Pneumococcal Infections

Updated: Jan 22, 2016
  • Author: Claudia Antonieta Nieves Prado, MD; Chief Editor: John L Brusch, MD, FACP  more...
  • Print
Overview

Practice Essentials

Pneumococcal infections are caused by Streptococcus pneumoniae, a gram-positive, catalase-negative organism commonly referred to as pneumococcus. S pneumoniae is the most common cause of community-acquired pneumonia (CAP), bacterial meningitis, bacteremia, and otitis media, as well as an important cause of sinusitis, septic arthritis, osteomyelitis, peritonitis, and endocarditis. Complications of each of these diagnoses are common. See the image below. Clinical signs and symptoms and physical examination findings alone cannot distinguish S pneumoniae disease from infections caused by other pathogens.

Empyema caused by Streptococcus pneumoniae. Antero Empyema caused by Streptococcus pneumoniae. Anteroposterior film. Courtesy of R. Duperval, MD.

Epidemiology

S pneumoniae can cause a wide variety of clinical symptoms owing to its ability to cause disease by either direct extension from the nasopharynx into surrounding anatomic structures or vascular invasion with hematogenous spread. Features that should prompt the clinician to consider pneumococcal infection include the following:

  • High-risk age groups (children younger than 5 years, particularly aged 2 years or younger; adults older than 55-65 years)
  • Conditions that cause immune deficits (eg, HIV infection, malignancy, or diabetes mellitus)
  • Conditions associated with decreased pulmonary clearance functions (eg, asthma, chronic bronchitis, or chronic obstructive pulmonary disease [COPD])
  • Presentation from late fall to early spring

Conditions that may develop by direct extension of S pneumoniae from the nasopharynx include the following:

  • Conjunctivitis
  • Otitis media
  • Sinusitis
  • Acute exacerbations of chronic bronchitis (AECB)
  • Pneumonia (which may be complicated by purulent pericarditis)

Conditions that may result from vascular invasion and hematogenous spread of S pneumoniae include the following:

  • Meningitis
  • Bacteremia (most common manifestation of invasive pneumococcal disease)
  • Joint and bone infections (osteomyelitis and septic arthritis)
  • Soft tissue infections (eg, myositis, periorbital cellulitis, abscess)
  • Peritonitis
  • Cardiac infections (eg, endocarditis)

See Clinical Presentation for more detail.

Diagnosis

If a pneumococcal infection is suspected or considered, Gram stain and culture of appropriate specimens should be obtained, when possible. Potential specimens may include 1 or more of the following:

  • Blood
  • Cerebrospinal fluid
  • Sputum
  • Pleural fluid or lung aspirate
  • Joint fluid
  • Bone
  • Other abscess or tissue specimens

All S pneumoniae isolates, regardless of the isolation site, should be tested for susceptibility to penicillin and cefotaxime or ceftriaxone. Susceptibilities based on the type of specimen (CSF versus other) were defined by the Clinical and Laboratory Institute (CLSI) in 2008. [1, 2]

Nonspecific laboratory tests that may support the diagnosis include the following:

  • Complete blood count and differential
  • Erythrocyte sedimentation rate (ESR)
  • C-reactive protein (CRP)

Imaging studies that may be helpful include the following:

  • Chest radiography
  • Ultrasonography of the chest
  • Computed tomography (CT) of the chest, sinuses, face, or affected bones or joints
  • Magnetic resonance imaging (MRI) of the brain (in meningitis) or affected bones and joints

Other modalities that may help define the extent of infection include the following:

  • Echocardiography
  • Middle-ear fluid aspiration
  • Pleural fluid aspiration
  • Chest tube thoracostomy or catheter placement
  • Video-assisted thoracoscopy (VATS) or pleural decortication
  • Joint fluid aspiration
  • Biopsy of bone, soft tissue, or muscle

See Workup for more detail.

