Practice Essentials
Streptococcus pneumoniae colonizes the upper respiratory tract of healthy individuals and is one of the most frequent causes of bacterial infection in children. Pediatric infections caused by this pathogen include otitis media (OM), sinusitis, occult bacteremia, pneumonia, meningitis, osteomyelitis, septic arthritis, pericarditis, and peritonitis. See the image below.
Sputum Gram stain from a patient with a pneumococcal pneumonia. Note the numerous polymorphonuclear neutrophils and gram-positive, lancet-shaped diplococci. Courtesy of C. Sinave, MD, personal collection.
Signs and symptoms
Children with pneumococcal infections usually have a temperature higher than 102°F, along with symptoms of specific infections, as follows:
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OM – Otalgia, upper respiratory symptoms, vomiting
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Sinusitis – Headache, facial tenderness (much less frequent than in adults), symptoms of upper respiratory tract infection lasting for 10 days or longer
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Occult bacteremia – Fever without a localizing source in children aged 2-24 months
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Pneumonia – Cough; chest pain, shortness of breath, or respiratory difficulty; malaise and poor appetite
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Meningitis – Stiff neck, vomiting, headache (older children); high fever (>103°F), lethargy, irritability, poor feeding, inconsolable crying [1]
Physical findings include the following:
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OM – Bulging, erythematous, or yellow tympanic membrane with poor mobility and purulent fluid seen behind the membrane
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Sinusitis – Tenderness to palpation over maxillary or frontal sinuses, nasal discharge of any color, swollen nasal turbinates
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Bacteremia – None, besides fever (≥102°F) and tachycardia associated with the fever
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Pneumonia – Crackles or decreased breath sounds in the area of lobar consolidation on chest auscultation, with egophony in patients with severe consolidation and dullness to percussion; retractions, tachypnea, or both
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Meningitis or other central nervous system (CNS) infection – Ill appearance; nuchal rigidity (may not be present before age 4 months); altered mental status with poor responsiveness (patient may present in comatose state); other neurologic abnormalities possible (eg, cranial nerve deficits, ataxia, weakness); poor perfusion and signs of shock in patients with concurrent pneumococcal sepsis
See Presentation for more detail.
Diagnosis
The following laboratory studies are indicated in patients with pneumococcal infections:
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White blood cell (WBC) count and differential
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Antigen tests (cerebrospinal fluid [CSF], urine)
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Gram stain (CSF, synovial fluid, pleural fluid)
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Culture (blood, CSF, pleural fluid, middle ear effusion, synovial fluid)
Specific testing recommendations for particular clinical syndromes are as follows:
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OM or sinusitis – Tympanocentesis and bacterial cultures of middle ear fluid if chronic OM is refractory to antibiotics
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Sinusitis – Culture of sinus fluid if sinusitis is refractory to antibiotics
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Occult bacteremia – Culture of blood (≥2 mL)
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Pneumonia – Blood culture; sputum cultures are difficult to obtain from children, and results may be falsely positive
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Meningitis (suspected) – Lumbar puncture with CSF analysis (cell count, protein levels, glucose levels, Gram stain, culture; antigen tests are needed only in cases of antibiotic pretreatment); blood culture
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Osteomyelitis or septic arthritis – Surgical biopsy or joint aspiration; culture of fluid or bone; blood culture
Imaging studies that may be helpful include the following:
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Chest radiography
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Computed tomography (CT) of the head (often unnecessary)
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Magnetic resonance imaging (MRI) of the head
See Workup for more detail.
Management
Antibiotic therapy and supportive care are indicated. The key to successful antibiotic therapy is achieving drug concentrations in the affected area of the body that are several times higher than the minimal inhibitory concentration (MIC) for S pneumoniae.
Recommendations for particular clinical situations include the following:
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OM or sinusitis (initial treatment) – Amoxicillin for 5-10 days (otitis media) or 10-21 days (sinusitis)
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OM or sinusitis that does not improve with standard-dose amoxicillin – High-dose amoxicillin, amoxicillin-clavulanate, cefuroxime, or ceftriaxone (IM)
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Pneumonia (outpatient) – Amoxicillin for 10 days
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Pneumonia (inpatient) – IV ceftriaxone until clinical improvement, then 10 days of outpatient treatment; in critical illness, addition of vancomycin should be considered
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Other invasive pneumococcal diseases – A third- or fourth-generation parenteral cephalosporin (ceftriaxone, cefotaxime, cefepime); in critical illness or the absence of clinical improvement, addition of vancomycin should be considered
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Meningitis – Ceftriaxone or cefotaxime; meropenem may be an alternative in cases of ceftriaxone resistance; vancomycin is always added until susceptibilities are known; rifampin may be added after 24-48 hours of improvement is not noted or the relevant MIC is high
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Penicillin allergy (OM, sinusitis, outpatient treatment of pneumonia) – Azithromycin (or other macrolide), clindamycin, cefuroxime (if there is no cephalosporin allergy), or cefprozil
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Penicillin allergy (inpatient treatment of pneumonia or other invasive infections) – IV ceftriaxone (if there is no cephalosporin allergy); alternatively, IV clindamycin or meropenem; vancomycin may be considered if the patient is severely ill and microbial susceptibility is unknown
See Treatment and Medication for more detail.
