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Diarrhea
Updated: Jan 31, 2020
Author: Stefano Guandalini, MD, AGAF; Chief Editor: Carmen Cuffari, MD

Overview

Practice Essentials
Diarrhea is the reversal of the normal net absorptive status of water and electrolyte absorption to secretion. The
augmented water content in the stools (above the normal value of approximately 10 mL/kg/d in the infant and
young child, or 200 g/d in the teenager and adult) is due to an imbalance in the physiology of the small and large
intestinal processes involved in the absorption of ions, organic substrates, and thus water.

Signs and symptoms

Acute diarrhea is defined as the abrupt onset of 3 or more loose stools per day and lasts no longer than 14 days;
chronic or persistent diarrhea is defined as an episode that lasts longer than 14 days. The distinction has
implications not only for classification and epidemiologic studies but also from a practical standpoint, because
protracted diarrhea often has different etiologies, poses different management problems, and has a different
prognosis.

The clinical presentation and course of diarrhea therefore depend on its cause and on the host. Consider the
following to determine the source/cause of the patient’s diarrhea:

Stool characteristics (eg, consistency, color, volume, frequency)

Presence of associated enteric symptoms (eg, nausea/vomiting, fever, abdominal pain)

Use of child daycare (common pathogens: rotavirus, astrovirus, calicivirus; Campylobacter, Shigella,
Giardia, and Cryptosporidium species [spp])

Food ingestion history (eg, raw/contaminated foods, food poisoning)

Water exposure (eg, swimming pools, marine environment)

Camping history (possible exposure to contaminated water sources)

Travel history (common pathogens affect specific regions; also consider rotavirus and Shigella, Salmonella,
and Campylobacter spp regardless of specific travel history, as these organisms are prevalent worldwide)

Animal exposure (eg, young dogs/cats: Campylobacter spp; turtles: Salmonella spp)

Predisposing conditions (eg, hospitalization, antibiotic use, immunocompromised state)

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 Signs and symptoms of diarrhea may include the following:

Dehydration: Lethargy, depressed consciousness, sunken anterior fontanel, dry mucous membranes,
sunken eyes, lack of tears, poor skin turgor, delayed capillary refill

Failure to thrive and malnutrition: Reduced muscle/fat mass or peripheral edema

Abdominal pain/cramping

Borborygmi

Perianal erythema

See Clinical Presentation for more detail.

Diagnosis

Fecal laboratory studies include the following:

Examination for ova and parasites

Leukocyte count

pH level: A pH level of 5.5 or less or the presence of reducing substances indicates carbohydrate
intolerance, which is usually secondary to viral illness

Examination of exudates for presence/absence of leukocytes

Cultures: Always culture for Salmonella, Shigella, and Campylobacter spp and Y enterocolitica in the
presence of clinical signs of colitis or if fecal leukocytes are present; look for Clostridium difficile in those
with diarrhea characterized by colitis and/or bloody stools; assess for Escherichia coli, particularly O157:H7,
with bloody diarrhea and a history of eating ground beef; screen for Vibrio and Plesiomonas spp with a
history of eating raw seafood or foreign travel

Enzyme immunoassay for rotavirus or adenovirus antigens

Latex agglutination assay for rotavirus

Other laboratory studies may include the following:

Serum albumin levels: Low in protein-losing enteropathies from enteroinvasive intestinal infections (eg,
Salmonella spp, enteroinvasive E coli)

Fecal alpha1-antitrypsin levels: High in enteroinvasive intestinal infections

Anion gap to determine nature of the diarrhea (ie, osmolar vs secretory)

Intestinal biopsy: May be indicated in the presence of chronic or protracted diarrhea, as well as in cases in
which a search for a cause is believed to be mandatory (eg, in patients with acquired immunodeficiency
syndrome [AIDS] or patients who are otherwise severely immunocompromised)

See Workup for more detail.

Management

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 Acute-onset diarrhea is usually self-limited; however, an acute infection can have a protracted course.
Management is generally supportive: In most cases, the best option for treatment of acute-onset diarrhea is the
early use of oral rehydration therapy (ORT).[1]

Pharmacotherapy

Vaccines (eg, rotavirus) can help increase resistance to infection. Antimicrobial and antiparasitic agents may be
used to treat diarrhea caused by specific organisms and/or clinical circumstances. Such medications include the
following:

Cefixime

Ceftriaxone

Cefotaxime

Erythromycin

Furazolidone

Iodoquinol

Metronidazole

Paromomycin

Quinacrine

Sulfamethoxazole and trimethoprim

Vancomycin

Tetracycline

Nitazoxanide

Rifaximin

See Treatment and Medication for more detail.

Background
Acute diarrhea is defined as the abrupt onset of 3 or more loose stools per day. The augmented water content in
the stools (above the normal value of approximately 10 mL/kg/d in the infant and young child, or 200 g/d in the
teenager and adult) is due to an imbalance in the physiology of the small and large intestinal processes involved in
the absorption of ions, organic substrates, and thus water. A common disorder in its acute form, diarrhea has many
causes and may be mild to severe.

Childhood acute diarrhea is usually caused by infection of the small and/or large intestine; however, numerous
disorders may result in diarrhea, including a malabsorption syndrome and various enteropathies. Acute-onset
diarrhea is usually self-limited; however, an acute infection can have a protracted course. By far, the most common
complication of acute diarrhea is dehydration.

