Infectious diseases are a major cause of disease in children. The widespread use of antibiotics has greatly reduced morbidity and mortality, but infections are still one of the most common types of problems encountered by physicians who care for children.

General Considerations

Fever is the primary sign that indicates an infectious process in children of all ages. Other than fever, however, many children do not display signs or symptoms indicative of the underlying disease. Twenty percent of febrile children, after history and physical examination, have fever without a source of infection. The physician’s dilemma is to separate children with a serious bacterial illness from those with a viral or nonserious bacterial illness. A serious bacterial illness is defined variably, but generally includes growth of a known bacterial pathogen from cerebrospinal fluid, blood, urine, or stool, as well as abscess or cellulitis and pneumonia with positive blood cultures. Children are generally divided into three groups for evaluation purposes: young children aged 3 months to 3 years, young infants aged 2-3 months, and neonates (≤1 month of age). There is no absolute demarcation between these ages. Rather, one age group fades into the next, and the physician is left to make a judgment about how to treat each child in the border ages.

Young children are much more likely to show outward signs of illness, and their evaluation is much easier than that of younger infants. Neonates are a separate diagnostic group, more likely to have infections with organisms seen in the newborn period and less likely to show overt clinical signs of infection.

No officially adopted, evidence-based guidelines have been published to guide physicians in the workup and management of febrile illnesses, although several papers have been written detailing suggested guidelines based on expert opinion, group consensus, and locally performed research studies. Baraff and colleagues published a set of useful practice guidelines that are summarized in Table 5-1.

The frequency and nature of serious bacterial illness is different in the three different age groups. Neonates younger than 1 month of age are the most difficult to diagnose. The rate of serious bacterial illness in nontoxic febrile neonates has been reported to be between 8.6% and 12.6%. However, existing screening protocols lack the sensitivity and negative predictive value to identify infants at low risk for these infections. For this reason, it is generally accepted that all febrile infants younger than 1 month of age be admitted to the hospital, given a complete sepsis workup, and treated with parenteral antibiotics pending the results of the workup. Of these infants, approximately 65% have a viral infection, 13% have a serious bacterial illness, and the rest have nonbacterial gastroenteritis, aseptic meningitis, or bronchiolitis. Of the infants with serious bacterial illnesses, roughly 7% have a urinary tract infection (UTI), with Escherichia coli being the most common pathogen. Three percent have bacteremia, with group B Streptococcus, Enterobacter, Listeria, Streptococcus pneumoniae, E coli, Enterococcus, and Klebsiella all being found. Fewer than 2% have meningitis, usually caused by Klebsiella, Listeria, and group B Streptococcus.

In evaluating infants older than 1 month of age, it is useful to first identify which infants are at low risk for a serious bacterial illness. The criteria for low risk are being previously healthy, having no focal source of infection found on physical examination, and having a negative laboratory evaluation, defined as a white blood cell (WBC) count of 5000-15,000/mm3, fewer than 1500 bands/mm3, normal urinalysis, and, if diarrhea is present, fewer than 5 WBCs per high-power field in the stool. Chest radiography is included in some, but not all, sets of criteria. Lumbar puncture may be performed at the physician’s discretion but should always be done if empiric antibiotics are to be used. Additional low-risk criteria are appearing nontoxic and having a good social situation with reliable follow-up. Low-risk, nontoxic-appearing infants may be treated as outpatients, with close follow-up. Most recommendations are to use empiric antibiotics, but some authors feel that antibiotics may be withheld if the infant can be followed closely. All toxic-appearing or non–low-risk infants should be hospitalized and treated with parenteral antibiotics. The risk of serious bacterial illness in toxic-appearing infants in this age group is about 17%. The overall frequency of such infections in this age group is roughly 9% overall and 1%-2% in low-risk infants, with most of the infections being UTIs, bacteremia, and bacterial enteritis. Meningitis accounts for slightly more than 1% of febrile infants.

Similar criteria may be used to evaluate children aged 3 months to 3 years. The most common serious bacterial illnesses in this group are bacteremia and UTIs. UTIs are present in nearly 5% of febrile infants younger than 12 months of age. In this group, 6%-8% of girls and 2%-3% of boys have UTIs. The rates are higher in those with higher temperatures. After 12 months of age, the prevalence of UTI is lower.

In this age group, the rate of bacteremia has been reported to be 3%-11%, with a mean of 4.3% if the temperature is 39°C (102.2°F) or higher. The most common organisms isolated are S pneumoniae (85%), Haemophilus influenzae type b (10%), and Neisseria meningitidis (3%). The rate of infection with H influenzae has fallen dramatically since the use of the Hib vaccine has become widespread, and the rate of pneumococcal bacteremia is expected to do likewise in the near future.

