13: Diarrhea, Acute

Clinically, it is probably most useful to define acute diarrhea as diarrhea (bowel movements of a looser consistency than usual that occur more than 3 times a day) that develops over a period of 1–2 days and lasts for less than 4 weeks. The differential diagnosis below uses pivotal points in a patient’s presenting symptoms to organize potential diagnoses into 3 categories: noninfectious, gastroenteritis, and infectious colitis. Noninfectious diarrhea is recognized by the lack of constitutional symptoms. Infectious diarrhea that presents with large volume (often watery) stool, constitutional symptoms, nausea and vomiting, and often abdominal cramps can be categorized as gastroenteritis. Infectious colitis presents with fever, tenesmus, and dysentery (stools with blood and mucus). This structure is easy to remember, focuses history taking, allows prognosticating, and is also a good framework on which to consider therapy. Figure 13-1 uses this framework to suggest therapy.

1. Noninfectious diarrhea

   1. Medications and other ingestible substances (some with osmotic effect)

      1. Sorbitol (gum, mints, pill fillers)

      2. Mannitol

      3. Fructose (fruits, soft drinks)

      4. Fiber (bran, fruits, vegetables)

      5. Lactulose

   2. Magnesium-containing medications

      1. Nutritional supplements

      2. Antacids

      3. Laxatives

   3. Malabsorption

      1. Lactose intolerance

      2. Pancreatitis

   4. Medications causing diarrhea through nonosmotic means

      1. Metformin

      2. Antibiotics

      3. Colchicine

      4. Digoxin

      5. Selective serotonin reuptake inhibitor antidepressants

2. Infectious diarrhea: gastroenteritis

   1. Viral (most common)

      1. Caliciviruses (including Norovirus)

      2. Rotovirus

   2. Bacterial

      1. Vibrio cholera

      2. Escherichia coli

      3. Shigella species

      4. Salmonella species

      5. Campylobacter species

      6. Yersinia enterocolitica

   3. Toxin-mediated

      1. Staphylococcus aureus

      2. Clostridium perfringens

      3. Bacillus cereus

3. Infectious diarrhea: inflammatory colitis

   1. Shigella species

   2. E coli

   3. Campylobacter species

   4. Salmonella species

   5. Y enterocolitica

   6. Clostridium difficile

   7. Klebsiella oxytoca

The pivotal point in this case presentation is the acute onset of watery diarrhea. The early predominance of nausea will also help in making a diagnosis. This presentation certainly speaks for an infectious cause. The low-grade fever and absence of dysentery make it likely that the diagnosis is in the category of gastroenteritis. Table 13-1 lists the differential diagnosis.

Leading Hypothesis: Norovirus

Textbook Presentation

Acute vomiting is usually the presenting symptom. The onset of diarrhea follows the vomiting. Mild abdominal cramping is common. Low-grade fever is common. All symptoms resolve completely by 3 days.

Disease Highlights

1. Calciviruses, of which Norovirus and closely related viruses such as Sapovirus are the most common, account for about 80% of adult viral gastroenteritis.

2. Most commonly occurs in winter.

3. Transmission

   1. Norovirus is easily transmissible via the fecal-oral route, in air-borne droplets, via food, and through fomites.

   2. Norovirus is probably the most common cause of food-borne diarrhea.

   3. Attack rates as high as 50% have been documented.

4. Incubation period is 1–2 days.

Evidence-Based Diagnosis

There are no diagnostic tests for norovirus available for routine clinical use; diagnosis is made by clinical presentation.

Treatment

1. Supportive care

   1. Most patients with acute diarrhea require only supportive care. Supportive care is meant to provide rehydration and symptom relief.

   2. Rehydration

      1. Oral rehydration is generally sufficient.

      2. For patients with mild diarrhea and little volume depletion, any oral fluids are appropriate rehydration. (Sports drinks, Pedialyte, and chicken soup are commonly prescribed.)