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 Although the term "acute gastroenteritis" is commonly used synonymously with "acute diarrhea," the former term is
a misnomer. The term gastroenteritis implies inflammation of both the stomach and the small intestine, whereas, in
reality, gastric involvement is rarely if ever seen in acute diarrhea (including diarrhea with an infectious origin); in
addition, enteritis is also not consistently present. Examples of infectious acute diarrhea syndromes that do not
cause enteritis include Vibrio cholerae– induced diarrhea and Shigella -induced diarrhea. Thus, the term acute
diarrhea is preferable to acute gastroenteritis.

Diarrheal episodes are classically distinguished into acute and chronic (or persistent) based on their duration.
Acute diarrhea is thus defined as an episode that has an acute onset and lasts no longer than 14 days; chronic or
persistent diarrhea is defined as an episode that lasts longer than 14 days. The distinction, supported by the World
Health Organization (WHO), has implications not only for classification and epidemiological studies but also from a
practical standpoint because protracted diarrhea often has a different set of causes, poses different problems of
management, and has a different prognosis.

Pathophysiology
Diarrhea is the reversal of the normal net absorptive status of water and electrolyte absorption to secretion. Such a
derangement can be the result of either an osmotic force that acts in the lumen to drive water into the gut or the
result of an active secretory state induced in the enterocytes. In the former case, diarrhea is osmolar in nature, as
is observed after the ingestion of nonabsorbable sugars such as lactulose or lactose in lactose malabsorbers.
Instead, in the typical active secretory state, enhanced anion secretion (mostly by the crypt cell compartment) is
best exemplified by enterotoxin-induced diarrhea.

In osmotic diarrhea, stool output is proportional to the intake of the unabsorbable substrate and is usually not
massive; diarrheal stools promptly regress with discontinuation of the offending nutrient, and the stool ion gap is
high, exceeding 100 mOsm/kg. In fact, the fecal osmolality in this circumstance is accounted for not only by the
electrolytes but also by the unabsorbed nutrient(s) and their degradation products. The ion gap is obtained by
subtracting the concentration of the electrolytes from total osmolality (assumed to be 290 mOsm/kg), according to
the formula: ion gap = 290 – [(Na + K) × 2].

In secretory diarrhea, the epithelial cells’ ion transport processes are turned into a state of active secretion. The
most common cause of acute-onset secretory diarrhea is a bacterial infection of the gut. Several mechanisms may
be at work. After colonization, enteric pathogens may adhere to or invade the epithelium; they may produce
enterotoxins (exotoxins that elicit secretion by increasing an intracellular second messenger) or cytotoxins. They
may also trigger release of cytokines attracting inflammatory cells, which, in turn, contribute to the activated
secretion by inducing the release of agents such as prostaglandins or platelet-activating factor. Features of
secretory diarrhea include a high purging rate, a lack of response to fasting, and a normal stool ion gap (ie, 100
mOsm/kg or less), indicating that nutrient absorption is intact.

Frequency
United States

In the United States, one estimate before the introduction of specific antirotavirus immunization in 2006 assumed a
cumulative incidence of 1 hospitalization for diarrhea per 23-27 children by age 5 years, with more than 50,000
hospitalizations. By these estimates, rotavirus was associated with 4-5% of all childhood hospitalizations and a

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 cost of nearly $ 1 billion.[2] Furthermore, acute diarrhea is responsible for 20% of physician referrals in children
younger than 2 years and for 10% in children younger than 3 years.

The impact of vaccination on rotavirus morbidity has been remarkable, with significant reduction of diarrhea-
associated hospitalizations and visits to emergency departments in children in the years 2007-2008 compared with
the prevaccine period.[3]

A study by Olortegui et al that included 2,082 children reported that 35% of the children experienced astrovirus
infections and astrovirus prevalence in diarrheal stools was 5.6%, and severity exceeded all enteropathogens
except rotavirus.[36]

International

In developing countries, an average of 3 episodes per child per year in children younger than 5 years is reported;
however, some areas report 6-8 episodes per year per child. In these settings, malnutrition is an important
additional risk factor for diarrhea, and recurrent episodes of diarrhea lead to growth faltering and substantially
increased mortality.[4] Childhood mortality associated with diarrhea has constantly but slowly declined during the
past 2 decades, mostly because of the widespread use of oral rehydration solutions; however, it appears to have
plateaued over the past several years.

Because the single most common cause of infectious diarrhea worldwide is rotavirus, and because a vaccine has
been in use for over 3 years now, a reduction in the overall frequency of diarrheal episodes is hoped for in the near
future.

A study by Lübbert et al found the incidence of Clostridium difficile infection in Germany in 2012 to be 83 cases per
100,000 population. The chance of recurrence increased with each relapse; an initial recurrence of the infection
was found in 18.2% of patients with index events, with 28.4% of these patients having a second recurrence and
30.2% of second-recurrence patients having a third recurrence.[5]

Mortality/Morbidity
Mortality from acute diarrhea is overall globally declining but remains high. Most estimates have diarrhea as the
second cause of childhood mortality, with 18% of the 10.6 million yearly deaths in children younger than age 5
years.

