S. pneumoniae is a gram-positive, lancet-shaped diplococcus that usually occurs in pairs. Under certain conditions, pneumococci may form chains, the length of which depends on the type of media in which the organism has been grown. S. pneumoniae is encapsulated, and capsular size varies considerably. With Gram stain, pneumococci may resemble other organisms, particularly alpha-hemolytic streptococci.

On solid media, encapsulated pneumococci produce shiny, round colonies approximately 1 mm in diameter. Serotypes 3, 8, and 37 form larger, mucoid colonies. As the cultures age, the center of the colony regresses, creating a central dimple. When grown on media containing blood, all pneumococci cause alpha-hemolysis of the surrounding erythrocytes. Pneumococci are facultative anaerobes and may be grown aerobically or anaerobically. Rarely, strains of S. pneumoniae are obligate anaerobes.

Optochin is helpful in identifying pneumococci because usually these organisms are sensitive to this agent and beta-hemolytic streptococci are resistant. Discs impregnated with Optochin are laid on pneumococcal cultures, and the plate is incubated overnight. Sensitivity is manifested by a zone of inhibition around the disc.

Pneumococci also may be identified by a bile solubility assay. When bile is added to a culture of pneumococci, prompt dissolution of the cocci occurs. The Quellung reaction permits rapid identification of pneumococci. This reaction is carried out by mixing equal volumes of the suspension of bacteria, antiserum, and methylene blue on a slide and examining the bacteria by light microscopy. Capsular swelling identifies genus, species, and serotype. The use of the Quellung reaction permits immediate identification of pneumococci from cultures or body fluids.

A rapid test to identify pneumococci growing in liquid culture uses latex particles coated with antibodies to all currently identified serotypes. This test is extremely useful, although selected strains of alpha-streptococci may cross-react with pneumococci.

Pneumococci typically are found in the pharynx of healthy people. S. pneumoniae organisms are spread from person to person in droplets from respiratory secretions. Infection of the upper respiratory tract aids the spread. In temperate climates, colonization and disease caused by pneumococci are seen more commonly in the winter and spring. Outbreaks of pneumococcal infection can occur in physically crowded settings, such as military barracks, prisons, and day-care centers.

Rates of colonization vary widely and depend on numerous variables, including age, race, population studied, and degree of exposure to children. The prevalence of colonization typically has been found to be between 25% and 50%, with some studies finding rates as high as 97%. Most children develop colonization at some point during their first few years of life. Rates of colonization gradually increase with age over the first 1 or 2 years of life, and the highest rates are associated with children receiving institutional care.

With the increase throughout the world in the prevalence of penicillin- and multiantibiotic-resistant pneumococci, numerous studies have attempted to define risk factors for colonization with resistant organisms. Factors that have been implicated include recent therapy with antimicrobial agents, age younger than 2 years, attendance in a child-care facility, residence in a chronic care facility, and recent hospitalization.

Ninety serotypes of S. pneumoniae have been identified worldwide, with the distribution of serotypes that account for infections varying according to region. A difference also has been noted between serotypes causing infections in adults and those infecting children. In North America, serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F are associated most commonly with infections in the pediatric age group. These same serotypes also have been found to account for most organisms with antibiotic resistance. Serotypes 1, 3 and 5 are found more commonly in older children and adults.

Immunity to S. pneumoniae depends on the presence of type-specific antibody to the capsular antigen of the organism. Immunity during the first few months of life apparently is derived from maternal antibody transferred passively to the fetus. Children younger than 2 years old respond poorly to the capsular polysaccharide antigen. This finding may explain the frequency of pneumococcal bacteremia in children between the ages of 3 months and 2 years.

Pneumococcal infection occurs more frequently in blacks than in whites, a finding that is not explained fully by the frequency of sickle cell disease in the black population, as well as in some Native American populations.

