White Blood Cell Count

An elevated white blood cell (WBC) count (>15,000/mm³) can be an indicator of bacteremia but is also present in many viral illnesses. Leukopenia (<5000/mm³) can also be a sign of SBI or early sepsis. Pneumococcal infection is classically associated with leukocytosis, whereas infection with N. meningitidis and H. influenzae may be present even with normal WBC counts. Lee and colleagues found that the rate of pneumococcal bacteremia increased from 0.5% in highly febrile children (>39.0° C) with a WBC count between 10,000 and 15,000/mm³ to 3.5% if the WBC count was 15,000 to 20,000/mm³ and up to 18% with a WBC count above 30,000/mm³.¹⁸

The WBC differential has also been used to risk stratify febrile children in various models; an increase in polymorphonuclear leukocytes and immature band forms increases the risk of bacterial disease. A rise in polymorphonuclear leukocytes is also seen early in some viral infections. An absolute neutrophil count (ANC) above 10,000/mm³ suggests increased risk of pneumococcal bacteremia in febrile children (0.8% for children with an ANC below 10,000/mm³ vs. 8% for children with an ANC above 10,000/mm³).¹⁹

Blood Culture

A blood culture is a useful diagnostic test when bacteremia is suspected. In infants and children, blood should be obtained after sterile preparation of the skin, which includes an alcohol preparation and swabbing of the skin with povidone-iodine solution, which is then allowed to dry. Many centers obtain blood for culture during intravenous catheter placement after sterile preparation of the skin has been performed. This technique has the advantage of eliminating a second venipuncture solely to obtain blood for culture, although the rates of contamination with this technique have been shown to be higher in children (9.1 vs. 2.8%).²⁰ The risks of contamination should be weighed against the ability to obtain blood through a separate venipuncture. The yield of a single blood culture in infants and small children is actually good. The routine sending of more than one sample is generally not needed, and bacteremia is often accurately detected even if only 0.5 to 1 mL of blood is obtained. The advent of automated blood culture systems led to the identification of true pathogens more quickly than by traditional methods, often within 24 hours. Pathogens isolated in the first 24 hours are more likely to be true pathogens than are bacteria isolated after 24 hours.²¹

Urinalysis and Urine Culture

UTIs are common causes of bacterial illness in febrile children. Accurate documentation of UTI is imperative both to diagnose the cause of a fever and to identify those infants who need follow-up radiographic imaging (typically voiding cystourethrography, renal ultrasonography, or both) to exclude anatomic abnormalities that will predispose them to further infection. The only reliable method to obtain urine in a non–toilet-trained child is bladder catheterization or suprapubic aspiration. Bag collection of urine is notoriously unreliable; up to 85% of cultures from bag specimens will be falsely positive (defined as a culture growing a single organism with >10⁵ colony-forming units [CFU]/mL or a mix of two or more organisms), which then places these children at risk for unneeded, potentially painful, and expensive follow-up diagnostic testing and antibiotics. A clean catch urine specimen is appropriate for older toilet-trained children.

UTI is defined as the combination of bacteriuria and pyuria. Bacteriuria in the absence of WBCs on microscopic examination represents asymptomatic bacteriuria. Urine is typically analyzed with a dipstick, followed by microscopic analysis of a centrifuged specimen of urine. Hoberman and colleagues described the test characteristics of an “enhanced” urinalysis, which is examination with a hemocytometer of an unspun specimen of urine for pyuria (defined as >10 WBCs per high-power field) or the presence of any bacteria per high-power field in Gram’s stain of unspun urine. They reported a negative predictive value of 99.8%, perhaps making urine culture unneeded if pyuria and bacteriuria are absent by use of the enhanced urinalysis method.²² Many centers are not using this enhanced method. Because dipstick and microscopic analysis have lower sensitivities, most experts recommend sending urine for culture in high-risk groups (febrile girls <24 months of age, uncircumcised boys <12 months of age, and circumcised boys <6 months of age).