Pathophysiology
Pneumococci are encapsulated, lancet-shaped, gram-positive diplococci. The bacteria are transmitted person to person via respiratory droplet contact. Pneumococci can cause disease either by direct spread from colonized mucosal surfaces (eg, otitis media) or by hematogenous spread (eg, meningitis following bacteremia). Mucosal irritation resulting from factors such as viral infection or smoke often is a predisposing factor for pneumococcal infection. Ninety serotypes have been identified, with varying degrees of pathogenicity. Serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F cause most invasive disease, and pneumococci with these serotypes are often resistant to penicillin.
Epidemiology
United States statistics
Invasive disease is most frequent in children younger than 2 years and in adults older than 65 years. Overall annual incidence of invasive disease in the United States is 15 cases per 100,000 individuals but widely varies by age, from 166 cases per 100,000 children younger than 2 years to 5 cases per 100,000 young adults. After the introduction of heptavalent conjugated pneumococcal vaccine, the rate of invasive pneumococcal disease (IPD) has trended down. [2, 3] In an active laboratory surveillance from 1997-2004, the IPD decreased by 40% from 11.8 cases to 7.2 cases per 100,000 live births. Among black infants, a marked decrease was noted in incidence of IPD from 17.1 cases to 5.3 cases per 100,000 live births compared with white infants with a decrease from 9.6 cases to 6.8 cases per 100,000 live births.
From 1999-2007, a 92% reduction in vaccine serotypes has been observed among both invasive and noninvasive isolates; during the same period, a 200% increase has been observed in vaccine-related or nonvaccine serotypes. Among these, serotypes 19A, 6C, 15, and 22F were predominantly noted. [4] The amoxicillin susceptibility was about 70% compared with 50% in macrolides. Serotype 6C is considered to be emerging as well. [5]
An increased frequency of disease and increased morbidity and mortality rates are seen in children younger than 2 years and in children with humoral immunodeficiency (eg, HIV infection, agammaglobulinemia, complement deficiency), absent or deficient splenic function (eg, splenectomy, sickle cell anemia), nephrotic syndrome, chronic renal failure, organ transplantation, immunosuppressive therapy, chronic pulmonary disease, cerebral spinal fluid (CSF) leak after skull fracture, cochlear implant, diabetes mellitus, and malignancy. Parental smoking invariably increases acute otitis media by about 64% compared to no history of parental smoking (56%).
Specific infections
Otitis media: Approximately 30% of children have at least one episode of pneumococcal otitis media by age 3 years. Pneumococci cause approximately 40% of otitis media cases. After the pneumococcal vaccination, nonvaccine serotype is encountered more frequently as a cause of otitis compared with vaccine serotypes.
Bacteremia: Pneumococci are responsible for as many as 85% of occult cases of bacteremia in children. Bacteremia is seen in 3-5% of children aged 3-36 months with fever higher than 102.5°F without another source. In the postvaccine licensure period, the annual episodes of pneumococcal bacteremia decreased from 7.2 episodes to 2.3 episodes per 100,000 emergency department visits in 1999. However, it increased to 2.8 episodes in 2004 and to 3.64 episodes per 100,000 emergency department visits in 2005. The rate of invasive disease due to serotype 19F in the conjugate vaccine has increased.
Pneumonia: S pneumoniae is the most common bacterial cause of childhood pneumonia, especially in children younger than 5 years.
Meningitis/CNS infections: S pneumoniae is the most common cause of bacterial meningitis in children. Yearly incidence in all age groups is 1-2 cases per 100,000 population.
Osteomyelitis/septic arthritis: Pneumococci are responsible for fewer than 10% of all cases of osteomyelitis and septic arthritis.
Other unusual infections caused by pneumococci are sporadic.