      3. For patients with more significant volume depletion, oral rehydration solutions should contain NaCl, KCl, HCO₃ or citrate, and glucose. The World Health Organization oral rehydration solution has the following composition:

         • (1) Sodium: 75 mmol/L

         • (2) Chloride: 65 mmol/L

         • (3) Glucose: 75 mmol/L

         • (4) Potassium: 20 mmol/L

         • (5) Citrate: 10 mmol/L

      4. If this solution is not available, patients can be instructed to mix the following in 1 L of water

         • (1) One-half teaspoon of salt

         • (2) One-quarter teaspoon of baking soda

         • (3) 8 teaspoons of sugar

      5. In patients who cannot tolerate oral rehydration or who are very volume depleted, IV fluids (lactated Ringer solution or normal saline) are indicated.

   3. Antidiarrheals (such as loperamide) are safe and effective for patients without dysentery. Using antidiarrheals in a patient with dysentery is not considered safe because evidence suggests they can:

      1. Cause prolonged fever

      2. Cause toxic megacolon and perforation

      3. Possibly increase the risk of hemolytic uremic syndrome (HUS) in patients with Shiga toxin–producing E coli (STEC).

   4. Antiemetics

   5. Diet

      1. BRAT diet (banana, rice, applesauce, toast) is often recommended.

      2. Dairy products should be avoided. (See discussion below).

2. Antimicrobial therapy

   1. Treatment other than supportive care is not necessary for norovirus-like illnesses.

   2. Empiric antimicrobial therapy is recommended for diarrheal infections only in limited circumstances. These circumstances never occur in patients with noninfectious diarrhea and almost never in patients with gastroenteritis. Specific circumstances are discussed throughout the chapter; general circumstances include the following:

      1. Dysentery

      2. Severe disease (profuse diarrhea with hypovolemia, high fever, severe abdominal pain, high band count)

      3. High suspicion for C difficile

      4. Travelers’ diarrhea

Empiric antimicrobial therapy for diarrhea is reasonable for patients with severe symptoms.

Most patients with acute diarrhea do not need diagnostic testing as the illness usually resolves without treatment and work up is usually unrewarding. (A detailed discussion of when evaluation is necessary appears in case 2). Data that support this are that only 2–12% of stool cultures are positive and 0.4–0.7% of tests for ova and parasites are positive in preselected populations. Patients and settings that indicate need for evaluation include:

1. Patients with bloody diarrhea (tests should include assay for Shiga toxin and C difficile toxin).

2. If an outbreak is suspected.

3. Patients at high risk for infecting others.

   1. Residents of long-term–care facilities

   2. Daycare workers

   3. Food service workers

   4. Healthcare workers

4. Patients with severe disease (dehydration, toxic appearance) or risk factors for poor outcome (immunosuppression, severe comorbid illnesses).

5. Patients with prolonged diarrhea (> 7 days) should be tested for parasitic causes (stool for ova and parasites).

Mr. C present is presenting with a clinical syndrome that is consistent with viral gastroenteritis. By recognizing this syndrome, you are able to reassure him that he should be better in the next 24–48 hours. Even if a diagnostic test for norovirus were available for routine use, the usefulness would be low because treatment is only supportive.

In most patients with an acute diarrheal illness, diagnostic testing is not helpful to the patient but may be important from a public health standpoint.

Alternative Diagnosis: Toxin-Mediated Gastroenteritis

Textbook Presentation

The presentation of this syndrome, most commonly caused by S aureus or C perfringens, usually includes acute-onset vomiting and crampy abdominal pain. Vomiting is the predominant symptom with diarrhea being mild and watery and fever being low grade. Because of the very short lag between ingestion and illness (2–8 hours), the culpable meal is usually the last one eaten. Recovery is very rapid (12–48 hours).

Disease Highlights

1. Toxin-mediated gastroenteritis (often referred to as food poisoning) is not an infection – it occurs when a preformed toxin, produced by bacteria, is ingested.

2. S aureus, C perfringens, or B cereus are the most common causes.

3. Although these organisms are the most common causes of food poisoning, they account for only about 1% of food-borne diarrheal illnesses.

   1. Viral causes probably account for most food-borne infections.

   2. Salmonella, Campylobacter, and E coli are the most common bacterial causes of food-borne infections.

   3. Table 13-2 presents recent data on the incidence of food-borne illnesses.

4. S aureus, C perfringens, and B cereus can often be recognized by the clinical and exposure history. Table 13-3 describes the clinical syndromes of these infections.

Illnesses presenting with the acute onset of vomiting and constitutional symptoms, often with abdominal cramping, are usually caused by viruses or bacteria that elaborate toxins.