Despite a progressive reduction in global diarrheal disease mortality over the past 2 decades, diarrhea morbidity in
published reports from 1990-2000 slightly increased worldwide compared with previous reports. In the United
States, an average of 369 diarrhea-associated deaths/year occurred among children aged 1-59 months during
1992-1998 and 2005-2006.[6] The vast majority of diarrhea-associated infant deaths were reported in 2005-2007,
with 86% of deaths occurring among low-birthweight (< 2500 g) infants.[7]

Furthermore, in countries in which the toll of diarrhea is highest, poverty also adds an enormous additional burden,
and long-term consequences of the vicious cycle of enteric infections, diarrhea, and malnutrition are devastating.
[4]

Sex

Most cases of infectious diarrhea are not sex specific. Females have a higher incidence of Campylobacter species
infections and hemolytic uremic syndrome (HUS).

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 Age

Viral diarrhea is most common in young children. Rotavirus and adenovirus are particularly prevalent in children
younger than 2 years. Astrovirus and norovirus usually infect children younger than 5 years. Yersinia enterocolitis
typically infects children younger than 1 year, and the Aeromonas organism is a significant cause of diarrhea in
young children.

Very young children are particularly susceptible to secondary dehydration and secondary nutrient malabsorption.
Age and nutritional status appear to be the most important host factors in determining the severity and the duration
of diarrhea. In fact, the younger the child, the higher is the risk for severe, life-threatening dehydration as a result of
the high body-water turnover and limited renal compensatory capacity of very young children. Whether younger
age also means a risk of running a prolonged course is an unsettled issue. In developing countries, persistent
postenteritis diarrhea has a strong inverse correlation with age.

Presentation

History
Acute diarrhea in developed countries is almost invariably a benign, self-limited condition, subsiding within a few
days. The clinical presentation and course of illness depend on the etiology of the diarrhea and on the host. For
example, rotavirus is more commonly associated with vomiting, dehydration, and a greater number of work days
lost than nonrotavirus gastroenteritis.

A prospective study conducted in the United States in 604 children aged 3-36 months in community settings
before the introduction of rotavirus vaccine found that the highest incidence of acute diarrhea was in
January and August, with an overall incidence of 2.21 episodes per person-year.[8] Close to 90% of
episodes were acute (ie, lasting < 14 d, with a median duration of 2 d and a median of 6 stools per day).

Diarrhea implies an increase in stool volume and diminished stool consistency.

In children younger than 2 years, diarrhea is defined as daily stools with a volume greater than 10
mL/kg.

In children older than 2 years, diarrhea is defined as daily stools with a weight greater than 200 g. In
practice, this typically means loose-to-watery stools passed 3 or more times per day.

Individual stool patterns widely vary; for example, breastfed children may normally have 5-6 stools
per day.

Flatulence associated with foul-smelling stools that float suggests fat malabsorption, which can be observed
with infection with Giardia lamblia.

Knowledge of the characteristics of consistency, color, volume, and frequency can be helpful in determining
whether the source is from the small or large bowel. Table 1 outlines these characteristics and
demonstrates that an index of suspicion can be easily generated for a specific set of organisms.

Table 1. Stool Characteristics and Determining Their Source (Open Table in a new window)

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 Stool Small Bowel Large Bowel
Characteristics

Appearance Watery Mucoid and/or bloody

Volume Large Small

Frequency Increased Highly increased

Possibly positive but never

Blood Commonly grossly bloody
gross blood

pH Possibly < 5.5 >5.5

Reducing
Possibly positive Negative
substances

WBCs < 5/high power field Commonly >10/high power field

Serum WBCs Normal Possible leukocytosis, bandemia

Invasive bacteria

Escherichia Coli (enteroinvasive,

Viral enterohemorrhagic)

Rotavirus Shigella species

Adenovirus Salmonella species

Calicivirus Campylobacter species

Astrovirus Yersinia species

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 Norovirus Aeromonas species

Plesiomonas species

Organisms
Enterotoxigenic bacteria

E coli

Klebsiella Toxic bacteria

Clostridium perfringens Clostridium difficile

Cholera species

Vibrio species

Parasites
Parasites
Giardia species
Entamoeba organisms
Cryptosporidium species

See the list below:

Associated systemic symptoms include the following:

Some enteric infections commonly have systemic symptoms, whereas others less commonly are
associated with systemic features.

Table 2 outlines the frequency of some of these symptoms with particular organisms. It also outlines
incubation periods and usual duration of symptoms of common organisms. Certain organisms (eg, C
difficile, Giardia, Entamoeba species) may be associated with a protracted course.

Table 2. Organisms and Frequency of Symptoms (Open Table in a new window)

Organism Incubation Duration Vomiting Fever Abdominal Pain

Rotavirus 1-7 d 4-8 d Yes Low No

Adenovirus 8-10 d 5-12 d Delayed Low No

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 Norovirus 1-2 d 2d Yes No No

Astrovirus 1-2 d 4-8 d +/- +/- No

Calicivirus 1-4 d 4-8 d Yes +/- No

Aeromonas species None 0-2 wk +/- +/- No

Campylobacter species 2-4 d 5-7 d No Yes Yes

C difficile Variable Variable No Few Few

C perfringens Minimal 1d Mild No Yes

Enterohemorrhagic E coli 1-8 d 3-6 d No +/- Yes

Enterotoxigenic E coli 1-3 d 3-5 d Yes Low Yes

Plesiomonas species None 0-2 wk +/- +/- +/-

Salmonella species 0-3 d 2-7 d Yes Yes Yes

Shigella species 0-2 d 2-5 d No High Yes

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 Vibrio species 0-1 d 5-7 d Yes No Yes

Y enterocolitica None 1-46 d Yes Yes Yes

Giardia species 2 wk 1+ wk No No Yes

Cryptosporidium species 5-21 d Months No Low Yes

Entamoeba species 5-7 d 1-2+ wk No Yes No

See the list below:

Daycare considerations are as follows:

Certain organisms are spread quickly in daycare. These organisms include rotavirus; astrovirus;
calicivirus; and Campylobacter, Shigella, Giardia, and Cryptosporidium species.

