eMedicine Specialties > Emergency Medicine > Pediatric

Fever in the Neonate and Young Child

Stella C Wong, DO, Assistant Professor, Department of Emergency Medicine, Emory University School of Medicine
Richard J Scarfone, MD, Associate Professor, Department of Pediatrics, University of Pennsylvania School of Medicine; Attending Physician and Director of Emergency Preparedness, Division of Emergency Medicine, The Children's Hospital of Philadelphia; Fred Henretig, MD, Director, Section of Clinical Toxicology, Professor, Medical Director, Delaware Valley Regional Poison Control Center, Departments of Emergency Medicine and Pediatrics, University of Pennsylvania School of Medicine, Children's Hospital

Updated: Aug 6, 2009

Introduction

Background

This article discusses the appropriate emergency department (ED) clinical and laboratory evaluation of young febrile children, particularly those younger than 3 years of age. Fever, the abnormal elevation of body temperature, has long been recognized by physicians as a sign of disease. Furthermore, the evaluation of the febrile child is one of the most commonly encountered emergency conditions in children, accounting for as many as 20% of pediatric emergency department (ED) visits.¹
 
Fever in children may be caused by a number of common and exotic diseases, including viral systemic syndromes and focal infections, bacteremia and septicemia, focal bacterial infections, parasitic and vector-borne infections, and noninfectious etiologies such as vasculitic and hypersensitivity disorders, drug and vaccine reactions, Kawasaki syndrome, and several poisonings, including salicylism. Pinpointing the minimal temperature elevation considered to be definitely abnormal for all children under all circumstances is difficult.¹  Factors such as excessive clothing, physical activity, hot weather, food digestion, and ovulation can raise temperature in the absence of disease. For the appropriately dressed child, at rest, a rectal temperature of 38^o C (100.4^o F) is defined as fever by most authors.²  

Optimal technique to measure rectal temperature is important for accuracy.³ This includes proper positioning and restraint in infants (prone, supine, or on the side with hips slightly flexed), depth of insertion (about 2-3 cm), and time for equilibration (2-3 minutes with glass thermometers, several seconds with electronic digital probes). Thermometer placement directly into a fecal mass should be avoided because fecal temperature may not have equilibrated with rapid fluctuations in body temperature, and thus may be falsely low as temperature rises rapidly. Oral and axillary temperatures usually are about 0.6^o C (1^o F) and 1.1^o C (2^o F) less than rectal temperatures, respectively.

Recent attempts to measure temperature with less invasive techniques include temperature‑sensitive pacifiers and forehead strips, both of which have been found to be unreliable in young children. However, one technique that has been found to be acceptable to parents and reliable in most settings is that of infrared tympanic membrane thermometry. Several studies in children have confirmed the reliability of this technique compared with rectal temperature, although others have questioned its accuracy in young infants, especially those younger than 3 months.⁴ The presence of otitis media or cerumen does not seem to adversely affect reliability. Temporal artery thermometry has also been utilized, but it has limited sensitivity for detecting temperatures in the lower end of the fever range.⁵

Since even low‑grade fever may be clinically significant in young infants and there is at least some doubt about the reliability of axillary, tympanic, or temporal artery measurements in this age group, it would seem prudent to rely on rectal temperatures in this population.³

Pediatricians have historically considered that febrile infants younger than 2-3 months of age require a more detailed and invasive diagnostic evaluation than older children. The reasons for this are several, including the relative immaturity of infantile host defenses and the potential for perinatally acquired infections, both of which result in an increased risk of bacteremia, sepsis, and significant bacterial focal infections. 

In addition, in this age group, the clinical assessment of "toxicity", or septic appearance, is difficult, as such judgment relies on observation of the child’s responsiveness and behavior, which in babies is so developmentally limited. Thus, the traditional management approach to such infants has consisted of  thorough clinical assessment, supplemented by a comprehensive laboratory evaluation (so-called sepsis workup), and followed typically by empiric parenteral antibiotic therapy and hospitalization pending culture results. Current evidence-based and consensus guidelines are reviewed in the sections to follow.