Pneumococci may invade from a site of colonization by hematogenous spread or by direct extension. Pneumococcal meningitis usually occurs after pneumococcal bacteremia, but it can also result from direct spread to the meninges as a sequela of a cerebrospinal fluid (CSF) leak that occurs after a temporal or basilar skull fracture. Pneumococcal otitis media usually results from the spread of pneumococci colonizing the nasopharynx via the eustachian tube into the middle ear.
Pneumococcal pneumonia is caused by aspiration of pneumococci that reside in the pharynx. Several studies document that a viral infection, including influenza, may compromise pulmonary defense mechanisms and predispose the individual to invasion by pneumococci. Although pneumococci most commonly produce otitis media, sinusitis, pneumonia, bacteremia, and meningitis, any organ system can be affected.

Identification of the specific factors responsible for pneumococcal infection and subsequent injury to the host continues to be an area of active research. The capsule of S. pneumoniae is known to aid the pneumococci by resisting phagocytosis, but the capsule itself is nontoxic. Specific serotypes associated with large capsules appear to be more virulent and to cause greater morbidity and mortality than do serotypes characterized by smaller capsules. Rough strains of pneumococci lacking a capsule are avirulent. Serotypes 1 and 3 more commonly cause pneumonia complicated by empysema than do other serotypes.

Some serotypes are associated more commonly with specific sites of infections than are others. For example, serotype 1 is found primarily in children with pneumonia, serogroup 19 with mastoiditis, and serotype 14 with pneumonia and cellulitis. Most researchers concur that elements of the cell wall are responsible for the initiation of the inflammatory response seen in pneumococcal infection. Specifically, peptidoglycan and teichoic acid have been found to be the two most potent inflammatory components of the cell wall and appear to initiate an inflammatory response by activating complement factor C3 via the alternative pathway.

Numerous pneumococcal proteins that may serve as virulence factors have been identified. Pneumolysin, an intracellular protein, is the best characterized of these proteins. Although it is not secreted by pneumococci, it is released on cell lysis as the infection progresses or on initiation of antimicrobial therapy. Pneumolysin has been shown to have numerous effects in vitro. At high concentrations, it forms transmembrane pores and results in lysis of most of the cell types found in the lung. It also has been shown to inhibit ciliary motion, to disrupt epithelial membranes, to interfere with neutrophil and lymphocyte function, and to stimulate the production of inflammatory cytokines. Other possible virulence factors include an immunoglobulin A protease, a neuraminidase, and an autolysin enzyme.

Deficiency of the terminal components of complement has been associated with recurrent pyogenic infection, including that caused by S. pneumoniae. Deficiency of complement factor C2 also appears to be associated with S. pneumoniae infection. Invasive pneumococcal disease is much more prevalent among persons with anatomic or functional asplenia and is particularly prevalent in patients with sickle cell disease and other hemoglobinopathies. These patients appear to be unable to activate C3 by the alternative pathway or to fix opsonin to the pneumococcal cell wall. Ineffective clearance of bloodborne bacteria in the absence of type-specific antibodies and abnormal activation of the alternate pathway for complement metabolism place the asplenic patient at risk for development of overwhelming infection. The efficacy of phagocytosis for S. pneumoniae is diminished in patients with B-cell and T-cell deficiency syndromes that lack opsonic anticapsular antibody and fail to produce agglutination and lysis of bacteria. These observations suggest that opsonization of the pneumococcus depends on the classic and alternate complement pathways and that recovery from pneumococcal disease depends on the development of anticapsular antibodies that act as opsonins and enhance phagocytosis and intracellular killing of pneumococcus.

Low levels of factor B or impairment of the properdin pathway and defective opsonization occur in physiologically normal persons during acute pneumococcal disease, findings suggesting that pneumococcal infection may develop in some people because of a transient preexisting depression of factor B or that acute pneumococcal infection may be accompanied by consumption of this component of the complement system. Complement factors C3 through C9 produce chemotactic and opsonic properties in serum, and each plays an important role in protection against pneumococcal infection.

Within body tissues, particularly the lung, the spread of infection is enhanced by the antiphagocytic properties of the capsular-specific soluble substance. Edema-promoting factors also play important roles in the pathogenesis of infection within the lung. After infection is established, the alveoli fill with serous fluid. Subsequently, polymorphonuclear leukocytes accumulate in the infected alveoli, causing consolidation. Ultimately, macrophages replace the leukocytes, and the exudate resolves. This sequence of events evolves over the course of 7 to 10 days, but it can be modified by the use of appropriate antimicrobial therapy.