AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Physiology of Temperature Control
• Approach to Patient
• Physical Examination
• Diagnostic Workup and Management
• Fever Without Source
• Guidelines for Treatment of Febrile Infants by Age Group
• Medications
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Physiology of Temperature Control
• Approach to Patient
• Physical Examination
• Diagnostic Workup and Management
• Fever Without Source
• Guidelines for Treatment of Febrile Infants by Age Group
• Medications
• Multimedia
• References

Background

Fever is one of the most common symptoms faced by pediatricians and emergency physicians. The clinical and laboratory approach to diagnosing and managing febrile illness in infants and toddlers remains challenging. This article provides general guidelines to assist the pediatrician and emergency physician in determining the appropriate diagnosis and treatment in the febrile child.

Definition of fever

The 3 methods of determining body temperature are orally, rectally, and via the axilla.

The oral route of determining temperatures is preferred in children older than 5 years. Typically, a mercury thermometer is placed under the tongue for 4 minutes with the lips closed. Newer (electronic) devices can ascertain oral temperatures more quickly. Reference range oral temperatures are 35.6-37.4°C (96.0-99.3°F).

The reference range for axillary temperatures is 37-37.4°C. Axillary temperatures are inaccurate and should not be used.

Rectal temperatures are obtained by placing a lubricated thermometer in the rectum for 4 minutes. The reference range is 36.1-38.0°C (97-100.3°F).

Typically, temperature fluctuates between a low of 36.1°C at around 4 am and a diurnal high of 37.9°C at around 6 pm. The variation is slight in children younger than 2 years, but, in children older than 2 years, the variation may range from the normal temperature by 0.8-1.2°C (1.4-2°F).

Fever is defined as a rectal temperature higher than or equal to 38°C (100.4°F). Occasionally, serious infectious diseases can be associated with a temperature of 100.4°F.

While bundling the child in blankets or clothing in cases of hypothermia or rectal temperatures less than 36°C has been associated with a rise in skin surface temperature, it is rarely responsible for appreciable increases in core temperature.

For excellent patient education resources, visit eMedicine's Children's Health Center. Also, see eMedicine's patient education article Fever in Children.

PHYSIOLOGY OF TEMPERATURE CONTROL

Section 3 of 11  

• Authors and Editors
• Introduction
• Physiology of Temperature Control
• Approach to Patient
• Physical Examination
• Diagnostic Workup and Management
• Fever Without Source
• Guidelines for Treatment of Febrile Infants by Age Group
• Medications
• Multimedia
• References

Human body temperature is maintained by the anterior hypothalamus. In response to a rise in temperature, the body dissipates heat via evaporation of water from the body surface and lungs and through radiation (60%), convection (12%), and conduction (3%). Simultaneously, the hypothalamus stimulates vasodilatation to increase insensible loss (for every 1°C elevation in temperature, a 10% insensible loss occurs) and activates the sweat glands to increase perspiration production.

The body responds to heat loss in 2 major ways. The hypothalamus stimulates the sympathetic centers, causing vasoconstriction. It also inhibits cholinergic stimulation of the sweat glands, preventing water evaporation from the skin.

Fever is produced predominately by endogenous pyrogens, primarily cytokines, such as interleukin-I and interleukin-VI, and probably tumor necrosis factor. These mediators circulate to the anterior hypothalamus, causing local rise of prostaglandin E₂ and subsequent increase in the set-point. Occasionally, fever is induced by pyrogenic material contained in organisms, such as group A Streptococcus. The streptococcal pyrogenic exotoxins act as "superantigens," resulting in the production of cytokines. Endogenous pyrogens are produced and released by macrophages after contact with infectious organisms. Vasculitic syndromes, hypersensitivity phenomena, and neoplasms may also induce their production and release. These endogenous pyrogens circulate in the blood and affect the central thermostat.

APPROACH TO PATIENT

Section 4 of 11  

• Authors and Editors
• Introduction
• Physiology of Temperature Control
• Approach to Patient
• Physical Examination
• Diagnostic Workup and Management
• Fever Without Source
• Guidelines for Treatment of Febrile Infants by Age Group
• Medications
• Multimedia
• References

Careful history taking may provide important clues to the diagnosis in the febrile child. Questions should include the age of the child, onset and duration of fever, and the degree of temperature, as well as the temperature-taking method, the child's behavior and activity levels, medications administered, and associated symptoms. The presence of similar symptoms in other family members or playmates may also be an important clue. Focus the past medical history on any underlying diseases or medications that may compromise host immunity, such as malignancy, asplenia, chronic steroid use, and/or chemotherapy.