The approach to febrile children in the age group of 3 months to 3 years has also been the subject of considerable interest and research. Children this age are more readily evaluated by physical examination findings and observation of general appearance than neonates and young infants. However, since the early 1970s, concern exists that clinically significant bacterial infections manifested solely by fever, without localizing signs or symptoms, may be missed by ordinary clinical evaluation. These have included particularly occult bacteremia and occult urinary tract infection. The indications for screening laboratory tests and blood and urine cultures have evolved considerably over time in the ensuing 4 decades, particularly as further research findings and newer immunization strategies have been implemented. In the following discussion, these new developments are highlighted and an evidence-based approach to this age group of febrile children is offered.

Pathophysiology

Fever is a complex phenomenon, involving the highly coordinated interplay of autonomic, neuroendocrine, and behavioral responses to a variety of infectious and noninfectious inflammatory challenges.¹ The febrile reaction is quite stereotyped and independent of precise causation.⁶  Various exogenous pyrogens (eg, toxins, infectious agents, antigen–antibody complexes) produce fever in humans by inducing the production of proteins, collectively termed endogenous pyrogens, by phagocytic leukocytes. These enter the circulation and interact with specialized receptor neurons in the preoptic, anterior hypothalamus. Signaling there leads to the production of prostaglandins, particularly PGE2, which is believed to be the critical mediator of the febrile response, and impacts on hypothalamic neurons that reset the thermostatic set point and result in several responses.

The major effect is on the vasomotor center and results in peripheral vasoconstriction of cutaneous beds with redirection of blood flow to deeper tissues, thus minimizing skin heat loss. Additionally, sweating is decreased; vasopressin secretion falls, resulting in lowered extracellular fluid volume that requires heating; and behavioral modifications such as shivering and seeking a warmer environment are stimulated. These effects combine to elevate body temperature. Very rarely, fever is the result of central nervous system dysfunction (eg, hypothalamic tumor, infarction) that alters the thermostatic set point directly, rather than via pyrogen induction.

There is evidence that increased body temperature impairs replication of many microbes and may aid phagocytic bactericidal activity.¹  The febrile response includes additional adaptive neuroendocrine effects. Glucose metabolism is lessened in favor of that based on lipolysis and proteolysis, thereby depriving bacteria of their preferred substrate. Fever‑induced anorexia also diminishes glucose availability to microbes. Hepatic synthesis of acute‑phase reactant proteins may result in binding divalent cations, which serve as growth factors for microorganisms. These effects combine to further enhance the host's response to microbial invasion.

Frequency

United States

Stanley et al reported that infants younger than 3 months with hyperpyrexia (core temperature >40°C) had a significantly increased prevalence of serious bacterial infection (SBI).⁷ Since the introduction of Haemophilus influenzae type B (Hib) vaccine, the number of Hib meningitis cases in children has decreased significantly.^8,9 Excluding the Pneumococcal Conjugate Vaccine (PCV7) studies, American College of Emergency Physicians (ACEP) Clinical Policies Committee reported that "The current prevalence of occult bacteremia among febrile children aged 3 to 36 months is most likely between 1.5% and 2%."¹⁰ PCV7 includes the following serotypes: 4, 6B, 9V, 14, 18C, 19F, and 23F.^11,12  The rate of occult bacteremia has decreased to less than 1% since the introduction of PCV7 in 2000.^13,14,15  

Whitney et al reported that the rates of invasive pneumococcal diseases (IPD) in children younger than 2 years old have declined 69% between 1998-1999 and 2001.¹²  In a "laboratory-based surveillance study" of children (<5 y old) in the Northern California Kaiser Permanente (NCKP) health care system, Black et al reported the average incidence of IPD decreased from 50.1 cases per 100,000 per year during pre-PCV 7 period (April 1996 to March 2000) to 4.9 cases per 100,000 per year after the introduction of PCV 7 (April 2000 to March 2005).¹⁶  

However, studies also show the incidence of other forms of bacteremia increased while the incidence of IPD decreased. In a quasi-experimental study of a cohort of children (<18 y old, n=188) at the Children's Hospital of Philadelphia (CHOP) from January 1999 to May 2005, Steenhoff et al reported the incidence of penicillin-resistance isolates increased from 25% (pre-PCV7) to 39% (post-PCV7), which was statistically significant (P<0.05). The incidence of bacteremia caused by vaccine (PCV7)-related serotypes also increased from 6% (pre-PCV7 period) to 35% (post-PCV7 period), which was also statistically significant (P<0.01). Vaccine-related serotypes was defined as "those of the same serogroup but not of the same serotype as PCV7".¹¹  