Occult pneumonia is rare in febrile children who have a normal WBC count and who do not have signs of lower respiratory infection, such as cough, tachypnea, rales, or rhonchi.

As in younger infants, toxic-appearing or non–low-risk infants should be hospitalized and treated with parenteral antibiotics. The rate of serious bacterial infections in toxic-appearing children in this age group has been reported to be 10%-90%, depending on the definition of toxic.

Low-risk, non–toxic-appearing children in this age group may be treated as outpatients. The use of empiric antibiotics pending culture results is left to the physician’s discretion. There is general consensus that bacteremia is a risk factor for development of infectious complications, such as meningitis. However, pneumococcal bacteremia responds well to oral antibiotics, so these drugs can be used in children who appear well despite having positive blood cultures.

Clinical Findings

Symptoms and Signs

The most important clinical decision is to decide which infants appear toxic and therefore need more aggressive evaluation and treatment. “Toxic” is defined as a picture consistent with the sepsis syndrome—lethargy, signs of poor perfusion, marked hypoventilation or hyperventilation, or cyanosis. “Lethargy” is defined as an impaired level of consciousness as manifested by poor or absent eye contact or by failure of the child to recognize parents or to interact with people or objects in the environment.

Fever is defined as temperature of 38°C (100.4°F) or higher. Rectal measurement is the only accurate way to determine fever. A careful, complete physical examination is necessary to exclude focal signs of infection. The skin should be examined for exanthems, cellulitis, abscesses, or petechiae. Between 2% and 8% of children of all ages with fever and a petechial rash have a serious bacterial infection, most often caused by N meningitidis. Common childhood infections such as pharyngitis and otitis media should be sought, and a careful lung examination should be done looking for evidence of pneumonia. The abdomen should be examined for signs of peritonitis or tenderness. A musculoskeletal examination should be done looking for evidence of osteomyelitis or septic arthritis. The neurologic examination should be directed toward the level of consciousness and should look for focal neurologic deficits.

Laboratory Findings

The laboratory investigation includes WBC count and differential, urinalysis and urine culture, blood culture, lumbar puncture with routine analysis and culture, and chest x-ray. If the child has diarrhea, stool cultures should be evaluated.

Treatment

All infants younger than 1 month of age should be hospitalized. An appropriate antibiotic regimen includes ceftriaxone (50 mg/kg/d) with or without gentamicin. In the past, ampicillin has been used routinely to cover the possibility of Listeria infection. Although it appears that the frequency of infection with Listeria is decreasing, ampicillin may be added to this regimen if the physician chooses.

Ceftriaxone is likewise an appropriate antibiotic for hospitalized older infants and children and for infants and children treated as outpatients. In infants 2-3 months of age, a single intramuscular dose of ceftriaxone should be given. The child should be reevaluated in 18-24 hours and a second dose of ceftriaxone given. If blood cultures are found to be positive, the child should be admitted for further treatment. If the urine culture is positive and the child has a persistent fever, the child should be admitted for treatment. If the child is afebrile and well, outpatient antibiotics may be used.

Table 5-1 presents guidelines that may be useful for investigating and treating febrile children.

Otitis Medi

Essentials of Diagnosis

• Preexisting upper respiratory infection (URI; 93%).
  
• Fever (25%).
  
• Ear pain (variable, depending on age).
  
• Bulging, immobile tympanic membrane that is dull gray, yellow, or red in color.
  
• Perforated tympanic membrane with purulent drainage (diagnostic).

General Considerations

Acute otitis media (AOM) is the most common reason that children see a physician, accounting for almost 30 million physician visits each year among children younger than 1 year of age. Almost all children have at least one episode of otitis media each year, and one-third have three or more episodes.

Pathogenesis

When cultures of middle ear fluid are done, S pneumoniae is found in about 35%, H influenzae in about 25%, and Moraxella catarrhalis in about 15%. Ten percent of effusions show more than one of these bacteria, and about 25% are sterile. Viruses are recovered in a large percentage of cases, with or without bacteria, but whether their role is causative or not remains unclear.

Prevention

There are several identified risk factors for otitis media, not all of which are easily modifiable for prevention of the disease. The chief risk factor is day care. Other risk factors include increased number of siblings in the house, exposure to tobacco smoke, pacifier use, formula feeding, and lower socioeconomic status. Children with abnormalities of the palatal architecture, such as those with cleft palate or Down syndrome, are at greatly increased risk. Widespread use of vaccines against H influenzae type b and S pneumoniae are not expected to have much impact on the disease, as the infection is generally caused by nontypeable Haemophilus and by strains of pneumococcus not covered by the pediatric 7-valent vaccine.