Increase in daycare usage has raised the incidence of rotavirus and Cryptosporidium species.

Food history can be helpful.

Ingestion of raw or contaminated food is a common cause of infectious diarrhea.

Organisms that cause food poisoning include the following:

Dairy food -Campylobacter and Salmonella species

Eggs -Salmonella species

Meats -C perfringens and Aeromonas, Campylobacter, and Salmonella species

Ground beef - Enterohemorrhagic E coli

Poultry -Campylobacter species

Pork -C perfringens, Y enterocolitica

Seafood - Astrovirus and Aeromonas, Plesiomonas, and Vibrio species

Oysters - Calicivirus and Plesiomonas and Vibrio species

Vegetables -Aeromonas species and C perfringens

Guidelines on fruit juice intake for children by the American Academy of Pediatrics recommend that

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 in the evaluation of children with chronic diarrhea, excessive flatulence, abdominal pain, and
bloating, the pediatrician should determine the amount of juice being consumed. [9]

Water exposure can contribute to diarrhea.

Water is a major reservoir for many organisms that cause diarrhea.

Swimming pools have been associated with outbreaks of infection with Shigella species; Aeromonas
organisms are associated with exposure to the marine environment.

Giardia, Cryptosporidium, and Entamoeba organisms are resistant to water chlorination; therefore,
exposure to contaminated water should raise index of suspicion for these parasites.

A history of camping suggests exposure to water sources contaminated with Giardia organisms.

Travel history may indicate a cause for diarrhea.

Enterotoxigenic E coli is the leading cause of traveler's diarrhea.

Rotavirus and Shigella, Salmonella, and Campylobacter organisms are prevalent worldwide and
need to be considered regardless of specific travel history.

Risk of contracting diarrhea while traveling is, by far, highest for persons traveling to Africa.

Travel to Central and South America and Eastern European countries is also associated with a
relatively high risk of contracting diarrhea.

Other organisms that are prevalent in particular parts of the world include the following:

Nonspecific foreign travel history - Enterotoxigenic E coli and Aeromonas, Giardia,

Plesiomonas, Salmonella, and Shigella species

Underdeveloped tropical visit -C perfringens

Travel to Africa -Entamoeba species, Vibrio cholerae

Travel to South America and Central America -Entamoeba species, V cholerae,

enterotoxigenic E coli

Travel to Asia -V cholerae

Travel to Australia -Yersinia species

Travel to Canada -Yersinia species

Travel to Europe -Yersinia species

Travel to India -Entamoeba species, V cholerae

Travel to Japan -Vibrio parahaemolyticus

Travel to Mexico -Aeromonas, Entamoeba, Plesiomonas, and Yersinia species

New Guinea -Clostridium species

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 Animal exposure can contribute to diarrhea.

Exposure to young dogs or cats is associated with Campylobacter organisms.

Exposure to turtles is associated with Salmonella organisms.

Certain medical conditions predispose patients to infection, including the following:

C difficile - Hospitalization, antibiotic administration

Plesiomonas species - Liver diseases or malignancy

Salmonella species - Intestinal dysmotility, malnutrition, achlorhydria, hemolytic anemia (especially

sickle cell disease), immunosuppression, malaria

Rotavirus - Hospitalization

Giardia species -Agammaglobulinemia, chronic pancreatitis, achlorhydria, cystic fibrosis

Cryptosporidia species - Immunocompromised or immunosuppressed state

Physical
The following may be observed:

Dehydration

Dehydration is the principal cause of morbidity and mortality.

Assess every patient with diarrhea for signs, symptoms, and severity.

Lethargy, depressed consciousness, sunken anterior fontanel, dry mucous membranes, sunken
eyes, lack of tears, poor skin turgor, and delayed capillary refill are obvious and important signs of
dehydration. Table 3 below details dehydration severity and symptoms.

Table 3. Dehydration Severity, Signs, and Symptoms (Open Table in a new window)

0-5% Dehydration 5-10% Dehydration 10% or More

Hydration
(Mild) (Moderate) (Severe)

General Well Restless Lethargic

Eyes Normal Sunken Very sunken

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 Tears Present Absent Absent

Mouth Moist Dry Very dry

Thirst Drinks normally Thirsty Drinks poorly

Skin Pinch retracts immediately Pinch retracts slowly Pinch stays folded

See the list below:

Failure to thrive and malnutrition

Reduced muscle and fat mass or peripheral edema may be clues to the presence of carbohydrate,
fat, and/or protein malabsorption.

Giardia organisms can cause intermittent diarrhea and fat malabsorption.

Abdominal pain

Nonspecific nonfocal abdominal pain and cramping are common with some organisms.

Pain usually does not increase with palpation.

