Pneumococcal Infections Clinical Presentation

After successful colonization, S pneumoniae can cause a wide variety of clinical symptoms. By direct extension from the nasopharynx, S pneumoniae infection can spread and then manifest as otitis media, sinusitis, tracheobronchitis, bronchitis, and pneumonia. By invasion and hematogenous spread, S pneumoniae infection can cause primary bacteremia, meningitis, osteomyelitis, pericarditis, endocarditis, myositis, septic arthritis, and peritonitis.

Factors that should prompt consideration of pneumococcal disease in patients with the above conditions include the following:

High-risk age groups

Children younger than 5 years, particularly aged 2 years or younger are at an increased risk of disease. In addition, absence of breastfeeding, exposure to cigarette smoke, daycare attendance, and lack of immunization with the pneumococcal conjugate vaccine further increase the risk of disease.

Adults older than 55-65 years are also at an increased risk of disease.

Immunodeficiencies

Conditions that cause immune deficits, including HIV infection, malignancy, diabetes mellitus, functional or actual absence of the spleen, humoral immunity defects, complement deficiencies, and neutrophil dysfunction, are associated with an increased risk of disease.

Conditions associated with decreased pulmonary clearance functions

These include asthma, chronic bronchitis, chronic obstructive pulmonary disease (COPD), viral infections, and active/passive cigarette smoke exposure.

Presentation in the late fall to early spring

Pneumococcal infections peak in late fall to early spring in the Northern Hemisphere.

Clinical signs and symptoms and physical examination findings alone do not distinguish S pneumoniae disease from that caused by other pathogens.

Conjunctivitis

Bacterial conjunctivitis is more likely to be bilateral and purulent than viral conjunctivitis.

S pneumoniae is found in up to one third of patients with bacterial conjunctivitis; the rate of isolates that are not susceptible to penicillin is increasing.

Otitis media

S pneumoniae is the most commonly isolated bacterial pathogen from children and adults with otitis media.

Several early studies suggested or showed that S pneumoniae otitis media is usually accompanied by fever and pain and that the fever is higher than in otitis media caused by other common bacterial pathogens.^[18]

Pneumococcal disease is less likely to resolve spontaneously.

Eustachian tube congestion caused by a preceding viral infection is common.

Increasing antibiotic resistance has led to decreased effectiveness of the antibiotics that were once used most commonly to treat otitis media.

S pneumoniae infection is the most common cause of mastoiditis, a complication of otitis media that was more common in the pre-antibiotic era; this complication is now more commonly associated with untreated or improperly treated cases of otitis media.

Sinusitis

As in otitis media, S pneumoniae is the most commonly isolated bacterial organism from patients with acute sinusitis.

Acute sinusitis manifestations may vary depending on the age of the patient and the developmental status of individual sinuses. In children younger than 5 years, infection is usually limited to the ethmoid and maxillary sinuses.

Acute sinusitis is usually preceded by a viral infection, leading to sinus mucosal swelling and ostia obstruction. This is followed by the development of a purulent discharge and cough.

Malodorous breath and worsening cough at night due to postnasal drip are often noted.

Acute exacerbations of chronic bronchitis (AECB)

Acute exacerbations of chronic bronchitis manifest as a change from baseline chronic symptoms. Symptoms include shortness of breath, increased production and/or purulence of sputum, increased sputum tenacity, and cough.

An estimated 80% of cases of acute exacerbations of chronic bronchitis are caused by infection, with about one half of those caused by aerobic bacteria, of which S pneumoniae is the most commonly isolated organism.

Symptoms such as sore throat, cold symptoms, and dyspnea may indicate a viral cause.^[33]

Pneumonia

Classic pneumococcal pneumonia often develops in older children and adults. It may be preceded by a viral illness that is followed by an acute onset of high fever—often with rigors, productive cough, pleural pain, dyspnea, tachypnea, tachycardia, sweats, malaise, and fatigue.

Patients typically appear ill and may have an anxious appearance. On careful physical examination, rales can be heard in most patients. About half of all patients exhibit dullness to percussion, and splinting due to pain may be seen. Signs of effusion/empyema may be found on examination and include dullness to percussion at the bases. Diaphragmatic motion that is decreased from that expected in light of the patient's tachypnea.

In children (particularly school-aged and younger children), the potential manifestations of pneumonia are broad and often nonspecific. These may include nonspecific mild respiratory symptoms, with or without a cough on initial presentation; tachypnea, dyspnea, and splinting: high fever; abdominal pain; abdominal distention; anorexia; emesis (often suggesting a primary gastrointestinal disease); meningeal signs due to meningeal irritation with right upper lobe pneumonias; or chest pain due to pleural irritation.

In elderly patients with pneumococcal pneumonia, tachypnea may be the primary presenting sign. Temperature elevations may be mild or absent.