Evidence-Based Diagnosis

1. There are no diagnostic tests for toxin-mediated gastroenteritis available for routine clinical use.

2. Toxin-mediated gastroenteritis should be considered in any patient with acute gastrointestinal symptoms and recent, suspect food intake.

Treatment

Treatment is supportive care.

Alternative Diagnosis: Gastroenteritis Caused by Salmonella Species

Textbook Presentation

The onset of disease is usually subacute with nausea, fever, and diarrhea. Fever and nausea often resolve over 1–2 days while diarrhea persists for 5–7 days. Patients usually have watery diarrhea with 6–8 bowel movements each day. Salmonella gastroenteritis may cause higher fevers than viral or preformed toxin disease. Dysentery may occur.

Disease Highlights

1. Salmonella species cause 3 major types of disease.

   1. Diarrheal illnesses

      1. Gastroenteritis

      2. Dysentery (discussed later in the chapter)

   2. Bacteremia

      1. Bacteremia develops in ~5% of patients.

      2. Usually a complication of gastroenteritis

      3. Endovascular infections and osteomyelitis may complicate bacteremia.

   3. Typhoid fever

      1. A systemic illness characterized by fever and abdominal pain caused by Salmonella typhi.

      2. Typhoid fever is distinct from gastroenteritis, which is caused by non-typhi Salmonella species.

      3. Although not generally considered a diarrheal illness, some patients have diarrhea as a predominant symptom.

      4. Although typhoid fever is a major problem worldwide, it is seen predominantly in the United States in unvaccinated travelers.

         • (1) Recent data show that 79% of American patients with typhoid had returned from foreign travel within the previous 30 days.

         • (2) Only 5% of the patients had received the typhoid vaccine.

      5. Typhoid fever should be considered in the differential diagnosis of a traveler with a febrile illness.

2. Gastroenteritis is the most common Salmonella-related disease in the United States. The estimated annual incidence of Salmonella is 1.23 million cases.

3. Salmonella is transmitted by:

   1. Food

      1. Eggs and poultry are most common sources.

      2. There are reports of infection from almost any type of food.

   2. Fecal-oral contact with infected patients

      1. Person-to-person transmission is less common than infection from contaminated food.

      2. Bacteria commonly remain in the stool for 4–5 weeks after infection.

   3. Animals also carry salmonella (reptiles most classically).

Evidence-Based Diagnosis

1. The gold standard for diagnosis of salmonella gastroenteritis remains stool culture.

2. There are tests with greater sensitivity, but none are used in routine clinical practice.

Treatment

1. Prevention: Because salmonella is heat sensitive, cooking food well and good hand washing practices prevent most infections.

2. Treatment

   1. Most salmonella infections require no treatment.

   2. The patients who should receive therapy beyond supportive care are those who have

      1. Severe disease (dehydration, dysentery, high fever)

      2. Immunocompromised status, including patients older than 65 years

      3. Elevated risk of focal infection

         • (1) Bacteremia

         • (2) Prosthetic joints or hardware

         • (3) Sickle cell anemia

      4. Typhoid fever

   3. Although most patients shed bacteria for weeks after infection, antibiotics should not be used in attempts to prevent transmission. Antibiotics do not shorten the duration of carriage and may prolong it.

The patient’s symptoms lasted 48–72 hours. He required no specific therapy. There were no suspicious food exposures and nobody else became ill. The case is consistent with a viral gastroenteritis such as that caused by norovirus. The lack of a suspicious diet history makes a toxin-induced food-borne illness (food poisoning) less likely.

The pivotal point in this presentation is the duration of the symptoms: 10 days. Other important features are the recent infectious gastrointestinal illness and recent exposure to antibiotics.

Because 10 days is prolonged when considering acute infectious diarrhea, noninfectious causes should be considered. Both the duration of symptoms and the recent gastroenteritis should raise the possibility of lactose intolerance. Lactose intolerance is common after gastroenteritis due to injury to the small bowel mucosa. Other potential diagnoses include recurrent gastroenteritis or antibiotic-associated diarrhea. Recurrent infectious gastroenteritis can occur since many of the bacteria that cause diarrhea can persist in the stool after clinical symptoms have resolved. This prolonged bacterial shedding also accounts for spread of the illness. This is especially common with Salmonella and Campylobacter. Antibiotic-associated diarrhea is another common entity, complicating between 2% and 25% of courses of antibiotics. The level of risk varies with the specific antibiotic. The prolonged nature of the illness should prompt consideration of the less typical pathogens, such as parasites; could our initial diagnosis have been incorrect? Table 13-4 lists the differential diagnosis.

