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Pneumococcus Streptococcus pneumoniae

Posted by on Tuesday, September 7, 2010, 3:39
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Streptococcus pneumoniae is a gram-positive, catalase-negative cocci that has remained an extremely important human bacterial pathogen since its initial recognition in the late 1800s. The term pneumococcus gained widespread use by the late 1880s, when it was recognized as the most common cause of bacterial lobar pneumonia.

Worldwide, S pneumoniae remains the most common cause of community-acquired pneumonia (CAP), bacterial meningitis, bacteremia, and otitis media. S pneumoniae infection is also an important cause of sinusitis, septic arthritis, osteomyelitis, peritonitis, and endocarditis and an infrequent cause of other less-common diseases.

Pneumococcal vaccination, particularly routine childhood pneumococcal conjugate vaccine (introduced in the United States in 2000), has led to decreased rates of invasive pneumococcal infections (>90%) caused by pneumococcal serotypes covered by the vaccine, as well as overall decreased rates of invasive disease (45% overall; 77% in children <5 y). In addition, herd immunity has led to decreased rates of disease in older children and adults.1,2,3

Pneumococcus Streptococcus pneumoniae

Pneumococcus Streptococcus pneumoniae

Many subsequent studies have shown increased rates of invasive and noninvasive disease caused by serotypes not covered by the vaccine, including serotypes 15, 19A, and 33F. Serotype 19A has received the most attention, not only because of increased disease rates associated with this serotype but also because of its increased association with drug resistance. Increased rates of invasive disease with such serotypes have caused the overall rates of invasive disease to remain somewhat steady since 2002, although still greatly reduced from rates prior to introduction of the conjugate vaccine.1,4,5,6,7,8,9,10,3

Data from 2006-2007 revealed that only 2% of invasive pneumococcal disease in children younger than 5 years in the United States was caused by serotypes contained in pneumococcal conjugate vaccine 7 (PCV7), while an additional 6 serotypes accounted for almost two thirds of invasive disease in this age group.11 Development of a vaccine containing additional serotypes continued, and pneumococcal conjugate vaccine 13 (PCV13) was approved by the FDA February 24, 2010.12

Despite an overall decreased incidence of otitis media caused by serotypes not covered by vaccination since the introduction of the conjugate pneumococcal vaccine, an increase in rates of disease caused by serotypes not covered by the vaccine has occurred, as well as an increase in rates of diseases caused by vaccine-covered serotypes in incompletely immunized children. The incidence of otitis media caused by serotype 19F has remained steady. Overall health care utilization for otitis media has decreased, as has the incidence of recurrent otitis media in some populations and studies.2,13,14,15
Pathophysiology

Adherence and invasion

S pneumoniae is an example of a typical extracellular bacterial pathogen. Pathogenicity requires adherence to host cells, along with the ability to replicate and to escape clearance and/or phagocytosis. The organism must then gain access to areas where it can manifest infection, either via direct extension or lymphatic or hematogenous spread.

The rates of pneumococcal colonization in healthy children and adults provide information about the success of adherence and replication of the pneumococcus. After colonization, organisms may gain access to areas of the upper and/or lower respiratory tracts (sinuses, bronchi, eustachian tubes) by direct extension. Under normal conditions in a healthy host, anatomic and ciliary clearance mechanisms prevent clinical infection. However, clearance may be inhibited by chronic (smoking, allergies, bronchitis) or acute (viral infection, allergies) factors, which can lead to infection. Alternatively, pneumococci may reach normally sterile areas, such as the blood, peritoneum, cerebrospinal fluid, or joint fluid, by hematogenous spread after mucosal invasion. In the absence of previously acquired serotype-specific antibodies (see below), clinically apparent infection is likely to occur.

Capsule

Other than some isolates associated with conjunctivitis outbreaks, essentially all clinical isolates of S pneumoniae are encapsulated. Repeating oligosaccharides that make up the capsule of an individual bacterial isolate are transported to the cell surface, where they bind tightly with the cell-wall polysaccharides. Based on antigenic differences within these capsular polysaccharides, 91 serotypes of S pneumoniae have been identified.

The virulence of each organism is determined in part by the makeup and amount of capsule present. In a pneumococcus-naive host (or in the absence of antibody to pneumococcal capsule) host-cell phagocytosis is severely limited because of the inhibition of phagocytosis and the inhibition of the activation of the classic complement pathway. In addition, in vitro and in vivo studies of clinical isolates have shown that pneumococci have the ability to obtain DNA from other pneumococci (or other bacteria) via transformation, allowing them to switch to serotypically distinct capsular types.

