Question

Jabari an 84-year-old man is hospitalized for a course of intravenous clindamycin to treat an infected tooth following a root canal procedure. A week later the patient develops profuse diarrhea: no blood is visible in the stool, but lab test was positive for blood. He is running fever with temperature of 101.9⁰ F. Physical examination reveals substantial abdominal tenderness and distension. White Blood Cells are elevated (Neutrophils 91%, monocytes 7%, lymphocytes 2%). THE microbial agent is enterotoxigenic escherichia coli.

1. What is the microbial agent? Describe the morphology (shape, arrangement, gram reaction) and cultural properties (O2 requirement, biochemical requirements, motility, etc.) for this microbe.
2. Explain the spread or the occurrence for this infection (cause and transmission) and pathogenicity (virulent factors) of this agent relevant to this case study.
3. Describe the diagnoses (source of specimen, lab tests, and results that confirm your microbe) and treatment (name of Rx, what it targets, why/how does it work against this microbe) also include the general management of this patient.

Answer 1

E. coli Infections
The gram-negative rod Escherichia coli is a common member of the normal microbiota of the colon. Although the vast majority of E. coli strains are helpful commensal bacteria, some can be pathogenic and may cause dangerous diarrheal disease. The pathogenic strains have additional virulence factors such as type 1 fimbriae that promote colonization of the colon or may produce toxins (see Virulence Factors of Bacterial and Viral Pathogens). These virulence factors are acquired through horizontal gene transfer.

Extraintestinal disease can result if the bacteria spread from the gastrointestinal tract. Although these bacteria can be spread from person to person, they are often acquired through contaminated food or water. There are six recognized pathogenic groups of E. coli, but we will focus here on the four that are most commonly transmitted through food and water.

Enterotoxigenic E. coli (ETEC), also known as traveler’s diarrhea, causes diarrheal illness and is common in less developed countries. In Mexico, ETEC infection is called Montezuma’s Revenge. Following ingestion of contaminated food or water, infected individuals develop a watery diarrhea, abdominal cramps, malaise (a feeling of being unwell), and a low fever. ETEC produces a heat-stable enterotoxin similar to cholera toxin, and adhesins called colonization factors that help the bacteria to attach to the intestinal wall. Some strains of ETEC also produce heat-labile toxins. The disease is usually relatively mild and self-limiting. Diagnosis involves culturing and PCR. If needed, antibiotic treatment with fluoroquinolones, doxycycline, rifaximin, and trimethoprim-sulfamethoxazole (TMP/SMZ) may shorten infection duration. However, antibiotic resistance is a problem.

Enteropathogenic E. coli (EPEC) can cause a potentially fatal diarrhea, especially in infants and those in less developed countries. Fever, vomiting, and diarrhea can lead to severe dehydration. These E. coli inject a protein (Tir) that attaches to the surface of the intestinal epithelial cells and triggers rearrangement of host cell actin from microvilli to pedestals. Tir also happens to be the receptor for Intimin, a surface protein produced by EPEC, thereby allowing E. coli to “sit” on the pedestal. The genes necessary for this pedestal formation are encoded on the locus for enterocyte effacement (LEE) pathogenicity island. As with ETEC, diagnosis involves culturing and PCR. Treatment is similar to that for ETEC.

The most dangerous strains are enterohemorrhagic E. coli (EHEC), which are the strains capable of causing epidemics.

EHEC can cause disease ranging from relatively mild to life-threatening. Symptoms include bloody diarrhea with severe cramping, but no fever. Although it is often self-limiting, it can lead to hemorrhagic colitis and profuse bleeding. One possible complication is HUS. Diagnosis involves culture, often using MacConkey with sorbitol agar to differentiate between E. coli O157:H7, which does not ferment sorbitol, and other less virulent strains of E. coli that can ferment sorbitol.

Serological typing or PCR testing also can be used, as well as genetic testing for Shiga toxin. To distinguish EPEC from EHEC, because they both form pedestals on intestinal epithelial cells, it is necessary to test for genes encoding for both the Shiga-like toxin and for the LEE. Both EPEC and EHEC have LEE, but EPEC lacks the gene for Shiga toxin. Antibiotic therapy is not recommended and may worsen HUS because of the toxins released when the bacteria are killed, so supportive therapies must be used.

