Pneumococci are fastidious microorganisms that require catalase to grow on agar plates. In the laboratory, pneumococci are identified by
Gram-positive lancet-shaped diplococci
Alpha-hemolysis on blood agar
Sensitivity to optochin
Lysis by bile salts
Pneumococci commonly colonize the human respiratory tract, particularly in winter and early spring. Spread is via airborne droplets.
True epidemics of pneumococcal infections are rare; however, some serotypes seem to be associated with outbreaks in certain populations (eg, military, institutional, homeless) particularly in crowded settings.
The pneumococcus capsule consists of a complex polysaccharide that determines serologic type and contributes to virulence and pathogenicity. Virulence varies somewhat within serologic types because of genetic diversity.
Currently, > 90 different pneumococcal serotypes have been identified based on their reaction with type-specific antisera. The pneumococcal polysaccharide capsule is critical for evading phagocytosis. Serotype 3 strains, which are more heavily encapsulated and tend to form more mucoid colonies than other serotypes, are common causes of invasive pneumococcal disease in adults. Most serious infections are caused by a small number of serotypes (3, 4, 6B, 9V, 14, 18C, 19F, and 23F) that are included in the 13-valent pneumococcal conjugate vaccine Pneumococcal Vaccine Pneumococcal disease (eg, otitis media, pneumonia, sepsis, meningitis) is caused by some of the > 90 serotypes of Streptococcus pneumoniae (pneumococci). Vaccines are directed against... read more . These serotypes cause about 90% of invasive infections in children and 60% in adults. However, these patterns are slowly changing, in part because of the widespread use of polyvalent vaccine. Serotype 19A, which is highly virulent and multidrug-resistant, has emerged as an important cause of respiratory tract infection and invasive disease; it is thus now included in the 13-valent pneumococcal conjugate vaccine.
Patients most susceptible to serious and invasive pneumococcal infections are
Those with chronic illness (eg, chronic cardiorespiratory disease, diabetes, liver disease, alcoholism)
Those with immunodeficiency or immunosuppression (eg, HIV)
Those with functional or anatomic asplenia
Those with sickle cell disease
Residents of long-term care facilities
Aborigines, Alaskan natives, and certain American Indian populations
Older people, even those without other disease, tend to have a poor prognosis with pneumococcal infections.
Damage to the respiratory epithelium by chronic bronchitis or common respiratory viral infections, notably influenza, may predispose to pneumococcal invasion.
Diseases Caused by Pneumococci
Pneumococcal diseases include
Primary pneumococcal infection usually involves the middle ear or lungs.
The diseases listed below are further discussed elsewhere in THE MANUAL.
Pneumococcal bacteremia Bacteremia Bacteremia is the presence of bacteria in the bloodstream. It can occur spontaneously, during certain tissue infections, with use of indwelling genitourinary or IV catheters, or after dental... read more can occur in immunocompetent and immunosuppressed patients; patients who have had splenectomy are at particular risk.
Bacteremia may be the primary infection, or it may accompany the acute phase of any focal pneumococcal infection. Pneumococcal bacteremia can be complicated by sepsis and septic shock Sepsis and Septic Shock Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by a dysregulated response to infection. In septic shock, there is critical reduction in tissue perfusion; acute failure... read more . When bacteremia is present, secondary seeding of distant sites may cause infections such as septic arthritis, meningitis, and endocarditis.
Despite treatment, the overall case-fatality rate for bacteremia is
15 to 20% in children (mainly in those who have meningitis, who are immunocompromised, and/or who have had splenectomy and have severe bacteremia) and in adults
30 to 40% in older people
Risk of death is highest during the first 3 days.
Pneumonia Overview of Pneumonia Pneumonia is acute inflammation of the lungs caused by infection. Initial diagnosis is usually based on chest x-ray and clinical findings. Causes, symptoms, treatment, preventive measures, and... read more is the most frequent serious infection caused by pneumococci; it may manifest as lobar pneumonia or, less commonly, as bronchopneumonia. Millions of cases of community-acquired pneumonia Community-Acquired Pneumonia Community-acquired pneumonia is defined as pneumonia that is acquired outside the hospital. The most commonly identified pathogens are Streptococcus pneumoniae, Haemophilus influenzae... read more occur each year in the US; when community-acquired pneumonia requires hospitalization, pneumococci are the most common bacterial etiologic agent in patients of all ages.