Management

Antibiotics are the mainstay of therapy. Treatments for specific infections may include the following:

  • Otitis media: In most cases, amoxicillin 80-90 mg/kg/day; if there is no improvement within 48-72 hours, amoxicillin-clavulanate or a second- or third-generation oral cephalosporin (or parenteral ceftriaxone for highly resistant pneumococci)
  • Sinusitis: Initial recommendations as for otitis media; in adult penicillin-allergic patients and patients who do not respond to initial therapy, switching to fluoroquinolones (not approved for children in this clinical situation) may be considered
  • Pneumonia: For penicillin-sensitive S pneumoniae (minimum inhibitory concentration [MIC] <2 μg/mL), penicillin G or amoxicillin is considered first-line therapy; for penicillin-resistant S pneumoniae infection (MIC ≥2 μg/mL), the choice of antimicrobial agent should be directed by susceptibility testing [3]
  • Meningitis: In children, a beta-lactam (penicillin, ceftriaxone, or cefotaxime) with or without vancomycin pending susceptibility testing; children with hypersensitivity to beta-lactams should receive vancomycin plus rifampin; meropenem and chloramphenicol have also been used; for adults with penicillin-sensitive S pneumoniae infection (MIC ≤ 0.06 μg/mL), intravenous penicillin G or ampicillin is first-line therapy; for penicillin-resistant pneumococcus (MIC ≥0.12 μg/mL), treatment with a third-generation cephalosporin (if ceftriaxone or cefotaxime MIC <1 μg/mL) or a third-generation cephalosporin plus vancomycin (if cefotaxime or ceftriaxone MIC ≥1 μg/mL) is recommended

Additional treatment measures that may be helpful for particular conditions are as follows:

  • Complicated pneumonia: Chest tube placement for drainage of pleural fluid; in more severe cases, VATS or decortication
  • Suspected septic arthritis or osteomyelitis: Collection of appropriate specimens for Gram stain, cell count, histology, or culture
  • Recurrent or chronic otitis media, periorbital or orbital cellulitis, or facial cellulitis: Surgical intervention

Measures for preventing pneumococcal infection include the following:

  • Behavior modification and risk factor reduction
  • Medical therapy
  • Antimicrobial prophylaxis (in selected patients) with recurrent otitis media.
  • Immunization

See Treatment and Medication for more detail.

Next:

Background

S pneumoniae is a gram-positive, catalase-negative coccus that has remained an extremely important human bacterial pathogen since its initial recognition in the late 1800s. The term pneumococcus gained widespread use by the late 1880s, when it was recognized as the most common cause of bacterial lobar pneumonia.

Worldwide, S pneumoniae remains the most common bacterial cause of community-acquired pneumonia (CAP). However, a recent study involving state-of-the-art diagnostic techniques for bacterial, viral, and fungal infections indicated that a specific pathogen was detected in only 38% of CAP cases. Of these cases, one or more viruses were retrieved in 23% of cases and bacteria in 11%. A combination of bacterial and viral pathogens was seen in 3%. Fungal and mycobacterial organisms accounted for 1%. Human rhinoviruses were isolated in 9% of cases and influenza virus in 6%. S pneumoniae remained the most common cause of bacterial CAP, at 5% of patients. [4]

S pneumoniae is a common cause of bacterial meningitis, bacteremia, and otitis media. S pneumoniae infection is also an important cause of sinusitis, septic arthritis, osteomyelitis, peritonitis, and endocarditis. Worldwide in 2000, 14.5 million estimated episodes of invasive pneumococcal disease were reported in children younger than 5 years, which correlates to more than 800,000 estimated deaths (11% of all deaths in this age group). [5]

Pneumococcal vaccination, particularly routine childhood pneumococcal conjugate vaccine (PCV; introduced in the United States in 2000), has led to decreased rates of invasive pneumococcal infections (>90%) caused by pneumococcal serotypes covered by the vaccine, as well as overall decreased rates of invasive disease (45% overall; 75% in children < 5 years). In addition, herd immunity has led to decreased rates of disease in older children and adults. [6, 7, 8]

 

Surveillance data following introduction and widespread uptake of 7-valent PCV (PCV7) immunization showed an astounding reduction in invasive disease of 100% in children younger than 5 years in the United States (94% in all ages) when considering disease caused by serotypes contained in PCV7. [5]

Many subsequent studies have shown increased rates of invasive and noninvasive disease caused by serotypes not covered by the vaccine, including serotypes 15, 19A, and 33F. An analysis of over 700 cases of invasive disease in completely immunized children (PCV7) showed that 96% were due to nonvaccine serotypes. An additional 6 serotypes accounted for almost two thirds of invasive infections in this age group.

An analysis of 653 invasive pneumococcal infections in the Spanish population before and after the implementation of PCV7 immunization showed an increased incidence of invasive disease in the postvaccine period, which was primarily due to nonvaccine serotypes and was associated with higher rates of complications, such as septic shock. Similar studies in the United States and other European countries have shown similar results, introducing the concept of replacement disease and its effects.