Clinical Findings

Symptoms and Signs

Despite the frequency with which physicians see children with otitis media, the diagnostic criteria are not standardized, and the diagnosis itself is often unclear. Otitis media most often begins with a URI, and as many as 93% of children with AOM have typical symptoms of URI. Symptoms of AOM may develop over only a few hours, or the onset may be more gradual. Ear pain is the most characteristic symptom. Younger children do not localize pain as obviously as older children. Fever is present only in about 25% and is more common in younger children. The tympanic membrane bulges and may be cloudy, yellow, or red in color. Erythema of the tympanic membrane may be caused by fever or by screaming, so this sign is of questionable reliability. The drum generally is immobile with pneumatic otoscopy or tympanometry. The infection is bilateral in half of affected children. The tympanic membrane ruptures in fewer than 5% of cases, but pus draining through a perforation is diagnostic.

Differential Diagnosis

As previously discussed, the primary illness that may be confused with AOM is acute URI. Many of the symptoms are identical, and findings in the tympanic membrane may be subtle and nondiagnostic.

Complications

Complications of otitis media fall into two main categories—suppurative and nonsuppurative. Suppurative complications may arise from direct extension of the infection into the surrounding bones or into the adjacent brain, such as mastoiditis, venous sinus thrombosis, and brain abscess. They may also arise from hematogenous spread of the bacteria from the middle ear, primarily sepsis and meningitis. The main suppurative complication is mastoiditis, which develops in about 1 in 1000 cases. Recent research shows that treatment of otitis media does not reduce the incidence of this complication. The bacteria responsible for hematogenous spread are principally S pneumoniae and H influenza.

Nonsuppurative complications are primarily those that arise from middle ear effusion and inflammation and scarring of the structures of the middle ear. Antibiotic treatment does not influence the persistence of middle ear effusions after otitis media, nor does it have any effect on long-term hearing and language development. In summary, it appears that complications of otitis media may not be preventable by antibiotic treatment.

Treatment

Although antibiotic treatment has long been the standard of care for children with AOM, research has shown that the benefits of antibiotics are much less clear than was believed in the past. As many as 59% of children have resolution of symptoms within 24 hours without treatment, and between 80% and 85% recover in 1-7 days without antibiotics. Antibiotic treatment reduces the persistence of symptoms at 2-7 days to 7%, or about a 12% reduction.

The high spontaneous resolution rate makes comparisons of treatments difficult. Narrow-spectrum antibiotics have the same success rate as broad-spectrum antibiotics, although adverse effects, primarily gastrointestinal, are more common with the latter. All guidelines recommend oral amoxicillin as first-line therapy. The AAP/AAFP (American Academy of Pediatrics/American Academy of Family Physicians) guideline recommends high-dose amoxicillin (80-90 mg/kg/d), as this dose has been found to be more effective against penicillin-resistant S pneumoniae than standard-dose treatment. However, the studies supporting high-dose therapy are based on bacteriologic cure; evidence that high-dose therapy is clinically superior is lacking. All guidelines recommend high-dose amoxicillin-clavulanate (90/6.4 mg/kg/d) as second-line treatment. Some also recommend various cephalosporins, including ceftriaxone, cefdinir, cefprozil, or cefuroxime, as second-line therapy or as first-line treatment for children with “non–type I” penicillin allergy. No guidelines recommend azithromycin, trimethoprim-sulfamethoxazole, erythromycin, or cefaclor, except in cases of severe penicillin allergy, or when the organism is known to be sensitive to one of these drugs. Studies also document that a 5-day course of antibiotics is as effective as the standard 10-day course. Thus, based on numerous studies, a recommended approach is to treat children with AOM using a 5-day course of narrow-spectrum antibiotics.

Another acceptable option is withholding antibiotic treatment for 48-72 hours, treating pain as needed, and beginning antibiotic therapy if the symptoms do not resolve within this time period. This may be considered in children over the age of 2 years if the presenting illness is not severe (fever <39°C [102.2°F] and mild or no pain). This is also an option for children between the ages of 6 months and 2 years, if the diagnosis of otitis media is uncertain and the symptoms are not severe.

It is important to note that studies have not adequately addressed the issues of treatment of children younger than 2 years of age and treatment of frequently recurrent or complicated otitis media. Physicians are left to their clinical judgment as to the best treatment for these children.

