AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
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INTRODUCTION

Section 2 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Parents often bring their febrile children who are 3 years old or younger to the ED for evaluation and treatment. The differential diagnosis of fever in children is broad. It includes simple viral infections, serious bacterial infections (SBIs), and bacteremia or septic shock.

Children with bacteremia or sepsis can present with or without fever depending on their state of health. Pyrexia or hypothermia can be a sign of sepsis. However, most children with bacteremia or sepsis have fever. In a child with fever, management and diagnostic testing are often a challenge for healthcare providers.

Recommendations and guidelines regarding the care of febrile children are frequently changed. These changes can be attributed to the introduction of new vaccines (eg, those for Haemophilus influenzae type B [HIB] and Streptococcus pneumoniae), to new research, to new diagnostic tests, and to advances in treatment. Clinicians must be comfortable in treating a sick child by combining their background knowledge with current recommendations.

Pathophysiology

Fever is defined as rectal temperature greater than 100.4°F (38°C). Use of a rectal thermometer is the most reliable method to measure temperature, and it is the preferred method in this clinical setting. Exogenous pyrogens, such as viruses, bacteria, and bacterial endotoxins, stimulate the release of endogenous pyrogens, such as interleukin-1. Endogenous pyrogens stimulate the anterior hypothalamus to set the body temperature to a higher level than before.

Children who are younger than 36 months are at increased risk for bacteremia or sepsis secondary to the immaturity of their immune system. According to a 2003 clinical policy of the American College of Emergency Physicians (ACEP), "Infants between 1 and 28 days old with a fever should be presumed to have a SBI."

Children in this are group may be febrile for 1 of 4 major reasons: fever of unknown source (FUS), (2) occult bacteremia, (3) SBI, or (4) sepsis. FUS is a febrile illness with no known source after complete history taking and physical examination. Viral infections are the most common causes of FUS in children. Occult bacteremia is a febrile illness with positive blood culture; however, by definition, no sign of systemic infection is seen. SBI includes bacteremia, sepsis, infections of the soft tissues or joints, meningitis, bacterial enteritis, bacterial pneumonia, and urinary tract infections (UTIs). Sepsis is bacteremia with signs of systemic infection, such as fever, hypothermia, hypotension, tachycardia, tachypnea, and mental status change (eg, lethargy, difficulty in consoling the child).

Frequency

United States

The prevalence of SBI in neonates (<1 mo) with FUS is 8.8-13.7%. For infants aged 1-2 months, the prevalence of SBI is 5-8.7%.

Stanley et al reported that infants aged <3 months with hyperpyrexia (core temperature >40°C) had a significantly increased prevalence of SBI.¹ UTI was the most common cause of SBI. However, children can be septic without having hyperpyrexia; therefore, history taking, physical examination, and clinical judgment are still the most important factors in caring for sick children.

Whitney et al (2003) reported that since the introduction of the conjugated pneumococcal vaccine (PCV7), rates of invasive pneumococcal diseases in children younger than 2 years old have declined 69% between 1998-1999 and 2001. Rates of positive blood cultures for S pneumoniae declined from 1.3% to 0.25% between 1998-1999 and 2002-2003 at the Cincinnati Children's Hospital and Medical Center (CCHMC).

If studies after the introduction of PCV7 are excluded, the prevalence of occult bacteremia in febrile children (aged 3-36 months old) is estimated to be 1.5-2%.

Mortality/Morbidity

Mortality and morbidity rates vary depending on the source of the infection. Bacteremia sometimes progresses to SBI.

• H influenzae has historically been the cause of most cases of occult bacteremia, which progressed to serious bacterial disease in 25% of patients; S pneumoniae infection progresses to SBI or focal bacterial infection in 1.5%.
• The introduction of vaccines dramatically affected the morbidity and mortality rates associated with bacteremia.
• In children aged 2-36 months, UTI is the most common SBI. The long-term effects of UTI can be serious if the infection is not diagnosed or treated. Untreated lower UTI can lead to upper-urinary-tract disease such as pyelonephritis. Pyelonephritis increases risk of renal scarring in children. Renal scarring can lead to hypertension and end-stage renal failure later in life.

