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.
Серотипи
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. 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.
Фактори ризику пневмококової інфекції
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.
Захворювання, спричинені пневмококами
Pneumococcal diseases include
Primary pneumococcal infection usually involves the middle ear or lungs.
The diseases listed below are further discussed elsewhere in THE MANUAL.
Пневмококова бактеріємія
Pneumococcal bacteremia 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. 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 pneumococcal bacteremia is about 20% but may be as high as 60% among older adults (1).
Risk of death is highest during the first 3 days of bacteremia.
Пневмококова пневмонія
Pneumonia 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 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 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.
Пневмококовий гострий середній отит
Acute otitis media in infants (after the neonatal period) and children is caused by pneumococci in approximately 20% of cases (1). 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.
Пневмококовий придатковий синусит
Paranasal sinusitis 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
Meningitis
Пневмококовий менінгіт
Acute purulent meningitis 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.
Complications after pneumococcal meningitis occur in up to 50% of patients (1) and may include
Hearing loss
Seizures
Intellectual disabilities
Behavioral disabilities
Motor deficits
Пневмококовий ендокардит
Acute bacterial endocarditis 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.
Пневмококовий септичний артрит
Septic arthritis, similar to septic arthritis caused by other gram-positive cocci, is usually a complication of pneumococcal bacteremia from another site.
Спонтанний пневмококовий перитоніт
Spontaneous pneumococcal peritonitis occurs most often in patients with cirrhosis and ascites, with no features to distinguish it from spontaneous bacterial peritonitis of other causes.
Довідковий матеріал щодо захворювань, спричинених пневмококами
1. Centers for Disease Control and Prevention (CDC): Pneumococcal Disease: Clinical Features. Accessed 03/17/2023.
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). 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.
Довідковий матеріал щодо діагностики
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.
Менінгококові інфекції
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.
Неменінгококові інфекції
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
Пневмококові вакцини
See Pneumococcal Vaccine for more information, including indications, contraindications and precautions, dosing and administration, and adverse effects. 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).
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. 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.
Антибіотики з метою профілактики
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.
Ключові моменти
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 children 2 months through 6 years of age by giving pneumococcal vaccination as part of a routine childhood vaccination schedule.
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.
Додаткова інформація
The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
Centers for Disease Control and Prevention (CDC): Recommended Child and Adolescent Immunization Schedule for ages 18 years or younger, United States, 2024
CDC: Recommended Adult Immunization Schedule for ages 19 years or older, United States, 2024
Advisory Committee on Immunization Practices (ACIP): Pneumococcal vaccine recommendations
