Klebsiella pneumoniae Case File

Klebsiella pneumoniae Case File

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

CASE 12

A 45-year-old homeless alcoholic man presents to the emergency room with fever and cough of 4-day duration. The cough is productive of thick, bloody phlegm. He complains of pain in the right side of his chest with coughing or taking a deep breath. He denies any other medical history and says he can’t remember the last time he saw a doctor. He doesn’t smoke cigarettes, drinks a pint of whiskey whenever he can get it, and denies drug use. On examination, he is dirty, disheveled, and appears malnourished. His temperature is 38.9°C (102°F), pulse 105 beats per minute, and respiratory rate is 30 breaths per minute. The lung examination is notable for decreased breath sounds and crackles in the right lower, posterior field. His white blood cell count is elevated. A chest x-ray reveals a dense right lower lobe infiltrate with evidence of a pulmonary abscess. Sputum samples are collected for Gram stain and culture, and a blood culture is sent. A bacterial etiology is suspected.

◆ What is the most likely organism to be isolated in the sputum and blood cultures?

◆ By what mechanism does this organism commonly develop antibiotic resistance?

ANSWERS TO CASE 12: Klebsiella pneumoniae

Summary: A 45-year-old alcoholic man has developed a bacterial cavitary pneumonia with evidence of a pulmonary abscess.

◆ Most likely organism to be isolated: Klebsiella pneumoniae

◆ Mechanism whereby Klebsiella commonly develops antibiotic resistance: Plasmid acquisition

CLINICAL CORRELATION

Klebsiella causes lower respiratory infections, wound soft tissue infections and is a common cause of hospital-acquired urinary tract infections (UTIs). Klebsiella pneumoniae is also associated with lobar pneumonia in a person with an underlying debilitating condition such as alcoholism or diabetes. Pneumonia caused by this organism tends to be necrotic, inflammatory, and hemorrhagic and has a high propensity for cavitation or abscess formation. Patients often produce thick, bloody sputum. Because of the destructive nature of the infection and the underlying debility of the patient, pneumonia caused by K. pneumoniae carries a high mortality.

Community-acquired pneumonia is usually the result of spread of organisms that normally reside in the upper respiratory tract into the lower respiratory tract. Organisms that have virulence factors that allow them to survive the host response in the lung can establish an infection. Patients with disruption of their immune defenses are at greater risk of infection. Klebsiella pneumoniae pneumonia is therefore considered an opportunistic infection because it is not a common cause of pneumonia in normally healthy patients. Symptoms of bacterial pneumonia are usually nonspecific and include malaise, anorexia, headache, myalgia, arthralgia, and fever. Klebsiella pneumoniae produces a severe acute, necrotic, and hemorrhagic pneumonia, which is evidenced by cavitary lung lesions on chest x-ray, pleural effusions, and possible abscess formation or empyema. Because of the hemorrhagic nature of the pneumonia, patients tend to have blood-tinged sputum.

Two uncommon species of Klebsiella are also causes of respiratory disease. Klebsiella rhinoscleroma is associated with chronic granulomatous disease of the upper respiratory mucosa (predominantly outside the United States), and K. ozaenae is associated with chronic atrophic rhinitis.

APPROACH TO SUSPECTED Klebsiella pneumoniae PNEUMONIA

Objectives

1. Know the structure, physiology, and virulence factors of K. pneumoniae.
2. Know the nature of the native and acquired antibiotic resistance of K. pneumoniae.

Definitions

Chronic obstructive pulmonary disease (COPD): A progressive lung disease that commonly results from heavy smoking and is evident by difficulty breathing, wheezing, and a chronic cough.

Empyema: Accumulation of pus in the pleural space around the lung.

DISCUSSION

Characteristics of Klebsiella Species

The genus Klebsiella, which belongs to the family Enterobacteriaceae includes five species, with the most clinically significant being K. pneumoniae. Klebsiella pneumoniae is a large, nonmotile, gram-negative rod with a prominent polysaccharide capsule. The capsule is antiphagocytic and retards leukocyte migration into an infected area.

Another virulence factor of K. pneumoniae is its propensity to develop resistance to multiple antibiotics. All strains of K. pneumoniae are innately resistant to ampicillin, because of the production of β-lactamase. Acquisition of resistance to other antibiotics usually occurs by transfer of plasmids from other organisms. Recently strains of nosocomially acquired K. pneumoniae have been isolated that produce an extended spectrum β- lactamase and therefore are resistant to all β-lactam antibiotics.

Diagnosis

Diagnosis of community-acquired pneumonia is made clinically based on symptoms of cough, especially with blood, and chest x-ray indicating infiltrates, cavitary lesions, or pleural effusions. Specific diagnosis of pneumonia is made by culture of expectorated sputum. Sputum samples must be of good quality (many white blood cells and rare squamous epithelial cells) represent the flora of the lower respiratory tract and not mouth flora. In a small percentage of cases of community-acquired pneumonia blood cultures will also be positive for the affecting organism.