Sex

Sepsis and bacteremia affect boys and girls equally. However, the incidence UTI varies with sex. Girls aged 1 year old or younger are 2 times more likely than similarly aged boys to have UTI (6.5% vs 3.3%). In girls aged 1-2 years, the incidence of UTI increases to 8.1%, whereas in boys the incidence decreases to 1.9%. Uncircumcised boys are at increased risk for UTIs.

Age

Age is an important factor in bacteremia and sepsis for 2 reasons. First, the immune system is not fully developed in young children. Second, the important pathogens vary with age.

Pathogens acquired at birth are most likely to affect neonates (<1 mo). By comparison, infants aged 1-3 months are at lower risk for neonatally acquired pathogens; however, they are at higher risk for community-acquired pathogens. Children aged 3 months or older are still at risk for community-acquired pathogens; however, they have a decreased risk of SBI or bacteremia.

CLINICAL

Section 3 of 11  

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History

Children can be septic without having hyperpyrexia; therefore, history taking, physical examination, and clinical judgment are still the most important factors in caring for sick children. History taking is an important part of clinical decision making.

• Clinicians should ask the patient's parents or caretakers about the following items when they bring in a febrile or ill-appearing child:
• • Immunization history, such as recent vaccination or a history of inadequate immunizations
  • History of exposure to sick contacts and treatments, such as antibiotics
  • Recent travel history
  • History of previous hospitalization, prematurity, or immunocompromised disease
  • History of change in eating or behavioral patterns, change in mental status
  • History of neglect or abuse
  • Documented fever at home, the duration of any fever, and the last treatment (if any) for the fever
• According to a 2003 clinical policy of the ACEP, "A response to antipyretic medication does not change the likelihood of a child having SBI and should not be used for clinical decision making."
• Environmental factors, such as being in the heat for a long time during the summer and being overdressed during the winter, may indicate a risk for hyperthermia.

Physical

Positive findings to look for during physical examination include the following:

• Vital signs: Rectal temperature, respiratory rate (RR), heart rate (HR), blood pressure (BP), pulse oximetry reading
• • The rectal temperature may indicate hypothermia or fever.
  • The RR may be increased (respiratory distress, respiratory tract diseases) or decreased (respiratory depression).
  • The HR may indicate tachycardia (dehydration, infection, cardiac etiology such as supraventricular tachycardia [SVT]) or bradycardia (hypoxia).
  • The BP may indicate hypotension.
  • The pulse oximetry reading (oxygen saturation) may be low (pneumonia, respiratory distress or depression, equipment malfunction).
  • Young infants are prone to hypoglycemia during illness. Blood sugar levels should be measured in an ill-appearing infant.
• Change in general appearance (eg, toxic, lethargic)
• • Head - Bulging or sunken fontanelle in young children
  • Eyes - Discharge, pupil size
  • Ears - Signs of ear infection (loss of light reflect, bulging, red and immobile tympanic membrane)
  • Nose - Discharge
  • Mouth - Dry mucus membrane or lesions
  • Throat - Erythema, exudates, lesions
  • Neck - Meningeal irritation or adenopathy
  • Heart - Murmur, rubs, tachycardia, bradycardia
  • Lungs - Abnormal lung sounds, such as wheezing, rhonchi, or rales
  • Abdomen - Rigidity, guarding, abnormal bowel sounds
  • Genitals - Rash, discharge
  • Neurologic status - Not consolable, lethargic
  • Extremities - Signs of osteomyelitis, cellulitis
  • Skin - Rash (especially petechial rash), cellulitis

Causes

Causes of bacteremia in children have been reported as follows²:

• Neonates (0-28 d) - Group B Streptococcus (GBS) species, Escherichia coli, Listeria monocytogenes, Enterococcus species
• Young infants (29-90 d) - Neonatal pathogens listed above and community-acquired pathogens listed below
• Older infants and children (3-36 mo) - S pneumoniae, Neisseria meningitidis, HIB (unimmunized), Group A Streptococcus species, E coli (pyelonephritis), Salmonella species (gastroenteritis), Staphylococcus aureus (osteomyelitis)