Serotype 19A has received the most attention, not only because of increased disease rates associated with this serotype, but also owing to its association with increased drug resistance. Increased rates of invasive disease with such serotypes caused the overall rates of invasive disease to remain somewhat steady starting in 2002, although these rates remain greatly reduced from rates prior to introduction of the conjugate vaccine.

For these reasons, work on the development of a vaccine containing additional serotypes continued. A 13-valent PCV (PCV13) was approved by the US Food and Drug Administration (FDA) on February 24, 2010 with the hope that its induced T-cell–dependent immune response would have increased efficacy in children and elderly persons. This potential benefit has yet to be demonstrated in elderly individuals. [6, 9, 10, 11, 12, 13, 14, 15, 8, 16, 17, 18, 5, 19, 20]

The 23-valent polysaccharide vaccine is more effective in decreasing pneumococcal bacteremia than pneumonia. As a result, mortality rates have decreased. Ongoing surveillance will help determine the effects of widespread routine immunization with PCV13 and its expanded serotype coverage on pneumococcal disease in children and adults.

In January 2013, the FDA approved PCV13 for the prevention of invasive pneumococcal disease in children and adolescents between 6 and 17 years of age. [21] In February 2013, the CDC's Advisory Committee on Immunization Practices (ACIP) voted for the use of the vaccine in children with immunodeficiencies. The panel recommends routine use of a single dose of PCV13 for children aged 6-18 years who have an immunocompromising condition (eg, sickle cell disease or HIV infection) and have not previously received the vaccine. [22]

 

Despite an overall decreased incidence of otitis media caused by serotypes covered by vaccination since the introduction of the conjugate pneumococcal vaccine, an increase in rates of disease caused by serotypes not covered by the vaccine has occurred, as well as an increase in rates of diseases caused by vaccine-covered serotypes in incompletely immunized children. The incidence of otitis media caused by serotype 19F has remained steady. Overall health care utilization for otitis media has decreased, as has the incidence of recurrent otitis media in some populations and studies. [7, 23, 24, 25]

Previous
Next:

Pathophysiology

Capsule

The capsule is composed of polysaccharides that cover the cell wall, which is made up of peptidoglycan and teichoic acid, characterizing the classic gram positive structure; It acts as the principal antiphagocytic and protective element that prevents access of the leukocytes to the underlying cell wall elements. The capsular polysaccharides have served as means of serotyping and identifying these organisms. The Quellung reaction is the criterion standard method for pneumococcal capsular serotyping. More than 9 serotypes of S pneumoniae have been identified; currently, serotypes 6, 14, 18, 19, and 23 are the most prevalent agents that cause infections. Serotyping provides important epidemiological information, especially with the widespread use of vaccination, but rarely provides timely clinical information.

The virulence of each organism is determined in part by two distinct states: opaque and transparent colony types that influence the capacity to evade host defenses. The nasopharynx is predominantly colonized by the transparent phenotype. Conversely, the opaque type predominates in lung, CNS, and bloodstream infections; it has increased capsular polysaccharide and produces more biofilm. [26] In addition, in vitro and in vivo studies of clinical isolates have shown that pneumococci have the ability to obtain DNA from other pneumococci (or other bacteria) via transformation, allowing them to switch to serotypically distinct capsular type.

Adherence and Invasion

S pneumoniae is an extracellular bacterial pathogen that can adhere avidly to the respiratory epithelium and mucus. It exhibits different surface proteins that recognize and attach to human cells. Pneumococcal surface protein C (PspC) binds to the poly-Ig receptor on epithelial cells, pneumococcal surface antigen A (PsaA) binds to E-cadherin on epithelial cells, pneumococcal adhesion and virulence factor A (PavA) binds to fibronectin, and enolase (Eno) binds to plasminogen that may bridge binding to host cells. Phospho-cholines interact with the receptor for platelet-activating on activated epithelial cells. Capsule, pneumolysin, and the ABC transporter Ami have also been implicated in adherence. [27]  S pneumoniae produces biofilm after binding to host cells. Biofilm production is regulated by external factors, such as temperature.