S pneumoniae is a common cause of bacterial CAP in HIV patients.

The most common complication of pneumococcal pneumonia is pleural effusion. Although up to 40% of patients with pneumococcal pneumonia may have pleural effusion, only an estimated 10% of these patients have enough fluid to aspirate, with only 2% of these patients meeting criteria for true empyema. S pneumoniae infection, along with Staphylococcusaureus infection, remains one of the most common causes of pediatric empyema.^{[18, 19, 34]}

Meningitis

As a cause of meningitis, S pneumoniae usually invades the meninges via the bloodstream. Recent studies have shown that this is most likely due to pneumococcal adherence to up-regulated platelet-activating factor on vascular endothelial meningeal surfaces.

S pneumoniae can also directly invade the meninges after basilar skull fractures or other trauma that compromises the dura and is the most common cause of recurrent bacterial meningitis in these patients.

In countries with routine-vaccination policies, S pneumoniae infection is the most common cause of sporadic bacterial meningitis in both children and adults.

Most patients with pneumococcal meningitis present non-acutely after hours to days of developing signs and symptoms. Presenting signs and symptoms may be nonspecific and include fever, irritability, emesis, lethargy, anorexia, and malaise.

Neurologic signs and symptoms are usually prominent and may include mental-status changes, delirium, lethargy, nuchal rigidity with positive Brudzinski and Kernig signs, cranial nerve palsies, and other focal neurological deficits.

A bulging fontanelle and poor feeding may be seen infants.

Elderly patients may present with more indolent signs, including increasing lethargy, nonresponsiveness, or coma.

Twenty to 25% of patients with pneumococcal meningitis experience seizures.

Bacteremia may be found when blood cultures are obtained.

Prolonged or secondary fevers are not uncommon but do not usually affect outcomes.

Complications of pneumococcal meningitis include hearing loss, seizures, learning disabilities, mental difficulties, and cranial nerve palsies. In a study from Denmark, 240 patients who survived pneumococcal meningitis were examined using audiometry.^[35] More than half (54%) had a hearing deficit, and 39% of those patients were not suspected of hearing loss at discharge from the hospital. Of the 240 patients, 7% had profound unilateral hearing loss, and another 7% had bilateral profound hearing loss. Significant risk factors for hearing loss included advanced age, the presence of comorbidity, and severity of meningitis. Audiometry should be performed on all patients who survive pneumococcal meningitis.

Pneumococcal meningitis carries a greater risk of death and significant neurological disabilities than does meningitis of other common bacterial causes (eg, Haemophilus influenzae type B [Hib] and Neisseria meningitidis).^{[18, 19, 34]}

Bacteremia

Bacteremia is the most common manifestation of invasive pneumococcal disease.

Most cases are primary bacteremia and are found in children younger than 2 years. It is estimated that S pneumoniae infection has been the cause of 90% of occult bacteremia (bacteremia without a source) cases in these children since the widespread use of the Hib vaccine. The incidence of occult bacteremia has decreased since the institution of routine pneumococcal immunization in infants.^{[36, 37]}

In adult patients, pneumococcal bacteremia is much more likely to be associated with another focal infection such as pneumonia, meningitis.

Signs, symptoms, and physical examination findings are usually nonspecific in patients with occult bacteremia due to pneumococcal infection.

In most patients, fever develops within 24 hours of positive culture findings. Higher temperatures are more often associated with the development of occult bacteremia.

A peripheral WBC count greater than 15,000 cells/μL is associated with the presence of occult bacteremia.

Bacteremia is less likely in patients with fever and signs or symptoms of focal infection (eg, otitis media).

Most cases of occult bacteremia spontaneously resolve.

Complications develop in an estimated 10% of patients with occult bacteremia and include meningitis, osteomyelitis, pneumonia, soft tissue and joint infections, and sepsis.

Patients with higher WBC counts and fever, those who have not undergone prior antibiotic therapy, and children younger than 20 months are at a higher risk for persistent bacteremia or the development of focal infection.^{[19, 18]}

Joint and bone infections

S pneumoniae infection is an uncommon cause of osteomyelitis and septic arthritis, causing approximately 4% and 20% of cases in children, respectively.

Septic arthritis: Pneumococcal septic arthritis usually manifests as painful, swollen, and hot joints. The ankles and knees are most commonly involved, and one or more joints may be affected. Blood or synovial cultures usually grow S pneumoniae. Up to half of patients with pneumococcal septic arthritis have concomitant osteomyelitis.

Osteomyelitis: The femur and humerus are most often involved in cases of pneumococcal osteomyelitis in children; the vertebral bones are often involved in adult patients. Up to 20% of patients with pneumococcal osteomyelitis develop long-term sequelae, similar to rates of osteomyelitis sequelae caused by other organisms. One clinical study performed by the Pediatric Multicenter Pneumococcal Surveillance Study Group (PMPSSG) showed that more than 40% of patients with joint and bone pneumococcal infections had associated bacteremia.^[38] Patients with prostheses or rheumatic fever are at increased risk for joint disease.