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

WORKUP

Section 5 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• CCHMC guidelines recommend the following 5 tests for infants (0-60 d) with FUS: CBC with differential, blood culture, urinalysis (UA), urine culture, and lumbar puncture (LP) (see Media file 1).
• • CBC: The normal WBC range is 5-15 X 10⁹/L (5000-15,000/mm³). Normal WBC band forms are <1.5 X 10⁹/L (<1500/mm³). WBC values should not be used in deciding to perform or withhold lumbar puncture (LP) to rule out meningitis.
  • Urinalysis: Urethral catheterization and percutaneous bladder aspiration are the methods of choice to obtain urine to avoid contamination. Sonography has become popular in many EDs. Chen et al reported that bedside sonography-guided urethral catheterization increased the success rate of urethral catheterization.³ They considered >2 mL of urine a sufficient amount for testing. A finding of >5-10 WBCs per high-powered field is an abnormal microscopic value, though results vary among clinicians and reports.
  • Urine culture: ACEP Clinical Policy in 2003 states, "Obtain a urine culture in conjunction with other urine studies when urinary tract infection is suspected in a child aged younger than 2 years because a negative urine dipstick or UA result in a febrile child does not always exclude urinary tract infection."

  • LP: LP should be performed in all neonates (<30 d). The threshold for performing LP in infants aged 31-60 days should be low, but LP may be omitted if they meet all of the low-risk criteria of the CCHMCC, as listed below:
    • Reliable follow-up is possible in 12-24 hours
    • Clinicians are confident that parents or caretakers can comply with appropriate observation and follow-up
    • The primary care physician and caretakers agree with the decision
    • No antibiotics have been started

• Other studies may include the following:
• • Stool culture if a child has diarrhea
  • Viral culture in the appropriate clinical setting
  • Chest radiography if a child has signs of respiratory distress such as tachypnea, abnormal breath sounds and decreased pulse oximetry
  • Possible neonatal evaluation for herpes simplex virus (HSV) if an infant is at high risk (eg, maternal HSV infection at delivery)
  • Rapid urine pneumococcal antigen assay
  • Test of C-reactive protein (CRP), though still controversial (Different studies have shown different results.)
• Viral infections are the most common cause of FUS in infants and children aged 2-36 months. CCHMC guidelines for treating these patients include several considerations, as listed below (see Media file 2).

• • A well-appearing child with an unremarkable history and who also meets the following criteria can be discharged home for observation without laboratory testing:
  • • Follow-up can be conducted in a reliable and timely (12-24 h) manner.
    • Clinicians are confident that the parents or caretakers can comply with appropriate observation and follow-up.
    • The primary care physician and caretakers agree with the decision.
  • Because UTI is the most common cause of SBI in this age group, clinicians have a low threshold for ordering both UA and urine cultures. The risk is increased in uncircumcised boys, boys younger than 6 months, girls younger than 2 years, Caucasian race, and fever (temperature at least 39°C).
  • Routine CBC and blood cultures are not recommended in well-appearing children (age older than 60 d) with no significant medical history and with complete immunization for their age. Stoll and Rubin found that the rate of S pneumoniae bacteremia in febrile children aged 2-36 months has declined since the use of PCV7.⁴ They concluded that, with continued use of PCV7, routine CBC and blood culture may no longer be needed in this group of children.
  • CBC with differential and blood cultures should be ordered in children who appear ill and who are at high risk for occult SBI. Major risk factors are an incomplete PCV7 series for the patient's age (refer to immunization schedules), age younger than 2 years, ill appearance, nonviral etiology, fever (temperature >40°C), unreliable follow-up, and known meningococcal contact.
• Chest radiography, LP, and/or stool cultures are indicated in children in whom pneumonia, meningitis, or gastroenteritis is highly suspected, respectively.
• • Chest radiographs should not be routinely performed for fever in the absence of lower respiratory tract findings, tachypnea, or hypoxemia.
  • Chest radiographs may be useful for the subset of patients with fever and leukocytosis in the absence of an alternative source of fever.

Imaging Studies

• See the indications for chest radiography as mentioned among Other studies above.

Other Tests

• See Lab Studies.