There are 2 recognized numbering systems based on pneumococcal serotypes. In the American system, the serotypes were numbered in order of discovery, with lower numbers corresponding to serotypes that more frequently cause clinical disease, meaning that they were identified earlier. The Danish numbering system is based on grouping of serotypes with similar antigenicity and is more widely accepted and used worldwide. Today, serotyping provides important epidemiological information, especially with the increasingly widespread use of vaccination, but rarely provides timely clinical information.

The Quellung reaction is demonstrated by combining sera of previously immunized animals with capsular antigen. Agglutination causes capsule refractility and the ability to observe the capsule microscopically.

Toxins and other virulence factors

Pneumococcal isolates produce few toxins; however, all serotypes produce pneumolysin, which is an important virulence factor that acts as a cytotoxin and activates the complement system. In addition, pneumolysin causes a release of tumor necrosis factor-alpha and interleukin-1.

Other potential virulence factors include cell surface proteins such as surface protein A and surface adhesin A and enzymes such as autolysin, neuraminidase, and hyaluronidase. The contributions of these substances to pneumococcal virulence are being studied extensively, and some are being investigated as potential vaccine constituents.

Complement activation

Much of the clinical severity of pneumococcal disease is due to the activation of the complement pathways and cytokine release, which induce a significant inflammatory response. S pneumoniae cell wall components, along with the pneumococcal capsule, activate the alternative complement pathway; antibodies to the cell wall polysaccharides activate the classic complement pathway. Cell wall proteins, autolysin, and DNA released from bacterial breakdown all contribute to the production of cytokines, inducing further inflammation.
Frequency
United States

Colonization

S pneumoniae remains an important pathogen in large part because of its ability to first colonize the nasopharynx efficiently. Studies performed in the United States prior to universal vaccination recommendations have shown average carriage rates of 40%-50% in healthy children and 20%-30% in healthy adults. Factors such as age, daycare attendance, composition of household, immune status, antibiotic use, and others obviously affect these numbers.16,17,18 With the implementation of childhood vaccination with the heptavalent conjugate vaccine for S pneumoniae, the colonization rates have decreased in children receiving the vaccine and in adults and other children in their household because of the phenomenon of herd immunity.

Most individuals who are colonized with S pneumoniae carry only a single serotype at any given time; the duration of colonization varies and depends on specific serotype and host characteristics. Invasive disease is usually related to recent acquisition of a new serotype. However, in most healthy hosts, colonization is not associated with symptoms or disease but allows for the continued presence of S pneumoniae within the population, allowing for prolonged low-level transmission among contacts.

S pneumoniae infection is the most common cause of CAP, bacterial meningitis, bacteremia, and otitis media in the United States. There is a clear seasonality, with infections peaking in the fall and winter months.

Noninvasive disease

Pneumococcal colonization allows for spread of organisms into the adjacent paranasal sinuses, middle ear, and/or tracheobronchial tree down to the lower respiratory tract. This spread results in specific clinical syndromes (sinusitis, otitis media, bronchitis, pneumonia) related to the noninvasive spread of the organisms.

Worldwide, the most common cause of death due to pneumococcal disease is pneumonia. In adults admitted to the hospital in the United States for pneumonia treatment, S pneumoniae remains the most common organism isolated. Until 2000, 100,000-135,000 patients were hospitalized for pneumonia proven to be caused by S pneumoniae infection in the United States annually. These numbers are likely a gross underestimate, as a definite cause is not determined in most cases of pneumonia treated each year. In addition, the actual rates are also likely decreasing owing to implementation of pneumococcal conjugate vaccination.19

S pneumoniae infection is an important cause of bacterial co-infection in patients with influenza and can increase the morbidity and mortality in these patients. This has been emphasized recently by the increased number of cases of invasive pneumococcal disease seen in association with increased rates of hospitalizations for influenza during the 2009 H1N1 influenza A pandemic.20 Postmortem lung specimens from patients who died of H1N1 influenza A from May to August of 2009 were examined for evidence of concomitant bacterial infection. Twenty-nine percent of the specimens showed evidence of bacterial co-infection, with almost half of these being S pneumoniae.21

S pneumoniae infection is estimated to cause over 6-7 million cases of otitis media annually in the United States. These numbers have likely decreased somewhat with the advent of universal vaccinations; however, S pneumoniae infection remains the most common cause of otitis media.22,18

Invasive disease

Statistics regarding invasive pneumococcal disease in the United States are based on active surveillance using the Centers for Disease Control and Prevention (CDC) Active Bacterial Core Surveillance (ABC) system. Calculations for 2008 estimated 43,000 (14.3 per 100,000 population) cases of invasive disease nationally, with 4,400 (1.5 cases per 100,000 population) deaths. Children younger than 5 years and adults older than 65 years are two identified age groups in whom rates of disease and death are increased. In 2008, rates of pneumococcal invasive disease in these groups were 20 per 100,000 population and 40.8 per 100,000 population, respectively. This compares with rates of 21.8 and 39.2 in 2007 and 23.2 and 43.3 in 2002, respectively. More than half of deaths due to invasive pneumococcal disease occur in adults with specific risk factors (age, immunosuppression) for severe disease. Such risk factors are an indication for vaccination.23
International

Despite the worldwide importance of disease due to S pneumoniae infection, very little information is available on the extent of pneumococcal disease, particularly in developing countries.

