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p. 1445

The most common complication of any diarrheal illness is loss of fluids

and electrolytes, which in extreme cases can lead to hypovolemia,

shock, and death. Depending on the degree of dehydration, fluid and

electrolyte losses are replaced intravenously or orally.

Case 69-1 (Questions 1, 2)

Classification of infectious diarrheas as either an inflammatory or

noninflammatory diarrheal illness provides a basis for preparing a

focused list of suspected pathogens, thus guiding the overall diagnostic

and therapeutic plan.

Case 69-1 (Questions 3–4)

Vibrio cholerae 01 and 0139 are toxigenic strains of Vibrio species,

which cause epidemic cholera; severe dehydration requiring vigorous

fluid replacement may be necessary. Non-cholera Vibrio species do not

possess the virulence factors required to cause epidemic cholera.

Antimicrobial treatment differs between toxigenic and non-toxigenic

Vibrio species.

Case 69-2 (Questions 1–3),

Case 69-3 (Questions 1, 2)

Salmonella species are classified as non-typhoidal and typhoidal

salmonellae. Non-typhoidalsalmonellae may cause the clinical

syndromes of gastroenteritis, bacteremia, and localized infection,

whereas typhoidalsalmonellae may cause typhoid fever and chronic

carriage. The role of antimicrobials in the management of salmonellosis

is based on the clinicalsyndrome, its severity, and underlying health

problems of infected persons.

Case 69-7 (Question 1),

Case 69-8 (Questions 1, 2),

Case 69-9 (Question 1),

Case 69-10 (Question 1),

Case 69-11 (Questions 1–7)

Severe dysentery caused by Shigella species is most commonly caused

by Shigella dysenteriae, whereas a milder illness is typically caused by

Shigella sonnei. Antimicrobials alleviate the symptoms of shigellosis, and

decrease the period of time that shigellae can be spread by person-toperson contact.

Case 69-12 (Questions 1–5),

Case 69-13 (Question 1)

Fluoroquinolone-resistance in Campylobacter species is a common

finding in both developed and underdeveloped areas of the world; when

indicated, macrolide antimicrobials are recommended.

Case 69-14 (Questions 1–3)

Travelers to destinations where acquisition of Travelers’ diarrhea (TD)

is a concern should bring a travel kit including medications (e.g.,

loperamide and antimicrobials) and instructions for self-treatment at the

onset of illness. The selected antimicrobial depends on the area of

Case 69-15 (Questions 1–6)

travel. Long-term postinfectious complications of TD may occur in

some returning travelers.

Escherichia coli O157:H7 is a specific toxin-producing strain of E. coli

bacteria that can lead to the severe sequelae of hemolytic uremic

syndrome.

Case 69-16 (Questions 3, 4)

Clostridium difficile infection causes a wide range of severity of illness.

Mild-to-moderate disease is typically treated with metronidazole as firstline therapy, and oral vancomycin is preferred for severe disease.

Case 69-17 (Question 6)

Severe C. difficile infection can be life-threatening and often

necessitates multiple therapeutic interventions.

Case 69-18 (Questions 4, 5)

p. 1446

p. 1447

PREVALENCE AND ETIOLOGY

Worldwide, diarrhea accounts for more than 2.5 million deaths annually,

1 mainly

affecting infants and children living in poverty.

2 Prolonged episodes of diarrhea lead

to malnutrition and in children contribute to impaired growth and developmental

delay.

2

In the United States, about 48 million foodborne diarrheal illnesses occur

each year, resulting in 128,000 hospitalizations and 3,000 deaths.

3

Infectious diarrhea is caused by the ingestion of food or water contaminated with

pathogenic microorganisms (e.g., bacteria, viruses, protozoa, or fungi) or their toxins

(Table 69-1).

2

In the United States, noroviruses account for about 50% of diarrheal

outbreaks, while common bacterial pathogens include Campylobacter, non-typhoidal

Salmonella, Shigella, and Shiga toxin–producing Escherichia coli.