Leading Hypothesis: Lactose Intolerance

Textbook Presentation

Lactose intolerance commonly presents as chronic symptoms of belching, bloating, flatulence, diarrhea, or abdominal pain in a person of susceptible ethnic background. The symptoms may be subacute or acute in the setting of infection or dietary changes. A suspicious dietary history should be present.

Disease Highlights

1. Most mammals become lactose intolerant after weaning. It is thought that some ethnicities evolved persistent lactase activity because of the importance of milk products as a calorie source in their environments.

2. Lactose intolerance is thus very common and predictable by ethnic background. It also worsens with age.

3. Episodes of small bowel infection can cause transient lactose intolerance. This is more common in people with low levels of lactase activity at baseline.

   It is common to see transient lactose intolerance after episodes of gastroenteritis.

4. Ethnic groups and native populations most likely to have low levels of lactase activity come from the following regions:

   1. Middle East and Mediterranean

   2. East Asia

   3. Africa

   4. Native American

5. Milk, ice cream, and yogurt have the highest levels of lactose.

6. Foods with high lactose and low fat (skim milk) tend to cause the most symptoms as these foods deliver lactose to the small intestine the fastest.

Evidence-Based Diagnosis

1. The diagnosis of lactose intolerance is generally a clinical one based on a suspicious history, in a patient with a susceptible background, whose symptoms resolve on a lactose-free diet.

2. More definitive tests, the lactose tolerance test or lactose breath hydrogen test, can be performed in patients in whom the diagnosis is likely but not clear historically.

Treatment

1. In general, lactose intolerance is treated by decreasing lactose intake.

2. Because people have variable levels of lactase activity, levels of tolerance differ from person to person.

3. Enzyme supplements are often helpful.

4. In acquired illness (eg, post gastroenteritis), lactase levels will eventually recover when the intestinal brush border regenerates.

5. Because of the high prevalence of mild lactose intolerance and the frequent exacerbation following gastroenteritis, patients with acute gastroenteritis should be advised to avoid dairy products for 2 weeks after recovery.

The patient does not appear to have an infectious cause of his diarrhea—at least not a bacterial or viral cause. This fact makes recurrence of his previous infection very unlikely. Antibiotic-associated diarrhea or diarrhea caused by a parasitic infection are still possible.

Alternative Diagnosis: Antibiotic-Associated Diarrhea

Textbook Presentation

Patients with antibiotic-associated diarrhea usually have symptoms of gastroenteritis or dysentery during antibiotic therapy. Upper abdominal symptoms of nausea and vomiting are rare.

Disease Highlights

1. There are really 2 distinct types of antibiotic-associated diarrhea: diarrhea related to an enteric pathogen (primarily C difficile) and diarrhea related to other effects of antibiotics.

2. Although any antibiotic can be associated with antibiotic-associated diarrhea, those most commonly responsible for both types of diarrhea are:

   1. Clindamycin

   2. Cephalosporins

   3. Ampicillin, amoxicillin, and amoxicillin-clavulanate

3. C difficile

   1. Accounts for 10–20% of antibiotic-associated diarrhea

   2. C difficile causes diarrhea via toxin-mediated effects onthe large bowel. This can present as severe diarrhea, often with symptoms of colonic inflammation and a high WBC count.

   3. Risk factors for C difficile include advanced age, hospitalization, and exposure to antibiotics.

   4. C difficile has been reported up to 6 months after a course of antibiotics.

   5. The incidence of community-acquired C difficile is rising. This may be related to increasing use of antibiotics as well as, possibly, to proton pump inhibitors and nonsteroidal antiinflammatory drugs.

   6. Recent reports also speak to the increasing severity of C difficile related to changes in the genetics dictating toxin production.