Children

In developing countries, pneumococcus remains the most common and important disease-causing organism in infants. Although exact numbers are difficult to obtain, it is estimated that pneumococcus infection is responsible for more than one million of the 2.6 million annual deaths due to acute respiratory infection in children younger than 5 years. Case fatality rates associated with invasive disease vary widely but can approach 50% and are greatest in patients with meningitis.22,24

Estimates of pneumococcal disease in Gambian children show high rates of infection in the first year of life (≥500 per 100,000 children).25 Latin American studies also show a particularly high risk in infants younger than 6 months, and children in southern India have higher rates of colonization at younger ages compared with US children, according to US clinical studies. Some particular populations, such as indigenous Australians and minority Israeli persons, also have disproportionately higher rates of disease, similar to the native Alaskan and native Indian populations in the United States, although determining the role of socioeconomic factors in the higher incidence of disease in these populations is difficult.25

In Europe, children younger than 2 years constitute the population most at risk for pneumococcal infection, with rates decreasing as persons age. The overall incidence of invasive disease is estimated to be somewhat lower in Europe (14 per 100,000 persons in Germany vs 35.8 per 100,000 persons in England vs 45.3 per 100,000 persons in Finland vs 90 per 100,000 persons in Spain vs 235 per 100,000 persons in the United States), although many have postulated that this may be due in part to the more liberal blood-culture collection practices in the American health care system.25,22

Adults

Even fewer data are available on the worldwide incidence of pneumococcal disease in adults. As in the United States, the most common cause of CAP in Europe is S pneumoniae infection, affecting approximately 100 per 100,000 adults each year. Overall rates of febrile bacteremia and meningitis are also similar, (15–19 per 100,000 adults and 1–2 per 100,000 adults, respectively), with the risk for these diseases increased in elderly and infant populations.26

Because no population-based data on pneumococcal disease in adults in developing countries are available, estimates of disease burden are based on small clinical studies, vaccine trials, extrapolation from data in developed countries, and studies of persons at high risk for disease. The information gleaned from these sources suggests that the incidence of and mortality rates associated with pneumococcal disease are high, with HIV-positive populations exhibiting particularly high rates of infection. Further studies are greatly needed.27,22
Mortality/Morbidity

Although exact rates are difficult to determine, the World Health Organization (WHO) estimates that, worldwide, 1.6 million deaths were caused by pneumococcal disease in 2005, with 700,000 to 1 million of these occurring in children younger than 5 years.28 Even in patients in developed countries, invasive pneumococcal disease carries a high mortality rate—an average of 10%–20% in adults with pneumococcal pneumonia, with much higher rates in those with risk factors for disease.29
Race

In the United States, invasive pneumococcal disease is more common in native Alaskans, Navajo and Apache Indians, and African Americans than in other ethnic groups. Some studies have shown this difference persists even when the results are controlled for socioeconomic factors, and the reasons for this discrepancy among certain populations are unclear.17
Sex

Most clinical studies of pneumococcal disease show a slight male predilection for disease; the reason for this is unclear.
Age

Children younger than 2 years carry the highest burden of S pneumoniae disease worldwide. In developed countries, the incidence is highest in those aged 6 months to 1 year, while, in developing countries, the disease is particularly common in children younger than 6 months.

Adults older than 55-65 years are the next most commonly affected age group worldwide.

Immunosuppressed persons of any age are at a higher risk for pneumococcal disease.
Clinical
History

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
o 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.
o 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.

Physical

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

Diseases due to direct extension

* Conjunctivitis
o Bacterial conjunctivitis is more likely to be bilateral and purulent than viral conjunctivitis.
o 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
o S pneumoniae is the most commonly isolated bacterial pathogen from children and adults with otitis media.
o 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.17
o Pneumococcal disease is less likely to resolve spontaneously.
o Eustachian tube congestion caused by a preceding viral infection is common.
o Increasing antibiotic resistance has led to decreased effectiveness of the antibiotics that were once used most commonly to treat otitis media.
o 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
o As in otitis media, S pneumoniae is the most commonly isolated bacterial organism from patients with acute sinusitis.
o 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.
o 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.
o Malodorous breath and worsening cough at night due to postnasal drip are often noted.
* Acute exacerbations of chronic bronchitis (AECB)
o 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.
o 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.
o Symptoms such as sore throat, cold symptoms, and dyspnea may indicate a viral cause.30
* Pneumonia
o 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.
o 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.
o 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.
o In elderly patients with pneumococcal pneumonia, tachypnea may be the primary presenting sign. Temperature elevations may be mild or absent.
o S pneumoniae is a common cause of bacterial CAP in HIV patients.
o 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 Staphylococcus aureus infection, remains one of the most common causes of pediatric empyema.17,18,31