PHYSICAL EXAMINATION

Section 5 of 11  

• Authors and Editors
• Introduction
• Physiology of Temperature Control
• Approach to Patient
• Physical Examination
• Diagnostic Workup and Management
• Fever Without Source
• Guidelines for Treatment of Febrile Infants by Age Group
• Medications
• Multimedia
• References

General appearance

Clinicians may gain an important first impression of a febrile child's general appearance during the interview. Observing the child in the parent's arms from afar yields a very useful assessment of the child's overall toxicity. Signs to evaluate include the child's alertness, color, respiratory status, responsiveness to other people or objects, feeding pattern, and age-appropriate gross motor activities (see the Table).

Integument

Skin examination is helpful in early detection of some of the more severe life-threatening infections. Look for evidence of poor perfusion, mottling, or petechial rashes, which are all signs of serious systemic illness.

• In Kawasaki syndrome, the clinician may note scarlatiniform, morbilliform, macular and papular erythema, multiformelike target lesions, urticarial plaques, or even pustules. Swollen erythematous hands or desquamation of distal digits can be found.
• Petechial rashes can occur in bacterial and rickettsial sepsis, such as meningococcemia and Rocky Mountain spotted fever.
• Osler nodes (ie, painful tender nodules primarily on the pads of the fingers and toes) and Janeway lesions (ie, painless, nontender, hemorrhagic, nodular lesions on the palms and soles, especially on the thenar and hypothenar eminence), although rare, may be found in children with endocarditis.
• Cellulitis is another common cause of fever in toddlers. Typically, the examiner notices localized signs of redness, warmth, and tenderness on the skin.
• Viral exanthems, such as those occurring in rubeola, varicella, coxsackievirus, and herpes simplex virus, help to readily identify the cause of fever. Note that human herpesvirus type 6 (HHV6), also known as exanthem subitum (ie, roseola infantum or sixth disease), has been found to be a common cause of fever in toddlers. Unlike the other types of herpes viruses, patients with HHV6 usually present with fever without rash. These infections are commonly associated with irritability, respiratory symptoms, and seizures in 3-13% of the cases.
• Patients with scarlet fever can present with sandpaper rash, Pastia lines, strawberry tongue, desquamation, and pharyngitis.

Head, eyes, ears, nose, mouth, and throat

The head, eyes, ears, nose, mouth, and throat are sites for some of the more common infections in children.

• The eyes may show conjunctivitis, periorbital cellulitis, or orbital cellulitis with signs such as decreased extraocular mobility, proptosis, decreased visual acuity, and papilledema.
• Tympanic membranes may show signs of acute otitis media with the cardinal signs of erythema, decreased motility, and loss of landmarks and light reflex.
• The nose, mouth, and throat may show inflammation or ulceration suggestive of upper respiratory infections, herpangina, herpetic gingivostomatitis, or streptococcal pharyngitis
• A prolonged course of upper respiratory infection may lead to sinusitis, suggested by 8 or more consecutive days of nasal discharge, daytime and nighttime cough, and, occasionally, sinus tenderness and postnasal drip.

Neck

• Cervical adenitis is another common complication of an extended course of upper respiratory infection. It usually appears as a well-circumscribed tender area of swelling upon examination of the neck.
• Retropharyngeal abscess is most commonly observed in children younger than 3 years. Patients may present with stridor and/or meningismus caused by irritation of the paravertebral ligaments.
• Patients with peritonsillar, retropharyngeal, and lateral pharyngeal wall abscesses may also present with a neck mass and tenderness. Peritonsillar abscesses are generally observed in older children and adolescents; patients usually show signs of dysphagia, voice changes (eg, a muffled voice), trismus, drooling, and deviation of the uvula to the contralateral side.

Cardiovascular system

Any new or worsening cardiac murmur, distant or muffled heart sounds, tachycardia out of proportion to fever, grunting respiration with relatively clear lungs, and hepatomegaly should make the examiner wary of possible endocarditis, pericarditis, or myocarditis. Although these may be caused by bacterial organisms, such as Staphylococcus aureus and Haemophilus influenzae, they may also result from viral infections, such as coxsackievirus B.

