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Pneumococcal Infections

by Larry M. Bush, MD, Maria T. Perez, MD

Streptococcus pneumoniae (pneumococci) are gram-positive, α-hemolytic, aerobic, encapsulated diplococci. In the US, pneumococcal infection annually causes about 7 million cases of otitis media, 500,000 cases of pneumonia, 50,000 cases of sepsis, 3,000 cases of meningitis, and 40,000 deaths. Diagnosis is by Gram stain and culture. Treatment depends on the resistance profile and includes a β-lactam, a macrolide, a respiratory fluoroquinolone, and sometimes vancomycin.

Pneumococci are fastidious microorganisms that require catalase to grow on agar plates. In the laboratory, pneumococci are identified by α-hemolysis on blood agar, sensitivity to optochin, and 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 (eg, military, institutional) populations.

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 serotypes have been identified. Most serious infections are caused by a small number of serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) that are included in the 13-valent pneumococcal conjugate vaccine. 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.

Risk factors

Patients most susceptible to serious and invasive pneumococcal infections are those with chronic illness (eg, chronic cardiorespiratory disease, diabetes, liver disease, alcoholism), immunosuppression (eg, HIV), functional or anatomic asplenia, or sickle cell disease, as well as residents of long-term care facilities, smokers, aborigines, Alaskan natives, and certain American Indian populations. The elderly, 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

  • Otitis media

  • Pneumonia

  • Sinusitis

  • Meningitis

  • Endocarditis

  • Septic arthritis

  • Peritonitis (rare)

Primary infection usually involves the middle ear or lungs. The diseases listed below are further discussed elsewhere in T he M anual .

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. When bacteremia is present, secondary seeding of distant sites may cause infections such as septic arthritis, meningitis, and endocarditis. Despite treatment, the overall mortality 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 and is 30 to 40% in the elderly; risk of death is highest during the first 3 days.

Pneumonia (see Pneumonia) is the most frequent serious infection caused by pneumococci; it may manifest as lobar pneumonia or, less commonly, as bronchopneumonia. About 4 million cases of community-acquired pneumonia occur each year in the US; when community-acquired pneumonia requires hospitalization, pneumococci are the most common 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. Lung abscess formation is rare.

Acute otitis media in infants (after the neonatal period) and children is caused by pneumococci in about 30 to 40% of cases (see Otitis Media (Acute)). More than one third of children in most populations develop acute pneumococcal otitis media during the first 2 yr of life, and pneumococcal otitis 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) have become the most common pneumococcal cause of acute otitis media. Complications include mild conductive hearing loss, vestibular balance dysfunction, tympanic membrane perforation, mastoiditis, petrositis, and labyrinthitis. 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.

Paranasal sinusitis (see 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 may extend into the cranium, causing cavernous sinus thrombosis; brain, epidural, or subdural abscesses; septic cortical thrombophlebitis; or meningitis.

Acute purulent meningitis (see Acute Bacterial Meningitis) 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 CNS. Complications after pneumococcal meningitis include hearing loss (in up to 50% of patients), seizures, learning disabilities, mental dysfunction, and palsies.

Endocarditis (see Infective Endocarditis) may result from pneumococcal bacteremia, even in patients without valvular heart disease, but is rare. Pneumococcal endocarditis may produce a corrosive valvular lesion, with sudden rupture or fenestration, leading to rapidly progressive heart failure.

Septic arthritis , similar to septic arthritis caused by other gram-positive cocci, is usually a complication of pneumococcal bacteremia from another site (see Acute Infectious Arthritis).

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 (see Peritonitis).

Diagnosis

  • 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.

Treatment

  • A β-lactam, macrolide, or a respiratory fluoroquinolone (eg, levofloxacin, moxifloxacin, gemifloxacin)

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 β-lactam or macrolide antibiotic, treatment has become more challenging because resistant strains have emerged. Strains highly resistant to penicillin, ampicillin, and other β-lactams are common worldwide. The most common predisposing factor to β-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 β-lactam.

Seriously ill patients with nonmeningeal infections caused by organisms that are highly 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. Fluoroquinolones (eg, moxifloxacin, levofloxacin, gemifloxacin) 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 β-lactam) is used.

All penicillin-resistant isolates have been susceptible to vancomycin so far, but parenteral vancomycin does not always produce concentrations in CSF 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

Infection produces type-specific immunity that does not generalize to other serotypes. Otherwise, prevention involves

  • Vaccination

  • Prophylactic antibiotics

Vaccines

Two pneumococcal vaccines are available: a conjugated vaccine against 13 serotypes (PCV13) and a polyvalent polysaccharide vaccine directed against the 23 serotypes (PPV23) that account for > 90% of serious pneumococcal infections in adults and children.

Conjugated vaccine is recommended for all children aged 6 wk through 59 mo. The schedule varies depending on age and underlying medical conditions (see Table: Recommended Immunization Schedule for Ages 0–6 yr). If vaccination is begun at age 6 mo, children should receive a 3-dose primary series at about 2-mo intervals, followed by a 4th dose at age 12 to 15 mo. The customary age for the first dose is 2 mo. If vaccination is begun at age 7 to 11 mo, a 2-dose primary series and a booster are given. From age 12 to 23 mo, 2 doses and no booster are given. From age 24 mo to 9 yr, children receive 1 dose. Adults with immunocompromising conditions, functional or anatomic asplenia, cerebrospinal fluid leaks, or cochlear implants and who have not previously received PPV23 should receive a dose of PCV13 first, followed by a dose of PPV23 at least 8 wk later.

Polysaccharide vaccine is ineffective in children < 2 yr but reduces invasive pneumococcal infection and bacteremia by 50% in adults. There is no documented reduction in pneumonia. Protection usually lasts many years, but one-time revaccination after 5 yr is recommended for patients with functional or anatomic asplenia, as well as for immunocompromised patients, and may be desirable in other highly susceptible people. The polysaccharide vaccine is indicated for adults 65 yr, for people 2 to 64 yr with increased susceptibility (see Gram-Positive Cocci:Risk factors), and before splenectomy. PPV23 should be followed by a PCV13 dose > 1 year later in patients who are immunocompromised or have functional or anatomic asplenia, CSF leaks, or cochlear implants and who previously received ≥ 1 doses of PPV23. The polysaccharide vaccine is not recommended for children < 2 yr or anyone hypersensitive to the vaccine’s components.

Prophylactic antibiotics

For functional or anatomic asplenic children < 5 yr, prophylactic penicillin V 125 mg po bid 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 po bid is recommended for older children or adolescents for at least 1 yr after splenectomy.

Key Points

  • Pneumococci cause many cases of otitis media and pneumonia and can also cause meningitis, sinusitis, 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 β-lactam or macrolide antibiotic.

  • Because resistance to β-lactam and macrolide antibiotics is increasing, seriously ill patients may be treated with an advanced-generation cephalosporin (eg, ceftriaxone, cefotaxime, ceftaroline) and/or a respiratory fluoroquinolone (eg, moxifloxacin, levofloxacin, gemifloxacin).

  • Routine vaccination is recommended for all children aged 6 wk through 59 mo, all adults 65 yr, and people of other ages with certain risk factors.

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • VANCOCIN
  • AVELOX
  • FACTIVE
  • RIFADIN, RIMACTANE
  • ROCEPHIN
  • IQUIX, LEVAQUIN, QUIXIN
  • CLAFORAN
  • No US brand name

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