CASE 20

A 59-year-old man with emphysema secondary to a 50 pack-year smoking history presents with a fever, chills,
chest pain, and cough. He had a “cold” with mild cough and congestion for approximately 3 days but then had
the abrupt onset of more severe symptoms. His temperature has been as high as 103°F (39.4°C), and he has had
shaking chills. His cough is productive of sputum that looks like “rust.” When he coughs or takes a deep
breath, he gets a sharp, stabbing pain in his left lower chest. He has been taking numerous over-the-counter
cold medications without relief and has had to use his ipratropium inhaler more often than usual. On
examination, he is quite ill appearing. His temperature is 101.9°F (38.8°C), pulse is 110 beats/minute, blood
pressure 110/60 mm Hg, and respiratory rate is 28 breaths/minute. His pulmonary examination is significant
for the presence of crackles and rhonchi in the left lower fields and expiratory wheezing heard in all other
fields. His heart is tachycardic but otherwise normal on auscultation. The remainder of his examination is
normal. His white blood cell count is markedly elevated. Findings on electrocardiography are normal. Chest
radiography shows a dense infiltration of the left lower lobe along with a pleural effusion on the left side.

What would you expect to see on Gram stain of a sputum sample?

What is the likely reservoir from which this patient’s pneumonia occurred?

ANSWERS TO CASE 20:

Streptococcus
Summary: A 59-year-old man complains of fever and cough with “rust” colored sputum. Chest radiography shows a
dense infiltration of the left lower lobe and a left pleural effusion.

• Most likely Gram stain findings: Multiple polymorphonuclear leukocytes (PMNs) and encapsulated gram-
positive cocci in pairs and short chains.
• Likely reservoir of this infection: Colonization of the upper airway (naso- or oropharynx) and aspiration into
the lower airways.

CLINICAL CORRELATION
Streptococci cause a wide range of diseases from localized skin and soft tissue infections to systemic infections
such as necrotizing fasciitis, endocarditis, and arthritis. Streptococcus pyogenes is commonly associated with
pharyngitis and its sequelae of rheumatic fever and glomerulonephritis, in addition to the skin and soft-tissue
infections previously mentioned. S. agalactiae is most well known for its association with neonatal meningitis
following vaginal colonization of the pregnant women.
S. pneumoniae is a cause of otitis media, sinusitis, bronchitis, pneumonia, and meningitis. S. pneumoniae
(pneumococcus) is the most frequent cause of bacterial pneumonia, otitis, and meningitis. It commonly colonizes
the upper airways in humans, more frequently in children than adults. Pneumococcal diseases occur when
organisms spread from the site of colonization to a distant, susceptible site. Pneumonia occurs when pneumococcus
is aspirated into the distal airways and multiplies in the alveoli. Pneumococcal pneumonia typically follows a
milder upper respiratory infection. Symptoms of pneumococcal pneumonia include cough, fever, chills, and
shortness of breath. Patients may also have increased white blood cells and anemia. A common complication of
pneumococcal pneumonia is pleural effusion, which occurs in up to 40% of patients. Meningitis either follows
sinusitis or otitis or occurs as a result of bacteremic spread of the organisms. Patients who are

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immunocompromised, elderly, or have underlying heart or lung disease, as well as those who are asplenic or are at
higher risk than normal for developing serious disease with S. pneumoniae.

APPROACH TO:
Suspected Pneumococcus Infection

OBJECTIVES
1. Know the structure and physiologic features common to the genus Streptococcus.
2. Know the virulence factors, epidemiology, and diseases associated with specific Streptococcus species.