Procedures

• See indications for LP as discussed above.
• In addition to history taking and physical examination, a clinician may also choose to use the Yale Observation Scale when evaluating infants. Scores are summarized as follows: 1 = normal, 3 = moderately impaired, and 5 = severely impaired. Incidences of serious illness are 2.7% for a score of 10 or less, 26% for a score of 11-15, and 92.3% for a score of 16 or more.⁵ Various observations are scored as follows:
• • For quality of cry, 1 = strong or no cry; 3 = whimper or sob; and 5 = weak cry, moan, or high-pitched cry.
  • For reaction to parents, 1 = brief cry or content, 3 = cries on and off, and 5 = persistent cry.
  • For state variation, 1 = awakens quickly, 3 = difficult to awaken, and 5 = no arousal or falls asleep.
  • For color, 1 = pink; 3 = acrocyanosis (cyanosis of the extremities); and 5 = pale, cyanotic, or mottled.
  • For hydration, 1 = eyes, skin, and mucus membranes moist; 3 = mouth slightly dry; and 5 = mucus membranes dry and eyes sunken.
  • For social response, 1 = alert or smiles; 3 = alert or brief smile; and 5 = no smile, anxious or dull.
• Although high scores correlate well with ill appearance and higher rates of SBI, low scores cannot be used to exclude SBI.

TREATMENT

Section 6 of 11  

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Prehospital Care

• Toxic or ill-appearing children should be transported to an ED for further workup and treatment.
• Airway management and securing intravenous (IV) access are part of the prehospital care, especially in toxic-appearing children.

Emergency Department Care

Children who are unstable or seriously ill need fluid resuscitation and/or pressors. Broad-spectrum antibiotics should be administered, and a search for the source of illness should be initiated. What is more difficult than evaluating a child in unstable condition is evaluating a child in stable condition with fever. The first step in developing a diagnostic and treatment strategy is assessing the child's risk for serious illness.

• Risk assessment by clinical presentation: Several clinical findings indicate an increased risk of bacteremia and/or sepsis.
  • Clinical presentation due to immaturity of the immune system or fever in infants younger than 3 months
  • Fever in children who are immunocompromised (Immunocompromised children may not be febrile even if they are septic.)
  • Fever in children who have not received the recommended vaccinations for their age
  • Hypothermia (core temperature <36.8°C or 98°F) in a child with a toxic or ill appearance
  • Social factors, such as unreliable caregivers, lack of access to healthcare, and others
• Risk assessment by age
  • 0-30 days old: All of these children are at increased risk for serious illness. Serious infection should be assumed in any neonates with a temperature >100.4°F. They should receive a full septic workup including LP (as described in Lab Studies). They should receive antibiotics and be admitted to the hospital.
  • 31-90 days old: Children of this age with a temperature >100.4°F should be thoroughly evaluated for serious illness.
• Screening criteria: Several methods for screening children have been described.
  • The Rochester criteria are used to identify febrile children at low risk for SBI. However, clinical judgment, careful history taking, and physical examination are still needed. If the child meets all of the criteria below, LP may be excluded, and he or she may be discharged with close follow-up. Antibiotics should not be administered. If any criterion is not met, LP should be performed, the child should be admitted, and antibiotics should be administered. The criteria for low risk are as follows:
    • The infant appears generally well.
    • The infant has been previously healthy. He or she was born at term (>37 weeks' gestation) and had had no perinatal antimicrobial therapy, no treatment of unexplained hyperbilirubinemia, no previous antimicrobial therapy, no previous hospitalization, no chronic illnesses, and no hospitalization longer than the mother's.
    • The infant has no evidence of skin, soft tissue, bone, joint, or ear infection.
    • The infant has a WBC count of 5-15 X 10⁹/L (5000-15,000/mm³), an absolute band cell count of 1.5 X 10⁹/L (1500/mm³) or less, a negative result on urine dip testing, 10 or fewer WBCs per high-powered field on microscopic examination of urine, and a stool smear with 5 or fewer WBCs per high-powered field on microscopic examination (in an infant with diarrhea).
• • The Baker method was based on a study of infants aged 29-56 days. As with the Rochester criteria, clinical judgment, careful history taking, and physical examination are still needed. In addition to the low-risk laboratory criteria listed below, children also had an observational score of 10 or less (see Procedures above) and no evidence of bacterial infection on physical examination. The Baker low-risk criteria are as follows:
    • WBC count <15 X 10⁹/L (15,000/mm³)
    • UA showing <10 WBC per high-powered field and few or no bacteria detected on bright-field microscopy
    • CSF showing <8 WBC/mm³ in a nonbloody specimen and a negative result on gram staining
    • No infiltrate seen on chest radiographs, as interpreted by ED physicians and radiologists
• History and physical examination: A complete history and physical examination are important factors in the care for a sick child (see the Clinical section above).
• Workup: See Lab Studies.
• Treatments and medication
• • Manage the airway (oxygen supplement or intubation as needed) and secure IV access if it was not established during prehospital care.
  • Monitor the patient's HR, BP, and pulse oximetry readings.
  • Administer IV fluids, such as normal sodium chloride solution with boluses (weight based) as needed for hypotension. Pressors should be given as needed for hypotension that does not respond to fluid.
  • Administer antipyretic medications (weight based) as needed for fever.
  • Administer antibiotics as indicated (see the Medication section below).
• Disposition
  • If the initial facility is not designed for pediatric inpatient care, transfer to a pediatric facility as needed after his or her condition is stabilized in the ED and after initial workup and treatments are completed.
  • All neonates aged 0-30 days should be admitted.
  • All infants aged 31-60 days should be admitted if their clinical presentation or laboratory data suggest that they are at high risk.
  • Infants aged 31-60 days may be discharged home if they meet all of the low-risk criteria as discussed above.
• • Several options should be considered in children aged 2-36 months:
    • Consider discharge without antibiotics in well-appearing children with a low risk, reliable caretakers with a safe home environment, and appropriate outpatient follow-up within 12-24 hours.
    • Consider discharge without antibiotics for well-appearing children with a positive viral illness (eg, due to respiratory syncytial virus [RSV], influenza, or enterovirus) and the other social factors mentioned above.
    • Consider discharge without antibiotics for well-appearing children with negative laboratory results and the other social factors mentioned above.
    • Consider discharge with outpatient antibiotics for well-appearing children who have positive diagnostic results or risk factors for bacteremia and the other social factors mentioned above.
    • Consider antibiotic therapy and admission for children who appear ill and who have clinical and/or laboratory findings consistent with SBI.