In a retrospective case series between September 1998 and August 2003 (n=352), Herz et al reported an increase in the incidence of bacteremia in children (3-36 months old) caused by Staphylococcus aureus, Escherichia coli, and Salmonella species.¹⁷ Singleton et al reported a 140% increase of nonvaccine serotypes IPD from 2001-2003 to 2004-2006 in Alaska Native children who were younger than 2 years old, and 28.3% of the cases (2004-2006) were caused by serotype 19A.¹⁸

Urinary tract infection (UTI) is the most common SBI in febrile infants and toddlers. The prevalence of UTI in children (2-24 months) with unknown source of fever is estimated to be 3-7%.^{10,19,20,21,22,23}  UTI was also reported to be found in 2.7-3.5% of children with a possible source of fever.^24,19,25

International

Richardson et al stated that "Infectious diseases remain a major cause of childhood mortality and morbidity in the United Kingdom".²⁶  Health care deficiency may be the cause.^26,27  

Mortality/Morbidity

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.^10,28,29,30 Renal scarring can lead to hypertension and end-stage renal failure later in life.^10,31 In addition to UTI, pneumonia, meningitis, bacteremia, and other SBI can also result if a serious infectious illness is not suspected or recognized.   

Race

Caucasian children are at higher risk for developing UTI.^24,19,25

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.¹⁰

Age

Age is an important factor in bacteremia and sepsis for at least the following 4 reasons. First, the immune system is not fully developed in young children. Second, the important pathogens vary with age. Third, infants are not scheduled to receive the first PCV immunization until they reach at least 6 weeks old. Fourth, young infants do not have the ability to demonstrate signs of an illness.³²  

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.³³

Clinical

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. See the 2008 immunization schedule.³⁴
  • History of maternal infections such as group B Streptococcus (GBS) and/or sexually transmitted diseases
  • History of exposure to sick contacts and treatments, such as antibiotics
  • Recent travel history
  • History of previous hospitalization, prolonged ICU stay, prematurity, or immunocompromised diseases
  • History of change in mental status, change in eating and/or behavioral patterns such as irritability, lethargy, or apnea
  • 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 the 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."¹⁰
• 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, septic arthritis (pseudoparalysis)
  • Skin - Rash (especially petechial rash), cellulitis, abscess, omphalitis

Causes

Causes of SBI in children have been reported as follows³³ :

• Neonates (0-28 d) - 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)

Differential Diagnoses

Other Problems to Be Considered

See Differentials for details.

Workup

Laboratory Studies

Infants younger than 4 weeks old

• Febrile neonates younger than 4 weeks old should have a full evaluation for sepsis. A full evaluation for sepsis consists of a complete blood cell count (CBC) with differential, blood culture, enhanced urinalysis (UA), urine culture, and a lumbar puncture (LP) to collect cerebrospinal fluid (CSF). CSF should be analyzed for cell counts, protein, glucose, and culture.
• A full evaluation for sepsis in febrile neonates is warranted because their risk for serious bacterial infection (SBI) is relatively high; even among those who otherwise meet low risk criteria, the rates of SBI are about 5%.
• Similarly, about 10% of febrile neonates who have documented respiratory syncytial virus or clinical bronchiolitis have SBI. This infection rate is about the same as for those without documented respiratory syncytial virus or clinical bronchiolitis; therefore, a full evaluation for sepsis should be performed for these patients.
• Evaluating febrile neonates for herpes simplex infection should be considered when the following risk factors are present: age younger than 3 weeks, vesicles, seizure, toxic or ill-appearing, CSF pleocytosis or red blood cells, or maternal history of herpes. Laboratory studies to screen for herpes infection may include vesicle fluid for culture and direct fluorescent antibody, swabbing nasopharynx, conjunctiva, and rectum for culture, or CSF for polymerase chain reaction testing and culture.
• One study determined that evaluating CSF for enterovirus by polymerase chain reaction testing reduced the duration of hospitalization and antibiotic use for young infants.

