis of urine, C-reactive protein (CRP), and pro-calcitonin (PCT) in the risk stratification process to identify infants at low risk for serious bacterial infection. Based on the presentation, one could also include a respiratory pathogen panel or tests for respiratory syncytial virus (RSV), influenza, gastrointestinal pathogens, and possibly a chest x-ray. Rochester criteria, Philadelphia criteria, and Boston criteria all recommend a full septic work up in infants less than 28 days of age presenting with fever regardless of other risk factors ²⁴⁾. After the wide use of the streptococcal vaccination, the prevalence of bacteremia in febrile infants has decreased. Gomez et al. ²⁵⁾ validated the “Step by Step” approach, which showed that risk stratification is a workable strategy to identify low-risk infants with fever. Infants with fever at high risk for serious bacterial infection may demonstrate evidence of leukocytes in the urine, and elevated pro-calcitonin (greater than 0.5 Ng/ml), CRP (greater than 20 mg/L) and absolute neutrophil count (ANC) (greater than 10,000/mm³). Wallace and Brown et al. ²⁶⁾ showed that the frequency of bacterial meningitis with urinary tract infection (UTI) is minimal. Greenhow et al. ²⁷⁾ concluded that 24% of well-appearing neonates with fever despite having no laboratory studies done and none of them had delayed bacteremia or meningitis. Recently some centers are using the cerebrospinal fluid (CSF) molecular testing which has a turn around time of two hours to aid in the evaluation and management of febrile neonates, especially during enteroviral season. This test is also useful if the CSF is contaminated with blood, to differentiate between bacterial and viral pathogens.

Rochester criteria

The Rochester criteria are used to assess febrile (temperature > 38°C) infants aged 28-60 days ²⁸⁾. The risk for occult bacteremia in well-appearing febrile infants is 7-9%; if all Rochester criteria are present, the risk is less than 1%. Infants at high risk were hospitalized with empiric antibiotics, and infants at low risk were discharged with follow-up in 24 hours ²⁹⁾.

The Rochester low-risk criteria for occult bacteremia include the following ³⁰⁾:

• Infant must appear generally well
• Infant has been previously healthy: Born at term (≥ 37 weeks’ gestation), no perinatal antimicrobial therapy, no treatment for unexplained hyperbilirubinemia, no previous antimicrobial therapy, no previous hospitalization, no chronic or underlying illness, not hospitalized longer than the mother
• Infant has no evidence of skin, soft-tissue, bone, joint, or ear infection
• Infant has the following laboratory values: white blood cell (WBC) count of 5,000-15,000 cells/μL, absolute band count of 1,500 bands/μL or less, less than 10 white blood cells (WBCs) per high-power field (HPF) on microscopic examination of the urine, less than 5 WBCs/HPF on microscopic examination of stool in an infant with diarrhea

Boston criteria

The Boston criteria are used to assess febrile (temperature > 38°C) infants aged 28-89 days ³¹⁾. Infants who met these criteria were managed as outpatients with 50 mg/kg ceftriaxone intramuscularly at the time of discharge. The scheduled follow-up visit was in 24 hours; 5.4% of patients had a serious bacterial infection at follow-up.

The Boston low-risk criteria for occult bacteremia are as follows ³²⁾:

• No immunizations or antimicrobials within the preceding 48 hours
• No evidence of dehydration or ear, soft-tissue, or bone infection
• Well appearing
• Caretaker available by telephone
• Infant has the following laboratory values: WBC count less than 20,000 cells/μL, CSF with WBC count less than 10 cells/μL ³³⁾, urinalysis with less than 10 white blood cells per high-power field (HPF) on microscopic examination, no infiltrate on chest radiograph (if one was obtained)

Philadelphia criteria

The Philadelphia criteria were used to assess febrile infants aged 29-60 days with fever (> 38.2°C). All high-risk patients were hospitalized and treated with empiric antibiotics. Low-risk patients were not treated with antibiotics, with follow-up in 24 hours. Sensitivity for identifying patients with a serious bacterial infection was 98%, specificity was 42%, positive predictive value was 14%, and the negative predictive value was 99.7%.

The Philadelphia low-risk criteria for occult bacteremia included the following:

• Well appearing
• White blood cell (WBC) count of less than 15,000 cells/μL
• Band-neutrophil ratio of less than 0.2
• Urinalysis reveals less than 10 white blood cells per high-power field (HPF) on microscopic examination and a negative urine Gram stain result
• CSF has less than 8 white blood cells (WBCs)/μL and a negative CSF Gram stain finding
• Chest radiograph does not have an infiltrate (if a radiograph was obtained)
• Stool has no blood and few or no white blood cells (WBCs) on the smear

Diagnostic studies in neonates

A full sepsis evaluation is often recommended in febrile neonates and young infants. This includes a complete blood cell (CBC) count, blood culture, urinalysis, urine culture, and cerebrospinal fluid (CSF) analysis and culture. These patients should be hospitalized with intravenous antibiotics pending results of these cultures.

A study by Cruz et al ³⁴⁾ analyzed the accuracy of individual complete blood cell count parameters to identify febrile infants with invasive bacterial infections. The study included 4313 infants, 1340 (31%) were aged 0 to 28 days, of which ninety-seven (2.2%) had an invasive bacterial infection. The study reported low sensitivities for common CBC parameter thresholds. WBC less than 5000/µL, was detected 10% of the time, white blood cell count ≥15,000/µL, 27%; absolute neutrophil count ≥10 000/µL, 18%; and platelets < 100 x10³ /µL, 7% ³⁵⁾.

