Pseudomonas aeruginosa Case File

Pseudomonas aeruginosa Case File

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

CASE 18

A 73-year-old man with a history of hypertension and type II diabetes mellitus presents to the physician’s office with excruciating left ear pain for the past 3 days. He also has noticed today that his speech seems a bit slurred, and his wife says that the left side of his face looks “droopy.” He has had so much pain and swelling that he hasn’t been able to put his hearing aid in for several days. He has had “swimmer’s ear” in the past, which responded to treatment with ear drops, but has not had any ear problems in several years. He cleans his ears daily with cotton swabs prior to putting in his hearing aid. He denies having a fever, but says that his blood sugars have been higher than usual for the past 2 days. On examination, his vital signs are normal, and he is in obvious pain. He has a prominent left-sided facial droop. His left ear is diffusely swollen, and he is tender on the pinna, the entire periauricular area, and mastoid. There is purulent drainage from the ear canal. You are unable to insert a speculum into the canal because of the swelling and pain. He has evidence of facial nerve palsy on the left side. Blood tests show an elevated white blood cell count and a markedly elevated erythrocyte sedimentation rate (ESR). Your diagnosis is malignant external otitis infection.

◆ What organism is the most likely cause of this infection?

◆ Which two toxins contribute to most of the systemic toxicity of this organism?

ANSWERS TO CASE 18: Pseudomonas aeruginosa

Summary: A 73-year-old man is diagnosed with malignant otitis externa.

◆ Organism most likely to cause this infection: Pseudomonas aeruginosa

◆ Which two toxins contribute to most of the systemic signs of infection: Lipopolysaccharide endotoxin and exotoxin A

CLINICAL CORRELATION

Pseudomonas causes numerous types of infections, with the common factor being that they are usually in a debilitated host. Pseudomonas aeruginosa is an opportunistic pathogen that is most commonly associated with nosocomial pneumonia. Pulmonary infections primarily occur in patients with underlying disease such as cystic fibrosis or chronic lung or heart disease, who have immune suppression, or who are on ventilators. Skin infections occur in patients whose skin has been disrupted either by burn or trauma. Skin lesions can also be a secondary effect of disseminated disease and are known as ecthyma gangrenosum. Other common infections include urinary tract infection in catheterized patients and chronic otitis. Malignant otitis externa, a severe external ear infection, which can potentially invade through the cranial bones and nerves, is seen primarily in the elderly and in diabetics. Other complications are uncommonly a result of Pseudomonas bacteremia, such as endocarditis, meningitis, and bone and joint infections.

APPROACH TO SUSPECTED Pseudomonas PATIENT

Objectives

1. Know the structural and physiologic characteristics of P. aeruginosa.
2. Know the virulence factors associated with P. aeruginosa.

Definitions

Periauricular: Around the external ear.

Erythrocyte sedimentation rate (ESR): A measure of the time it takes for red blood cells to settle, which is a nonspecific measure of inflammation.

Ecthyma gangrenosum: Pustular skin lesions that later become necrotic ulcers and can lead to gangrene.

DISCUSSION

Characteristics of Pseudomonas Species

Pseudomonas species is a ubiquitous, aerobic gram-negative bacillus. At least ten species are included in the genus that can cause disease in humans. Some of the closely related organisms have been transferred to their own genus, such as Burkholderia cepacia, formerly Pseudomonas cepacia. Pseudomonas aeruginosa is the most common cause of human infections. It is motile as a result of the presence of polar flagellae. It is found commonly in the environment and has a predilection for moist areas. Reservoirs in nature include soil, vegetation, and water. Reservoirs in a hospital include sinks, toilets, mops, respiratory therapy, and dialysis equipment. It exhibits intrinsic resistance to many antibiotics and disinfectants. It has minimal growth requirements and can be easily cultured on many media in a wide range of temperatures. It has multiple virulence factors. Pseudomonas adheres to host cells by pili and nonpili adhesins. It produces a polysaccharide capsule that allows the organism to adhere to epithelial cells, inhibits phagocytosis, and confers protection against antibiotic activity. Patients with cystic fibrosis are more likely to be infected with a strain whose colony appears mucoid because of the presence of the capsule.

Pseudomonas produces multiple toxins and enzymes, which contribute to its virulence.

Its lipopolysaccharide endotoxin and exotoxin A appear to cause most of the systemic manifestations of Pseudomonas disease. Exotoxin A blocks protein synthesis in host cells, causing direct cytotoxicity. It mediates systemic toxic effects as well. It is similar in function to diphtheria toxin but is structurally and immunologically distinct. Endotoxin contributes to the development of many of the symptoms and signs of sepsis, including fever, leukocytosis, and hypotension.

Antibiotic resistance is another important aspect of its virulence. It is intrinsically resistant to numerous antibiotics and has acquired resistance to others through various means. The polysaccharide capsule prevents the penetration of many antibiotics into Pseudomonas. Penetration of antibiotic into the Pseudomonas cell is usually through pores in the outer membrane. Mutation of these porin proteins appears to be a primary mechanism of its antibiotic resistance. Multidrug efflux pumps and b-lactamase production also contribute to the antibiotic resistance that so frequently complicates the treatment of Pseudomonas infections.