Infants aged 5-8 weeks old

• Most febrile infants aged 5-8 weeks presenting to the ED warrant a full evaluation for SBI because they are difficult to judge clinically and because ED physicians can not ensure adequate follow-up.
• The threshold for performing an LP in these infants should be low, but an LP may be omitted in well-appearing infants who have blood and urine studies obtained and when the following apply:
  • Reliable follow-up is possible in 12-24 hours.
  • Clinicians are confident that parents or caretakers can comply with appropriate observation and follow-up.
  • No antibiotics have been started.
• Urinary tract infection (UTI) is the most common SBI in this age group.
• Urethral catheterization is the method of choice to obtain urine to avoid contamination with skin flora. Urine collected in a bag placed on the perineum is often contaminated and should not be evaluated for bacterial culture.
• An enhanced UA (hemocytometer cell count and Gram stain of unspun urine) is more sensitive than a standard UA.
• Since negative urine dipstick or UA results in febrile young children do not always exclude UTI, urine cultures should be performed regardless of UA results.
• Chest radiographs do not need to be obtained routinely in those without signs of respiratory disease.
• Additional studies such as stool cultures are performed selectively. 

Children aged 2-24 months old

• Viral infections are the most common cause of fever in young children aged 2-24 months. Well-appearing children with unremarkable histories and physical examinations may be discharged home without laboratory testing or presumptive use of antibiotics.
• An LP should be considered for those who are irritable, lethargic, inconsolable, or toxic appearing.
• The rates of bacteremia and invasive pneumococcal disease have dramatically declined following the license of the polyvalent pneumococcal vaccine in 2000. This vaccine protects against the 7 pneumococcal serotypes that cause 85% of invasive pneumococcal disease in children, including nearly all of the serotypes that are highly penicillin resistant.
• The routine acquisition of CBC and/or blood cultures to screen for occult bacteremia in immunocompetent children is strongly discouraged for the following reasons:
  • The peripheral white blood cell count has a low positive predictive value for bacteremia.
  • Bacteremia rates are less than 1% in the postpneumococcal vaccine era.
  • Bacteremia spontaneous resolution rates (without antibiotics) are greater than 90%; therefore, few children with pneumococcal bacteremia develop complications.
  • High false-positive blood culture rates from contamination leads to unnecessary testing and/or hospitalizations.
  • Indiscriminate testing is costly and invasive.
• Similarly, the presumptive use of broad-spectrum antibiotics is strongly discouraged because of low bacteremia and complication rates, high costs, adverse drug reactions, increasing rates of antibiotic resistance due to indiscriminate antibiotic use, and because the outcomes for febrile young children not treated presumptively with parenteral antibiotics are uniformly good.
• A blood culture should be obtained in children ill enough to warrant an LP as described above, those exhibiting signs of shock, or those with a petechial rash.
• As with younger infants, UTI is the most common cause of SBI in this age group. Clinicians should have a lower threshold for ordering UA and urine cultures than for screening for bacteremia, especially for those with risk factors.
• For boys, risk factors for UTI include age younger than 6 months and being uncircumcised.
• For girls, risk factors for UTI include age younger than 12 months, Caucasian race, temperature above 39°C, illness for 2 days or more, and absence of any other source for fever.
• In particular, clinicians should have a lower threshold for UTI screening for Caucasian girls; in 2 separate studies, UTI rates were as high as 17% in this group.
• Diarrhea most commonly has a viral etiology in this age group. The presence of diarrhea with blood or mucus or recent use of antibiotics may be indications for ordering stool cultures to assess for a bacterial etiology.

Imaging Studies

• Chest radiographs should not be routinely performed for fever alone, in the absence of lower respiratory tract findings or hypoxemia.
• Chest radiographs are most useful for those with high fever, focal pulmonary examination findings, rales, grunting, flaring, retractions, or hypoxia, or for the subset of patients with leukocytosis (if obtained) in the absence of an alternative source of fever.

Other Tests

• Erythrocyte sedimentation rate and C-reactive protein are nonspecific tests of inflammation that are rarely useful in the assessment of the acutely ill febrile infant or child.

Procedures

• Suprapubic aspiration of the bladder for urine should be discouraged. Urethral catheterization is less invasive, less painful, and is associated with a higher yield of urine.
• Lumbar punctures should be considered for febrile infants and children who are younger than 8 weeks old; have a full anterior fontanelle; are persistently irritable, inconsolable, or lethargic; or have a petechial rash.