Consultations

• Most pediatric infections are managed by pediatricians. In a pediatric facility, consult necessary specialists (eg, infectious disease specialist) as needed for unusual infections or diagnostic considerations.
• In a nonpediatric facility, consult a pediatrician in a pediatric facility regarding management and disposition, especially when hospitalization is warranted for the child.

MEDICATION

Section 7 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Vaccinations

Recommended pneumococcal vaccination schedules can be found at the Immunization Initiatives Web site of the American Academy of Pediatrics.

Antibiotics

Neonates aged 0-30 days should be treated with combination of IV ampicillin and a third-generation cephalosporin or gentamicin. For infants aged 31-60 days, third-generation IV cephalosporin alone is recommended as first-line therapy. IV ampicillin is recommended in addition to a third-generation cephalosporin for severely ill infants aged 31-60 days or for infants in this age group with UTI. Children aged 2-36 months should be treated with antibiotics as indicated.

In addition to the antibiotics discussed above, vancomycin is also being used in settings where methicillin-resistant S aureus (MRSA) is prevalent or suspected.

Antivirals

According to CCHMC guidelines, neonates younger than 30 days and at high risk for neonatal HSV infection, acyclovir is recommended.

Drug Category: Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Drug Name	Gentamicin (Garamycin)
Description	Aminoglycoside antibiotic for gram-negative bacteria including Pseudomonas species. Synergistic with beta-lactamase against enterococci. Interferes with bacterial protein synthesis by binding to 30S and 50S ribosomal subunits. Dosing regimens numerous and adjusted for CrCl, changes in volume of distribution, body space into which agent must distribute. May be given IV/IM. Trough level should be drawn on third or fourth dose, 0.5 h before dosing; may draw peak level 0.5 h after 30-min infusion. Effective in combination with ampicillin for GBS and enterococcal infection. For children, IV preferred; IM may be used if IV access difficult.
Adult Dose	Serious infections and normal renal function: 3 mg/kg/dose IV q8h; loading dose: 1-2.5 mg/kg IV; maintenance dose: 1-1.5 mg/kg IV q8h Extended dosing regimen for life-threatening infection: 5 mg/kg/d IV/IM q6-8h
Pediatric Dose	0-4 weeks and <1200 g: 2.5 mg/kg/dose IV/IM q18h <7 days and 1200-2000 g: 2.5 mg/kg/dose IV/IM q12h <7 days and >2000 g: 2.5 mg/kg/dose IV/IM q12h >7 days and 1200-2000 g: 2.5 mg/kg/dose IV/IM q8h >7 days and >2000 g: 2.5 mg/kg/dose IV/IM q8h
Contraindications	Documented hypersensitivity; non–dialysis-dependent renal insufficiency
Interactions	Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of neuromuscular blocking agents (prolonged respiratory depression may occur); coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (not treated with dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment

Drug Name	Cefotaxime (Claforan)
Description	Third-generation cephalosporin with broad gram-negative spectrum, decreased efficacy against gram-positive organisms, and increased efficacy against resistant organisms. Arrests bacterial cell-wall synthesis by binding to 1 or more penicillin-binding proteins, inhibiting bacterial growth. Safety profile more favorable than that of aminoglycosides. When administered parenterally, offers antimicrobial efficacy against many gram-negative pathogens common in first few days of life (eg, E coli, untypeable H influenzae, Klebsiella species, other enteric organisms). Crosses blood-brain barrier into CNS reasonably well and theoretically poses less risk of renal toxicity or ototoxicity than gentamicin and other aminoglycosides (common alternatives). Compared with gentamicin, more costly, more rapid emergence of resistant organisms in closed environment (eg, NICU), slightly narrower range of susceptible gram-negative organisms, and outcomes in a randomized controlled trial of neonates not superior.
Adult Dose	Moderate-to-severe infection: 1-2 g IV/IM q6-8h Life-threatening infection: 1-2 g IV/IM q4h
Pediatric Dose	<7 days: 50 mg/kg/dose IV/IM q12h >7 days: 50 mg/kg/dose IV/IM q8h
Contraindications	Documented hypersensitivity
Interactions	Probenecid may increase levels; coadministration with furosemide and aminoglycosides may increase nephrotoxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in severe renal insufficiency (high doses may cause CNS toxicity); superinfections, and promotion of nonsusceptible organisms with prolonged or repeated therapy; associated with severe colitis

Drug Name	Ceftriaxone (Rocephin)
Description	Third-generation cephalosporin with broad-spectrum, gram-negative activity. Decreased efficacy against gram-positive organisms; increased efficacy against resistant organisms. Bactericidal activity from inhibiting cell-wall synthesis by binding to 1 or more penicillin-binding proteins. Antimicrobial effect by interfering with synthesis of peptidoglycan, major structural component of bacterial cell wall. Bacteria lyse because of ongoing activity of cell-wall autolytic enzymes while cell-wall assembly is arrested. Highly stable in presence of beta-lactamases (penicillinase and cephalosporinase) of gram-negative and gram-positive bacteria. Approximately 33-67% of dose excreted unchanged in urine; rest secreted in bile and ultimately feces as microbiologically inactive compounds. Reversibly binds to human plasma proteins; binding reported to decrease from 95% at plasma concentrations <25 mcg/mL to 85% at 300 mcg/mL.
Adult Dose	1-4 g/d IV/IM divided q12-24d; not to exceed 4 g/d
Pediatric Dose	50-100 mg/kg/d IV/IM divided q12-24h; not to exceed 4 g/d
Contraindications	Documented hypersensitivity
Interactions	Probenecid may increase levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in severe renal insufficiency (high doses may cause CNS toxicity); superinfections, and promotion of nonsusceptible organisms may occur with prolonged or repeated therapy; caution in breastfeeding

Drug Name	Nafcillin (Nallpen)
Description	Initial therapy for suspected penicillin G–resistant streptococcal or staphylococcal infections. Initially use parenteral therapy in severe infections. Change to PO therapy as condition warrants. Because of thrombophlebitis, particularly in children or elderly patients, administer parenterally for only short term (1-2 d); change to PO as clinically indicated.
Adult Dose	250 mg to 1 g PO q4-6h 500 mg to 1 g IV/IM q4-6h
Pediatric Dose	<1 month: 50-100 mg/kg/d IV divided q6-12h >1 month: 100-200 mg/kg/d IV divided q4-6h; not to exceed 12 g/d 50-100 mg/kg/d PO divided qid
Contraindications	Documented hypersensitivity
Interactions	Warfarin resistance when administered concurrently; bacteriostatic action of tetracycline derivatives may decrease effects
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	To optimize therapy, determine causative organisms and susceptibility; treatment should be >10 d to eliminate infection and prevent sequelae (eg, endocarditis, rheumatic fever); obtain cultures after treatment to confirm eradication