A positive urine culture is defined as the growth of more than 10,000 CFU/mL of a uropathogen from urine obtained from a catheterized or suprapubic sample. In older children, in whom urine is typically obtained from a clean catch specimen, a higher threshold of more than 100,000 CFU/mL is typically used.

Lumbar Puncture

A sample of cerebrospinal fluid (CSF) should be obtained from any child with signs and symptoms of meningitis. Fluid should be obtained with the smallest pencil-point or noncutting spinal needle possible (typically a 22-gauge spinal needle) and sent for cell counts, manual differential, Gram’s staining, culture, and measurement of CSF protein and glucose concentrations. Meningoencephalitis due to HSV is a potential cause of fever, particularly in children, and if it is suspected, sending of CSF for HSV polymerase chain reaction testing is indicated. The CSF in bacterial meningitis typically contains more than 1000 WBCs/mL, although there is considerable overlap in the CSF profile of bacterial and viral meningitis, making a determination of viral or aseptic meningitis difficult on the basis of CSF parameters such as cell count, protein, and glucose; thus CSF culture of a pathogenic bacterium is the “gold standard.” A prediction rule has been developed and validated to differentiate bacterial from aseptic meningitis.²³ Children who lack all of the following criteria have a low risk (0.1%) of bacterial meningitis: positive CSF Gram’s stain, CSF ANC of at least 1000 cells/mL, CSF protein concentration of at least 80 mg/dL, peripheral blood ANC of at least 10,000 cells/mL, and history of seizure before or at the time of presentation. This may obviate the need for empirical antibiotic therapy and hospital admission in some children who are at low risk for bacterial meningitis.

Contraindications to lumbar puncture include cellulitis over the proposed site of puncture, cardiopulmonary instability, bleeding diathesis or platelet count below 50,000/µL, focal neurologic deficits, and signs of increased intracranial pressure, including papilledema. In these patients, lumbar puncture should be deferred until the child is stable, and blood should be obtained for culture while the child is treated empirically, recognizing that up to 50% of children with meningitis will not have bacteremia.²⁴

CSF contaminated by blood, or a traumatic lumbar puncture, can make interpretation of cell counts and differentials difficult. In these cases, fluid should be obtained for Gram’s stain and culture and the child treated presumptively for meningitis until culture data are available. Nigrovic and co-workers have shown that risk factors for a traumatic lumbar puncture include operator experience, excessive patient movement during the procedure, advancement of the needle with the stylet in place, and lack of local anesthesia.²⁵

Stool Studies

Stool studies are indicated in patients in whom bacterial gastroenteritis may be a cause of fever. A stool guaiac test for blood as well as Gram’s stain for WBCs should be performed. Presence of more than 5 WBCs per high-power field in the stool of a febrile child should trigger a culture of stool for Salmonella, Shigella, Campylobacter, enterotoxigenic Escherichia coli, and Yersinia species. Patients with sickle cell disease are at particular risk for focal complications such as osteomyelitis from Salmonella infection.

Chest Radiography

Chest radiographs may be useful in the workup of the febrile child and are indicated when hypoxemia, respiratory distress, tachypnea, or focal findings on lung examination are present. Children younger than 6 months may present with tachypnea as the sole finding of bacterial pneumonia. Truly occult pneumonia can also occur, particularly in the highly febrile child (>39.0° C) without apparent source of fever. Bachur and associates found that 26% of children with temperature above 39.0° C and WBC counts higher than 20,000 had radiographic evidence of pneumonia.²⁶ Of note, this study was done in the era before the conjugate pneumococcal vaccine.