With focal abdominal pain worsened by palpation, rebound tenderness, or guarding, be alert for
possible complications or for another noninfectious diagnosis.

Borborygmi: Significant increases in peristaltic activity can cause an audible and/or palpable increase in
bowel activity.

Perianal erythema

Frequent stools can cause perianal skin breakdown, particularly in young children.

Secondary carbohydrate malabsorption often results in acidic stools.

Secondary bile acid malabsorption can result in a severe diaper dermatitis that is often characterized
as a "burn."

Causes

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 Although infectious agents are by far the most common cause for sporadic or endemic episodes of acute diarrhea,
one should not dismiss other causes that can lead to the same presentation.

Causes of diarrhea with acute onset include the following:

Infections

Enteric infections (including food poisoning

Extraintestinal infections

Drug-induced

Antibiotic-associated

Laxatives

Antacids that contain magnesium

Opiate withdrawal

Other drugs

Food allergies or intolerances

Cow's milk protein allergy

Soy protein allergy

Multiple food allergies

Olestra

Methylxanthines (caffeine, theobromine, theophylline)

Disorders of digestive/absorptive processes

Glucose-galactose malabsorption

Sucrase-isomaltase deficiency

Late-onset (adult-type) hypolactasia, resulting in lactose intolerance

Chemotherapy or radiation-induced enteritis

Surgical conditions

Acute appendicitis

Intussusception

Vitamin deficiencies

Niacin deficiency

Folate deficiency

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 Vitamin toxicity

Vitamin C

Niacin, vitamin B3

Ingestion of heavy metals or toxins (eg, copper, tin, zinc)

Ingestion of plants (eg, hyacinths, daffodils, azalea, mistletoe, Amanita species mushrooms

Infectious causes of acute diarrhea in developed countries

Viruses

Rotavirus - 25-40% of cases

Norovirus - 10-20% of cases

Calicivirus - 1-20% of cases

Astrovirus - 4-9% of cases

Enteric-type adenovirus - 2-4% of cases

Bacteria

Campylobacter jejuni - 6-8% of cases

Salmonella - 3-7% of cases

E Coli - 3-5% of cases

Shigella - 0-3% of cases

Y enterocolitica - 1-2% of cases

C difficile - 0-2% of cases

Vibrio parahaemolyticus - 0-1% of cases

V cholerae - Unknown

Aeromonas hydrophila - 0-2% of cases

Parasites

Cryptosporidium - 1-3% of cases

G lamblia - 1-3% of cases

A study by Yi et al of 207 stool samples from hospitalized children in metropolitan Atlanta, Ga, with health-care–
associated vomiting and/or diarrhea found that 20 children (10%) were positive for rotavirus and 7 children (3%)
were positive for norovirus. The results indicated that these pathogens have an important role in pediatric
nosocomial illness.[10]

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 DDx

Differential Diagnoses
Appendicitis

Carcinoid Tumor

Giardiasis

Glucose-galactose malabsorption

Intestinal Enterokinase Deficiency

Intestinal Protozoal Diseases

Intussusception

Meckel Diverticulum Imaging

Microvillus Inclusion Disease

Pediatric Crohn Disease

Pediatric Hyperthyroidism

Pediatric Irritable Bowel Syndrome (IBS)

Pediatric Malabsorption Syndromes

Pediatric Short Bowel Syndrome

Protein Intolerance

Shigella Infection

Sinonasal Manifestations of Cystic Fibrosis

Ulcerative Colitis Imaging

Workup

Workup

Laboratory Studies
The following may be noted in patients with diarrhea:

In patients with diarrhea, a stool pH level of 5.5 or less or presence of reducing substances indicates
carbohydrate intolerance, which is usually secondary to viral illness and transient in nature.

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 Enteroinvasive infections of the large bowel cause leukocytes, predominantly neutrophils, to be shed into
stool. Absence of fecal leukocytes does not eliminate the possibility of enteroinvasive organisms. However,
presence of fecal leukocytes eliminates consideration of enterotoxigenic E coli, Vibrio species, and viruses.

Examine any exudates found in stool for leukocytes. Such exudates highly suggest colitis (80% positive
predictive value). Colitis can be infectious, allergic, or part of inflammatory bowel disease (Crohn disease,
ulcerative colitis).

Many different culture mediums are used to isolate bacteria. Table 3 lists common bacteria and optimum
culture mediums for their growth. A high index of suspicion is needed to choose the appropriate medium.

With stool not cultured within 2 hours of collection, refrigerate at 4°C or place in a transport medium.
Although stool cultures are useful when positive, yield is low.

Always culture stool for Salmonella, Shigella, and Campylobacter organisms and Y enterocolitica in the
presence of clinical signs of colitis or if fecal leucocytes are found.

Look for C difficile in persons with episodes of diarrhea characterized by colitis and/or blood in the stools.
Remember that acute-onset diarrheal episodes associated with C difficile may also occur without a history
of antibiotic use.

Bloody diarrhea with a history of ground beef ingestion must raise suspicion for enterohemorrhagic E coli. If
E coli is found in the stool, determine if the type of E coli is O157:H7. This type of E coli is the most
common, but not only, cause of HUS.

History of raw seafood ingestion or foreign travel should prompt additional screening for Vibrio and
Plesiomonas species.