The best treatment for children with frequent recurrences of otitis media is another area of study. The best evidence is that children will only benefit from daily antibiotic prophylaxis if they have had more than three episodes in 6 to 18 months. The magnitude of benefit is small, with a reduction of about one episode per year. Antibiotics studied have primarily been narrow-spectrum drugs, such as erythromycin, amoxicillin, sulfisoxazole, and trimethoprim-sulfamethoxazole. Insertion of tympanostomy tubes as treatment for persistent otitis media with middle ear effusions has not been found to improve developmental outcomes.

Prognosis

In general, children with otitis media recover uneventfully. The half-life of the middle ear effusion is about 4 weeks, with 10% persistence at 4 months. Repeated courses of antibiotics have no effect on these effusions and should not be used.

Pharyngitis

Sore throat is a common problem in pediatrics, leading to millions of physician office each year. However, obtaining a clear diagnosis as to the cause of this problem is far from simple. The most important diagnosis to make is infection with group A β-hemolytic streptococci (GABHS), which is responsible for about 15% of cases of pharyngitis. Antibiotic treatment has only a modest effect on the course of the disease, but adequate treatment with antibiotics effectively prevents the important complication of rheumatic fever. Non-GABHS occasionally cause pharyngitis but do not lead to rheumatic fever. Viruses of many sorts cause the vast majority of cases, including some cases of exudative pharyngitis. Adenoviruses can cause pharyngoconjunctival fever, with exudative pharyngitis and conjunctivitis. Epstein-Barr virus causes infectious mononucleosis, which commonly produces other signs, such as generalized lymphadenopathy and splenomegaly, in addition to exudative pharyngitis. Herpesviruses and coxsackie viruses can cause ulcerative stomatitis and pharyngitis. Most viruses, however, cause signs and symptoms that overlap with those of GABHS. The literature contains numerous recommendations for diagnosis and treatment, but there is no clear consensus as to the most accurate or most cost-effective method for evaluation and treatment of the child with a sore throat.

Essentials of Diagnosis

• Moderate to severe tonsillar swelling.
  
• Moderate to severe tender anterior cervical lymphadenopathy.
  
• Scarlatiniform rash (depending on the strain of bacteria).
  
• Absence of moderate to severe viral symptoms (cough, nasal congestion).

General Considerations

GABHS cause approximately 15% of cases of sore throat in children. The infection is uncommon in children younger than 3-5 years of age and in adolescents older than 11-15 years of age.

Clinical Findings

Symptoms and Signs

Clinical symptoms and signs overlap those of viral pharyngitides and URIs. The Centor criteria have been validated for adults but not for children. Attia and colleagues proposed a predictive model for GABHS after examining a large number of signs and symptoms. The findings most highly correlated with GABHS are moderate to severe tonsillar swelling, moderate to severe tender anterior cervical lymphadenopathy, scarlatiniform rash, and the absence of moderate to severe coryza. If all four of these are present, the likelihood of GABHS is 95%. Excluding scarlatiniform rash, the presence of the remaining three gives a probability of greater than 65%. In the absence of moderate to severe tonsillar enlargement, moderate to severe lymphadenopathy, and scarlatiniform rash and in the presence of moderate to severe coryza, the likelihood of GABHS is less than 15%.

Laboratory Findings

Rapid antigen detection tests are commonly used in practice. Although the sensitivities of these assays may be reported as very high in laboratories, in practice they may have a false-negative rate as high as 20%. The sensitivity and specificity of throat culture is dependent on technique and may also have a false-negative rate of 10%-20%. Another complicating factor is the inability of either rapid antigen testing or culture to distinguish between a true streptococcal infection and a viral infection in a child who is an otherwise asymptomatic carrier. Carrier rates among asymptomatic children may be as high as 17%, depending on the age of the child and the season of the year. Centers for Disease Control and Prevention (CDC) recommends treating only rapid-antigen or culture proven streptococcal disease to avoid promoting antibiotic resistance in other pharyngeal bacteria.

Complications

Complications of GABHS fall into two main categories: nonsuppurative and suppurative. The nonsuppurative complications are rheumatic fever and post-streptococcal glomerulonephritis. The main suppurative complications are peritonsillar and retropharyngeal abscess (see section Peritonsillar Abscess, later).

Acute rheumatic fever follows about 3% of cases of untreated GABHS. The cause is still not fully understood, but the prevailing theory is that there is some similarity between certain streptococcal antigens and certain myocardial proteins leading to antistreptococcal antibody recognition and interaction with the myocardial proteins. There is great geographic variability in the incidence of this disease. Rheumatic fever can be prevented by treatment of GABHS, even if treatment is delayed for up to 9 days, but a full 10 days of treatment is necessary for complete prevention. Post-streptococcal glomerulonephritis likewise seems to be caused by a poorly understood antigen-antibody reaction. Unlike rheumatic fever, glomerulonephritis is not prevented by treatment of GABHS.