Rapid Viral Antigen Testing

Many clinical laboratories have the ability to perform rapid viral antigen testing for such common pediatric viral illnesses as influenza A and B and RSV. The presence of a viral “source” for the fever in an ill child may obviate the need for expensive, painful, and lengthy diagnostic workups for bacterial processes. Bonner and colleagues evaluated the impact of physician knowledge of the presence of a positive rapid influenza assay result.²⁷ The investigators studied 391 patients aged 2 months to 21 years who presented with classic signs and symptoms of influenza. Of these patients, more than half had positive rapid assays for influenza, and the investigators noted that significantly fewer laboratory and radiographic studies were ordered if the treating clinician was aware of these results. There were also fewer antibiotics prescribed. A large multicenter trial of febrile infants 60 days of age or younger revealed a decreased risk (2.5 vs. 11.7%) if the infant was influenza positive.²⁸

RSV is also a frequent cause of fever in children. As previously noted, RSV decreases but does not completely eliminate the risk of SBI in children. This is especially true of UTI in infants younger than 28 days.

Infants 0 to 28 Days of Age

Children presenting with temperature above 38.0° C who are younger than 28 days are at particularly high risk for bacterial illness, with rates as high as 12% quoted in the literature.30,31 Often, fever is the only manifestation of potentially life-threatening disease, and other signs and symptoms may be exceedingly subtle. This has led to an aggressive approach to diagnostic testing, empirical antibiotic therapy, and hospitalization in this age group, even if the child appears well.

Children in this age group often present with nonspecific complaints, such as irritability, lethargy, poor feeding, and grunting. Besides fever, other signs of serious illness include a bulging fontanel, mottled extremities, petechiae, and tachypnea. Bacterial pathogens in this age group include group B streptococcus, L. monocytogenes, N. meningitidis, S. pneumoniae, and E. coli. Viral pathogens, including RSV and HSV, are also important considerations. Neonatal HSV infection in particular carries a high degree of morbidity and mortality and should be considered in any febrile neonate with a maternal history of genital herpes, who appears ill, who presents with fever and seizure, who has cutaneous vesicles on physical examination, or who has evidence of transaminitis or coagulopathy. HSV meningoencephalitis should also be considered in patients with fever and CSF pleocytosis but a negative CSF Gram’s stain. The risk period for HSV disease tends to be between 2 and 12 days of age (Fig. 167-2). Other noninfectious causes of a septic-appearing neonate include the acute salt-wasting crisis associated with congenital adrenal hyperplasia and undiagnosed duct-dependent congenital heart disease.

Because of the high risk of bacterial pathogens and the difficulty in clinical assessment of children younger than 28 days, these patients require an aggressive diagnostic evaluation, including a complete septic workup. This consists of a complete blood count (CBC) with differential, blood culture, urinalysis and urine culture, and lumbar puncture. Lumbar puncture is indicated even in the presence of a UTI because of the risk of concomitant meningitis.³² All children in this age group should be admitted to the hospital with empirical antibiotics until culture data become available. Appropriate parenteral antibiotic regimens include ampicillin (100 mg/kg/24 hr divided every 6 hours) plus either gentamicin (5 mg/kg/24 hr divided every 8 to 12 hours) or cefotaxime (150 mg/kg/24 hr divided every 8 hours). Ceftriaxone should be avoided in infants younger than 28 days because of a theoretic risk of inducing acute bilirubin encephalopathy as ceftriaxone causes bilirubin to be displaced from its protein binding sites. Empirical acyclovir should be added if risk factors for HSV disease exist (60 mg/kg/24 hr, divided every 8 hours).

Infants 29 to 90 Days of Age

Although there is a relative consensus as to the evaluation and management of febrile infants younger than 28 days, there is debate about the appropriate workup for the slightly older febrile infants. Ill-appearing children of any age should have a complete sepsis evaluation performed and be admitted to the hospital with empirical antibiotic therapy. Appropriate antibiotic therapy for high-risk children includes coverage of neonatal pathogens such as L. monocytogenes and group B streptococci as well as coverage against H. influenzae, N. meningitidis, and S. pneumoniae. Ampicillin, 50 to 100 mg/kg every 6 hours, plus cefotaxime, 50 mg/kg every 8 hours parenterally, is one alternative. Vancomycin, 40 to 60 mg/kg intravenously (IV) every 6 to 8 hours, should be considered if S. pneumoniae resistant to penicillins and cephalosporins is suspected.