Some P. aeruginosa strains produce a diffusable pigment: pyocyanin, which gives the colonies a blue color; fluorescein, which gives them a yellow color; or pyorubin, which gives them a red-brown color. Pyocyanin also seems to aid in the virulence of the organism by stimulating an inflammatory response and by producing toxic oxygen radicals.

Diagnosis

Diagnosis of malignant otitis externa is by the common clinical features of otorrhea, painful edematous ear canal with a purulent discharge. Culture of the discharge from the internal ear grows P. aeruginosa in most cases. Pseudomonas aeruginosa grows readily on routine laboratory media. Preliminary identification can be made by colony morphology particularly if typical green pigment is produced. Pseudomonas aeruginosa appears as a clear to dark colony on MacConkey agar, indicating that it does not ferment lactose. Colonies of P. aeruginosa are β-hemolytic and dark colored, as a result of pigment production and blood agar media. The organisms are motile, and therefore colonies appear spread. It does not ferment glucose, is oxidase positive, and is therefore not a part of the Enterobacteriaceae family, but is considered a nonfermenter. Pseudomonas aeruginosa can be distinguished from some of the other closely related species by its ability to grow at a wide range of temperatures, up to as high as 42°C (107.6°F). The colonies also have a distinct odor, sometimes considered a grape-like odor. Confirmatory identification can be made by numerous commercially available identification systems.

Treatment and Prevention

Treatment of malignant otitis externa includes surgery to remove necrotic tissue and pus and appropriate antibiotics. Treatment with two antibiotics to which the organism is susceptible is optimal. Pseudomonas aeruginosa is usually inherently resistant to multiple antibiotics. Most are susceptible to the antipseudomonal penicillins, such as piperacillin and ticarcillin and to the newer fluoroquinolones as well as the aminoglycosides. Imipenem is often reserved for treatment of infections caused by drug-resistant strains.

COMPREHENSION QUESTIONS

[18.1] A severely burned firefighter develops a rapidly disseminating bacterial infection while hospitalized. “Green pus” is noted in the burned tissue and cultures of both the tissue and blood yield small oxidase-positive gram-negative rods. Which of the following statements most accurately conveys information about this organism?

A. Endotoxin is the only virulence factor known to be produced by these bacteria.

B. Humans are the only known reservoir hosts for these bacteria.

C. The bacteria are difficult to culture because they have numerous growth requirements.

D. These are among the most antibiotic resistant of all clinically relevant bacteria.

E. These highly motile bacteria can “swarm” over the surface of culture media.

[18.2] The fluoroquinolone resistance seen with increasing frequency in P. aeruginosa infections is best explained by which of the following mechanisms?

A. Changes in the structure or composition of the cell envelope that make it more difficult for the antibiotic to gain entrance

B. Enzymatic cleavage of the antibiotic molecule

C. Inactivation of the antibiotic by enzymatic acetylation

D. Overproduction of the cellular target that the antibiotic attacks

E. Removal of the antibiotic from the cell interior by a membrane pump

[18.3] An aerobic, oxidase positive organism is isolated from the sputum of a 12-year-old cystic fibrosis patient with pneumonia and lung abscesses. On culture the organisms have a “fruity” odor and form greenish colonies. The etiologic agent of the respiratory tract infection is most likely to be which of the following?

A. Chlamydia pneumoniae

B. Klebsiella pneumoniae

C. Pseudomonas aeruginosa

D. Serratia marcescens

E. Streptococcus pneumoniae

Answers

[18.1] D. Pseudomonas aeruginosa is an obligate aerobe that grows on many types of culture media, sometimes producing a sweet or grapelike odor. It often produces a nonfluorescent bluish pigment (pyocyanin) which diffuses into agar or pus fluids. Many strains also produce a fluorescent pigment (pyoverdin), which gives a greenish color. One of the most significant problems with Pseudomonas infections is the high level of natural resistance to many antimicrobials that this widespread environmental opportunist exhibits.

[18.2] E. Clinically significant infections with P. aeruginosa should not be treated with single-drug therapy, because the bacteria can develop resistance when single drugs are employed. The newer quinolones, including ciprofloxacin, are active against Pseudomonas. Quinolones inhibit bacterial DNA synthesis by blocking DNA gyrase. The fluorinated forms of ciprofloxacin and norfloxacin have low toxicity and greater antibacterial activity than the earlier forms. Plasmids code for enzymes that determine the active transport of various antimicrobials across the cell membrane.

[18.3] C. All of the options are potential etiologic agents for pneumonias in humans. The laboratory descriptions of the organism best fits P. aeruginosa (also see the answer for Question 18.1).

MICROBIOLOGY PEARLS ❖ Pseudomonas aeruginosa is most commonly treated with a â-lactam such as piperacillin or cefepime plus an aminoglycoside such as tobramycin. ❖ Pseudomonas aeruginosa is an opportunistic pathogen that is most often found in hospital environments as a source of nosocomial infection. ❖ Pseudomonas aeruginosa is a nonfermentative gram-negative bacilli that is oxidase positive.

REFERENCES

Murray PR, Rosenthal KS, Pfaller MA. Pseudomonas and related organisms. In: Murray PR, Rosenthal KS, Pfaller MA. Medical Microbiology, 5th ed. St. Louis, MO: Mosby, 2005:587–615. 

Sparling PF, Handsfield HH. Pseudomonas aeruginosa. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases, 5th ed. Philadelphia, PA: Churchill Livingstone, 2000:2310–27.

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