Invasion is promoted by phospho-cholines. After interacting with the PAF receptor, it is inserted into the host cell via endocytosis, causing translocation of bacteria through the endothelium. This is particularly important for translocation over the blood-brain barrier during meningitis development. Bacteria surface coat is changed via gene expression to avoid host defenses and complete translocation. Invasion is also mediated by adhesins and pneumolysin; pneumolysin is a cytotoxin that induces apoptosis of epithelial cells by membrane pore formation, resulting in access to subendothelium. Intraalveolar replication of pneumococci, penetration into the interstitium, and dissemination into the bloodstream are among other functions of pneumolysin. [28]

Much of the clinical severity of pneumococcal disease results from the activation of the complement pathways and cytokine release, which induce a significant inflammatory response. S pneumoniae cell wall components, along with the pneumococcal capsule, activate the alternative complement pathway; antibodies to the cell wall polysaccharides activate the classic complement pathway. Cell wall proteins, autolysin, and DNA released from bacterial breakdown all contribute to the production of cytokines, inducing further inflammation.

Previous
Next:

Frequency

United States

Colonization

S pneumoniae remains an important pathogen in large part because of its ability to first colonize the nasopharynx efficiently. Studies performed in the United States prior to universal vaccination recommendations have shown average carriage rates of 40%-50% in healthy children and 20%-30% in healthy adults. Factors such as age, daycare attendance, composition of household, immune status, antibiotic use, and others obviously affect these numbers. [29, 30, 31] With the implementation of childhood vaccination with the heptavalent conjugate vaccine for S pneumoniae, the colonization rates have decreased in children receiving the vaccine and in adults and other children in their household because of the phenomenon of herd immunity.

Most individuals who are colonized with S pneumoniae carry only a single serotype at any given time; the duration of colonization varies and depends on specific serotype and host characteristics. Invasive disease is usually related to recent acquisition of a new serotype. However, in most healthy hosts, colonization is not associated with symptoms or disease but allows for the continued presence of S pneumoniae within the population, allowing for prolonged low-level transmission among contacts.

S pneumoniae infection is the most common cause of CAP, bacterial meningitis, bacteremia, and otitis media in the United States. There is a clear seasonality, with infections peaking in the fall and winter months. [32]

Noninvasive disease

Pneumococcal colonization allows for spread of organisms into the adjacent paranasal sinuses, middle ear, and/or tracheobronchial tree down to the lower respiratory tract. This spread results in specific clinical syndromes (sinusitis, otitis media, bronchitis, pneumonia) related to the noninvasive spread of the organisms.

Worldwide, the most common cause of death due to pneumococcal disease is pneumonia. In adults admitted to the hospital in the United States for pneumonia treatment, S pneumoniae remains the most common organism isolated. Until 2000, 100,000-135,000 patients were hospitalized for pneumonia proven to be caused by S pneumoniae infection in the United States annually. These numbers are likely a gross underestimate, as a definite cause is not determined in most cases of pneumonia treated each year. In addition, the actual rates are also likely decreasing owing to implementation of pneumococcal conjugate vaccination. [33]

S pneumoniae infection is an important cause of bacterial co-infection in patients with influenza and can increase the morbidity and mortality in these patients. This has been emphasized recently by the increased number of cases of invasive pneumococcal disease seen in association with increased rates of hospitalizations for influenza during the 2009 H1N1 influenza A pandemic. [34] Postmortem lung specimens from patients who died of H1N1 influenza A from May to August of 2009 were examined for evidence of concomitant bacterial infection. Twenty-nine percent of the specimens showed evidence of bacterial co-infection, with almost half of these being S pneumoniae. [35]

S pneumoniae infection is estimated to cause over 6-7 million cases of otitis media annually in the United States. These numbers have likely decreased somewhat with the advent of universal vaccinations; however, S pneumoniae infection remains the most common cause of otitis media. [36, 31]

Invasive disease

Statistics regarding invasive pneumococcal disease in the United States are based on active surveillance using the Centers for Disease Control and Prevention (CDC) Active Bacterial Core Surveillance (ABC) system. Calculations for 2010 estimated 39,750 (12.9 cases per 100,000 population) cases of invasive disease nationally, with 4,000 (1.3 cases per 100,000 population) estimated deaths. (Comparable 2008 data showed 44,000 (14.5 cases per 100,000 population) episodes of invasive disease with 4,500 (1.5 cases per 100,000 population) deaths. [6]