Soft tissue infections

Although uncommon, S pneumoniae infection can be a cause of mild-to-serious soft tissue infections, including cellulitis, myositis, periorbital cellulitis, and abscess, particularly in some compromised hosts (eg, those with SLE). Most patients have WBC counts greater than 15,000 cells/μL and elevated temperatures. Physical findings are related to the site of infection and usually include redness, warmth, and tenderness of the involved area. Movement may be limited by pain and/or swelling. The incidence of soft tissue infections is increased in persons with HIV infection or underlying connective tissue disease; however, most affected individuals are otherwise healthy and respond well to antibiotic therapy.^[18]

Peritonitis

Overall, primary peritonitis (peritonitis caused by the spread of organisms via blood or lymph to the peritoneal cavity) is rare, accounting for less than 20% of peritonitis cases.

S pneumoniae is the most commonly isolated organism in patients with primary peritonitis.

Primary peritonitis in children is usually associated with underlying conditions such as nephrotic syndrome or other immunocompromising diseases.

In adults, primary peritonitis is usually associated with cirrhosis.

Females with severe pelvic inflammatory disease due to S pneumoniae infection may develop peritonitis. In such cases, organisms may gain access to the peritoneum via the fallopian tubes from the female genital tract. This is the only invasive disease caused by S pneumoniae infection that is more common in females.

Other persons at risk for peritonitis include persons with gastrointestinal injury, ulcers, or malignancy.

Presenting symptoms of peritonitis include abdominal pain, anorexia, emesis, diarrhea, and fever; children with right lower quadrant abdominal pain are often initially investigated for appendicitis.

Cardiac infections

In the antibiotic era, pneumococcal cardiac infections are rare.

Endocarditis: Involvement of native aortic and mitral valves are most common; infection can lead to valve destruction, heart failure, and embolization. Presenting signs and symptoms are typical of those seen in other causes of endocarditis and include fever, new or changing murmurs, muscle and/or joint pains, sweating, fatigue, anorexia, and skin findings. In alcoholics, may be part of the triad of endocarditis, pneumonia, and meningitis.

Pericarditis: Prior to the widespread use of antibiotics, S pneumoniae infection was the most common cause of purulent pericarditis in children; now, infection in childhood is extremely rare, and nearly all cases of pneumococcal pericarditis occur in adults. Symptoms, signs, and examination findings may include chest and/or pleuritic pain; radiating pain to the neck, abdomen, shoulder, or back; orthopnea; dry cough; extremity swelling; anxiety; fatigue; fever; pericardial rub; and muffled heart sounds.

S pneumoniae is an encapsulated, gram-positive, catalase-negative cocci that grows as a facultative anaerobe. These organisms often appear on Gram stain as lancet-shaped diplococci that grow in chains (see image below). On blood and chocolate agar plates, a green zone (alpha-hemolysis; due to the breakdown of hemoglobin by pneumolysin) surrounds the colonies. Other identifying properties include sensitivity to optochin (which distinguishes it from other alpha-hemolytic streptococci) and bile solubility.

Predisposing conditions to pneumococcal infection are broad and often overlap; they include the following:

• Exposure

  • Cigarette smoke
  • Alcohol
  • Glucocorticosteroids
  • Cold
  • Stress
  • Prior respiratory infections (including influenza)
  • Daycare attendance
  • Homeless shelters
  • Military training
  • Prisons
  • Malnutrition
  • Lack of exposure to breastmilk
• Defects in clearance of pneumococci from the blood

  • Congenital asplenia
  • Splenectomy
  • Decreased splenic function due to autosplenectomy due to sickle cell disease
• Defects in clearance from sinopulmonary tissue or inflammatory conditions

  • Asthma
  • COPD
  • Cigarette smoking
  • Influenza and other respiratory viral infections
• Defective antibody formation

  • Primary
    • Congenital agammaglobulinemia
    • Common variable hypogammaglobulinemia
    • Selective immunoglobulin G (IgG) subclass deficiency
  • Secondary
    • Lymphoma
    • Chronic lymphocytic leukemia
    • Multiple myeloma
    • HIV infection
• Defective complement (primary or secondary): Absent or decreased amounts of C1, C2, C3, or C4
• Abnormalities in polymorphonuclear leukocytes

  • Decreased levels associated with cyclic neutropenia, drug-induced neutropenia, or aplastic anemia
  • Decreased function caused by conditions such as alcoholism, cirrhosis, diabetes mellitus, renal insufficiency, and steroid therapy
• Other

  • Age (children < 2 y and elderly persons)
  • Fatigue
  • Chronic disease
  • Hospitalization^[19]