Pleural effusion Pleural Effusion Pleural effusions are accumulations of fluid within the pleural space. They have multiple causes and usually are classified as transudates or exudates. Detection is by physical examination and... read more occurs in up to 40% of patients, but most effusions resolve during drug treatment. Only about 2% of patients develop empyema, which may become loculated, thick, and fibrinopurulent; empyema has been most commonly associated with S. pneumoniae serotype 1. Lung abscess due to S. pneumoniae is uncommon in adults but occurs more frequently in children; serotype 3 is the usual pathogen, but other pneumococcal serotypes may be involved.
Pneumococcal acute otitis media
Acute otitis media Otitis Media (Acute) Acute otitis media is a bacterial or viral infection of the middle ear, usually accompanying an upper respiratory infection. Symptoms include otalgia, often with systemic symptoms (eg, fever... read more in infants (after the neonatal period) and children is caused by pneumococci in about 30 to 40% of cases. More than one third of children in most populations develop acute pneumococcal otitis media during the first 2 years of life, and pneumococcal otitis media commonly recurs. Relatively few serotypes of S. pneumoniae are responsible for most cases. After universal immunization of infants in the US beginning in 2000, nonvaccine serotypes of S. pneumoniae (particularly serotype 19A—not in the original protein-conjugated pneumococcal vaccine) have become the most common pneumococcal cause of acute otitis media.
Mild conductive hearing loss
Vestibular balance dysfunction
Tympanic membrane perforation
Intracranial complications are rare in developed countries but may include meningitis, epidural abscess, brain abscess, lateral venous sinus thrombosis, cavernous sinus thrombosis, subdural empyema, and carotid artery thrombosis.
Pneumococcal paranasal sinusitis
Paranasal sinusitis Sinusitis Sinusitis is inflammation of the paranasal sinuses due to viral, bacterial, or fungal infections or allergic reactions. Symptoms include nasal obstruction and congestion, purulent rhinorrhea... read more may be caused by pneumococci and may become chronic and polymicrobic.
Most commonly, the maxillary and ethmoid sinuses are affected. Infection of the sinuses causes pain and purulent discharge and may extend into the cranium, causing the following complications:
Cavernous sinus thrombosis
Brain, epidural, or subdural abscesses
Septic cortical thrombophlebitis
Acute purulent meningitis Acute Bacterial Meningitis Acute bacterial meningitis is rapidly progressive bacterial infection of the meninges and subarachnoid space. Findings typically include headache, fever, and nuchal rigidity. Diagnosis is by... read more is frequently caused by pneumococci and may be secondary to bacteremia from other foci (notably pneumonia); direct extension from infection of the ear, mastoid process, or paranasal sinuses; or basilar fracture of the skull involving one of these sites or the cribriform plate (usually with cerebrospinal fluid leakage), thus giving bacteria in the paranasal sinuses, nasopharynx, or middle ear access to the central nervous system.
Typical meningitis symptoms (eg, headache, stiff neck, fever) occur.
Complications after pneumococcal meningitis include
Hearing loss (in up to 50% of patients)
Acute bacterial endocarditis Infective Endocarditis Infective endocarditis is infection of the endocardium, usually with bacteria (commonly, streptococci or staphylococci) or fungi. It may cause fever, heart murmurs, petechiae, anemia, embolic... read more may result from pneumococcal bacteremia, even in patients without valvular heart disease, but pneumococcal endocarditis is rare.
Pneumococcal endocarditis may produce a corrosive valvular lesion, with sudden rupture or fenestration, leading to rapidly progressive heart failure requiring valve replacement. Austrian syndrome is a rare condition characterized by the triad of pneumococcal meningitis, pneumonia, and endocarditis due to S. pneumoniae and has a high fatality rate. Native aortic valve insufficiency is the most common cause of heart failure in affected patients.