Respiratory system

• Tachypnea, nasal flaring, retractions, and auscultatory abnormalities (such as decreased breath sounds, wheezing, rales, and rhonchi) can suggest pneumonia, bronchiolitis, and tracheobronchitis.
• Inspiratory stridor or a barking cough that is worse at night in a fully immunized child younger than 2 years may suggest laryngotracheobronchitis or croup.
• A more rapidly progressive process associated with a toxic appearance could suggest bacterial tracheitis or the life-threatening yet increasingly rare disease of epiglottitis.

Abdomen

• In a simple case of viral gastroenteritis, abdominal examination findings are usually benign.
• Other gastrointestinal diseases to consider include hepatitis, cholangitis, appendicitis, peritonitis, and pancreatitis.
• Patients with an acute abdomen (as occurs in appendicitis) can present with anorexia, low-grade fever, right lower quadrant tenderness over the McBurney point, psoas sign, and/or obturator sign.
• Patients with a perforated appendix may demonstrate signs of diffuse abdominal pain with rebound tenderness, rigidity, and guarding.

Genitourinary system

One of the more common causes of fever is urinary tract infection (UTI). This diagnosis can be extremely subtle in the preverbal child. A high index of suspicion should be maintained for UTI for highly febrile children, particularly white girls younger than 1 year. Suprapubic or flank tenderness, while helpful, is often absent in young children, who may instead present with vomiting or diarrhea.

Musculoskeletal system

• In septic arthritis, a swollen joint with tenderness, erythema, increased warmth, and decreased range of motion may be appreciated.
• Patients with osteomyelitis present with the constellation of fever, irritability, malaise, restriction of movement of the involved extremity, and signs of localized inflammation.
• Patients with myositis, most commonly associated with outbreaks of influenza A, may present with severe muscle pain, especially in the calf muscles.

Poisonings

• Accidental ingestions are quite common among toddlers. Salicylates, in particular, may cause fever when toxic levels are ingested.
• Other less common ingestions causing fever include phenothiazines, antidepressants, atropine, amphetamines, and other anticholinergic medications.

DIAGNOSTIC WORKUP AND MANAGEMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Physiology of Temperature Control
• Approach to Patient
• Physical Examination
• Diagnostic Workup and Management
• Fever Without Source
• Guidelines for Treatment of Febrile Infants by Age Group
• Medications
• Multimedia
• References

Consider several factors when assessing patients with fever. These features include (1) age of the patient, (2) status of the patient's immune system, (3) degree of toxicity, (4) signs and symptoms of life-threatening diseases such as meningitis and epiglottitis, and (5) any localizing features on history and/or physical examination. Perform laboratory and imaging studies where warranted.

Because of parental "fever phobia," physicians are frequently confronted with the use of antipyretics for febrile children. Acetaminophen has become the drug of choice for most parents, and its use is almost overzealous. Some evidence exists that improper use may cause harm.

Acetaminophen is a para-aminophenol derivative that inhibits cyclooxygenase and the formation and release of prostaglandin. It is absorbed in the gastrointestinal tract and reaches a peak plasma concentration in 30-60 minutes. Adverse effects include allergic reactions and hepatotoxicity following overdose, which may lead to organ degeneration and even death. Base dosing for acetaminophen on weight (10-15 mg/kg per dose) and do not exceed 5 doses within 24 hours. If fever persists despite therapeutic doses, sponge bathing in tepid water is an effective adjunctive means of antipyresis.

Ibuprofen is a nonsteroidal anti-inflammatory propionic acid derivative that also inhibits the biosynthesis of prostaglandin. It is also absorbed in the gastrointestinal tract and reaches its peak plasma concentration in 2 hours. As with acetaminophen, its metabolism takes place in the liver. Base dosing on weight at 10 mg/kg per dose once every 6-8 hours.

Discourage the alternating use of acetaminophen and ibuprofen. Both of these are metabolized in the liver, and alternating the two may cause confusion in administration and subsequent overdosing, leading to hepatotoxicity and even death. Toddlers and children generally tolerate low-grade fever well. The use of antipyretics is often unnecessary.