Table 4. Common Bacteria and Optimum Culture Mediums (Open Table in a new window)

Organism Detection Method Microbiologic Characteristics

Aeromonas Oxidase-positive flagellated gram-

Blood agar
species negative bacillus (GNB)

Rapidly motile curved gram-negative rod

Campylobacter
Skirrow agar (GNR); Campylobacter jejuni 90% and
species
Campylobacter coli 5% of infections

Cycloserine-cefoxitin-fructose-egg (CCFE) Anaerobic spore-forming gram-positive

C difficile agar; enzyme immunoassay (EIA) for toxin; rod (GPR); toxin-mediated diarrhea;
latex agglutination (LA) for protein produces pseudomembranous colitis

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 C perfringens None available Anaerobic spore-forming GPR; toxin-
mediated diarrhea

MacConkey eosin-methylene blue (EMB) or

E coli Lactose-producing GNR
Sorbitol-MacConkey (SM) agar

Plesiomonas
Blood agar Oxidase-positive GNR
species

Blood, MacConkey EMB, xylose-lysine-

Salmonella
deoxycholate (XLD), or Hektoen enteric Nonlactose non–H2S-producing GNR
species
(HE) agar

See the list below:

Culture mediums used to isolate bacteria include the following:

Blood agar - All aerobic bacteria and yeast; detects cytochrome oxidase production

MacConkey EMB agar - Inhibits gram-positive organisms; permits lactose fermentation

XLD agar; HE agar - Inhibits gram-positive organisms and nonpathogenic GNB; permits lactose
fermentation H2S production

Skirrow agar - Selective for Campylobacter species

SM agar - Selective for enterohemorrhagic E coli

CIN agar - Selective for Y enterocolitica

TCBS agar - Selective for Vibrio species

CCFE agar - Selective for C difficile

Rotavirus antigen can be identified by enzyme immunoassay and latex agglutination assay of the stool. The
false-negative rate is approximately 50%, and false-positive results occur, particularly in the presence of
blood in the stools.

Adenovirus antigens can be detected by enzyme immunoassay. Only serotypes 40 and 41 are able to
induce diarrhea.

Examination of stools for ova and parasites is best for finding parasites. Perform stool examination every 3
days or every other day.

The leukocyte count is usually not elevated in viral-mediated and toxin-mediated diarrhea. Leukocytosis is

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 often but not constantly observed with enteroinvasive bacteria. Shigella organisms cause a marked
bandemia with a variable total white blood cell count.

At times, a protein-losing enteropathy can be found in patients with extensive inflammation in the course of
enteroinvasive intestinal infections (eg, Salmonella species, enteroinvasive E coli). In these circumstances,
low serum albumin levels and high fecal alpha1-antitrypsin levels can be found.

Other Tests
Because the pathogenesis of diarrhea can be either osmolar (due to the presence of an excess of unabsorbed
substrates in the gut lumen) or secretory (due to active anion secretion from the enterocytes), the anion gap in the
stools is occasionally used to ascertain the nature of the diarrhea. The stool anion gap is calculated according to
the formula: 290 - [(Na+K) X 2]. If the value is more than 100, osmolar diarrhea can be assumed to be present. If
the value is less than 100, the diarrhea has a secretory origin.

Procedures
Intestinal biopsy is not required in evaluating an otherwise healthy child with acute-onset diarrhea, but it may be
indicated in the presence of chronic or protracted diarrhea, as well as in cases in which a search for a cause is
believed to be mandatory (eg, in patients with acquired immunodeficiency syndrome [AIDS] or patients who are
otherwise severely immunocompromised).

Treatment

Medical Care
In 2003 the Center for Disease Control (CDC) put forth recommendations for the management of acute pediatric
diarrhea in both the outpatient and inpatient settings including indication for referral.[1]

Indications for medical evaluation of children with acute diarrhea include the following:

Younger than 3 months

Weight of less than 8 kg

History of premature birth, chronic medical conditions, or concurrent illness

Fever of 38ºC or higher in infants younger than 3 months or 39ºC or higher in children aged 3-36 months

Visible blood in the stool

High-output diarrhea

Persistent emesis

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 Signs of dehydration as reported by caregiver, including sunken eyes, decreased tears, dry mucous
membranes, and decreased urine output

Mental status changes

Inadequate responses to oral rehydration therapy (ORT) or caregiver unable to administer ORT

The report also includes information on assessment of dehydration and what steps should be taken to adequately
treat acute diarrhea.

Treatment of dehydration due to diarrhea includes the following:

Minimal or no dehydration

Rehydration therapy - Not applicable

Replacement of losses

Less than 10 kg body weight - 60-120 mL oral rehydration solution for each diarrhea stool or
vomiting episode

More than 10 kg body weight - 120-140 mL oral rehydration solution for each diarrhea stool or
vomiting episode

Mild-to-moderate dehydration

Rehydration therapy - Oral rehydration solution (50-100 mL/kg over 3-4 h)

Replacement of losses

Less than 10 kg body weight - 60-120 mL oral rehydration solution for each diarrhea stool or
vomiting episode

More than 10 kg body weight - 120-140 mL oral rehydration solution for each diarrhea stool or
vomiting episode

Severe dehydration

Rehydration therapy - Intravenous lactated Ringer solution or normal saline (20 mL/kg until perfusion
and mental status improve), followed by 100 mL/kg oral rehydration solution over 4 hours or 5%
dextrose (half normal saline) intravenously at twice maintenance fluid rates