Various strategies (herein referred to as the Rochester, Philadelphia, and Boston criteria) for the evaluation of well-appearing children have been reported, compared, and retested in the literature.33–35 Each strategy has unique features, including the definition of fever (38.0° C vs. 38.2° C), the study population (0-3 months of age, 1-2 months of age, and 1-3 months of age), the clinical and laboratory variables studied, and the disposition (hospitalization with or without antibiotics or outpatient treatment with or without antibiotics). Each strategy seeks to identify a set of low-risk criteria that, if met, will allow less aggressive treatment or the withholding of empirical antibiotic therapy. The three main strategies are highlighted in Table 167-2. Baraff synthesized the recommendations of the Rochester, Philadelphia, and Boston criteria into an algorithm for the management of the previously healthy febrile infant 29 to 90 days of age (Fig. 167-3).³⁶ To be low risk, the child had to have been previously healthy with an uncomplicated nursery stay, to be nontoxic clinically, and to have no focal source of bacterial infection. Low-risk laboratory criteria in this schema included a normal WBC count (between 5000 and 15,000 WBCs/mm³), fewer than 1500 bands/mm³, normal urinalysis (negative Gram’s stain and <5 WBCs per high-power field), and negative CSF Gram’s stain and cell counts (<8 WBCs/mm³), if obtained. When diarrhea was present, fewer than 5 WBCs per high-power field was the threshold for low risk.

Once the child is deemed to be at low risk by these criteria, two options are available to the clinician on the basis of the Philadelphia and Boston criteria. The first management strategy calls for a CBC, blood culture, urinalysis, and urine culture. Once these studies have been obtained and the results are normal, the child may be discharged with close outpatient follow-up. The second option, based on the Boston criteria, calls for a complete sepsis evaluation, including lumbar puncture, followed by empirical treatment with ceftriaxone (50 mg/kg IV or intramuscularly [IM]) and reevaluation within 24 hours. The important difference between these two strategies is that empirical antibiotics should not be administered unless a complete sepsis evaluation is performed, including a lumbar puncture. Otherwise, if a lumbar puncture is not initially performed and the child returns for reevaluation and a lumbar puncture is subsequently performed with the finding of CSF pleocytosis, pretreatment with antibiotics makes interpretation of culture results difficult. Thus a child with a possible viral process may be subjected to inpatient admission and 14 days of parenteral antibiotic therapy.

Infants 3 to 36 Months of Age

Fever in children 3 to 36 months of age is incredibly common; most cases represent self-limited viral illnesses. Common causes of fever in this age group include viral upper respiratory infections, croup, bronchiolitis, stomatitis (typically caused by HSV or Coxsackievirus), gastroenteritis, roseola, and fifth disease (parvovirus B19 infection). Focal infections, such as pyelonephritis, periorbital cellulitis, bacterial pharyngitis (group A streptococcus), septic arthritis, retropharyngeal abscess, meningitis, and bacterial pneumonia, also become common in this age group. Typically, these focal infections are apparent on the basis of history and physical examination findings, and diagnostic testing and treatment should be directed accordingly.

The history in this age group should focus on the duration of illness, associated symptoms that may focus the evaluation, immunization history (particularly vaccination for H. influenzae type B and pneumococcus), and sick contacts. A thorough physical examination is essential to rule out serious focal infection, such as meningitis. Young children may demonstrate inconsolable irritability or lethargy as the sole manifestation of meningitis; furthermore, classic meningeal signs, such as nuchal rigidity, are seen in less than 27% of infants (0-6 months) with bacterial meningitis.³⁷