FEVER WITHOUT SOURCE

Section 7 of 11  

• Authors and Editors
• Introduction
• Physiology of Temperature Control
• Approach to Patient
• Physical Examination
• Diagnostic Workup and Management
• Fever Without Source
• Guidelines for Treatment of Febrile Infants by Age Group
• Medications
• Multimedia
• References

The approach to patients who have fever without source has long been in debate. Multiple complex decisions must be made to ensure optimal care for these patients and prevent serious sequelae while discouraging the inappropriate usage of antibiotics. Clinical and laboratory predictors are often used in trying to identify infants and children at risk for serious bacterial infection. Predictors used more frequently include (1) age of the patient, (2) presenting temperature, (3) absolute neutrophil count (ANC), (4) white blood cell (WBC) count, (5) absolute band count (ABC), and (6) the Yale Observation Scale. The first 3 predictors appear to be the most sensitive.

GUIDELINES FOR TREATMENT OF FEBRILE INFANTS BY AGE GROUP

Section 8 of 11  

• Authors and Editors
• Introduction
• Physiology of Temperature Control
• Approach to Patient
• Physical Examination
• Diagnostic Workup and Management
• Fever Without Source
• Guidelines for Treatment of Febrile Infants by Age Group
• Medications
• Multimedia
• References

These guidelines may hopefully serve to reduce unnecessary costs while optimizing the care of children with fever. These guidelines are not intended to be used rigidly. Physicians may diverge from them based on the need of the individual child.

Stratifying infants into low- and high-risk groups is possible using a number of previously validated criteria. The most commonly used screening criteria are known as the Rochester criteria. To be categorized as low-risk using the Rochester criteria requires that the patient be previously healthy with no prior antibiotic therapy, no prior hospitalization, and no history of prematurity or complicated neonatal course. On physical examination, the patient should appear to be nontoxic (ie, having a high level of consciousness with good eye contact and interaction with persons or objects in the environment, nonirritable, easily consolable).

Patients should not have cyanosis and should not show any signs of poor perfusion, marked hypoventilation, or hyperventilation. Also, patients should show no signs of focal infections, such as cellulitis, pneumonia, otitis media, and joint or bone infection. The low-risk criteria also include negative findings on laboratory screening with a WBC count of 5,000-15,000 cells/µL and a normal result on urine dip for leukocytes and nitrates (or <10 WBCs per high-power field [HPF]).

Newborns aged 0-28 days

The rate of bacteremia is 2-3% in all febrile infants younger than 2 months; the rate of bacteremia in the first month of life is 7-8%, which is double that of the infants aged 3-24 months. The risk of serious bacterial infection in nontoxic infants aged 0-60 days ranges from 4-16%.

Because the Rochester criteria are not routinely used to screen febrile infants for meningitis, the authors advocate performing a sepsis evaluation and hospitalizing the patient for parenteral antimicrobial therapy pending culture results. The sepsis workup includes complete blood cell (CBC) count, blood culture, urine analysis (UA), catheterized or suprapubic urine culture, cerebral spinal fluid (CSF) cell count, and CSF Gram stain and culture. If diarrhea is present, patients should have less than 5 WBCs/HPF in a Gram-stained smear of the stool. The risk of serious infections among the low-risk infants in this age group is very small. Jaskiewicz et al (1994) found the Rochester criteria to yield a negative predictive value of 99.3% for the detection of serious bacterial infection in children.

Similarly, Baraff et al (1992) found the risk of bacteremia to be about 1.1% and the risk of meningitis about 0.5% in patients classified as low-risk. However, most physicians perform a full sepsis workup (ie, CBC count, blood culture, UA, catheterized or suprapubic urine culture, CSF examination and culture) in all high- and low-risk infants in this age group, followed by hospitalization for parenteral antimicrobial therapy (eg, ampicillin/gentamicin or ampicillin/cefotaxime) pending culture results. No chest radiograph is necessary in the absence of respiratory symptoms or signs because the mean probability of finding an infiltrate on chest radiograph in asymptomatic infants is low.

Please see Image 1 for treatment of febrile newborns aged 0-28 days.

High-risk newborns aged 4-8 weeks (29-56 d)

This includes both toxic-appearing infants and nontoxic-appearing infants who do not meet low-risk criteria. As in the category of newborns aged 0-28 days, these infants deserve a full sepsis workup, followed by hospitalization for parental antimicrobials while waiting for culture results.