4. K oxytoca

   1. Newly recognized cytotoxin-producing bacteria capable of causing antibiotic-associated hemorrhagic colitis.

   2. Much less common than C difficile.

5. Patients with antibiotic-associated diarrhea not related to C difficile usually have mild disease that occurs either during or immediately after a course of antibiotics. Possible causes of this type of diarrhea are numerous:

   1. Change in intestinal flora

   2. Nonantimicrobial effect of antibiotics such as the promotility effects of erythromycin

   3. Enteric infections other than C difficile

Evidence-Based Diagnosis

1. Certain features make the diagnosis of antibiotic-associated diarrhea not associated with C difficile likely.

   1. History of previous antibiotic-associated diarrhea not associated with C difficile.

   2. Mild to moderate symptoms

2. C difficile colitis

   1. Diagnosed by identification of either the toxin in the stool or by demonstration of the classic pseudomembranous colitis on endoscopy.

   2. Culture, although highly sensitive and specific, is not frequently used because it is slow and because there are nontoxin-producing strains of C difficile that are not clinically important.

   3. Polymerase chain reaction (PCR) has become the diagnostic standard: sensitivity, ≥ 90%; specificity, ≥ 97%.

3. If a clinical syndrome consistent with C difficile colitis persists despite negative PCR, sigmoidoscopic exam of the colon is recommended. If symptoms do not resolve and evaluation for C difficile is negative, stool cultures to rule out another antibiotic-associated enteric infection are reasonable.

Treatment

1. Antibiotic-associated diarrhea not related to C difficile infection usually resolves with discontinuation of antibiotics. Other useful treatments include:

   1. Probiotic agents reduce the risk of antibiotic-associated diarrhea and probably shorten an episode once it has occurred.

   2. Antidiarrheals

2. The treatment of C difficile is as follows:

   1. Avoid antidiarrheals

   2. When possible, patients with C difficile infection should discontinue the causative antibiotic.

   3. Infection control practices should be instituted to limit spread of the infection.

   4. Antibiotics

      1. First-line therapy for patients without severe disease is oral metronidazole. This is the case for an initial infection or a recurrence.

      2. First-line therapy for severe disease is oral vancomycin. For patients with the most severe disease, IV vancomycin can be added to oral vancomycin. Intracolonic vancomycin has been used in patients with severe ileus.

      3. Vancomycin is also suggested for patients with a second recurrence.

      4. Surgical therapy (colectomy) is sometimes necessary for patients with perforation, toxic megacolon, or severe ileus.

   5. Relapse complicates 20–25% of cases of treated C difficile.

   6. Treatment with donor feces, given by enema or nasojejunal infusion has been shown to be effective in patients with multiple relapses.

Alternative Diagnosis: Giardia lamblia

Textbook Presentation

Giardiasis can present as either acute or chronic diarrhea. It usually occurs in patients with exposure to infected water supplies, although person-to-person transmission can occur. Symptoms usually include diarrhea, nausea, abdominal cramps, bloating, flatulence, and foul-smelling stools.

Disease Highlights

1. Giardia is the most common parasitic cause of diarrhea in the United States.

2. Most infections in the United States result from ingestion of contaminated water (from streams and lakes).

3. Cases most commonly occur in children age 1–9 or adults age 30–39.

4. Incidence peaks annually during the summer and early fall when people most commonly participate in water sports and camping.

5. Although usually sporadic, there are occasional outbreaks related to contamination of bodies of water used for recreation and drinking supplies.

6. Common symptoms

   1. Diarrhea occurs in 96% of cases.

   2. Weight loss is present in 62% of cases.

   3. Abdominal cramps occur in 61% of cases.

   4. Greasy stools are present in 57% of cases.

   5. Belching, flatulence, and foul-smelling stools are commonly reported.

7. Fever is uncommon.

8. Chronic infection occurs in about 10% of untreated patients.

9. If evaluation for Giardia is negative and there is no response to empiric therapy, other organisms should also be considered.

