Merck Manual

Please confirm that you are a health care professional

honeypot link

Pneumococcal Infections

By

Larry M. Bush

, MD, FACP, Charles E. Schmidt College of Medicine, Florida Atlantic University;


Maria T. Vazquez-Pertejo

, MD, FACP, Wellington Regional Medical Center

Reviewed/Revised May 2023
View PATIENT EDUCATION

Streptococcus pneumoniae (pneumococci) are gram-positive, alpha-hemolytic, aerobic, encapsulated diplococci. Pneumococcal infection is a major cause of otitis media, pneumonia, sepsis, meningitis, and death. Diagnosis is by Gram stain and culture. Treatment depends on the resistance profile and includes either a beta-lactam, a macrolide, a respiratory fluoroquinolone, a pleuromutilin, or sometimes vancomycin.

Pneumococci are fastidious microorganisms that require catalase to grow on agar plates. In the laboratory, pneumococci are identified by

  • Gram-positive lancet-shaped diplococci

  • Catalase-negative

  • 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 or settings (eg, military, congregate settings, people who are homeless), particularly in crowded settings.

Serotypes

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 serotypes 3, 4, 6B, 9V, 14, 18C, 19F, and 23F, which are included in the most often initially given PCV15 and PCV20 pneumococcal conjugate 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 . 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 now included in the 15- and 20-valent pneumococcal conjugate vaccines. Additional infection-causing serotypes have been included in the updated 15- and 20-valent pneumococcal conjugate vaccines.

Risk factors for pneumococcal infection

Patients most susceptible to serious and invasive pneumococcal infections include those with one or more of the following characteristics:

  • Chronic illness (eg, chronic cardiorespiratory disease, diabetes, liver disease, alcohol use disorder)

  • Immunodeficiency or immunosuppression (eg, HIV, congenital and acquired hypogammaglobulinemia [eg, from multiple myeloma], iatrogenic)

  • Congenital or acquired asplenia

  • Sickle cell disease or other hemoglobinopathies

  • Residents of long-term care facilities

  • Smokers

  • Aboriginal people, Alaska Native, and certain other American Indian populations

  • Chronic renal failure or nephrotic syndrome

  • Cochlear implant

  • CSF leak

  • Generalized cancer

  • Hodgkin disease

  • Leukemia

  • Lymphoma

  • Solid organ transplants

Older adults, 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 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.

Risk of death is highest during the first 3 days of bacteremia.

Pneumococcal pneumonia

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 Community-Acquired Pneumonia occur each year in the United States; 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 are usually classified as transudates or exudates. Detection is by physical examination,... read more Pleural Effusion 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 Otitis Media (Acute) in infants (after the neonatal period) and children is caused by pneumococci in approximately 20% of cases (1 Diseases caused by pneumococci reference Streptococcus pneumoniae (pneumococci) are gram-positive, alpha-hemolytic, aerobic, encapsulated diplococci. Pneumococcal infection is a major cause of otitis media, pneumonia, sepsis... read more ). 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 United States beginning in 2000, serotypes of S. pneumoniae (particularly serotype 19A, which was not in the original protein-conjugated pneumococcal vaccine) have become the most common pneumococcal causes of acute otitis media.

Complications include

  • Mild conductive hearing loss

  • Vestibular balance dysfunction

  • Tympanic membrane perforation

  • Mastoiditis

  • Petrositis

  • Labyrinthitis

Intracranial complications are rare in high-resource 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

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

  • Meningitis

Pneumococcal meningitis

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 resulting 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.

  • Hearing loss

  • Seizures

  • Intellectual disabilities

  • Behavioral disabilities

  • Motor deficits

Pneumococcal endocarditis

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

Spontaneous pneumococcal peritonitis

Diseases caused by pneumococci reference

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 pneumococcal capsule becomes visible microscopically after binding of the capsule with type-specific antiserum, which causes capsular swelling. After the addition of methylene blue, the pneumococcal cells stain dark blue and are surrounded by a sharply demarcated halo, which represents the outer edge of the capsule.

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%) (1 Diagnosis reference Streptococcus pneumoniae (pneumococci) are gram-positive, alpha-hemolytic, aerobic, encapsulated diplococci. Pneumococcal infection is a major cause of otitis media, pneumonia, sepsis... read more ). 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.

Diagnosis reference

  • 1. Laijen W, Snijders D, Boersma WG: Pneumococcal urinary antigen test: Diagnostic yield and impact on antibiotic treatment. Clin Respir J 11(6):999–1005, 2017. doi: 10.1111/crj.12453

Treatment of Pneumococcal Infections

  • A beta-lactam, macrolide, respiratory fluoroquinolone (eg, levofloxacin, moxifloxacin), tetracycline (eg, doxycycline, 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 antibiotics within the past several months. Resistance to macrolide antibiotics has also increased significantly; these antibiotics are not recommended as monotherapy for hospitalized patients with community-acquired pneumonia.

