Escherichia coli Case File

Escherichia coli Case File

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

CASE 9

A 21-year-old woman presents with a 3-day duration of discomfort with urination and increased urinary frequency. She has noted that her urine has a strong odor as well. She denies fever, abdominal pain, back pain, vaginal discharge, or skin rash. She is sexually active and takes oral contraceptive pills. On examination, she is comfortable appearing and afebrile. She has no costovertebral angle tenderness. Abdominal exam is notable only for suprapubic tenderness. Microscopic examination of the sediment of a centrifuged urine sample reveals 10–15 white blood cells per high power field and numerous bacteria.

◆ What type of organism would a Gram stain of the urine most likely show?

◆ What is the most common etiologic agent of this infection?

◆ What is the most likely reservoir of this infection?

◆ What is the most likely mechanism by which this organism infects the urinary tract?

ANSWERS TO CASE 9: Escherichia coli

Summary: A 21-year-old woman has urinary frequency and dysuria. The urinalysis shows numerous white blood cells.

◆ Organism most likely to be seen on Gram stain: Gram-negative rod

◆ Most common etiologic agent: Escherichia coli

◆ Most likely reservoir for the organism: Patient’s own gastrointestinal (GI) tract

◆ Most likely mechanism of introduction of organism into the urinary tract: Urethral contamination by colonic bacteria followed by ascension of the infection into the bladder

CLINICAL CORRELATION

Escherichia coli is the most commonly found aerobic, gram-negative bacilli in the GI tract of humans. Escherichia coli is responsible for over 80 percent of all urinary tract infections (UTIs), along with other clinical diseases including gastroenteritis, sepsis, and neonatal meningitis. The E. coli that causes diarrhea is usually acquired from the environment, whereas most other infections caused by E. coli are acquired endogenously. Much of the diarrhea resulting from E. coli is acquired in developing countries particularly in travelers to these countries. The serotypes that are associated with travelers’ diarrhea can be grouped based on their method of pathogenesis: enterotoxigenic, enterohemorrhagic, enteroaggregative, and enteroinvasive strains. These strains produce toxins, which account for their invasiveness as well as decreased absorption in the GI tract. Most of these cause a self-limited diarrhea with the exception of enterohemorrhagic E. coli, frequently associated with E. coli serotype O157:H7, causing a bloody diarrhea, which is usually acquired from eating poorly cook meat from an infected cow. Complications of infection with this organism include hemolytic uremic syndrome (HUS), which is a triad of hemolytic anemia, thrombocytopenia, and renal failure. HUS is a significant cause of acute renal failure in children.

UTIs caused by E. coli are associated with organisms from the GI tract or vagina ascending up to the bladder. These organisms can colonize the vagina and be introduced into the bladder during instrumentation or sexual intercourse. Those serotypes that produce adhesions, which mediate adherence of the organisms to epithelial cells in the urinary tract are more likely to cause infections. The majority of cases of uncomplicated and complicated pyelonephritis are caused by E. coli, a complication of a UTI, where the organisms continue to ascend from the bladder to the kidney.

APPROACH TO SUSPECTED Escherichia coli UTI

Objectives

1. Know the structure, characteristics, and virulence factors of E. coli.
2. Know the pathogenic groups and toxins involved in diarrhea caused by E. coli.

Definitions

Pyelonephritis: Infection of the kidney.

Cystitis: Infection of the bladder.

Hemolytic uremic syndrome (HUS): A syndrome characterized by hemolytic anemia, thrombocytopenia (low platelets), and acute renal failure.

DISCUSSION

Characteristics of Escherichia coli

Escherichia coli is a member of the family Enterobacteriaceae (see Table 9-1 for an abbreviated list). All members of this family have in common the fact that they ferment glucose, are oxidase negative, and reduce nitrates to nitrites. Many members of the family Enterobacteriaceae, like E. coli, are normal flora of the human GI tract.

Escherichia coli produces numerous adhesins, which allow the organism to attach to cells in the urinary and gastrointestinal tracts. This prevents the bacteria from being flushed from these organs by the normal passage of urine or intestinal motility. Escherichia coli also can produce several exotoxins, involved in the pathogenesis of diarrhea, including shiga toxins, heat-stable toxins, heat-labile toxins, and hemolysins. Hemolysin HlyA is particularly important in producing an inflammatory response in the urinary tract, whereas most of the other exotoxins are more pathogenic in the GI tract.

Table 9-1

ABBREVIATED LISTING OF ENTEROBACTERIACIAE

Shigella

Salmonella

Escherichia

Enterobacter

Klebsiela

Serratia

Proteus

Figure 9-1. Structures used for antigenic identification in Enterobacteriaceae.

Escherichia coli are divided into serogroups based on the O antigen found on the lipopolysaccharide (LPS) of the cell membrane and the H antigen found on the flagella (Figure 9-1).

Diagnosis

The diagnosis of a UTI is made by urinalysis and urine culture. Complications such as pyelonephritis would be indicated by fever and flank pain. On urinalysis, the presence of white blood cells or leukocyte esterase and bacteria are suggestive of a true infection. Definitive diagnosis of the etiology is made by culture of the urine. Escherichia coli is easily grown on most culture media. A quantitative urine culture from a symptomatic patient should demonstrate greater than 105 colony-forming units (CFUs) bacteria/mL urine to be considered significant. Escherichia coli would appear as pink colonies on MacConkey agar indicating fermentation of lactose. A rapid spot indole test would give a preliminary identification of E. coli, which would be confirmed by biochemical analysis.