   1. This is especially true in patients who are immunocompromised.

   2. Other organisms that may cause disease are:

      1. Cryptosporidium

      2. Cyclospora cayetanensis

      3. Isospora belli

Evidence-Based Diagnosis

1. G lamblia

   1. Sensitivity of stool ova and parasites for Giardia is 50–70% for 1 stool sample.

   2. Sensitivity is over 90% for 3 samples.

   3. Antigen assays sensitive to over 90%.

2. Other organisms

   1. Cryptosporidium can be identified on stool antigen assay.

   2. C cayetanensis and I belli can be identified on acid-fast stain.

Treatment

1. The treatment of choice for G lamblia infection is oral metronidazole.

2. Empiric therapy is often recommended.

The pivotal points in this case are the presence of bloody stools, abdominal pain, and fever. This symptom complex makes diarrhea caused by a bacterial infection likely. The organisms that commonly cause bloody diarrhea are Shigella species, Campylobacter species, and E coli. Salmonella species, Y enterocolitica, and C difficile also may cause bloody diarrhea. Noninfectious causes, such as ischemia or ulcerative colitis, should also be considered.

Clinically, it is impossible to differentiate between the different causes of bacterial diarrhea. That said, it is important to know organisms’ recognizable symptom complexes because these can give clues to the causative organism and guide empiric therapy. Table 13-5 lists the differential diagnosis.

Leading Hypothesis: Campylobacter Infection

Textbook Presentation

Presenting symptoms of Campylobacter infection are usually diarrhea and abdominal pain. The diarrhea is often profuse and watery and associated abdominal pain can be severe, sometimes mimicking appendicitis. The fever usually resolves over the first 2 days of the illness, while the diarrhea and abdominal pain may last 4–6 days.

Disease Highlights

1. Campylobacter species are among the most commonly isolated pathogens in patients with diarrhea and are a common cause of bloody stool.

2. The incidence of Campylobacter diarrhea is generally about 13/100,000 persons with about 2.4 million persons affected each year.

3. In 1 recent study of patients arriving at emergency departments with bloody diarrhea, the breakdown of diagnoses were:

   1. Shigella in 15.3% of patients

   2. Campylobacter in 6.2% of patients

   3. Salmonella in 5.2% of patients

   4. Shiga toxin–producing E coli in 2.6% of patients

   5. Other cause in 1.6% of patients

4. Common aspects of the presentation are

   1. Constitutional symptoms before gastrointestinal disease

   2. Bloody diarrhea beginning after 2–3 days of watery diarrhea

5. Campylobacter infection can (rarely) be associated with extraintestinal complications.

   1. Reactive arthritis

   2. Guillain-Barré syndrome

6. Bacteria commonly remain in the stool for 4–5 weeks and reinfection can occur.

Evidence-Based Diagnosis

1. Although stool cultures are most likely to be negative (even in patients with bloody diarrhea), they can be useful in some circumstances.

   1. Campylobacter and Shigella infections clearly benefit from treatment.

   2. Inappropriate treatment of salmonella (treating mild or moderate non-typhi infection) is not helpful and may lead to prolonged carriage.

   3. Culture results can be very useful from a public health standpoint.

2. Stool cultures are the only way to distinguish organisms as many studies of the clinical characteristics of patients with diagnostic stool cultures demonstrate the overlap of the clinical syndromes.

   Even organisms that are generally considered to be common causes of dysentery (Shigella, Campylobacter, Salmonella) are at least as likely to cause non-bloody diarrhea and a gastroenteritis-type illness.

3. The decision making regarding whether to send stool cultures considers ways to increase the yield of the cultures (both in terms of positive results and clinical utility). Consider the following questions:

   1. Is there a clinical suspicion for a specific disease that requires treatment?

      1. Severely ill patient (fever, dysentery, abdominal pain); about 30% of patients with dysentery have positive cultures (compared with 1–6% of all patients).

      2. Suspicious exposure (travel, high-risk sexual behavior, antibiotics)

         • (1) Traveler’s diarrhea (usually E coli) can usually be treated empirically.

         • (2) Other infections associated with travel (Entamoeba histolytica, G lamblia) benefit from treatment.

   2. Does the patient have an underlying disease that makes treatment more necessary?

      • (1) Immunosuppression

      • (2) Inflammatory bowel disease

   3. Are there public health reasons that a diagnosis needs to be made?

      • (1) Possible outbreak of food-borne illness

      • (2) Patient might potentially spread disease (healthcare worker, daycare worker, food handler).

   4. Is there a reason not to culture?

      • (1) Stool cultures and ova and parasite exams of patients in whom diarrhea develops after being hospitalized for another cause are particularly unrevealing.