Children younger than 5 years and adults older than 65 years are 2 identified age groups in whom rates of disease and death are increased. In 2010, rates of pneumococcal invasive disease in these groups were estimated to be 19 per 100,000 population and 36 per 100,000 population, respectively. This compares with rates of 20.2 and 40.4 in 2008, 21.8 and 39.2 in 2007, and 23.2 and 43.3 in 2002, respectively. More than half of deaths due to invasive pneumococcal disease occur in adults with specific risk factors (age, immunosuppression) for severe disease. Such risk factors are an indication for vaccination. [6, 37]

International

Despite the worldwide importance of disease due to S pneumoniae infection, very little information is available on the extent of pneumococcal disease in developing countries. A review of the available literature does show an increase in reports of incidence, prevalence, complications, and vaccine effects in many areas of Europe, Asia, and Australia.

Children

In developing countries, pneumococcus remains the most common and important disease-causing organism in infants. Although exact numbers are difficult to obtain, it is estimated that pneumococcal infections are responsible for more than one million of the 2.6 million annual deaths due to acute respiratory infection in children younger than 5 years. Case fatality rates associated with invasive disease vary widely but can approach and surpass 50% and are greatest in patients with meningitis; one quarter to more than one half of those who survive develop long-term sequelae of infection. [36, 38]

Estimates of pneumococcal disease in Gambian children show high rates of infection in the first year of life (≥500 per 100,000 children). [39] Latin American studies also show a particularly high risk in infants younger than 6 months, and children in southern India have higher rates of colonization at younger ages compared with US children, according to US clinical studies. Some particular populations, such as indigenous Australians and minority Israeli persons, also have disproportionately higher rates of disease, similar to the native Alaskan and native Indian populations in the United States, although determining the role of socioeconomic factors in the higher incidence of disease in these populations is difficult. [39]

In Europe, children younger than 2 years constitute the population most at risk for pneumococcal infection, with rates decreasing with age. The overall incidence of invasive disease is estimated to be somewhat lower in Europe (14 per 100,000 persons in Germany vs 35.8 per 100,000 persons in England vs 45.3 per 100,000 persons in Finland vs 90 per 100,000 persons in Spain vs 235 per 100,000 persons in the United States), although many have postulated that this may be due in part to the more liberal blood-culture collection practices in the American health care system. [39, 36]

Adults

Even fewer data are available on the worldwide incidence of pneumococcal disease in adults. As in the United States, the most common cause of CAP in Europe is S pneumoniae infection, affecting approximately 100 per 100,000 adults each year. Overall rates of febrile bacteremia and meningitis are also similar, (15–19 per 100,000 adults and 1–2 per 100,000 adults, respectively), with the risk for these diseases increased in elderly and infant populations. [40]

Because no population-based data on pneumococcal disease in adults in developing countries are available, estimates of disease burden are based on small clinical studies, vaccine trials, extrapolation from data in developed countries, and studies of persons at high risk for disease. The information gleaned from these sources suggests that the incidence of and mortality rates associated with pneumococcal disease are high, with HIV-positive populations exhibiting particularly high rates of infection. Further studies are greatly needed. [41, 36]

Previous
Next:

Mortality/Morbidity

Although exact rates are difficult to determine, the World Health Organization (WHO) estimates that, worldwide, 1.6 million deaths were caused by pneumococcal disease in 2005, with 700,000 to 1 million of these occurring in children younger than 5 years. [42] Even in patients in developed countries, invasive pneumococcal disease carries a high mortality rate—an average of 10-20% in adults with pneumococcal pneumonia, with much higher rates in those with risk factors for disease. [43, 44]

Race

In the United States, invasive pneumococcal disease is more common in native Alaskans, Navajo and Apache Indians, and African Americans than in other ethnic groups. Some studies have shown this difference persists even when the results are controlled for socioeconomic factors, and the reasons for this discrepancy among certain populations are unclear. [30]

Sex

Most clinical studies of pneumococcal disease show a slight male predilection for disease; the reason for this is unclear.

Age

Children younger than 2 years carry the highest burden of S pneumoniae disease worldwide. In developed countries, the incidence is highest in those aged 6 months to 1 year, while, in developing countries, the disease is particularly common in children younger than 6 months.

Adults older than 55-65 years are the next most commonly affected age group worldwide.

Immunosuppressed persons of any age are at a higher risk for pneumococcal disease.

Previous