Prior research has focused on assessment of children in this age group for the presence of occult bacteremia. It was found that a small percentage of highly febrile children (>39.0° C) 3 to 36 months of age were bacteremic.36,38–41 These children were noted to be highly febrile but lacked any localizing signs of infection. No historical or physical examination findings were sufficiently sensitive or specific to identify cases of occult bacteremia, making universal diagnostic testing necessary.^42–44 A typical workup included a CBC and blood culture, and empirical antibiotic therapy was prescribed for children with WBC counts above 15,000/mm³. Empirical antibiotics were justified on the basis of studies that revealed treatment with antibiotics prevented focal sequelae of bacteremia such as meningitis and shortened the duration of fever.^45–47 Before the advent of almost universal immunization against S. pneumoniae, the rate of occult bacteremia was approximately 3%, and although pneumococcal bacteremia resolves without therapy up to 75% of the time, a small proportion of children have sepsis or focal infections such as meningitis. Pneumococcal meningitis has a high degree of morbidity and mortality, including permanent neurologic disability, hearing loss, and death.^48,49 Since the advent of Prevnar (conjugate pneumococcal vaccine), the number of invasive pneumococcal infections caused by vaccine-serogroup isolates among eight U.S. children’s hospitals has decreased more than 75% among children younger than 24 months. Because of the decline in invasive pneumococcal disease brought on by vaccination, the cost-effectiveness of mandatory blood testing has been called into question.^50,51 Lee and colleagues evaluated the cost-effectiveness of various management strategies: no workup, relying on clinical judgment, blood culture, blood culture plus empirical antibiotics, WBC count plus blood culture and empirical antibiotics, and WBC count plus selective blood culture for WBC counts above 15,000 and empirical antibiotics. They found that at rates of pneumococcal bacteremia greater than 1.5%, obtaining a WBC count plus selective blood culture and empirical antibiotics were the most cost-effective approach. At rates of pneumococcal bacteremia less than 0.5%, strategies that used empirical testing and treatment were no longer cost-effective. They concluded that at lower rates of bacteremia, clinical judgment is more useful in selecting out high-risk populations who might benefit from selective testing and treatment.⁵²

Although the incidence of pneumococcal bacteremia has declined in infants 3 to 36 months of age because of the aggressive campaign to vaccinate, infants 3 to 6 months of age have not yet completed the primary series of immunizations against S. pneumoniae and to a lesser extent H. influenzae. Thus, highly febrile infants (>39.0° C) without an apparent source on examination should be considered at risk for occult bacteremia and consideration given to obtaining a WBC count and blood culture as a screen. Empirical antibiotic therapy should be reserved for infants with WBC counts above 15,000/mm³ or those with an ANC ≥10,000/mm³. Although the conjugate pneumococcal vaccine contains antigens from the seven most common serotypes that cause invasive disease, there are approximately 90 serotypes that are capable of infecting humans. Continued bacterial surveillance is necessary to ensure that other serotypes do not rise in incidence to fill the void left by vaccination. No clinical prediction algorithm correctly identifies all patients with meningococcal disease.⁵³ Additional signs and symptoms that may suggest meningococcemia are purpuric rash, bandemia, limb pain, and exposure to a person with the disease. An appropriate flow diagram for the workup of febrile infants 3 to 36 months of age is presented in Figure 167-4.

Children Aged 3 Years to Adulthood

The incidence of occult bacteremia decreases after 3 years of age. Focal infections such as streptococcal pharyngitis, septic arthritis, pneumonia, peritonsillar abscess (most often in adolescents), and cellulitis become more common. Viral pathogens are also common, such as infectious mononucleosis. Infection with atypical pathogens, such as Mycoplasma pneumoniae, should also be considered in children presenting with pneumonia. Skin infections secondary to community-acquired methicillin-resistant Staphylococcus aureus (CMRSA) are also becoming more common. CMRSA occurs in all age groups but has clustered among such children as wrestlers (associated with contaminated wrestling mats) and football players (infected equipment).54,55 This diagnosis should be considered in all children who present with pyogenic skin infection and skin abscesses. Appropriate therapy includes incision and drainage of the abscess cavity. Antibiotic therapy in addition to incision and drainage for simple abscesses has not been shown to hasten resolution of the infection but should be considered for patients with large abscesses (>5 cm), with cellulitis, or with fever.⁵⁶ The antibiotics used are dependent on local resistance patterns but could include trimethoprim-sulfamethoxazole or clindamycin.