Low-risk newborns aged 4-8 weeks (29-56 d)

For infants aged 29-56 days, the risk for serious bacterial infection ranges from 0.4-2.7%. Even in the well-appearing febrile child with no focus of infection on physical examination, a sepsis workup as outlined above should still be performed. However, if the parent is deemed reliable, if close follow-up care can be ensured, and if the findings on workup categorize the patient in the low-risk category, the patient can be observed as an outpatient. The decision to use ceftriaxone while cultures are pending is an option left to the physician depending on the physician's and patient's level of comfort in the setting of the low, but nonzero, risk of occult infection. In order to embark on an outpatient management approach, face-to-face follow-up within 18-24 hours must be assured. Recall and admit to the hospital for parenteral antimicrobial treatment any infants with positive findings on blood, urine, or CSF cultures.

Infants aged 0-56 days with positive respiratory syncytial virus (RSV)

The question often arises as to what to do with the febrile newborn aged less than 57 days who has RSV infection. Does RSV infection preclude serious bacterial infection in this age group? Levine et al demonstrated in a multicenter, prospective, cross-sectional study that, although the rate of systemic bacterial infection is much less in neonates with RSV, they still have a significant amount of UTIs (10.1% in RSV-negative febrile neonate vs 5.1% in RSV-positive neonate). The study did not state that there was a significant difference between bacteremia and meningitis. Melendez et al conducted a retrospective chart review of 3000 infants aged less than 90 days with fever and clinical bronchiolitis that demonstrated similar findings. They found that the incidence of UTI in the group was 2%. Therefore, in infants aged less than 60 days with RSV infection or bronchiolitis, ruling out serious bacterial infections such as UTIs, meningitis, and bacteremia is important.

Please see Image 2 for treatment of febrile newborns aged 29-56 days.

Febrile children aged 3-36 months

For all patients aged 3-36 months, the management decisions are mostly based on the degree of toxicity and the height of the temperature. The Yale Observation Scale is a reliable method of determining the degree of illness. It consists of 6 variables: quality of cry, reaction to parent stimulation, state variation, color, hydration, and response. A score of 10 or less has a risk of 2.7% for serious bacterial infection. A score of 16 or greater has a 92% risk of serious bacterial infection.

With regards to the height of the temperature, Hoberman et al (1994) found that 6.5% of patients with a temperature of 39.0°C or more had a UTI and that white females with that temperature had a 17% incidence rate of UTI. In this age group, the prevalence of bacteremia correlates with the height of fever. Children with temperatures from 39-39.5°C (102.2-103°F) have about a 2-4% risk for having occult bacteremia. Those with temperatures higher than 39.5°C (103°F) have approximately a 5% chance of having occult bacteremia.

Summary of the Yale Observation Scale

Children with a total WBC count greater than 20,000/µL or an ANC of 12,000/µL or more carry a risk of occult bacteremia close to 20%. The bacteria most often isolated from the blood of children with bacteremia are Streptococcus pneumoniae (85-90%), Neisseria meningitidis, Streptococcus pyogenes, and Salmonella species.

The overall risk for children with bacteremia without antimicrobial therapy was quoted to be 21% for persistent bacteremia and 9% for meningitis. With the virtual elimination of Haemophilus influenzae because of routine immunization against this organism, current numbers are likely to be much lower than previously cited. In general, children in this age group with a temperature lower than 39°C should be assessed clinically. Laboratory tests or antibiotics are unnecessary if the child appears well.

Controversy exists about the management of the well-appearing child with temperatures higher than 39°C and no focus (or a minor upper respiratory focus) of infection. A meta-analysis conducted by Bulloch et al (1997) involving the use of empiric antibiotics in older infants and children with fever concluded that no significant outcome advantage exists for antibiotic therapy. The extravagant use of antibiotics may accelerate drug resistance, increase healthcare cost, and lead to development of partially treated meningitis.

A well-circulated practice guideline for the management of this problem has recommended a CBC count, blood culture, UA, and urine culture in girls younger than 2 years and boys younger than 6 months. According to those recommendations, children with WBC counts equal to or higher than 15,000/µL or an ANC higher than 10,000/µL should receive ceftriaxone IM at a dose of 50 mg/kg as empiric therapy for possible occult bacteremia.

Reevaluate these patients in 18-24 hours and administer a second dose of ceftriaxone to provide antibiotic coverage until blood culture results have been negative for 48 hours. While most would concur that children should be screened for UTI, some maintain that the incidence of bacteremia and its complications has declined dramatically over the past decade; therefore, no blood work is necessary and only close outpatient follow-up is needed for these patients. With the introduction of the new heptavalent conjugate vaccine active against the most virulent pneumococcal serotypes, the incidence of bacteremia has declined further, providing additional support to this approach.