DEFINITIONS
RHONCHI: A vibration of the chest wall that can be felt with the hand and sounds like a dull roaring or
murmuring

CYTOKINES: Proteins produced by leukocytes that act as mediators of a further inflammatory response

DISCUSSION
Characteristics of Streptococcus
The genus Streptococcus contains multiple species that are differentiated either by their cell wall carbohydrate
group antigen, their hemolysis on blood agar, or their biochemical reactivity. Not all streptococci, including S.
pneumoniae, possess a carbohydrate cell wall antigen. Streptococci are facultative anaerobes that require carbon
dioxide for growth. Streptococci are gram-positive cocci that form either pairs or chains, whereas S.
pneumoniae is made up of elongated, lancet shaped, gram-positive cocci usually in pairs or short chains.
Virulent strains of pneumococcus are encapsulated by a polysaccharide capsule. Strains unencapsulated are
easily cleared by host defenses. Colonization is facilitated by binding of the pneumococcus to epithelial cells by
surface protein adhesins, producing secretory IgA protease, which prevents host immunoglobulin A from binding
to it and producing pneumolysin, which destroys phagocytic and ciliated epithelial cells by creating pores in
their cell membranes. Phagocytosis is limited by the antiphagocytic nature of the polysaccharide capsule and by
the inhibition of the oxidative burst of pneumolysin required for intracellular killing. Much of the tissue damage
caused by pneumococcal infections is mediated by the inflammatory response of host defense systems. The
complement system is activated by teichoic acid, peptidoglycan fragments, and pneumolysin. Cytokine production
is stimulated, causing more inflammatory cells to migrate to the site of infection. Hydrogen peroxide is produced
by pneumococcus, which causes tissue damage via reactive oxygen intermediates.
Antibiotic resistance in pneumococcus is an increasing problem. Penicillin resistance has developed, primarily
via mutations in penicillin-binding proteins in the cell wall. This is a consequence of mutations in the cellular DNA
and from acquisition of DNA from both other pneumococci and other bacteria with which pneumococcus comes in
contact. Efflux pumps also confer some degree of resistance to antibiotics.

DIAGNOSIS
Diagnosis of pneumococcal pneumonia is made based on clinical signs and symptoms, chest radiography
demonstrating infiltration of a single lobe, and sputum Gram stain with many PMNs and gram-positive cocci in
pairs and chains. Confirmation of the diagnosis can be made by culturing the organisms from sputum, blood, or
both. S. pneumoniae grows rapidly on routine laboratory media, including blood and chocolate agar. Colonies on
blood agar demonstrate β-hemolysis (green color) and may be slightly to extremely mucoid because of their
polysaccharide capsule. Colonies are differentiated from viridans streptococci by sensitivity to optochin and bile
solubility. Although optochin susceptibility is considered definitive, the addition of bile to a colony will identify the
organism as S. pneumoniae if the colony lyses and disappears within a few minutes.
More rapid diagnosis of pneumococcal pneumonia can be made using the urinary antigen test.

TREATMENT AND PREVENTION

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Treatment of uncomplicated pneumonia is usually with either a quinolone or a macrolide, such as azithromycin.
Complicated or disseminated pneumococcal disease is usually treated with penicillin or cefotaxime, depending on
susceptibility of the isolate to penicillin. Treatment of the other streptococcal species is usually with penicillin, but
in serious infections treatment should be based on the individual isolate susceptibility. Otitis media and sinusitis due
to streptococcus may be treated with amoxicillin. Pharyngitis due to group A streptococcus can be treated with
penicillin or amoxicillin. Streptococcal pharyngitis may in rare cases lead to rheumatic fever, glomerulonephritis,
and arthritis. Treatment does not prevent glomerulonephritis. Adult and pediatric vaccines directed against
pneumococcal capsular antigens are available, and current guidelines recommend universal vaccination of
children, persons older than 65 years of age, and others at high risk for invasive pneumonia, such as persons with
chronic liver/heart/lung disease, diabetes, smokers, and immunocompromised patients.