Replacement of losses

Less than 10 kg body weight - 60-120 mL oral rehydration solution for each diarrhea stool or
vomiting episode

More than 10 kg body weight - 120-140 mL oral rehydration solution for each diarrhea stool or
vomiting episode

If unable to drink, administer through nasogastric tube or intravenously administer 5%

dextrose (one fourth normal saline) with 20 mEq/L potassium chloride

ORT is the cornerstone of treatment, especially for small-bowel infections that produce a large volume of watery
stool output. ORT with a glucose-based oral rehydration syndrome must be viewed as by far the safest, most

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 physiologic, and most effective way to provide rehydration and maintain hydration in children with acute diarrhea
worldwide, as recommended by the WHO; by the ad hoc committee of European Society for Pediatric
Gastroenterology, Hepatology and Nutrition (ESPGHAN); and by the American Academy of Pediatrics.[11]
However, the global use of ORT is still insufficient. Developed countries, in particular the United States, seem to be
lagging behind despite studies that demonstrate beyond doubt the efficacy of ORT in emergency care settings, in
which intravenous rehydration unduly continues to be widely privileged.

Not all commercial ORT formulas promote optimal absorption of electrolytes, water, and nutrients. The ideal
solution has a low osmolarity (210-250) and a sodium content of 50-60 mmol/L. Administer maintenance fluids plus
replacement of losses. Educate caregivers in methods necessary to replace this amount of fluid. Administer small
amounts of fluid at frequent intervals to minimize discomfort and vomiting. A 5-mL or 10-mL syringe without a
needle is a very useful tool. The syringe can be quickly used to place small amounts of fluid in the mouth of a child
who is uncooperative. Once the child becomes better hydrated, cooperation improves enough to take small sips
from a cup. This method is time intensive and requires a dedicated caregiver. Encouragement from the physician is
necessary to promote compliance. Oral rehydration is now universally recommended to be completed within 4
hours.

The addition of zinc to oral rehydration solution has been proven effective in children with acute diarrhea in
developing countries and is recommended by the WHO.[12] However, no evidence suggests efficacy in children
living in developed countries, in which the prevalence of zinc deficiency is assumed to be extremely low.

The composition of almost all other beverages (carbonated or not) that are commercially available and frequently
used in children with diarrhea is completely inadequate for rehydration or for maintaining hydration, considering the
sodium content, which is invariably extremely low, and osmolarity that is often dangerously elevated. For instance,
Coca-Cola, Pepsi-Cola, and apple juice have an osmolarity of 493, 576, and 694-773, respectively.

However, research conducted in a community clinic in Nicaragua indicated that green tea and pomegranate extract
combined with a standard oral rehydration solution help children with diarrhea improve faster.[13] Results showed
the average time to achieve a Bristol Stool Scale (BSS) score of 4 or less was significantly shorter in the extract
group than in the control group (3.1 vs 9.2 hours, respectively). In addition, a BSS score of 4 or less in the first
bowel movement after treatment was achieved by more patients in the extract group than the control group (60%
vs 29%, respectively). BSS scores in the extract group were maintained on day 2.[13]

At completion of hydration, resumption of feeding is strongly recommended. In fact, many studies convincingly
demonstrate that early refeeding hastens recovery. Also, robust evidence suggests that, in the vast majority of
episodes of acute diarrhea, refeeding can be accomplished without the use of any special (eg, lactose-free or soy-
based) formulas.

Antimotility agents are not indicated for infectious diarrhea, except for refractory cases of Cryptosporidium
infection. Antimicrobial therapy is indicated for some nonviral diarrhea because most is self-limiting and does not
require therapy.

Therapies recommended for some nonviral diarrheas include the following:

Aeromonas species: Use cefixime and most third-generation and fourth-generation cephalosporins.

Campylobacter species: Erythromycin shortens illness duration and shedding.

C difficile: Discontinue potential causative antibiotics. If antibiotics cannot be stopped or this does not result
in resolution, use oral metronidazole or vancomycin. Vancomycin is reserved for the child who is seriously
ill.

C perfringens: Do not treat with antibiotics.

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 Cryptosporidium parvum: Administer paromomycin; however, effectiveness is not proven. Nitazoxanide, a
newer anthelmintic, is effective against C parvum.

Entamoeba histolytica: Metronidazole followed by iodoquinol or paromomycin is administered in

symptomatic patients. Asymptomatic carriers in nonendemic areas should receive iodoquinol or
paromomycin.

E coli: Trimethoprim-sulfamethoxazole (TMP-SMX) should be administered if moderate or severe diarrhea

is noted; antibiotic treatment may increase likelihood of hemolytic-uremic syndrome (HUS). Parenteral
second-generation or third-generation cephalosporin is indicated for systemic complications.

G lamblia: Metronidazole or nitazoxanide can be used.

Plesiomonas species: Use TMP-SMX or any cephalosporin.

Salmonella species: Treatment prolongs carrier state, is associated with relapse, and is not indicated for
nontyphoid-uncomplicated diarrhea. Treat infants younger than 3 months and high-risk patients (eg,
immunocompromised, sickle cell disease). TMP-SMX is first-line medication; however, resistance occurs.
Use ceftriaxone and cefotaxime for invasive disease.