Pneumococcal septic arthritis
Septic arthritis Acute Infectious Arthritis Acute infectious (septic) arthritis is a joint infection that evolves over hours or days. The infection resides in synovial or periarticular tissues and is usually bacterial—in younger adults... read more , similar to septic arthritis caused by other gram-positive cocci, is usually a complication of pneumococcal bacteremia from another site.
Spontaneous pneumococcal peritonitis
Spontaneous pneumococcal peritonitis occurs most often in patients with cirrhosis and ascites, with no features to distinguish it from spontaneous bacterial peritonitis Spontaneous Bacterial Peritonitis (SBP) Spontaneous bacterial peritonitis (SBP) is infection of ascitic fluid without an apparent source. Manifestations may include fever, malaise, and symptoms of ascites and worsening hepatic failure... read more of other causes.
Diagnosis of Pneumococcal Infections
Gram stain and culture
Pneumococci are readily identified by their typical appearance on Gram stain as lancet-shaped diplococci.
The characteristic capsule can be best detected using the Quellung test. In this test, application of antiserum followed by staining with India ink causes the capsule to appear like a halo around the organism. The capsule is also visible in smears stained with methylene blue.
Culture confirms identification; antimicrobial susceptibility testing should be done. Serotyping and genotyping of isolates can be helpful for epidemiologic reasons (eg, to follow the spread of specific clones and antimicrobial resistance patterns). Differences in virulence within a serotype may be distinguished by techniques such as pulsed-field gel electrophoresis and multilocus sequence typing.
The urine antigen detection test has high specificity (> 90%) but poor sensitivity (50 to 80%) and is greatly influenced by concurrent bacteremia. The positive predictive value (the proportion of patients with a positive test that actually have the disease) is high (> 95%). However, the negative predictive value (the proportion of patients with a negative test that are actually disease free) is low, so a negative urine antigen test should not be used to rule out pneumococcal disease.
Treatment of Pneumococcal Infections
A beta-lactam, macrolide, respiratory fluoroquinolone (eg, levofloxacin, moxifloxacin, gemifloxacin), tetracycline (eg, omadacycline), or pleuromutilin (eg, lefamulin)
If pneumococcal infection is suspected, initial therapy pending susceptibility studies should be determined by local resistance patterns.
Although preferred treatment for pneumococcal infections is a beta-lactam or macrolide antibiotic, treatment has become more challenging because resistant strains have emerged. Strains highly resistant to penicillin, ampicillin, and other beta-lactams are common worldwide. The most common predisposing factor to beta-lactam resistance is use of these drugs within the past several months. Resistance to macrolide antibiotics has also increased significantly; these drugs are no longer recommended as monotherapy for hospitalized patients with community-acquired pneumonia.
Intermediately resistant organisms may be treated with usual or high doses of penicillin G or another beta-lactam.
Seriously ill patients with nonmeningeal infections caused by organisms that are resistant to penicillin can often be treated with ceftriaxone, cefotaxime, or ceftaroline. Very high doses of parenteral penicillin G (20 to 40 million units/day IV for adults) also work, unless the minimum inhibitory concentration of the isolate is very high, indicating resistance. Fluoroquinolones (eg, moxifloxacin, levofloxacin, gemifloxacin), omadacycline, and lefamulin are effective for respiratory infections with highly penicillin-resistant pneumococci in adults. Evidence suggests that the mortality rate for bacteremic pneumococcal pneumonia is lower when combination therapy (eg, macrolide plus beta-lactam) is used.
All penicillin-resistant isolates have been susceptible to vancomycin so far, but parenteral vancomycin does not always produce concentrations in cerebrospinal fluid adequate for treatment of meningitis (especially if corticosteroids are also being used). Therefore, in patients with meningitis, ceftriaxone or cefotaxime, rifampin, or both are commonly used with vancomycin.