COMPREHENSION QUESTIONS
20.1 A 12-hour-old newborn has a temperature of 103°F (39.4 °C). Blood culture grows gram-positive cocci in
chains. This is most likely to be which of the following?
A. Group A Streptococcus (S. pyogenes)
B. Group B Streptococcus (S. agalactiae)
C. Salmonella species
D. S. pneumoniae
20.2 A 3-year-old is diagnosed with bacterial meningitis. Cerebrospinal fluid grows out gram-positive cocci in short
chains and diplococci. This is most likely to be which of the following?
A. Group B Streptococcus
B. Salmonella
C. Staphylococcus aureus
D. Streptococcus pneumoniae
20.3 Which of the following is the primary virulence factor of S. pneumoniae?
A. Bile solubility
B. Optochin production
C. Pili
D. Polypeptide capsule
E. Polysaccharide capsule
20.4 Which of the following is true regarding meningitis with S. pneumoniae?
A. Cephalosporins are always effective.
B. One desires a concentration of antibiotics in the cerebral spinal fluid 10 times the minimal inhibition
concentration.
C. Penicillin is always effective.
D. Resistance is not increasing in S. pneumoniae.

ANSWERS
20.1 B. This is a newborn with fever and sepsis. Most human infections caused by streptococci involve the group A
organisms (S. pyogenes). The group B streptococci (agalactiae) are members of the female genital tract and are
important causes of neonatal sepsis and meningitis. They are usually β-hemolytic (similar to group A),
hydrolyze hippurate and give a positive response in the so-called Christie–Atkins–Munch–Peterson test.
Detection of the infection and prompt antimicrobial treatment is necessary because the infections may become
life threatening. S. pneumoniae organisms are important in meningitis cases in young children, but they are
more frequently seen as diplococci forms rather than long chains.

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20.2 D. S. pneumoniae is responsible for 10% to 20% of meningitis cases in children ages 1 month to 15 years.
Neisseria meningitidis range from 25% to 40%, whereas Haemophilus influenzae may be involved in 40% to
60%. Group A and B streptococci appear to be involved only 2% to 4% of the time. Under the conditions
described above, S. pneumoniae would be the most likely etiologic agent. Gram-positive diplococci are also
consistent with S. pneumoniae infection.
20.3 E. The polysaccharide capsule is the main virulence factor of S. pneumonia; it allows tight adherence to host
cells and resists phagocytosis. Bile solubility and optochin sensitivity are presumptive identification tests that
identify S. pneumoniae from other α-hemolytic streptococci. The polysaccharide capsule occurs in dozens of
antigenic types, but types 1 to 8 are responsible for approximately 75% of the cases of pneumococcal
pneumonia. Vaccines are available that give approximately 90% protection and usually contain 23 types of
carbohydrates for US-licensed preparation.
20.4 B. Because pneumococci are sensitive to many antimicrobial drugs, early treatment usually results in rapid
recovery. Antibody response (the active immunity of the host) seems to play a diminished role today. Penicillin
G is the drug of choice, but 5% to 10% of the isolates in the United States are penicillin resistant (minimal
inhibitory concentration [MIC] ≥ 2 μg/mL), and 20% are moderately resistant (0.1 –1 μg/mL). Instances of
resistance to cephalosporins, tetracycline, and erythromycin have been demonstrated, although pneumococci
remain susceptible to vancomycin. In reference to penicillin therapy, one rule of thumb is to aim for a
concentration of 10 times the MIC in the cerebrospinal fluid (CSF).

MICROBIOLOGY PEARLS

S. pneumoniae is a common cause of otitis media and meningitis.

Because of the increasing incidence of penicillin resistance of S. pneumoniae, empiric therapy of
disseminated disease is with ceftriaxone.
S. pneumoniae is an α-hemolytic streptococci susceptible to optochin.

REFERENCES
Murray PR, Rosenthal KS, Pfaller MA. Streptococcus. In: Murray PR, Rosenthal KS, Pfaller MA. Medical
Microbiology. 5th ed. St. Louis, MO: Mosby; 2005:237-258.
Musher DM. Streptococcus pneumoniae. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of
Infectious Diseases. 6th ed. Philadelphia, PA: Churchill Livingstone; 2005: 2392-2411.