There is also a second peak in incidence of meningococcal disease in adolescent children with an attack rate of 1.2 infections per 100,000 population. As opposed to infants, adolescents with meningococcal infection are more likely to present with meningococcemia (40 vs. 20%) and shock (69 vs. 27%) and to have a fatal outcome (22.5 vs. 4.6%). Meningococcal disease typically is manifested with one of three clinical syndromes: meningitis, bacteremia, or a combination of the two. College students residing in dormitories are at particular risk for infection, with attack rates of 3.2/100,000 population.⁵⁷ The history in cases of meningococcal infection is often one of rapidly progressive fever, headache, and stiff neck. Shock, altered mental status or frank coma, petechiae or purpura, seizures, and myalgias are also seen. Some of the first signs of meningococcal infection include leg pain, cold hands and feet, and abnormal skin mottling.⁵⁸ Children exposed to a patient with meningococcemia, particularly those with close contact with nasopharyngeal secretions, and who have any of the presenting signs should receive a full septic workup, admission to the hospital, and empirical treatment with antibiotics until results of blood and CSF cultures are known. Appropriate initial therapy for children suspected of having meningococcal infection is ceftriaxone 100 mg/kg IV.

In January 2005, the Food and Drug Administration approved the quadrivalent meningococcal conjugate vaccine (Menactra) for use in adolescents. This vaccine is a polysaccharide-protein conjugate directed against the four serotypes that cause most cases of invasive meningococcal disease in humans. The Advisory Committee on Immunization Practices recommends vaccination of adolescents at their 11- or 12-year-old well-child checkup, and the American Academy of Pediatrics (AAP) has also advised that all college freshmen living in dormitories be vaccinated. Use of the vaccine is associated with a 67% decrease in invasive disease and a 66% decrease in carriage rates.⁵⁹

Oncology Patients

Children with cancer, particularly those undergoing treatment with cytotoxic chemotherapy, are at particular risk for sepsis and bacterial infection.⁷¹ These life-threatening infections are most common during periods of profound neutropenia. Neutropenia is defined as an ANC of less than 500/mL or an ANC of less than 1000/mL that is falling. Children with cancer also frequently have indwelling catheters, predisposing them to surgical line infections.

Causative organisms include both gram-positive and gram-negative bacteria. Staphylococci and streptococci as well as Pseudomonas are frequent pathogens. Often, patients with focal infection may not present with classic signs because of their leukopenia. Focal infections specific to cancer patients include stomatitis and typhlitis, which is a necrotizing enterocolitis of the terminal ileum and cecum.

Children presenting with fever and possible neutropenia require prompt evaluation. Blood should be obtained for a CBC and manual differential as well as culture. If a central line infection is suspected, a separate culture specimen from the line should be obtained. Once appropriate laboratory studies are obtained, empirical antibiotic therapy should be initiated without waiting for the laboratory results. Appropriate monotherapy antibiotic regimens include cefepime, 50 mg/kg IV every 8 hours, and ceftazidime, 50 mg/kg IV every 8 hours. Vancomycin, 40 to 60 mg/kg every 6 to 8 hours, should be added for antistaphylococcal coverage in children with suspected central line infections or skin and soft tissue infections. Children with fever and neutropenia are rarely if ever treated as outpatients; if so, ceftriaxone 50 mg/kg IV every 24 hours is given, and close follow-up is essential.

Acquired Immunodeficiency Patients

Children with the acquired immunodeficiency syndrome (AIDS) are at risk for bacterial infection due to a whole host of different organisms, some common, some uncommon. Infections specific to AIDS include cryptococcosis and infection with Mycobacterium tuberculosis, Mycobacterium avium-intracellulare, and Pneumocystis jiroveci (carinii). Viral infections, such as cytomegalovirus and Epstein-Barr virus infections, are also common.

Laboratory evaluation should be directed by the history and physical examination. Early initiation of broad-spectrum antibiotic therapy is warranted.