Treatment

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

Clinicians first need to perform prehospital care if it has not already been completed. Children who are unstable or seriously ill need fluid resuscitation, pressors, or both. 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 an unstable condition is evaluating a child in a 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 health care, and others
• Temperature upon ED arrival
  • A common dilemma involves the young infant brought to the ED with a description of either tactile fever alone (eg, the baby "felt warm" but temperature was not taken), or fever confirmed by rectal temperature at home but is afebrile on arrival. One study found that history of tactile fever in such infants may not correlate with subsequent fever, whereas an elevated rectal temperature measured at home does correlate in a significant minority.⁴³ However, all such infants who were found to have serious bacterial infections were observed to have had an abnormal initial clinical profile and/or laboratory workup.
  • Thus, a careful clinical evaluation should be performed in all young infants with any history of fever, including one or more repeat temperatures over 1-2 hours in the ED after the baby is unbundled. In the infant younger than 2-3 months with a reliable history of elevated rectal temperature, a "sepsis workup," as detailed below, should be considered seriously along with a subsequent disposition based on age, the evolution of temperature pattern, clinical findings, and laboratory results. The infant with only a history of tactile fever, whose repeated rectal temperature remains normal and who has an entirely normal clinical evaluation may be assessed as not requiring laboratory studies. All such infants discharged home still warrant close follow‑up and continued short‑term monitoring of rectal temperature.¹

Workup

See Workup.

Lab Studies

See Lab Studies.

Treatments and medication (also see Medication)

• Manage the airway (oxygen supplement or intubation as needed) and secure intravenous access if it was not established during prehospital care.
• Monitor the patient's heart rate (HR), blood pressure (BP), and pulse oximetry readings.
• Administer intravenous 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 as needed for fever.
• Administer antibiotics as indicated.

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 0-28 days old should be admitted.^44,24,45
• Infants/children older than 28 days old may be discharged home if they are well-appearing and meet all of the low-risk criteria (see below), otherwise, admission is warranted.^{44,24,46,47,48,49,50}
• Low-risk criteria
  • Did not receive antibiotics within the past 48 hours
  • No dehydration, lethargy, irritability, or wheezing
  • No focal source of infection on physical examination (except otitis media)
  • Laboratory tests    
    • CSF <8 WBC/hpf
    • WBC between 5 and 15,000 and band:poly <0.2
    • UA <10 WBC/hpf
    • Chest radiograph without infiltrate (if obtained)
    • Caretaker is available by phone for follow-up and can bring the patient back to ED in 24 hours as needed

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

Antibiotics, antivirals, and antipyretics agents are indicated for successful treatment of bacteremia and sepsis in neonates and children. Preventive therapy by following the CDC immunization guidelines is the cornerstone of well-baby checkups throughout childhood and adolescence.

Antibiotic agents

Obtain blood culture before administering antibiotics. Neonates aged 0-30 days should be treated with combination of IV ampicillin and a third-generation cephalosporin or gentamicin.⁴⁴ For infants aged 31-60 days, a third-generation IV cephalosporin alone is recommended as first-line therapy.^44,51,52 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.^44,51,52,53 In addition to the antibiotics discussed above, vancomycin should be considered in settings where MRSA is prevalent or suspected. Children aged 2-36 months should be treated with antibiotic(s) as indicated. 

Ampicillin (Principen)

Broad-spectrum penicillin. Interferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms. Alternative to amoxicillin when unable to take medication orally.

Dosing

Adult

Not applicable for adults

Pediatric

Neonates: 50-100 mg/kg/dose IV q12h
50-100 mg/kg/d PO divided q4-6h or 100-400 mg/kg/d IV/IM divided q4-6h

Interactions

Probenecid and disulfiram elevate ampicillin levels; allopurinol decreases ampicillin effects and has additive effects on ampicillin rash; may decrease effects of oral contraceptives

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal failure; evaluate rash and differentiate from hypersensitivity reaction

Vancomycin (Lyphocin, Vancocin, Vancoled)

Used in prophylaxis. Potent antibiotic directed against gram-positive organisms and active against Enterococcus species. Useful in the treatment of septicemia and skin structure infections. Indicated for patients who can not receive, have failed to respond to penicillins and cephalosporins, or have infections with resistant staphylococci. For abdominal penetrating injuries, it is combined with an agent active against enteric flora and/or anaerobes.
To avoid toxicity, current recommendation is to assay vancomycin trough levels after third dose drawn 0.5 h prior to next dosing. Use creatinine clearance to adjust dose in patients with renal impairment.
Used in conjunction with gentamicin for prophylaxis in penicillin-allergic patients undergoing gastrointestinal or genitourinary procedures.