Acute bacterial diarrheal disease is a worldwide problem of enormous magnitude. In recent years a number of bacteria have been added to the list of recognized etiologic agents causing acute diarrheal disease. This was made possible by our increased understanding of the mechanisms by which such bacteria cause diarrhea and by the development of methods to detect these bacterial enteropathogens. We are now able to define an etiologic agent in 50-80% of cases of acute diarrhea, depending on the particular population. The bacterial agents recently incriminated as important causes of diarrhea include E coli Y. enterocolitica, B. cereus, C. fetus, V. parahemolyticus, and many other coliform organisms. Establishment of an enteric infection depends upon a complex interplay between host defense mechanisms and bacterial virulence factors adapted to overcome these defenses. Bacterial enteropathogens cause diarrhea primarily by elaborating enterotoxins (which also requires the organisms to adhere to the surface of the intestinal cell) and by invading the intestinal mucosa. The number of known bacterial enterotoxins has rapidly increased. Enterotoxins cause intestinal secretion and diarrhea by stimulating the adenyl cyclase system or the guanyl cyclase system and by other mechanisms yet to be defined. The ability of enterotoxigenic bacteria to adhere to the intestine involves a specific binding interaction between bacterial structures called pili or fimbriae and specific receptors on the surface of intestinal cells. Both bacterial pili and the intestinal receptors are under genetic control. A variety of other bacteria, Salmonellae, Shigellae, Y. enterocolitica etc, must invade the mucosa to cause diarrheal disease. The ability to invade is essential to the pathogenesis of disease and requires particular surface characteristics of the bacterium as well as the active participation of both the bacterium and the host cell. The bacteria probably elaborate substances that signal the host cell to initiate the invasive process, i.e. endocytosis. The mechanism by which invasive bacteria evoke intestinal secretion is uncertain but is probably a multifactorial process involving products elaborated by the mucosal acute inflammatory reaction and enterotoxins elaborated by the bacteria.

Blood test. A complete blood count test can help indicate what's causing your diarrhea.
Stool test. Your doctor might recommend a stool test to see if a bacterium or parasite is causing your diarrhea.
Flexible sigmoidoscopy or colonoscopy. Using a thin, lighted tube that's inserted in your rectum, your doctor can see inside your colon. The device is also equipped with a tool that allows your doctor to take a small sample of tissue (biopsy) from your colon. Flexible sigmoidoscopy provides a view of the lower colon, while colonoscopy allows the doctor to see the entire colon.

A full blood count: Anemia may suggest malnutrition, bleeding ulcerations, or IBD.
Liver function tests: These will include testing albumin levels.
Tests for malabsorption: These will check the absorption of calcium, vitamin B-12, and folate. They will also assess iron status and thyroid function.
Erythrocyte sedimentation rate and C-reactive protein: Raised levels may indicate IBD.
Tests for antibodies: These may detect celiac disease.
Stool tests: Doctors can identify parasites, bacteria, and a few viruses in stool cultures. Stool tests can also reveal microscopic blood, white blood cells, and other clues for diagnosis.

Diarrheal illness caused by bacterial pathogens is a global health problem and remains one of the most common complaints prompting patients to seek medical care. Strategies to increase the yield of stool culture and new rapid diagnostic tests can improve diagnostic ability. Emerging antimicrobial resistance among the common bacterial causes of diarrhea has made treatment more challenging. Emerging fluoroquinolone resistance is a particular concern. Recent studies of rifaximin, a nonabsorbed antibiotic for the treatment of bacterial diarrhea, have shown favorable results. Rifaximin may represent a much-needed addition to the armamentarium against bacterial agents

Two potentially serious complications of diarrhea are dehydration (in cases of severe and frequent diarrhea) and malabsorption (in cases of chronic diarrhea).

Diarrhea can also indicate a wide range of underlying chronic conditions. Diagnosis and treatment can help prevent further problems.