3

Table 69-1

Predisposing Factors, Symptoms, and Therapy of Gastrointestinal Infections

Pathogen

Predisposing

Factors Symptoms

Diagnostic

Evaluations

Drug of

Choice

a

,

c Alternatives

a

,

Salmonella (nontyphoidal)

b

Ingestion of

contaminated

poultry, raw milk,

custards, and cream

fillings; foreign

travel

Nausea, vomiting,

diarrhea, cramps,

fever,

tenesmus.Incubation:

6–72 hours

Fecal

leukocytes,

stool culture

Fluoroquinolone,

azithromycin,

third-generation

cephalosporins

Amoxicillin,

TMP–SMX

Salmonella

(typhoidal)

Ingestion of

contaminated food;

foreign travel

High fever,

abdominal pain,

headache, dry cough

Fecal

leukocytes,

stool culture,

Fluoroquinolone,

azithromycin,

third-generation

TMP–SMX,

amoxicillin

blood culture cephalosporins

Shigella Ingestion of

contaminated salad,

raw vegetables,

swimming in water

contaminated with

sewage; foreign

travel

Fever, dysentery,

cramps,

tenesmus.Incubation:

24–48 hours

Fecal

leukocytes,

stool culture

Fluoroquinolone,

azithromycin,

ceftriaxone

TMP–SMX,

ampicillin

Campylobacter Contaminated eggs,

raw milk, or poultry;

foreign travel

Mild-to-severe

diarrhea; fever,

systemic malaise.

Incubation: 24–72

hours

Fecal

leukocytes,

stool culture

Erythromycin,

azithromycin

–

Clostridium

difficile

Antibiotics,

antineoplastics

Mild-to-severe

diarrhea, cramps

C. difficile

toxin, C.

difficile

culture,

colonoscopy

Metronidazole Vancomycin

Staphylococcal

food poisoning

Custard-filled

bakery products,

canned food,

processed meat, ice

cream

Nausea, vomiting,

salivation, cramps,

diarrhea; usually

resolves in 8

hours.Incubation: 2–

6 hours

– Supportive

therapy only

–

Travelers’

diarrhea

(Enterotoxigenic

Escherichia coli,

Campylobacter)

Contaminated food

(vegetables and

cheese), water;

foreign travel

Nausea, vomiting,

mild-to-severe

diarrhea, cramps

Stool culture See Table 69-3 –

Shiga

toxin–producing

Escherichia coli

(E. coli

O157:H7)

Beef, raw milk,

water

Diarrhea, headache,

bloody

stoolsIncubation: 48–

96 hours

Stool cultures

on

MacConkey’s

sorbitol

Supportive

therapy only

–

Cryptosporidiosis Immunosuppression,

day-care centers,

contaminated water,

animal handlers

Mild-to-severe

diarrhea (chronic or

self-limited); large

fluid volume

Stool

screening for

oocytes,

PCR, ELISA

See Chapter 77,

Opportunistic

Infections in

HIV-Infected

Patients

–

Viral

gastroenteritis

Community-wide

outbreaks,

contaminated food

Nausea, diarrhea

(self-limited),

cramps. Incubation:

16–48 hours

Special viral

studies

Supportive

therapy only

–

aSources: Navaneethan U, Giannella RA. Mechanisms of infectious diarrhea. Nat Clin Pract Gastroenterol Hepatol

2008;5:637; DuPont HL. Acute infectious diarrhea in immunocompetent adults. N Engl J Med. 2014;370:1532. See

text for doses and duration of therapy.

bNot all cases require antibiotic therapy. See text for details.

c

If susceptible. See text for details.

ELISA, enzyme-linked immunosorbent assay; PCR, polymerase chain reaction; TMP–SMX, trimethoprim–

sulfamethoxazole.

p. 1447

p. 1448

This chapter focuses on the diagnosis and management of the common microbial

causes of acute infectious diarrhea.

DEFINITIONS

Diarrhea is often defined as three or more episodes of loose stools or any loose stool

with blood during a 24-hour period, which may be accompanied by nausea, vomiting,

or abdominal cramping.

3 The duration of illness is considered acute if symptoms are

present for less than 2 weeks duration, persistent if symptoms last for 14 to 29 days,

and chronic if symptoms last ≥30 days.

3 Classifying diarrheal syndromes as either a

noninflammatory (watery diarrhea) or an inflammatory (bloody diarrhea) illness

provides a basis for predicting the most likely microbial cause for the intestinal

illness.

1

PATHOGENESIS

The pathogenesis of infectious diarrhea involves an interplay among bacterial

virulence factors, host factors, and predisposing factors to infection. Diarrhea is

more likely to occur in the setting in which an imbalance among these factors favors

the enteropathogen.