Invasive disease

* Meningitis
o 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.
o 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.
o In countries with routine-vaccination policies, S pneumoniae infection is the most common cause of sporadic bacterial meningitis in both children and adults.
o 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.
o 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.
o A bulging fontanelle and poor feeding may be seen infants.
o Elderly patients may present with more indolent signs, including increasing lethargy, nonresponsiveness, or coma.
o Twenty to 25% of patients with pneumococcal meningitis experience seizures.
o Bacteremia may be found when blood cultures are obtained.
o Prolonged or secondary fevers are not uncommon but do not usually affect outcomes.
o Complications of pneumococcal meningitis include hearing loss (up to half of patients), seizures, learning disabilities, mental difficulties, and cranial nerve palsies.
o 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).17,18,31
* Bacteremia
o Bacteremia is the most common manifestation of invasive pneumococcal disease.
o 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.32,33
o In adult patients, pneumococcal bacteremia is much more likely to be associated with another focal infection such as pneumonia, meningitis.
o Signs, symptoms, and physical examination findings are usually nonspecific in patients with occult bacteremia due to pneumococcal infection.
o In most patients, fever develops within 24 hours of positive culture findings. Higher temperatures are more often associated with the development of occult bacteremia.
o A peripheral WBC count greater than 15,000 cells/μL is associated with the presence of occult bacteremia.
o Bacteremia is less likely in patients with fever and signs or symptoms of focal infection (eg, otitis media).
o Most cases of occult bacteremia spontaneously resolve.
o Complications develop in an estimated 10% of patients with occult bacteremia and include meningitis, osteomyelitis, pneumonia, soft tissue and joint infections, and sepsis.
o 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.18,17
* 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.
o 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.
o 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.34
+ Patients with prostheses or rheumatic fever are at increased risk for joint disease.
* Soft tissue infections
o 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).
o Most patients have WBC counts greater than 15,000 cells/μL and elevated temperatures.
o 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.
o 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.17
* Peritonitis
o 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.
o S pneumoniae is the most commonly isolated organism in patients with primary peritonitis.
o Primary peritonitis in children is usually associated with underlying conditions such as nephrotic syndrome or other immunocompromising diseases.
o In adults, primary peritonitis is usually associated with cirrhosis.
o 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.
o Other persons at risk for peritonitis include persons with gastrointestinal injury, ulcers, or malignancy.
o 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.
o 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.
o 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.

Causes

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.

Sputum Gram stain from a patient with a pneumococ…
Sputum Gram stain from a patient with a pneumococcal pneumonia. Note the numerous polymorphonuclear neutrophils and gram-positive, lancet-shaped diplococci. Courtesy of C. Sinave, MD, personal collection.

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Sputum Gram stain from a patient with a pneumococ…

Sputum Gram stain from a patient with a pneumococcal pneumonia. Note the numerous polymorphonuclear neutrophils and gram-positive, lancet-shaped diplococci. Courtesy of C. Sinave, MD, personal collection.

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

* Exposure
o Cigarette smoke
o Alcohol
o Glucocorticosteroids
o Cold
o Stress
o Prior respiratory infections (including influenza)
o Daycare attendance
o Homeless shelters
o Military training
o Prisons
o Malnutrition
o Lack of exposure to breastmilk
* Defects in clearance of pneumococci from the blood
o Congenital asplenia
o Splenectomy
o Decreased splenic function due to autosplenectomy due to sickle cell disease
* Defects in clearance from sinopulmonary tissue or inflammatory conditions
o Asthma
o COPD
o Cigarette smoking
o Influenza and other respiratory viral infections
* Defective antibody formation
o Primary
+ Congenital agammaglobulinemia
+ Common variable hypogammaglobulinemia
+ Selective immunoglobulin G (IgG) subclass deficiency
o 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
o Decreased levels associated with cyclic neutropenia, drug-induced neutropenia, or aplastic anemia
o Decreased function caused by conditions such as alcoholism, cirrhosis, diabetes mellitus, renal insufficiency, and steroid therapy
* Other
o Age (children <2 y and elderly persons)
o Fatigue
o Chronic disease
o Hospitalization18

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