Vaccination
The inclusion of the pneumococcal conjugate vaccine in the routine pediatric immunization schedule has markedly decreased the incidence of invasive pneumococcal disease. The vaccine is about 50-60% efficacious in reducing otitis media caused by the vaccine strains of S pneumoniae compared with 80-100% in preventing invasive disease. In children younger than 5 years, IPD has decreased from 98.7 cases per 100,000 population in 1998-99 to 23.4 cases per 100,000 population in 2005, with 77% reduction. [6, 7] An increase in serotype 19A from 2.6 cases in 98-99 to 9.3 cases in 2005 has been reported in this age group.
A study by Greenhow et al that retrospectively reviewed 57,733 blood cultures from children 3 to 36 months old reported that the incidence of Streptococcus pneumoniae bacteremia decreased from 74.5 per 100,000 children to 3.5 per 100,000 in the post-PCV-13 period, a 95.3% reduction. [8]
A study that compared the pneumococcal prevaccination period of 2005-2008 to 2014 reported that incidence of otitis media decreased from 41.5% in children < 5 and 20.9% in children >5. The study also reported significant reductions in sinusitis and other upper respiratory tract infections and a decreased incidence of pneumonia by 28.6% in children < 5. [9]
International statistics
Pneumococcal pneumonia is estimated to cause 1.2 million deaths per year worldwide in children younger than 5 years.
Race-, sex-, and age-related demographics
An increased incidence of invasive pneumococcal disease has been documented in Blacks, American Indians (White Mountain Apache, Navajo), and Alaskan Eskimos.
Pneumococcal disease is slightly more frequent in males than in females, with a male-to-female ratio of 3:2 for pneumococcal bacteremia.
Pneumococcal infections are most common in children aged 1-24 months.
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Otitis media and bacteremia are most common in children aged 6 months to 2 years.
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Sinusitis is most common in children 2 years and older.
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Pneumonia and meningitis are most common in children younger than 5 years.
Prognosis
Morbidity/mortality
Death resulting from complications of pneumococcal otitis, sinusitis, bacteremia, and pneumonia is rare in otherwise healthy children. As a complication of pneumonia, pneumococcal empyema is not infrequent, even in developed countries, and it remains a significant problem in developing nations.
The case-fatality rate for pneumococcal meningitis is 5-10%. Between 25-35% of children with pneumococcal meningitis develop permanent neurologic sequelae (eg, hearing deficits, paralysis, hydrocephalus). The risk of fulminant pneumococcal infection and death in the high-risk patient population outlined above (eg, children with humoral immunodeficiency, functional asplenia, nephrotic syndrome) is much higher than the risk in otherwise healthy children.
A study that described the epidemiology, serotype distribution, clinical presentations, and outcomes of invasive pneumococcal diseases (IPD) in children with and without comorbidity reported that in children with comorbidity, IPD results in higher mortality, and a large proportion of disease is due to serotypes not included in current conjugate vaccines. [10, 11]
Complications
Complications are as follows:
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Meningitis - Subdural empyema, hydrocephalus, hearing loss, developmental delay, spasticity, mental retardation, and neurologic weakness
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Otitis media - Mastoiditis and cavernous sinus thrombosis
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Sinusitis - Intracranial abscess, periorbital/orbital cellulitis, subperiosteal abscess, cavernous sinus or sagittal sinus thrombosis, and meningitis
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Bacteremia - Osteomyelitis, endocarditis, and meningitis
In a population-based case study conducted in 2 regions in the United Kingdom, the authors analyzed 100 patients aged 3-20 years who were diagnosed with pneumococcal meningitis before age 14 years. Children who were diagnosed with pneumococcal meningitis had been noted to have statistically significant impairment in several areas of cognitive, functional, social, and psychological development, including hearing loss, compared with the control group. Overall, the intelligence quotient (IQ) and several areas of quality of life were reportedly lower among those who had pneumococcal meningitis. [12]
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Sputum Gram stain from a patient with a pneumococcal pneumonia. Note the numerous polymorphonuclear neutrophils and gram-positive, lancet-shaped diplococci. Courtesy of C. Sinave, MD, personal collection.
Tables
Drug |
Sensitive, MIC mcg/mL |
Resistant isolate, MIC mcg/mL |
|
Intermediate resistance |
Resistant |
||
Penicillin/amoxicillin |
≤0.06 |
0.1-1 |
≥2 |
Cefotaxime or ceftriaxone |
Nonmeningeal ≤1, meningeal ≤0.5 |
Nonmeningeal 2, meningeal 1 |
Nonmeningeal ≥4, meningeal ≥2 |