Prevention of Pneumococcal Infections
Infection produces type-specific immunity that does not generalize to other serotypes. Prevention involves
See Pneumococcal Vaccine Pneumococcal Vaccine Pneumococcal disease (eg, otitis media, pneumonia, sepsis, meningitis) is caused by some of the > 90 serotypes of Streptococcus pneumoniae (pneumococci). Vaccines are directed against... read more for more information, including indications Indications Pneumococcal disease (eg, otitis media, pneumonia, sepsis, meningitis) is caused by some of the > 90 serotypes of Streptococcus pneumoniae (pneumococci). Vaccines are directed against... read more , contraindications and precautions Contraindications and Precautions Pneumococcal disease (eg, otitis media, pneumonia, sepsis, meningitis) is caused by some of the > 90 serotypes of Streptococcus pneumoniae (pneumococci). Vaccines are directed against... read more , dosing and administration Administration Pneumococcal disease (eg, otitis media, pneumonia, sepsis, meningitis) is caused by some of the > 90 serotypes of Streptococcus pneumoniae (pneumococci). Vaccines are directed against... read more , and adverse effects Adverse Effects Pneumococcal disease (eg, otitis media, pneumonia, sepsis, meningitis) is caused by some of the > 90 serotypes of Streptococcus pneumoniae (pneumococci). Vaccines are directed against... read more . See also the vaccine schedules for children and adults from the Centers for Disease Control and Prevention (CDC) and pneumococcal vaccine recommendations from the Advisory Committee on Immunization Practices (ACIP).
Two pneumococcal vaccines Pneumococcal Vaccine Pneumococcal disease (eg, otitis media, pneumonia, sepsis, meningitis) is caused by some of the > 90 serotypes of Streptococcus pneumoniae (pneumococci). Vaccines are directed against... read more are available:
Pneumococcal conjugated vaccine ( PCV13 PCV13 Pneumococcal disease (eg, otitis media, pneumonia, sepsis, meningitis) is caused by some of the > 90 serotypes of Streptococcus pneumoniae (pneumococci). Vaccines are directed against... read more ): A conjugated vaccine against 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F)
Pneumococcal polysaccharide vaccine ( PPSV23 PPSV23 Pneumococcal disease (eg, otitis media, pneumonia, sepsis, meningitis) is caused by some of the > 90 serotypes of Streptococcus pneumoniae (pneumococci). Vaccines are directed against... read more ): A polyvalent polysaccharide vaccine directed against the 23 serotypes (1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, 33F) that account for > 90% of serious pneumococcal infections in adults and children
The vaccine schedules vary depending on age and medical conditions present in the patient. All children 2 months through 6 years of age should receive PCV13 as part of the routine childhood vaccination schedule Recommended Immunization Schedule for Ages 0–6 Years as should all people 65 years of age or older and people of other ages who have certain high-risk conditions Indications Pneumococcal disease (eg, otitis media, pneumonia, sepsis, meningitis) is caused by some of the > 90 serotypes of Streptococcus pneumoniae (pneumococci). Vaccines are directed against... read more .
For functional or anatomic asplenic children < 5 years of age, prophylactic penicillin V 125 mg orally 2 times a day is recommended. The duration for chemoprophylaxis is empiric, but some experts continue prophylaxis throughout childhood and into adulthood for high-risk patients with asplenia. Penicillin 250 mg orally 2 times a day is recommended for older children or adolescents for at least 1 year after splenectomy.
Pneumococci cause many cases of otitis media and pneumonia and can also cause meningitis, sinusitis, endocarditis, and septic arthritis.
Patients with chronic respiratory tract disease or asplenia are at high risk of serious and invasive pneumococcal infections, as are immunocompromised patients.
Treat uncomplicated or mild infection with a beta-lactam or macrolide antibiotic.
Because resistance to beta-lactam and macrolide antibiotics is increasing, seriously ill patients may be treated with an advanced-generation cephalosporin (eg, ceftriaxone, cefotaxime, ceftaroline), a respiratory fluoroquinolone (eg, moxifloxacin, levofloxacin, gemifloxacin), tetracycline (eg, omadacycline), or pleuromutilin (eg, lefamulin).
Severe or bacteremic pneumococcal pneumonia is treated with combination therapy (eg, macrolide plus beta-lactam).
Routine vaccination with PCV13 is recommended for all children aged 2 months through 6 years, people of other ages with certain risk factors, and for adults ≥ 65 years based on shared clinical decision making.
Routine vaccination with PPSV23 is recommended for all adults ≥ 65 years and under certain clinical circumstances for people age 19 to 64 years.
The following are some English-language resources that may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
Drugs Mentioned In This Article
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