Drug Name	Vancomycin (Vancocin)
Description	Bacteriocidal agent against most aerobic and anaerobic gram-positive cocci and bacilli. Especially important in treating MRSA. Recommended when coagulase-negative staphylococcal sepsis is suspected. Rifampin, gentamicin, or cephalothin may be required with endocarditis or CSF shunt infection by coagulase-negative staphylococci.
Adult Dose	500 mg q6-8h IV for 7-10 d or 1 g IV q12h for 7-10 d
Pediatric Dose	<1200 g: 15 mg/kg/dose IV qd 1200-2000 g: 10 mg/kg/dose IV q12h >2000 g: 10 mg/kg/dose IV q8h
Contraindications	Documented hypersensitivity
Interactions	Erythema, histaminelike flushing, and anaphylactic reactions may occur when administered with anesthetics; with concurrent aminoglycosides, risk of nephrotoxicity may increase above that with aminoglycoside monotherapy; coadministration with nondepolarizing muscle relaxants may enhance neuromuscular blockade
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in renal failure, neutropenia; red man syndrome caused by too-rapid IV infusion (give dose over a few minutes) but rare when dose given over 2 h IV or PO or IP administration; red man syndrome is not an allergic reaction

Drug Category: Antiviral

Infants are at risk for neonatal HSV infections if they are delivered vaginally and if the mother has known HSV infection during delivery.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Inpatient Care

• All neonates aged 0-30 days and toxic-appearing children should be hospitalized for antibiotic treatments.
• Antibiotic treatment should not be discontinued until all cultures show no bacterial growth after 48 hours.

Further Outpatient Care

• Major factors in outpatient care are reliability of caretakers, close follow-up with primary care physicians, and an ED protocol for notification if cultures are positive.
• Children who have a positive CSF culture should return to the hospital for IV antibiotics and admission.
• Primary care physicians or ED physicians should notify caretakers if a child has a positive blood culture. The child must be reevaluated.
• Primary care physicians or ED physicians should notify caretakers if a child has a positive urine culture.
• • The child can be treated as outpatient with close follow-up if he or she continues to appear well.
  • The child should return either to the ED or to the primary care physician's office if his or her clinical presentation worsens after discharge.

Transfer

• If the treating facility is not a pediatric facility, transfer the patient to a pediatric facility as needed after his or her condition is stabilized and the initial workup and treatments are administered in ED.

Complications

• Serious bacterial infection
• Septic shock
• Organ damage from hypoperfusion or untreated infections
• Long-term adverse effects later in life

Prognosis

• The prognosis depends on the patient's age, the severity of the disease, the duration of the disease, the time from when the patient seeks medical care to treatment, the patient's medical history, and other factors.

Patient Education

• A child's immunizations should be kept up to date.
• The importance of fever, especially during the first 3 months of an infant life, should be emphasized.
• The importance of close follow-up should be communicated.
• Caretakers might ask their healthcare providers for educational materials or resources, and providers should be prepared to respond.
• For excellent patient education resources, visit eMedicine's Blood and Lymphatic System Center. Also, see eMedicine's patient education article Sepsis (Blood Infection).

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Special Concerns

• Immunocompromised patients
• Lack of reliable caretakers or safe home environment
• Lack of reliable outpatient follow-up
• History of abuse or neglect
• Immunizations are not up to date for age

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  ED management of fever of unknown source in neonates and infants aged 0-60 days. Adapted from Cincinnati Children's Hospital Medical Center.
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Media type:  Image

Media file 2:  ED management of fever of unknown source in infants and children aged 2-36 months. Adapted from Cincinnati Children's Hospital Medical Center.
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Media type:  Image

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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Article Last Updated: Feb 1, 2006