Dosing

Adult

500 mg to 2 g/d IV divided tid/qid 7-10 d

Pediatric

Neonates: 10-15 mg/kg/dose IV/IM q12-24h
40 mg/kg/d IV divided tid/qid 7-10 d

Interactions

Erythema, histaminelike flushing, and anaphylactic reactions may occur when administered with anesthetic agents; taken concurrently with aminoglycosides, risk of nephrotoxicity may increase above that with aminoglycoside monotherapy; effects in neuromuscular blockade may be enhanced when coadministered with nondepolarizing muscle relaxants

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in renal failure and neutropenia; red man syndrome is caused by too rapid IV infusion (dose given over a few min) but rarely happens when dose given IV over 2 h administration or as PO or IP administration; red man syndrome is not an allergic reaction

Gentamicin

Aminoglycoside antibiotic for gram-negative coverage 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 are numerous and are adjusted based on CrCl and changes in volume of distribution, as well as body space into which agent needs to distribute. Each regimen must be followed by, at least, trough level 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 group B Streptococcus or Enterococcus.

Dosing

Adult

Not applicable for adults

Pediatric

<4 weeks and <1200 g: 2.5 mg/kg/dose IV q18h
<7 days and >1200 g: 2.5 mg/kg/dose IV q12h
>7 days and 1200 g: 2.5 mg/kg/dose IV q8h
IV dosage preferred; IM is poorly absorbed but may be used if IV access difficult

Interactions

Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; because 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)

Contraindications

Documented hypersensitivity; non–dialysis-dependent renal insufficiency

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment

Cefotaxime (Claforan)

Third-generation cephalosporin with broad gram-negative spectrum, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms. Arrests bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins, which, in turn, inhibits bacterial growth. Used for septicemia and treatment of gynecologic infections caused by susceptible organisms.

Dosing

Adult

Moderate-to-severe infections: 1-2 g IV/IM q6-8h
Life-threatening infections: 1-2 g IV/IM q4h

Pediatric

Neonates: 50-100 mg/kg/dose IV/IM q12h
Infants and children: 50-180 mg/kg/d IV/IM divided q4-6h
For meningitis, use dose at higher end of dosage range
>12 years: Administer as in adults

Interactions

Probenecid may increase cefotaxime levels; coadministration with furosemide and aminoglycosides may increase nephrotoxicity

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in severe renal insufficiency (high doses may cause CNS toxicity); superinfections, and promotion of nonsusceptible organisms may occur with prolonged use or repeated therapy; has been associated with severe colitis

Ceftriaxone (Rocephin)

Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Bactericidal activity results from inhibiting cell wall synthesis by binding to one or more penicillin-binding proteins. Exerts antimicrobial effect by interfering with synthesis of peptidoglycan, a major structural component of bacterial cell wall. Bacteria eventually lyse due to the ongoing activity of cell wall autolytic enzymes while cell wall assembly is arrested.
Highly stable in presence of beta-lactamases, both penicillinase and cephalosporinase, of gram-negative and gram-positive bacteria. Approximately 33-67% of dose excreted unchanged in urine, and remainder secreted in bile and ultimately in feces as microbiologically inactive compounds. Reversibly binds to human plasma proteins, and binding has been reported to decrease from 95% bound at plasma concentrations <25 mcg/mL to 85% bound at 300 mcg/mL.

Dosing

Adult

Uncomplicated infections: 250 mg IM once as a single dose
Severe infections: 1-2 g IV qd, or divided bid; not to exceed 4 g/d

Pediatric

Neonates >7 d: 25-50 mg/kg/d IV/IM; not to exceed 125 mg/d
Infants and children: 50-75 mg/kg/d IV/IM divided q12h; not to exceed 2 g/d

Interactions

Probenecid may increase ceftriaxone levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity

Contraindications

Documented hypersensitivity; hyperbilirubinemic neonates, particularly those who are premature

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in severe renal insufficiency (high doses may cause CNS toxicity); superinfections, and promotion of nonsusceptible organisms may occur with prolonged use or repeated therapy; caution in breastfeeding women; may displace bilirubin from albumin-binding sites increasing the risk of kernicterus; caution with gallbladder, biliary tract, liver, or pancreatic disease; caution in patients with history of colitis or penicillin hypersensitivity

Nafcillin

Initial therapy for suspected penicillin G-resistant streptococcal or staphylococcal infections. Use parenteral therapy initially in severe infections. Change to oral therapy as condition warrants.
Due to thrombophlebitis, particularly in elderly persons, administer parenterally only for short term (1-2 d); change to oral route as clinically indicated.

