Proteus mirabilis Case File

Proteus mirabilis Case File

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

CASE 17

A 35-year-old woman presents to the emergency department with right flank pain. She reports that she had a few days of urinary urgency, frequency, and burning which she tried to treat herself by drinking cranberry juice. Earlier today she started having a severe, colicky pain on her whole right side. She has had a fever, and when she urinated this morning she noticed that it appeared to have blood. She’s had a few urinary tract infections (UTIs) in the past but nothing like this. She is on no medications regularly and has no other significant medical history. On examination, she has a temperature of 37.5°C (99.5°F), her other vital signs are normal, and she appears to be in pain. Notable on examination is some tenderness on the right flank but no masses, rebound tenderness, or guarding on palpation of her abdomen. She has costovertebral angle tenderness on the right side but not the left. Her peripheral white blood cell count is elevated. A urinalysis shows the presence of leukocyte esterase, blood, and a high pH. An abdominal CT scan reveals an obstructing stone in the right ureter causing hydronephrosis of the right kidney.

◆ What organism is likely to be responsible for this infection?

◆ What is the cause of the high pH of this patient’s urine?

ANSWERS TO CASE 17: Proteus mirabilis

Summary: A 35-year-old woman presents with a UTI and nephrolithiasis (kidney stones). The urine has a high pH.

◆ Organism most likely to be responsible for this infection: Proteus mirabilis.

◆ Mechanism of high pH in urine: Proteus produces urease, which splits urea into carbon dioxide and ammonia, raising the urinary pH.

CLINICAL CORRELATION

Proteus species are normal flora of the gastrointestinal tract and predominantly associated with hospital-acquired UTIs as well as bacteremia, osteomyelitis, empyema, and neonatal encephalitis. Proteus causes UTIs after urethral contamination with fecal bacteria followed by ascension into the bladder. Most infections occur in patients with structural abnormalities or longterm catheters of the urinary tract. Proteus infections can result in significant renal damage by several mechanisms. Proteus produces large amounts of urease, which breaks down urea into carbon dioxide and ammonia and results in elevated urinary pH levels. High urinary pH can contribute to direct renal toxicity and also can result in increased urinary stone formation. Urinary stones can result in further renal damage by obstructing urine flow and serving as a focus of ongoing infection. Crystalline material tends to build up inside of a long-term catheter leading to biofilm formation. This can essentially block flow through the catheter. Proteus is also among the most common causes of bacteremia in the family Enterobacteriaceae often associated with underlying disease such as diabetes, malignancy, or heart or lung disease. Bacteremia is usually secondary to a primary UTI. Pediatric meningitis with Proteus species, especially in the first week of life, has a high mortality rate and a predilection for abscess formation when the organism gains access to the brain. It is hypothesized that the organisms gain entry into the blood through the umbilicus and from the blood they disseminated into the brain.

APPROACH TO Proteus mirabilis INFECTION

Objectives

1. Know the structure and characteristics of P. mirabilis.
2. Know the mechanisms by which P. mirabilis produces renal damage.

Definitions

Nephrolithiasis: The presence of calculi (solid, crystalline) that develop in the kidney and pass through the genitourinary tract.

Hydronephrosis: Enlargement of the kidney because of an abnormality such as the presence of stones.

DISCUSSION

Characteristics of Proteus Species

The genus Proteus includes five species, the most common of which are P. mirabilis and P. vulgaris. Proteus species are commonly found in the environment and as normal flora in the intestinal tract of humans and other animals. Proteus mirabilis, like other members of the Enterobacteriaceae family, is a nonspore-forming, facultative anaerobic, gram-negative bacillus. Proteus has fimbriae, which facilitate attachment to uroepithelium, and flagellae, which provide the motility required for ascending infection. Proteus also has the ability to transform from a single cell form to a multicell elongated (swarmer) form. The swarmer cells are more likely to be associated with cellular adherence in the kidney as demonstrated in an animal model of infection. Hemolysin, which induces cell damage by forming pores, may also play a role in establishment of pyelonephritis.