      • (2) Consider limiting in-hospital cultures to the following circumstances:

        • (a) Onset of diarrhea within 3 days of admission

        • (b) Onset > 3 days but

          • (i) Patient is older than 65 years and has comorbidities.

          • (ii) Patient has HIV infection.

          • (iii) Neutropenia is present.

          • (iv) Extraintestinal manifestations are present.

          • (v) There is an outbreak of diarrhea in the hospital.

      • (3) Testing for C difficile as a cause of diarrhea in the hospital is always appropriate.

4. Patients with more severe clinical presentations, including high fever, abdominal pain, and dysentery, should always have stool cultures sent.

5. Diagnostic tests other than stool cultures are useful in certain situations.

   1. C difficile toxin for patients exposed to antibiotics or proton pump inhibitors

   2. Shiga toxin to identify enterohemorrhagic E coli (EHEC) in all patients with bloody diarrhea

   3. Fecal leukocytes may be helpful in deciding which patients are more likely to have positive stool cultures.

      1. Sensitivity, 73%; specificity, 84%

      2. LR+, 4.56; LR–, 0.32

   4. WBC

      1. WBC is neither sensitive nor specific for the presence of invasive bacterial infections.

      2. A marked left shift, at least if the band count is > neutrophil count, suggests bacterial etiology in general and Shigella in particular.

Treatment

1. Severe diarrhea with blood should be treated empirically while cultures are pending.

2. Empiric therapy is generally with a quinolone.

3. Some very important caveats should be kept in mind when empirically treating suspected bacterial diarrhea or dysentery.

   1. Antibiotics shorten the course of diarrhea caused by Shigella and Campylobacter.

   2. There is quinolone resistance in some strains of Campylobacter, so empiric therapy should be broadened to include a macrolide if the suspicion for Campylobacter is high or if the patient is very ill.

   3. Antibiotics should probably be withheld if the patient is at high risk for EHEC (see below).

   4. Antibiotics are only beneficial for salmonella infections in the case of typhoid or severe disease.

Remember that antidiarrheals should never be used for patients with dysentery or signs of invasive infection (tenesmus, blood or mucus in stool, high fever, and severe abdominal pain).

Alternative Diagnosis: Shigella Infection

Textbook Presentation

Shigella infection often begins with fever and constitutional symptoms. Diarrhea is initially watery and may become bloody. The diarrhea can be very frequent. Tenesmus is often prominent.

Disease Highlights

1. Although there is a spectrum of disease (some Shigella species can cause milder disease), a patient who is systemically ill with classic dysentery (frequent bloody stools with tenesmus) is most likely to have Shigella infection.

2. Incidence is estimated at about 6 cases/100,000 people.

3. Shigella is a highly infectious organism with as few as 10 organisms causing disease.

Evidence-Based Diagnosis

1. Because of the highly invasive nature of Shigella, some of the tests that reveal colonic inflammation are more useful in detecting Shigella than other organisms.

   1. Sensitivity of band count > 1% = 85%.

   2. Sensitivity of fecal leukocytes is at least 70%.

2. Stool culture is gold standard.

Treatment

1. Shigella dysentery clearly benefits from treatment.

2. The drug of choice is oral ciprofloxacin.

Alternative Diagnosis: Enterohemorrhagic E coli (EHEC)

Textbook Presentation

The presentation of E coli depends on the type. EHEC usually presents with diarrhea and abdominal pain. The pain is often worse in the right lower quadrant. Bloody diarrhea is very common, while nausea, vomiting, and fever are not.

Disease Highlights

1. Nomenclature

   1. EHEC is a group of E coli that elaborates Shiga toxin. The associated disease is caused by the effects of the toxin.

   2. EHEC is also called “Shiga toxin–producing” E coli, (STEC) or verocytotoxigenic E coli (VTEC).

   3. Common strains of EHEC are O104:H4 and O157:H7 (the most common strain in the United States).

   4. Other than EHEC, there are 4 types of E coli that cause diarrheal illness in adults. Information about the E coli diseases other than EHEC is listed in Table 13-6.

2. Symptoms of EHEC include bloody diarrhea (seen in most infected patients), severe abdominal pain, and absence of fever.