CSF studies

A lumbar puncture for CSF examination is recommended in all neonates younger than 28 days if empiric antibiotics are to be given or if the neonate had a seizure. CSF should be assessed for WBC count and differential, glucose level, protein level, Gram stain, and routine culture. CSF should be assayed for herpes simplex virus (HSV) using polymerase chain reaction (PCR) in all neonates in the first 28 days of life who appear ill, who have mucocutaneous lesions, or who have had a seizure.

Enterovirus PCR analysis should be performed on the CSF during the summer enteroviral season.

Urine and stool studies

Because the incidence of urinary tract infections (UTIs) is high in this age group, a urine specimen should be obtained for urinalysis and urine culture. A negative urine dipstick or urinalysis finding alone does not exclude the diagnosis of a UTI; only a negative urine culture finding can exclude this diagnosis ³⁶⁾. A urine culture should be obtained via either a suprapubic aspiration or urethral catheterization, because bag urine specimens are frequently contaminated.

A study by Tzimenatos et al ³⁷⁾ that included an analysis of data from 4147 febrile infants ≤60 days old reported that for the 289 infants with a UTI and colony counts ≥50,000 CFUs/mL, a positive urinalysis regardless of bacteremia showed sensitivities of 0.94; 1.00 with bacteremia; and 0.94 without bacteremia. Specificity in all groups was 0.91.

A stool culture is recommended when blood, mucus, or both are present in the stool; when diarrhea is present; and when more than 5 white blood cells (WBCs) per high-power field (HPF) are noted on methylene blue stain of fresh stool.

Pulmonary studies

A chest radiograph should be considered for neonates with signs of respiratory illness such as cough, coryza, tachypnea, rales, rhonchi, retractions, grunting, nasal flaring, or wheezing. During respiratory viral season, an attempt should be made to identify a respiratory viral etiology using direct fluorescent antigen (DFA) detection or PCR and viral culture on nasal wash specimens.

Diagnostic studies in Young Infants

In infants older than 28 days, low risk criteria are well defined. The reference range white blood cell (WBC) count is 5,000-15,000 cells/μL. The band count should be less than 1500 cells/μL. However, the WBC count alone has poor sensitivity and specificity for identifying young infants with bacteremia and meningitis; thus, the decision to perform a sepsis workup should not be based on the WBC count alone.

Urine and stool studies

Because the incidence of urinary tract infections (UTIs) is still high in this age group, obtain a urine specimen for urinalysis and urine culture. In one study, only 20% of febrile infants with the diagnosis of pyelonephritis had pyuria. A urine culture should be obtained by either a suprapubic aspiration or urethral catheterization, because bag urine specimens are frequently contaminated.

A stool culture is recommended when blood, mucus, or both are present in the stool, when diarrhea is present, and when more than 5 WBCs per high-power field (HPF) are noted on methylene blue stain of fresh stool.

Pulmonary studies

Chest radiography should be considered for infants with signs of respiratory illness, such as cough, coryza, tachypnea, rales, rhonchi, retractions, grunting, nasal flaring, or wheezing. During respiratory viral season, an attempt should be made to identify a respiratory viral etiology using direct fluorescent antigen (DFA) detection or polymerase chain reaction (PCR) and viral culture on nasal wash specimens.

Baby with fever treatment

The ill-appearing neonate requires a full septic work and broad-spectrum antibiotic coverage with ampicillin and cefotaxime, the combination of which covers 100% of early neonatal infections and 93% of late-onset bacteremia ³⁸⁾. Gentamicin and penicillin can cover 94% of early infections ³⁹⁾. Cefotaxime does not treat some Escherichia coli, Pseudomonas, Enterococci, Acinetobacter, and Listeria monocytogenes. Use of Cefotaxime in the NICU can cause outbreaks of drug-resistant nosocomial infections, which is a serious concern in many centers. Pediatric Infectious diseases specialist consider empiric treatment of neonatal herpes with intravenous Acyclovir if the CSF has an elevated red cell count or in any ill-looking neonate with suspected herpes ⁴⁰⁾. Some doctors admit and empirically treat ill-looking infants and infants with risk factors while waiting for the cultures.

Fluid resuscitation is different to treat septic shock. In term neonate, the fluid bolus is 20 ml/kg as rapidly as possible up to 60 ml/kg, whereas in the preterm neonate the fluid bolus comprises 10 ml/kg in 30 minutes and repeat if needed and then vasopressor support for the fluid refractory shock with dopamine and dobutamine ⁴¹⁾. For catecholamine-resistant shock consider milrinone for old shock with poor LV function and normal blood pressure, nitrous oxide for low blood pressure and poor right ventricular function, vasopressin, or terlipressin and inotropes for warm shock and low blood pressure and consider extracorporeal membrane oxygenation (ECMO) if the child develops persistent fetal circulation.

Based on the laboratory data, you can risk stratify the well-looking febrile infants greater than 21 days of age with no risk factors and with no source of invasive infection into high risk, medium risk and low risk. You can safely observe low-risk infants at home or in the hospital without empiric treatment, meanwhile high-risk infants are observed and treated in the hospital. You also can observe medium-risk infants in the hospital or at home before treating them empirically ⁴²⁾. If in doubt admit them to the pediatric unit for observation while waiting for the culture results ⁴³⁾.

Baby with fever prognosis

Prognosis is excellent if treated early in full-term neonates. The prognosis is different in premature and very premature infants.

The outcome of well looking febrile infants is excellent with a care coordination between the emergency medicine providers and hospitalist service. Early recognition is the most important factor in decreasing the morbidity and mortality in neonatal sepsis. The septic premature infants require a dedicated team and cooperation among various specialists like the neonatologist, pediatric infectious disease specialists, intensivist and with specialized centers to provide ECMO for the optimum outcome. Take the help of the pharmacists and infectious disease specialists in choosing and in calculating the doses for the of empiric antibiotics in premature and full-term infants both in early onset and late onset neonatal sepsis.