Diagnosis

Diagnosis of a UTI is initially by the urinalysis followed by a culture. The presence of leukocyte esterase, which is an indicator of the presence of white blood cells, in this patient indicated a presumptive UTI. The increased urinary pH as well as the evidence of a stone by CT indicated an obstructive process. Gram stain of the urine may be helpful if a significantly large number of organisms are present in the urine (greater than 105 colonies per milliliter). Culture of urine would likely be diagnostic after 24 hours. Members of the family Enterobacteriaceae, the most common cause of UTIs in an otherwise healthy young person, should grow rapidly on blood as well as MacConkey agars. The presence of greater than or equal to 105 CFU/mL in the urine of a single organism would indicate a significant pathogen. Proteus is easily identified on a MacConkey agar plate as a clear colony (nonlactose fermenter). The obvious swarm seen on blood agar would indicate a Proteus species. Definitive confirmation of P. mirabilis would be made by biochemical tests included in most commercially available identification systems. A quick test to differentiate P. mirabilis and P. vulgaris would be indole positivity in the latter.

Treatment and Prevention

Proteus species are usually among the most susceptible genera of all of the Enterobacteriaceae, most susceptible to penicillin, although it is not uncommon for them to be resistant to tetracyclines. Proteus vulgaris, however, tends to be resistant to more antimicrobials than P. mirabilis. As is the case with most bacteria, new resistance mechanisms are being seen in otherwise susceptible organisms.

COMPREHENSION QUESTIONS

[17.1] A 78-year-old patient with an episode of acute urinary retention was catheterized. Three days later, he developed fever and suprapubic pain. Culture of the urine revealed a thin film of bacterial growth over the entire blood agar plate, and the urease test was positive. Which of the following is the most likely organism to cause this infection?

A. Escherichia coli

B. Helicobacter pylori

C. Morganella morganii

D. Proteus mirabilis

E. Enterococcus faecalis

[17.2] A urinary tract infection as a result of P. mirabilis facilitates the formation of kidney stones because the organism does which of the following?

A. Destroys blood vessels in the kidney

B. Exhibits “swarming” motility

C. Ferments many sugars

D. Produces a potent urease

E. Secretes many exotoxins

[17.3] A 55-year-old woman is noted to have pyelonephritis with shaking chills and fever. Blood cultures are obtained, and the Gram stain is read preliminarily as consistent with Proteus species. Which of the following bacteria also may be the etiology?

A. Escherichia coli

B. Group B Streptococcus

C. Staphylococcus aureus

D. Streptococcus pyogenes

Answers

[17.1] D. Proteus species produce infections in humans only when the bacteria leave the intestinal tract. They are found in UTIs and produce bacteremia, pneumonia, and focal lesions in debilitated patients or those receiving intravenous infusions. Proteus mirabilis is a common cause of UTI. Proteus species produce urease, making urine alkaline and promoting stone formation. The rapid motility of these organisms is evidenced by “swarming,” a thin film of organisms over the entire agar plate.

[17.2] D. Proteus species produce a urease, which hydrolyzes urea leading to ammonia, which alkalinizes the urine (leading to a higher pH).

[17.3] A. Both proteus and E. coli are gram-negative rod bacilli. Escherichia coli is the most common isolate in UTIs.

MICROBIOLOGY PEARLS ❖ The ability of Proteus species to swarm is an important virulence mechanism in causing UTIs. ❖ The swarming nature of Proteus also is an early diagnostic indicator as to the organism’s identity. ❖ Proteus species have the ability to produce obstructive stones because of the presence of the urease enzyme. ❖ Proteus mirabilis is the most common cause of Proteus infections.

REFERENCES

Mobley HLT, Belas R. Swarming and pathogenicity of proteus mirabilis in the urinary tract. Trends Microbiol 1995;3:280–84. 

Murray PR, Rosenthal KS, Pfaller MA. Enterobacteriaceae. In: Murray PR, Rosenthal KS, Pfaller MA. Medical Microbiology, 5th ed. St. Louis, MO: Mosby, 2005:323–38. 

O’Hara CM, Brenner FW, Miller JM. Classification, identification, and clinical significance of proteus, providencia and morganella. Clin. Microbiol. Rev 2000;13:534–46.

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