Sickle Cell Disease

Febrile children with sickle cell disease are at particular risk for overwhelming infection.⁷² In fact, infection is the most common cause of sickle cell–related death, occurring in up to 40% of patients with sickle cell disease who die. Recurrent episodes of splenic infarction lead to functional asplenia early in life. Thus these patients are at particular risk for infection with encapsulated organisms, including S. pneumoniae and H. influenzae. Because of this risk of bacterial disease, it is recommended that all children with sickle cell disease be completely immunized. Prophylaxis with penicillin is recommended in children younger than 5 years, after which it can be safely discontinued in children who have not had a prior severe pneumococcal infection or surgical splenectomy.⁷³ The dose of penicillin is 125 mg orally twice daily until 3 years of age (at about 14 kg) and 250 mg orally twice daily after 3 years of age.⁷⁴

High-risk criteria for bacterial infection include toxic appearance, temperature higher than 40° C, abnormal WBC count (<5000 or >30,000 WBCs/mm³), and noncompliance with penicillin prophylaxis. Sickle cell patients are at particular risk for Salmonella osteomyelitis. All patients presenting with fever and sickle cell disease should have a blood specimen drawn for CBC, reticulocyte count, and culture. A reticulocyte count is important as many infections (e.g., parvovirus B19) can induce life-threatening aplastic crisis. Infection also predisposes children with sickle cell disease to acute chest syndrome.⁷⁵ Common causes of infection include Chlamydia pneumoniae, Mycoplasma, RSV, S. aureus, and S. pneumoniae. Further laboratory and radiographic evaluation should be directed by the presenting history and physical examination findings.

High-risk patients should be admitted for further evaluation and antibiotic therapy. Low-risk patients may be treated with a single dose of intravenous or intramuscular antibiotics, typically ceftriaxone 50 mg/kg, and discharged to close outpatient follow-up. All patients should be reevaluated within 24 hours or sooner if the clinical condition deteriorates.

Osteomyelitis typically is manifested with fever and bone pain. As patients with sickle cell disease may have frequent bone pain due to vaso-occlusive crisis, the diagnosis often can be difficult. All patients should have a blood specimen drawn for CBC with differential, erythrocyte sedimentation rate, and culture; a radionuclide bone scan or magnetic resonance imaging may help localize the infection. If Salmonella infection is suspected, a stool sample should be sent for culture.

Congenital Heart Disease

Children with congenital heart disease are at high risk for cardiovascular complications in the setting of febrile illness. Often, relatively minor viral illness can produce significant changes in cardiac function or make it difficult for children to be compliant with their oral medications. Children with congenital heart disease are also at risk for infective endocarditis. Infective endocarditis is heralded by fever and possibly a changing or worsening cardiac murmur. The modified Duke criteria for the diagnosis of endocarditis are presented in Box 167-2.⁷⁶

Endocarditis is typically caused by S. aureus, viridans streptococci, Streptococcus bovis, enterococci, or infection with organisms from the HACEK group (Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella species, and Kingella kingae). Children with suspected endocarditis should have blood culture specimens drawn and be admitted to the hospital for treatment and echocardiography. The American Heart Association recommends that initial antibiotic therapy be with ceftriaxone, 100 mg/kg IV or IM every 24 hours, or vancomycin, 40 mg/kg IV every 24 hours. Therapy is typically continued at least 4 weeks. Ceftriaxone can be combined with gentamicin, 3 mg/kg IV divided every 8 hours, if a shorter treatment duration (2 weeks) is desired.⁷⁷ See Chapter 171 for a more complete discussion.

Ventriculoperitoneal Shunts

Children presenting with fever in the setting of ventriculoperitoneal shunts are at risk for shunt infection. If shunt infection is suspected, neurosurgical consultation should be obtained and a sample of CSF obtained. This is typically accomplished by sterile aspiration of fluid from the shunt reservoir. S. aureus and Staphylococcus epidermidis are the usual causative organisms. If altered mental status is present, a computed tomography scan should be obtained to assess ventricular size. Children with suspected shunt infection are typically managed as inpatients, and antibiotics should begin as soon as possible.