Klebsiella pneumoniae will grow rapidly producing large mucoid colonies on routine laboratory media. Colonies are often extremely mucoid and will tend to drip into the lid of the plate while incubating in an inverted position. Pink colonies will be evident on MacConkey agar indicating their fermentation of lactose. Confirmatory identification is made for other members of the family Enterobacteriaceae by commercially available identification systems using a combination of sugar fermentation and enzyme production. Both K. oxytoca and especially K. rhinoscleromatis are slower growing than K. pneumoniae and the other Enterobacteriaceae. All Klebsiella species are very closely related with nearly identical biochemical reactions, except for the fact that K. pneumoniae is indole negative, and K. oxytoca is indole positive. Commercial identification systems have a difficult time differentiating these species.

Treatment and Prevention

Treatment of K. pneumoniae pneumonia would be based on the susceptibility of the isolate. Treatment can be complicated by the presence of multidrug-resistant strains. Most strains are susceptible to extended spectrum cephalosporins such as cefepime as well as fluoroquinolones such as moxifloxacin. In cases of strains that produce an extended spectrum β-lactamase, the treatment of choice would be imipenem or meropenem.

Prevention of community-acquired pneumonia would involve avoidance of high-risk activities such as smoking or drinking in excess. Prevention of spread in the hospital would involve appropriate infection control procedures to isolate patients with multidrug-resistant organisms. Klebsiella oxytoca has similar susceptibility patterns as K. pneumoniae and can also produce extended spectrum β-lactamases.

COMPREHENSION QUESTIONS

[12.1] The most common mechanism by which K. pneumoniae attains its antibiotic resistance is by plasmid acquisition. Which of the following best describes the direct transfer of a plasmid between two bacteria?

A. Competence

B. Conjugation

C. Recombination

D. Transduction

E. Transformation

[12.2] A specimen of thick, bloody sputum from a hospitalized 80-year-old patient with diabetes mellitus and difficulty in breathing is sent for laboratory analyses. The tests yield heavy growth of a lactose-positive, nonmotile, gram-negative rod with a large capsule. Which of the following bacteria is most likely to be the cause of the pulmonary problems?

A. Enterobacter aerogenes

B. Escherichia coli

C. Klebsiella pneumoniae

D. Pseudomonas aeruginosa

E. Yersinia pseudotuberculosis

[12.3] A 65-year-old diabetic man presents to the emergency room with a severe productive cough producing thick bloody sputum resembling a “currant-jelly” like appearance. Culture using MacConkey agar reveals pink colonies, with large mucoid colonies on routine laboratory media. Which of the following organisms is most likely responsible for this patient’s pneumonia?

A. Enterobacter cloacae

B. Escherichia coli

C. Klebsiella pneumoniae

D. Pseudomonas aeruginosa

E. Serratia marcescens

[12.4] The O antigens that are used to help characterize members of the Enterobacteriaceae family are found on which of the following?

A. Capsules

B. Endotoxins

C. Exotoxins

D. Fimbriae

E. Flagella

Answers

[12.1] B. The three important processes by which DNA is transferred between bacteria are via transformation, transduction, and conjugation. Transformation is defined as the uptake of soluble DNA by a recipient cell. Transduction refers to the transfer of DNA by a virus from one cell to another. Conjugation refers to the direct transfer of soluble DNA (plasmids) between cells. Examples of such plasmids are the sex factors and the resistance (R) factors.

[12.2] C. Whereas all of the above listed organisms are gram-negative rods, only K. pneumoniae fulfill all of the laboratory criteria listed in the question, such as the presence of a very large capsule, which gives a striking mucoid appearance to its colonies.

[12.3] C. Patients with K. pneumoniae infections usually have predisposing conditions such as alcoholism, advanced age, chronic respiratory disease, and diabetes. The “currant-jelly” sputum distinguishes K. pneumoniae from the other organisms. Infections can lead to necrosis and abscess formation. Please refer to the discussion for Question 12.2.

[12.4] B. There are three surface antigens associated with several members of the Enterobacteriaceae. The cell wall antigen (somatic or O antigen) is the outer polysaccharide portion of the lipopolysaccharide (LPS/endotoxin). The H antigen is on the flagellar proteins (Escherichia and Salmonella). The capsular or K polysaccharide antigen is particularly prominent in heavily encapsulated organisms such as Klebsiella.

MICROBIOLOGY PEARLS ❖ Klebsiella pneumoniae are a common cause of hospital-acquired UTIs. ❖ Patients with diabetes or COPD or who drink alcohol excessively are predisposed to pneumonia with K. pneumoniae. ❖ Klebsiella pneumoniae produces a large mucoid colonies on agar plates as a result of the presence of a polysaccharide capsule that also acts to allow the organism to avoid phagocytosis.

REFERENCES

Baldwin DR, MacFarlane JT. Community Acquired Pneumonia in Infectious Diseases. Philadelphia, PA: Mosby, 1999;2(27):1–10. 

Eisenstein BI, Zaleznik DF. Enterobacteriaceae. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases, 5th ed. Philadelphia, PA: Churchill Livingstone, 2000:2294–310. 

Murray PR, Rosenthal KS, Pfaller MA. Enterobacteriaceae. In: Murray PR, Rosenthal KS, Pfaller MA. Medical Microbiology, 5th ed. St. Louis, MO: Mosby, 2002:223–38.

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