3. Incidence varies year to year but is generally 1–2 cases/100,000 people.

4. EHEC is associated with the HUS.

   1. HUS is the simultaneous presence of a microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury.

   2. HUS occurs mainly in children and affects 5–10% of children infected with EHEC.

   3. About 5% of cases HUS/thrombotic thrombocytopenic purpura in adults are related to EHEC.

Evidence-Based Diagnosis

1. Patients infected with EHEC are significantly more likely than patients infected with other pathogens to

   1. Report bloody diarrhea

   2. Provide visibly bloody specimens

   3. Not report fever

   4. Have abdominal tenderness

   5. Have a WBC > 10,000/mcL

   6. Have any fecal leukocytes in their specimen (70.5% vs. 39.5%)

2. If an organism is isolated from a patient with bloody diarrhea, it is most likely to be Shigella or Campylobacter. On the other hand, a patient infected with EHEC is more likely to have bloody diarrhea than a patient with Shigella or Campylobacter infection.

3. Positive culture or detected Shiga toxin are considered diagnostic.

4. Culture/toxin testing for EHEC often must be specifically requested.

Treatment

1. Treatment of EHEC is controversial.

2. Studies have reported no effect, an increase in risk of HUS, and beneficial effects with antibiotics.

3. Antibiotics are generally thought to not be indicated in the treatment of EHEC.

The resolution of this case is not surprising. The decision to treat the patient was based on her ill appearance and the fact that her presentation was thought to be consistent with Campylobacter infection. Even though stool cultures have the highest yield in patients with bloody stool, about two-thirds of the cultures will still be negative. Also not surprising is her rapid improvement.

Travelers’ Diarrhea

Textbook Presentation

Patients with traveler’s diarrhea usually become ill in the first 5 days of their trips from a temperate climate to a tropical one. They usually have mild symptoms of a gastroenteritis-like illness. Patients are often better by the time they return home.

Disease Highlights

1. Up to 10 million cases yearly

2. The highest risk destinations for traveler’s diarrhea are in Asia, Africa, and South and Central America.

3. Disease usually occurs in the first 5 days (with a peak onset at 4 days) and resolves in 1–5 days.

4. Symptoms are usually of mild to moderate diarrhea but more severe symptoms can occur.

5. Although the predominant cause of traveler’s diarrhea is enterotoxigenic E coli (ETEC), any bacteria, virus, or parasite can be causative. It is important to consider infections particularly common in certain locations.

   1. St. Petersburg: G lamblia

   2. Wilderness streams in Western United States: G lamblia

   3. Nepal: Cyclospora, G lamblia

   4. India: E histolytica

6. Because these infections usually occur far from the patient’s physician, the doctor’s role is usually advisory.

   1. Prevention

      1. Ensure clean water

         • (1) Boiled, filtered, or chemically purified local water.

         • (2) Carbonated beverages and bottled water

      2. Gastric acidity is natural prevention; temporarily discontinue proton pump inhibitors or H₂-blockers if safe to do so.

      3. Antibiotics

         • (1) Only recommended for traveler at particularly high risk for complications or for very high stakes trips.

         • (2) Rifaximin is the most commonly recommended agent.

         • (3) Bismuth is also effective, taken before meals and at bedtime.

      4. CDC Web site has very useful information for patients.

   2. Advise patients of common mistakes.

      1. Ice and mixed drinks are often made with contaminated water.

      2. Ensure bottled water is sealed and not just bottled tap water.

      3. As the parasitologist B. H. Kean once said, “The only way to clean lettuce is with a blowtorch."

      4. Any food heated for a prolonged time is potentially dangerous.

      5. Fruit is only safe if the traveler peels it.

      6. A recent study reported that among table top sauces collected from restaurants in Guadalajara and tested for diarrheogenic E coli, 4 of 43 contained ETEC and 14 of 32 contained enteroaggregative E coli (EAEC).

Treatment

1. Supportive care

2. Avoid antidiarrheals if dysentery is present.

3. Antibiotics are warranted.

   1. Ciprofloxacin, azithromycin, and rifamaxin are the preferred agents.

   2. Consider causes of traveler’s diarrhea other than ETEC (such as giardiasis, amebiasis), which require different therapies.