Treatment and Prevention

Treatment of UTIs is based on the affecting organism and its susceptibility to antibiotics. Common antimicrobials chosen include trimethoprim sulfamethoxazole, or a fluoroquinolone. Most E. coli are resistant to ampicillin and penicillin. Recurrent UTIs are quite common, particularly in young

women. Prevention can include consumption of large amounts of liquid and attention to totally emptying the bladder during urination. Fluid and electrolyte replacement should be administered to patients with E. coli diarrhea; however, antimicrobial treatment should not be administered. Escherichia coli diarrhea is best prevented by improved hygiene.

COMPREHENSION QUESTIONS

[9.1] Escherichia coli can be classified by their characteristic virulence properties and different mechanisms that cause disease. To which group does the verotoxin producing E. coli 0157:H7 serotype belong?

A. Enteroaggregative E. coli (EAEC)

B. Enterohemorrhagic E. coli (EHEC)

C. Enteroinvasive E. coli (EIEC)

D. Enteropathogenic E. coli (EPEC)

E. Enterotoxigenic E. coli (ETEC)

[9.2] Several children are hospitalized with bloody diarrhea and severe hematological abnormalities. A 4-year-old girl dies of kidney failure shortly after admittance. An epidemiological investigation establishes that all of the patients developed symptoms following consumption of hamburgers from the same fast-food restaurant chain. Which of the following organisms is most likely to be responsible for the outbreak?

A. Campylobacter jejuni

B. non-O1 serogroup of Vibrio cholerae

C. O157:H7 serotype of Escherichia coli

D. Shigella dysenteriae

E. Salmonella typhimurium

[9.3] A Gram stain of an isolate from voided urine in a patient with a UTI reveals the presence of pink rods. Further biochemical analysis reveals that these bacteria ferment glucose, reduce nitrates to nitrites and are unable to synthesize the following reaction:

2H+ + 2e- + ½O2 → H2O

Which of the following characterize the above test results?

A. Escherichia coli

B. Neisseria gonorrhoeae

C. Proteus vulgaris

D. Pseudomonas aeruginosa

E. Staphylococcus aureus

F. Streptococcus pyogenes

[9.4] A 7-year-old child with bloody diarrhea is admitted after laboratory results indicating anemia and abnormal kidney function. After testing, it is determined that the etiologic agent is an E. coli that is most likely to produce which of the following?

A. Endotoxin

B. Exotoxin

C. LT toxin

D. ST toxin

E. Verotoxin

[9.5] Several days after an appendectomy a patient develops a high fever, dangerously low blood pressure, and disseminated intravascular coagulation (DIC). Based on these and other findings, a diagnosis of septicemia as a result of an enteric gram-negative rod is made. Which of the following cytokines is most likely to be responsible for the fever, low blood pressure, and DIC?

A. IFN-γ

B. IL-2

C. IL-10

D. TGF-β

E. TNF-α

Answers

[9.1] B. All of the above classes of E. coli cause diarrhea. However, only EHEC produce a verotoxin that has many properties that are similar to Shiga toxin. EHEC has been associated with hemorrhagic colitis, a severe form of diarrhea, and with HUS. HUS is a disease resulting in acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia.

[9.2] C. Escherichia coli 0157:H7 strains are classically associated with outbreaks of diarrhea after ingestion of undercooked hamburger at fastfood restaurants. Many cases of hemorrhagic colitis and its associated complications can be prevented by thoroughly cooking ground beef. The other organisms listed can cause GI disturbances; however, E. coli is the classic disturbing pathogen in this case. Shigella dysenteriae produces a heat-labile enterotoxin that affects the gut and central nervous system and is a human disease that is transmitted via a fecal-oral route. Salmonella and Campylobacter are associated with poultry and eggs primarily, whereas Vibrio is associated mainly with seafood.

[9.3] A. The biochemical reaction described above is catalyzed by the enzyme oxidase. Thus, E. coli is the only bacteria listed that is a gram-negative rod (pink), ferments glucose, converts nitrates to nitrites, and is oxidase negative.

[9.4] E. The verotoxin produced by E. coli is similar to Shiga toxin, causing bloody diarrhea. Please refer to the discussion for Question 9.1.

[9.5] E. The acute phase response involves the increase in the levels of various plasma proteins (C-reactive protein and mannose-binding proteins) and is part of innate immunity. These proteins are synthesized and secreted by the liver in response to certain cytokines such as IL-1, IL-6, and TNF-α (produced after exposure to microorganisms) as nonspecific responses to microorganisms and other forms of tissue injury. Specifically, endotoxin (LPS) from gram-negative bacteria has the ability to activate macrophages that, in turn, synthesize TNF-α. TNF-α then functions to cause fever and hemorrhagic tissue necrosis (inflammatory reaction/immune response).

MICROBIOLOGY PEARLS ❖ Escherichia coli is the most common cause of UTIs in otherwise healthy patients. ❖ Escherichia coli can easily be identified following growth of a flat lactose fermenter on MacConkey agar that is indole positive. ❖ Many serotypes of E. coli are associated with traveler’s diarrhea.

REFERENCES

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.

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