Susceptibility or resistance to beta-lactam antibiotics (penicillin and the extended-spectrum cephalosporins ceftriaxone and cefotaxime) depends on the site of infection and minimal inhibitory concentration (MIC) breakpoints. Susceptible organisms have MICs below the breakpoint, and resistant organisms have MICs above the breakpoint. MIC breakpoints typically are higher for nonmeningeal pneumococcal infection than for meningeal infection.

Meningeal pneumococcal infections

MIC breakpoints for patients with meningeal pneumococcal infection:

  • Penicillin-susceptible strains: MIC ≤ 0.06 mcg/mL

  • Penicillin-resistant strains: MIC ≥ 0.12 mcg/mL

  • Cefotaxime- and ceftriaxone-susceptible strains: MIC ≤ 0.5 mcg/mL

  • Cefotaxime- and ceftriaxone-intermediate strains: MIC > 0.5 to ≤ 1.0 mcg/mL

  • Cefotaxime- and ceftriaxone-resistant strains: MIC > 1.0 mcg/mL

If the penicillin MIC is ≤ 0.06 mcg/mL, treatment of meningeal pneumococcal infection may be with IV penicillin; however, ceftriaxone or cefotaxime is preferable.

If the penicillin MIC is ≥ 0.12 mcg/mL and the ceftriaxone or cefotaxime MIC is ≤ 0.5 mcg/mL, treatment is with ceftriaxone or cefotaxime.

If the ceftriaxone or cefotaxime MIC is ≥ 1.0 mcg/mL, treatment is with ceftriaxone or cefotaxime plus vancomycin.

Nonmeningeal pneumococcal infections

MIC breakpoints for patients with nonmeningeal pneumococcal infection:

  • Penicillin-susceptible strains: MIC ≤ 2 mcg/mL

  • Penicillin-intermediate strains: MIC > 2.0 to ≤ 4.0 mcg/mL

  • Penicillin-resistant strains: MIC > 4.0 mcg/mL

  • Cefotaxime- and ceftriaxone-susceptible strains: MIC ≤ 1 mcg/mL

  • Cefotaxime- and ceftriaxone-intermediate strains: MIC > 1.0 to ≤ 2.0 mcg/mL

  • Cefotaxime- and ceftriaxone-resistant strains: MIC > 2.0 mcg/mL

Seriously ill patients with nonmeningeal infections caused by organisms that are resistant to penicillin can often be treated with ceftriaxone or cefotaxime. Very high doses of parenteral penicillin G (20 to 40 million units/day IV for adults) also work, unless the MIC of the isolate is very high, indicating resistance.

Fluoroquinolones (eg, moxifloxacin, levofloxacin), 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 is commonly used with vancomycin.

Prevention of Pneumococcal Infections

Infection produces type-specific immunity that does not generalize to other serotypes. Prevention involves

  • Vaccination

  • Prophylactic antibiotics

Pneumococcal vaccines

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 pneumococcal vaccination as part of a routine childhood vaccination schedule Childhood Vaccination Schedules Vaccination has been extremely effective in preventing serious disease and in improving health worldwide. Because of vaccines, infections that were once very common and/or fatal (eg, smallpox... read more . Pneumococcal vaccination is also recommended for adults 19 to 64 years of age who have certain chronic medical conditions or other risk factors and at age > 65 years for all other adults.

Prophylactic antibiotics

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.

Key Points

  • Streptococcus pneumoniae (pneumococci) bacteria are gram-positive, alpha-hemolytic, aerobic, encapsulated diplococci.

  • 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 patients who are immunocompromised.

  • 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 or cefotaxime) based on minimal inhibitory concentration (MIC); other options include a respiratory fluoroquinolone (eg, moxifloxacin, levofloxacin), a tetracycline (eg, omadacycline), or a pleuromutilin (eg, lefamulin).

  • Severe or bacteremic pneumococcal pneumonia is treated with combination therapy (eg, a macrolide plus a beta-lactam).

  • Prevent pneumococcal infection in adults by giving additional pneumococcal vaccination at age 19 to 64 years for those who have certain chronic medical conditions or other risk factors and at age > 65 years for all other adults.

More Information

The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.

Drugs Mentioned In This Article

Drug Name Select Trade
Pneumovax 23, Pnu-Imune-23 , Prevnar, Prevnar 13 , Prevnar 20, VAXNEUVANCE
PROVAYBLUE, Urolene Blue
Emtet-500, Panmycin, Sumycin
Principen
Ceftrisol Plus, Rocephin
Claforan
FIRVANQ, Vancocin, Vancocin Powder, VANCOSOL
Pfizerpen
Avelox, Avelox ABC Pack, Avelox I.V., MOXEZA, Vigamox
Iquix, Levaquin, Levaquin Leva-Pak, Quixin
NUZYRA
Xenleta, Xenleta Solution
Beepen VK, Veetids
View PATIENT EDUCATION
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
quiz link

Test your knowledge

Take a Quiz! 
iOS ANDROID
iOS ANDROID
iOS ANDROID
TOP