Treatment

Treatment of GABHS may accomplish two things—quicker resolution of disease and prevention of some complications. Treatment of the acute infection may shorten the course of the disease by a small amount, although untreated disease will resolve within several days in most children. It is not clear whether immediate antibiotic treatment offers greater benefit than symptomatic treatment. It is generally believed that treatment reduces the rate of suppurative complications, but for many children who present with peritonsillar abscess, the initial streptococcal infection would not have been recognized in its earlier stages.

Currently, no GABHS are resistant to penicillin or cephalosporins. For reasons that are unclear, numerous studies show that cephalosporins have higher rates of clinical and bacteriologic success than penicillin. However, penicillin V is still considered the drug of choice for children who are not allergic to penicillin. There is no agreement as to the best alternative in penicillin-allergic children. Because of increasing resistance to erythromycin in some areas, clindamycin is often recommended. It is well established that 10 days of treatment is necessary to achieve the maximum possibility of bacterial eradication from the pharynx. However, for reasons that are unclear, streptococci persist in the pharynx in about 10% of treated children, regardless of which antibiotic is used. There is no consensus as to the best way to deal with this phenomenon.

Prognosis

Streptococcal pharyngitis is ordinarily a benign, self-limited disease. Morbidity and mortality are primarily related to the previously mentioned complications. Antibiotic treatment can eliminate many but not all of these.

Essentials of Diagnosis

• Severe sore throat.
  
• Odynophagia.
  
• High fever.
  
• Unilateral pharyngeal swelling with deviation of the uvula.

General Considerations

Peritonsillar abscess is the most common deep space head and neck infection in children, accounting for almost half of these infections. It is most commonly caused by infection with GABHS. The exact cause is unknown, but it is thought that the infection usually spreads from the tonsil itself into the deep spaces behind the tonsil, where it produces a collection of pus. It can occur in children of all ages, as well as in adults, but it affects older children and adolescents more than younger children. It is almost always unilateral.

Clinical Findings

Symptoms and Signs

Most children with peritonsillar abscess have had symptoms of pharyngitis for 1-7 days before presenting with symptoms related to the abscess. Many of these children have been treated with antibiotics for pharyngitis before developing the abscess. The most common symptoms are severe throat or neck pain, painful swallowing, high fever, and poor oral intake, sometimes with dehydration. The most common physical signs are cervical adenopathy, uvular deviation, and muffled voice with trismus. Symptoms are less clear and the examination more difficult in younger children, and young children who cannot cooperate may have to be examined under sedation.

Laboratory Findings

The WBC count is usually elevated, with a left shift. Throat cultures for streptococci are positive in only about 16% of specimens.

Imaging Studies

Computed tomography and ultrasound studies of the neck often show the abscess, but the diagnosis is generally made by history and physical examination.

Differential Diagnosis

The chief disease in the differential diagnosis is epiglottitis. This infection is uncommon in an era of widespread immunization against H influenzae type B, but the clinical picture may be identical in young children. Examination in the operating room under sedation may be necessary to establish the diagnosis.

Complications

Prompt treatment is necessary, because untreated abscesses may spread into other deep spaces in the head and neck. The airway may be compromised by swelling, especially in younger children. If the abscess ruptures into the throat, aspiration of pus may cause pneumonia.

Treatment

The treatment is drainage of the abscess, either by incision or by needle aspiration. This is generally done by an otolaryngologist or a surgeon familiar with the anatomy of the neck. Tonsillectomy is often done at the discretion of the surgeon, either at the time of the acute infection or shortly thereafter. Antibiotics effective against streptococci and staphylococci, such as nafcillin or ceftriaxone, are indicated, initially intravenously. Once cultures of the pus indicate the causative organism, treatment may be focused according to its antibiotic sensitivities.

Prognosis

Children generally recover uneventfully once appropriate treatment is begun, but they may be at increased risk for a second infection.

Essentials of Diagnosis

• Nonspecific respiratory infection in infants and young children.
  
• In older children, respiratory symptoms—coryza, conjunctivitis, pharyngitis, dry cough.
  
• In older children, pronounced high fever, myalgia, headache, malaise.

General Considerations

Influenza is a respiratory virus that causes a respiratory infection of variable severity in children. Although influenza itself is a benign, self-limited disease, its sequelae, primarily pneumonia, can cause serious illness and occasionally death.

Pathogenesis