Dosing

Adult

250 mg to 1 g PO q4-6h
Alternatively, 500 mg to 1 g IV/IM q4-6h

Pediatric

<4 kg (neonates): 10 mg/kg IV/IM bid
4-40 kg: 25 mg/kg IV/IM bid
Alternatively, 100-200 mg/kg/d IV/IM in 4-6 divided doses
PO dosing for children: 50 mg/kg/d PO divided qid

Interactions

Associated with warfarin resistance when administered concurrently; effects may decrease with bacteriostatic action of tetracycline derivatives

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

To optimize therapy, determine causative organisms and susceptibility; >10 d treatment to eliminate infection and prevent sequelae (eg, endocarditis, rheumatic fever); take cultures after treatment to confirm that infection is eradicated

Antiviral agents

Infants are at risk for neonatal HSV infections if they are delivered vaginally and if the mother has known HSV infection during delivery. Acyclovir is recommended for presumed neonatal herpes simplex virus (HSV) infection. Specimen(s) should be collected before antiviral therapy.^44,54

Acyclovir (Zovirax)

Prodrug activated by phosphorylation by virus-specific thymidine kinase (TK); inhibits viral replication. Herpes virus but not host cell TK uses acyclovir as purine nucleoside, converting it to acyclovir monophosphate (nucleotide analog). Guanylate kinase converts monophosphate form to diphosphate and triphosphate analogs that inhibit viral DNA replication.
Affinity for viral TK. After phosphorylation, causes DNA chain termination when DNA polymerase acts on it. Inhibits HSV-1 and HSV-2 activity. Patients have less pain and speeded resolution of cutaneous lesions when used within 48 h of rash onset. May prevent recurrent outbreaks. Early therapy imperative.
Double dose suggested for HSV proctitis or ocular infections. Ocular infections can also be treated with topical acyclovir. Oral suspension 40 mg/mL available.

Dosing

Adult

First episode of mucocutaneous HSV: 200 mg PO 5 times/d or 400 mg tid for 7-10 d or until clinical resolution occurs
Recurrent genital herpes: 200 mg PO 5 times/d for 5 d
Chronic suppressive therapy: 400 mg PO bid or 200 mg 3-5 times/d; reevaluate after 1 y
HSV encephalitis: 10 mg/kg/dose IV q8h for 10-14 d
Severe infection in immunocompromised host: 5-10 mg/kg/dose IV q8h for 5-10 d

Pediatric

First episode of mucocutaneous HSV: 20-30 mg/kg/d PO in 5 divided doses for 7-10 d
Severe infections in immunocompromised children: 10 mg/kg/dose IV q8h for 7 d
Herpes encephalitis: 20 mg/kg/dose IV q8h for 10-14 d

Interactions

Concomitant probenecid or zidovudine prolongs half-life and increases CNS toxicity

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in renal failure or with nephrotoxic drugs

Antipyretic agents

Administer antipyretics for fever (ie, temperature >100.4 ºF).

Hay et al studied whether administering a combination of acetaminophen and ibuprofen for fever in children was superior to administration of acetaminophen alone or ibuprofen alone.⁵⁵ Dosage was calculated as acetaminophen 15 mg/kg/dose and ibuprofen 10 mg/kg/dose. Children aged 6 months to 6 years whose fever could be managed at home (37.5-41 degrees Celsius) were included. Use of acetaminophen and ibuprofen improved time without fever during the first 4 hours and was superior to acetaminophen alone, but not ibuprofen alone. The combination also decreased fever 23 minutes faster than acetaminophen alone, but no faster than ibuprofen alone. Time without fever during the first 24 hours was improved with the combination compared with either acetaminophen or ibuprofen.

Ibuprofen (Advil, Motrin)

One of the few NSAIDs indicated for reduction of fever.

Dosing

Adult

200-400 mg PO q4-6h while symptoms persist; not to exceed 3.2 g/d

Pediatric

6 months to 12 years: 4-10 mg/kg/dose PO tid/qid; not to exceed 2.4 g/d
>12 years: Administer as in adults

Interactions

Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; simultaneous administration with low-dose aspirin may decrease aspirin's cardioprotective and stroke preventive effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, beta-blockers, and diuretic effect of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; may increase phenytoin or lithium serum levels

Contraindications

Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in coagulation abnormalities or during anticoagulant therapy

Acetaminophen (Tylenol, Tempra)

Inhibits action of endogenous pyrogens on heat-regulating centers; reduces fever by a direct action on the hypothalamic heat-regulating centers, which, in turn, increase the dissipation of body heat via sweating and vasodilation.