Please see Image 3 for treatment of febrile children aged 3-36 months.

The era of Prevnar

H influenzae type b (Hib) was the most common causative agent of occult bacteremia and serious bacterial illness, prior to the introduction of the Hib vaccine. After the Hib vaccine was introduced, S pneumoniae became the most common causative agent. Since Prevnar was introduced, a drastic decline in S pneumoniae bacteremia and serious bacterial infections has occurred.

The heptavalent pneumococcal conjugate vaccine, Prevnar, is composed of 7 pneumococcal antigens (polysaccharide serotypes 4, 6B, 9V, 14, 19F, and 23F and an oligosaccharide serotype 18C). It provides potential serotype and serogroup cross-protection for 88% of the cases of bacteremia, 82% of the cases of meningitis, and 71% of the cases of pneumococcal otitis media in US children younger than 6 years. After 3 doses, 92-100% of the children had at least 0.15 mcg/mL (the minimum concentration of protective anticapsular antibody that has been proposed) of antibody against all 7 of the vaccine serotypes. These serologic correlates of protection have been proposed based on experimental models and extrapolated from similar (eg, H influenzae type b) encapsulated organisms. Its true efficacy is still unknown.

In a 2001 prospective surveillance study by Kaplan et al, the incidence of disease in children aged less than 24 months decreased by 58% in 2001 and by 66% in 2002. The incidence of bacteremia pre-Hib, post-Hib/pre-Prevnar, and post-Hib/post-Prevnar is 2.8%, 2%, and 0.68%, respectively. Using the data from the Lee and Harper study, the likelihood ratio for a WBC count 15,000/µL or greater is 3.74. Using the Fagan nomogram, this leads to a small change of posttest probability of 2%. The likelihood ratio for WBC 20,000/µL or greater is 6.00, which gives a posttest probability of 4%. Therefore, in the well-appearing, otherwise-healthy febrile infant aged 3-24 months who has received Prevnar and has a WBC of at least 20,000/µL the probability of bacteremia is about 4%.

The widespread use of heptavalent pneumococcal conjugate vaccine has led to a significant reduction of occult bacteremia. Clinicians should consider raising the WBC cutoffs to at least 20,000/µL before the administration of empiric antibiotics.

MEDICATIONS

Section 9 of 11  

• Authors and Editors
• Introduction
• Physiology of Temperature Control
• Approach to Patient
• Physical Examination
• Diagnostic Workup and Management
• Fever Without Source
• Guidelines for Treatment of Febrile Infants by Age Group
• Medications
• Multimedia
• References

Antipyretic agents inhibit central synthesis and release of prostaglandins that mediate the effect of endogenous pyrogens in the hypothalamus, thus, promoting the return of the set-point temperature to normal. Acetaminophen inhibits prostaglandin synthetase centrally, thus providing potent inhibition of cyclooxygenase in the central nervous system. The dose for toddlers is 10-15 mg/kg per dose PO q4-6h, not to exceed 5 doses per 24h. Acetaminophen is contained in many over-the-counter products in varying concentrations. Combined use with these products may result in cumulative doses exceeding the recommended maximum dose. Ibuprofen also inhibits prostaglandin synthesis, centrally as well as peripherally. The dose for toddlers is 10 mg/kg per dose PO q6-8h. Caution in patients with coagulation abnormalities or other conditions where the antiplatelet effect may increase the risk of bleeding

Antibiotics are used for suspected bacteremia or bacteruria. Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Whenever feasible, guide antibiotic selection by blood culture sensitivity.

Ampicillin inhibits the biosynthesis of cell wall mucopeptides. It acts against gram-positive organisms (excluding beta-lactamase–positive S aureus), enterococci, gram-negative organisms (eg, Escherichia coli, and Proteus, Klebsiella, and Salmonella species), and beta-lactamase–negative H influenzae. The standard pediatric dose is 50-100 mg/kg/d IV divided q6h for mild-to-moderate infections. For severe infections, the dose is 200-400 mg/kg/d IV divided q6h. Adverse effects include glossitis, stomatitis, nausea, vomiting, black "hairy" tongue, enterocolitis, pseudomembranous colitis, diarrhea, hypersensitivity reactions, increased serum glutamic-oxaloacetic transaminase, anemia, thrombocytopenia, thrombocytopenic purpura, leukopenia, and agranulocytosis.