Bacterial Virulence Factors

Enteropathogens possess virulence factors that contribute to the organism’s

pathogenicity.

2 Enterotoxins targeting the small bowel cause net movement of fluid

into the gut lumen, leading to voluminous watery stools and potentially lifethreatening dehydration. Cytotoxins targeting the colon cause direct mucosal damage,

leading to fever and bloody diarrhea. Invasive properties of Shigella species and

invasive strains of E. coli allow these bacteria to invade and destroy epithelial cells,

causing bloody or mucoid stools. Some enteropathogens induce a vigorous host

response through the release of proinflammatory cytokines from intestinal epithelial

cells, leading to diarrhea. Finally, adhesions allow enteropathogens to attach to and

colonize the gastrointestinal (GI) mucosa, facilitating toxin delivery, invasion,

dissemination, or host cell lysis.

2

Host Defenses

The human GI tract possesses numerous defense mechanisms to protect against

enteric infection. Normal bacterial flora compete for space and nutrients with

potentially pathogenic organisms, or produce substances, e.g., short-chain fatty acids,

that are inhibitory to enteropathogens.

2 Gastric acidity of the stomach prevents acidsusceptible pathogens from passing from the stomach into the intestinal tract, whereas

gastrointestinal mucus and mucosal tissue integrity provide physical barriers against

infection. Intestinal immunity includes defensins that are bactericidal to some

enteropathogens, local production of antibodies, and toll-like receptors that

recognize enteropathogens and activate the immune response.

2

Intestinal peristalsis

moves bacteria and their toxins along and out of the GI tract. Finally, specific host

genetic factors are protective against enteric infection.

3

Predisposing Factors

Inadequate sanitation facilities increase the risk that local inhabitants and travelers

will be exposed to contaminated food and water. Outbreaks of foodborne or

waterborne illnesses in both industrialized and developing countries facilitate the

spread of infectious organisms. Industrialized countries that rely on imported food

items risk the possibility of importation of contaminated food products.

4

Immunocompromised hosts, such as organ transplant recipients and patients receiving

immunosuppressive therapies, are more susceptible to intestinal infection.

Institutional settings such as day-care centers, hospitals, and extended-care facilities

are high-risk settings for dissemination of disease. Finally, poor personal hygiene is

a risk for infectious diarrhea.

Table 69-2

Pharmacologic Agents that May Promote Gastrointestinal Infection

Drug Mechanism

Antacids, H2

-receptor antagonists, proton-pump

inhibitors

Increase of gastric pH; passage of viable pathogens to

lower gut

Antibiotics Alteration of intestinal flora

Cancer chemotherapy Unclear but may include the antimicrobial activity of

chemotherapeutic agents, or chemotherapy-induced

intestinal damage and necrosis favoring an anaerobic

environment for the growth of C. difficile.

Source: DuPont HL. Acute infectious diarrhea in immunocompetent adults. N Engl J Med. 2014;370:1532; Cohen

SH et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society of

Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect

Control Hosp Epidemiol. 2010;31:431; Anand A, Glatt AE. Clostridium difficile infection associated with

antineoplastic chemotherapy: a review. Clin Infect Dis. 1993;17:109.

The use of pharmacologic agents, e.g., drugs that increase gastric pH (Table 69-2),

increases the risk for infection with acid-susceptible pathogens such as Salmonella

species and Vibrio cholerae.

5 The use of proton-pump inhibitors predisposes patients

to Clostridium difficile diarrhea.

MANAGEMENT OVERVIEW

Rehydration Therapy

The most common complication of any diarrheal illness is loss of fluids and

electrolytes, which in extreme cases can lead to hypovolemia, shock, and death.

1

Depending on the degree of dehydration, fluid and electrolyte losses are replaced

intravenously (IV) or orally. Once replacement of fluid and electrolyte losses is

completed, additional laboratory tests and drug therapies can be considered.

Laboratory Tests

Inflammatory diarrheal illnesses are characterized by the presence of bloody or

mucoid stools. Therefore, stool specimens with red blood cells (RBCs) or occult

blood, or those that contain large numbers of white blood cells, suggest infection

attributable to invasive pathogens.

6

Identification of bacterial toxins in stool specimens is a useful diagnostic tool. For

example, because only the toxigenic strains of C. difficile are pathogenic, the

presence or absence of bacterial toxins in stool specimens is more important than a

positive culture for the organism.

7

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