Dosing

Adult

325-650 mg PO q4h; not to exceed 4 g/d

Pediatric

<12 years: 10-15 mg/kg/dose PO q4-6h prn; not to exceed 2.6 g/d
>12 years: 325-650 mg PO q4h; not to exceed 4 g/d

Interactions

Rifampin can reduce analgesic effects of acetaminophen; coadministration with barbiturates, carbamazepine, hydantoins, and isoniazid may increase hepatotoxicity

Contraindications

Documented hypersensitivity; known G-6-PD deficiency

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Hepatotoxicity possible in chronic alcoholics following various dose levels; severe or recurrent pain or high or continued fever may indicate a serious illness; acetaminophen contained in many OTC products and combined use with these products may result in toxicity due to cumulative doses exceeding recommended maximum dose; carefully explain instructions and precise product to use (liquid concentrations vary), emphasize using correct measuring device

Follow-up

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 culture results 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 on an outpatient basis 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.

Inpatient & Outpatient Medications

See Medication for details.

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.

Deterrence/Prevention

Provide education to parents regarding the signs or symptoms of a serious bacterial infection, the importance of following the recommended immunization schedule and seeking immediate medical attention if a child should present any signs or symptoms of a serious bacterial infection. 

Complications

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

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’s life, should be emphasized.
• The importance of close follow-up should be communicated.
• Caretakers might ask their health care 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

Medicolegal Pitfalls

• Failure to recognize/suspect occult bacteremia, serious bacterial infection (SBI), and/or sepsis
• Failure to properly workup or treat fever or unknown source (FUS)
• Failure to transfer/admit a child to the hospital for further testing and treatment when it is indicated
• Failure to administer antibiotics and/or antiviral when it is indicated
• Failure to ask about a child's immunization status
• Failure to consult a pediatrician when it is indicated

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

Media file 1: 2008 Immunization Schedule

Acrobat PDF available at http://img.medscape.com/pi/emed/ckb/emergency_medicine/756148-799743-800286-1489479.pdf.

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Keywords

fever in babies, fever in young children, febrile infants and young children, serious bacterial infection, SBI, heptavalent pneumococcal conjugate vaccine (PCV7), children in the emergency department, bacteremia, sepsis, UTI, urinary tract infection, pneumonia, meningitis 

Contributor Information and Disclosures

Author

Stella C Wong, DO, Assistant Professor, Department of Emergency Medicine, Emory University School of Medicine
Stella C Wong, DO is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, American College of Osteopathic Emergency Physicians, American Osteopathic Association, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Richard J Scarfone, MD, Associate Professor, Department of Pediatrics, University of Pennsylvania School of Medicine; Attending Physician and Director of Emergency Preparedness, Division of Emergency Medicine, The Children's Hospital of Philadelphia
Richard J Scarfone, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Pediatrics
Disclosure: Nothing to disclose.

Fred Henretig, MD, Director, Section of Clinical Toxicology, Professor, Medical Director, Delaware Valley Regional Poison Control Center, Departments of Emergency Medicine and Pediatrics, University of Pennsylvania School of Medicine, Children's Hospital
Disclosure: Nothing to disclose.

Medical Editor

Kirsten A Bechtel, MD, Associate Professor, Department of Pediatrics, Yale University School of Medicine; Attending Physician, Department of Pediatric Emergency Medicine, Yale-New Haven Children's Hospital
Kirsten A Bechtel, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Wayne Wolfram, MD, MPH, 
Wayne Wolfram, MD, MPH is a member of the following medical societies: American Academy of Emergency Medicine, American Academy of Pediatrics, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Richard G Bachur, MD, Associate Professor of Pediatrics, Harvard Medical School; Associate Chief and Fellowship Director, Attending Physician, Division of Emergency Medicine, Children's Hospital of Boston
Richard G Bachur, MD is a member of the following medical societies: American Academy of Pediatrics, Society for Academic Emergency Medicine, and Society for Pediatric Research
Disclosure: Nothing to disclose.

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, Michael H Goodyear, DO, Stuart A Friedman, DO, and Mary Beth Crawford, MD, to the development and writing of this article.

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