Streptococcus Case File

Streptococcus Case File

Eugene C.Toy, MD, Cynthia Debord, PHD, Audrey Wanger, PHD, Gilbert Castro, PHD, James D. Kettering, PHD, Donald Briscoe, MD

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 39.4°C (103°F), and he’s 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 overthe-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 38.8°C (101.9°F), pulse is 110 beats per minute, blood pressure 110/60 mm Hg, and respiratory rate is 28 breaths per 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. An electrocardiogram is normal. A chest x-ray 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 male complains of fever and cough, with “rust” colored sputum. A chest x-ray 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. Streptococcus agalactiae is most well known for its association with neonatal meningitis following vaginal colonization of the pregnant women.

Streptococcus pneumoniae is a cause of otitis media, sinusitis, bronchitis, pneumonia, and meningitis. Streptococcus 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 percent of patients. Meningitis either follows sinusitis or otitis or occurs as a result of bacteremic spread of the organisms. Patients that are immunocompromised, elderly, or have underlying heart or lung disease, as well as those that are asplenic, 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 grampositive cocci that form either pairs or chains, whereas S. pneumoniae are elongated, lancet shaped, gram-positive cocci, and are usually in pairs or short chains.

Virulent strains of pneumococcus are encapsulated by a polysaccharide capsule. Strains that are 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 pneumolysin’s inhibition of the oxidative burst 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 penicillinbinding 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 x-ray 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

the sputum and/or blood. Streptococcus 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

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 should be based on the individual isolate susceptibility. Adult and pediatric vaccines directed against pneumococcal capsular antigens are available, and current guidelines recommend universal vaccination of children, persons over the age of 65, and others at high risk for pneumonia, such as persons with diabetes or chronic lung disease.

COMPREHENSION QUESTIONS

[20.1] A newborn has a temperature of 39.4°C (103°F). Blood culture grows gram-positive cocci in chains. This is most likely to be which of the following?

A. Group A Streptococus (Streptococcus pyogenes)

B. Group B Streptococcus (Streptococcus agalactiae)

C. Salmonella species

D. Streptococcus 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. Most human infections caused by streptococci involve the group A organisms (S. pyogenes). The group B streptococci 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 CAMP test (Christie, Atkins, Munch-Peterson). Detection of the infection and prompt antimicrobial treatment is necessary because the infections may become life-threatening. Streptococcus pneumoniae organisms are important in meningitis cases in young children, but are more frequently seen as diplococci forms rather than long chains.

[20.2] D. Streptococcus pneumoniae is responsible for 10–20 percent of meningitis cases in children ages 1 month to 15 years. Neisseria meningitidis range from 25 to 40 percent, whereas Haemophilus influenzae may be involved in 40–60 percent. Group A and B streptococci appear to be involved only 2–4 percent of the time. Under the conditions described above, S. pneumoniae would be the most likely etiologic agent.

[20.3] E. 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 1–8 are responsible for approximately 75 percent of the cases of pneumococcal pneumonia. Vaccines are available that give approximately 90 percent protection and usually contain 23 types of carbohydrates for the United States–licensed preparation.

[20.4] B. Because pneumococci are sensitive to many antimicrobial drugs, early treatment usually results in rapid recovery. Antibody response (host’s active immunity) seems to play a diminished role today. Penicillin G is the drug of choice, but 5–10 percent of the isolates in the United States are penicillin resistant (MIC ≥2 μg/mL), and 20 percent are moderately resistant (0.1–1 μg/mL). Resistance to cephalosporins, tetracycline, and erythromycin has 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 CSF.

MICROBIOLOGY PEARLS ❖ Streptococcus 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. ❖ Streptococcus pneumoniae is an á-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, 2005:237–58. 

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.

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