Ceftriaxone is a third-generation cephalosporin that inhibits cell wall synthesis. It acts against gram-positive organisms, including beta-lactamase–producing organisms, but not enterococci, methicillin-resistant S aureus, and Listeria species. It is active against gram-negative species (eg, E coli, H influenzae, Moraxella catarrhalis and Proteus, Klebsiella, Enterobacter, Citrobacter, and Pseudomonas species) but not Acinetobacter species. It is variable in its activity against Bacteroides fragilis and Pseudomonas species. The pediatric dose is 50-100 mg/kg/d IV divided q12-24h. Adverse effects include hypersensitivity, colitis, transient elevations of blood urea nitrogen and serum creatinine, prolonged prothrombin time (PT), and gallbladder disease.

Cefotaxime is also a third-generation cephalosporin that shares similar activities with ceftriaxone. It also inhibits cell wall synthesis. Dosage is 100-150 mg/kg/d IV divided q6-8h, and the meningitic dose is 200 mg/kg/d IV divided q6-8h. Adverse effects include hypersensitivity, GI discomfort (eg, nausea, vomiting, diarrhea, colitis), neutropenia, increased liver enzymes, and transient elevations of blood urea nitrogen and creatinine.

Gentamicin is an aminoglycoside that inhibits normal protein synthesis in susceptible organisms. It is active against gram-positive organisms (except methicillin-resistant S aureus and Streptococcus faecium), gram-negative organisms (but not Xanthomonas maltophilia, Pseudomonas cepacia, or Flavobacterium species), and anaerobes. Dosing for the pediatric population with normal renal function is 6-7.5 mg/kg/d IV divided q8h for children, 7.5 mg/kg/d IV divided q8h for infants and neonates, and 5 mg/kg/d IV divided q12h for premature neonates and full-term neonates aged 1 wk or younger.

Gentamicin can be neurotoxic (eg, involvement of the vestibular and auditory branches of the eighth cranial nerve, peripheral neuropathy, encephalopathy) and nephrotoxic. Toxicity is increased with concomitant use of aminoglycoside antibiotics and cephalosporins. Other adverse effects include Fanconilike syndrome with aminoaciduria and metabolic acidosis, respiratory depression, lethargy, decreased appetite, weight loss, hypotension and hypertension, rash, nausea, vomiting, stomatitis, increased salivation, pseudotumor cerebri, transient hepatomegaly, and splenomegaly.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Physiology of Temperature Control
• Approach to Patient
• Physical Examination
• Diagnostic Workup and Management
• Fever Without Source
• Guidelines for Treatment of Febrile Infants by Age Group
• Medications
• Multimedia
• References

Media file 1:  Treatment of febrile newborns aged 0-28 days.
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Media file 2:  Treatment of febrile infants aged 29-56 days.
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Media file 3:  Treatment of febrile children aged 3-36 months.
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REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Physiology of Temperature Control
• Approach to Patient
• Physical Examination
• Diagnostic Workup and Management
• Fever Without Source
• Guidelines for Treatment of Febrile Infants by Age Group
• Medications
• Multimedia
• References

• Adam HM. Fever and host responses. Pediatr Rev. Sep 1996;17(9):330-1. [Medline].
• Alpern ER, Alessandrini EA, Bell LM. Occult bacteremia from a pediatric emergency department: current prevalence, time to detection, and outcome. Pediatrics. Sep 2000;106(3):505-11. [Medline].
• Atkins E, Bodel P. Fever. N Engl J Med. Jan 6 1972;286(1):27-34. [Medline].
• Bachur R, Harper MB. Reevaluation of outpatients with Streptococcus pneumoniae bacteremia. Pediatrics. Mar 2000;105(3 Pt 1):502-9. [Medline].
• Baker MD, Bell LM, Avner JR. The efficacy of routine outpatient management without antibiotics of fever in selected infants. Pediatrics. Mar 1999;103(3):627-31. [Medline]. [Full Text].
• Baraff LJ, Bass JW, Fleisher GR, et al. Practice guideline for the management of infants and children 0 to 36 months of age with fever without source. Agency for Health Care Policy and Research. Ann Emerg Med. Jul 1993;22(7):1198-210. [Medline].
• Baraff LJ, Oslund SA, Schriger DL, Stephen ML. Probability of bacterial infections in febrile infants less than three months of age: a meta-analysis. Pediatr Infect Dis J. Apr 1992;11(4):257-64. [Medline].
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Article Last Updated: May 23, 2006