Shigella species: Treatment shortens illness duration and shedding but does not prevent complications.
TMP-SMX is first-line medication; however, resistance occurs. Cefixime, ceftriaxone, and cefotaxime are
recommended for invasive disease.

V cholerae: Treat infected individuals and contacts. Doxycycline is the first-line antibiotic, and erythromycin
is second-line antibiotic.

Yersinia species: TMP-SMX, cefixime, ceftriaxone, and cefotaxime are used. Treatment does not shorten
disease duration; reserve for complicated cases.

Consultations
See the list below:

Surgeon

Certain organisms cause abdominal pain and bloody stools.

Symptoms resembling appendicitis, hemorrhagic colitis, intussusception, or toxic megacolon may be

appreciated.

If the infectious etiology in individuals with such symptoms is not certain, seek consultation with a
surgeon.

Infectious-disease specialist: Consider consultation with an infectious-disease specialist for any patient who
is immunocompromised because of HIV infection, chemotherapy, or immunosuppressive drugs because
atypical organisms are more likely, and complications can be more serious and fulminate.

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 Diet
Breastfed infants with acute diarrhea should be continued on breast milk without any need for interruption. In fact,
breastfeeding not only has a well-known protective effect against the development of enteritis, it also promotes
faster recovery and provides improved nutrition. This is even more important in developing countries, where with-
drawal of breastfeeding during diarrhea has been shown to have a deleterious effect on the development of
dehydration in infants with acute watery diarrhea.

Bananas, rice, applesauce, and toast diet

A banana, rice, applesauce, and toast (BRAT) diet was introduced in the United States in 1926 and
has enjoyed vast popularity. However, no evidence shows that this diet is useful, and its poor protein
content may be a contraindication; therefore, it is not recommended.

A strong body of evidence now suggests that resuming the prediarrhea diet is perfectly safe and
must be encouraged, obviously respecting any (usually temporary) lack of appetite.

Lactose ingestion

Although rotavirus can cause secondary transient lactose intolerance, this finding is believed to be
generally not clinically relevant; use lactose-containing formulas in all individuals with diarrhea.

In an incident of worsening of diarrhea proven to be secondary to a clinically important lactose

malabsorption in infants positive for rotavirus, a very transient use of lactose-free formulas (5-6 d)
can be considered.

Guidelines

Guidelines Summary
British Society of Gastroenterology guidelines for the investigation of chronic diarrhoea in adults[35]

Clinical assessment

Recommend a careful detailed history to plan investigations.

Recommend screening blood tests for the exclusion of anemia, celiac disease, etc, as well as stool tests for
inflammation.
Recommend making a positive diagnosis of irritable bowel syndrome (IBS) following basic blood and stool
screening tests.

Cancer or inflammation

Recommend excluding colorectal cancer in those with altered bowel habit ± rectal bleeding by colonoscopy.
Suggest use of testing for fecal blood loss by fecal immunochemical testing in primary or secondary care,
either as an exclusion test or to guide priority of investigations in those with lower gastrointestinal symptoms
(chronic diarrhea) but without rectal bleeding.
Fecal calprotectin is recommended to exclude colonic inflammation in those suspected with IBS and under
the age of 40.

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 Secondary clinical assessment

If symptoms persist despite normal first-line investigations and treatment, then referral for further
investigations is recommended.
We recommend blood and stool tests to exclude malabsorption and common infections (especially in the
immunocompromised or elderly).

Common disorders

In those with functional bowel or IBS-diarrhea, a positive diagnosis of bile acid diarrhea should be made
either by selenium-75-homocholic acid taurine ( 75SeHCAT) testing or serum bile acid precursor 7α-
hydroxy-4-cholesten-3-one (7αHCO, or 7αC4) (depending on local availability).
Recommend colonoscopy with biopsies of the right and left colon (not rectal) to exclude microscopic colitis.

Malabsorption

If lactose maldigestion is suspected, suggest hydrogen breath testing (if available) or withdrawal of dietary
lactose/carbohydrates from the diet.
Magnetic resonance (MR) enterography (MRE) is recommended for evaluation of small bowel abnormalities
depending on availability.
Video capsule endoscopy (VCE) is recommended for assessing small bowel abnormalities depending on
local availability.
We do not recommend small bowel barium follow through or barium enteroclysis for the evaluation of small
bowel abnormalities because of its poor sensitivity and specificity.
Recommend enteroscopy only for targeted lesions identified by MRE or VCE and not for diagnosis of
chronic diarrhea.
Recommend fecal elastase testing when fat malabsorption is suspected. We do not recommend para-
aminobenzoic acid (PABA) testing.
MR imaging (MRI) (rather than computed tomography (CT)) is recommended for assessing structural
anomalies of the pancreas in suspected chronic pancreatitis.
If small bowel bacterial overgrowth is suspected, we recommend an empirical trial of antibiotics, as there is
insufficient evidence to recommend routine hydrogen or methane breath testing.

Surgical and structural disorders

We recommend use of anorectal manometry and endoanal ultrasound only when other local pathology has
been excluded and conservative measures exhausted.
Recommend radiologic modalities for the investigation of fistulae—MRI or CT with contrast follow through.

Rare causes

Diarrhea due to hormone secreting tumors is rare; hence, we recommend testing only when other causes of
diarrhea have been excluded.

Canadian Association of Gastroenterology (CAG) diagnostic and treatment guidelines for bile acid diarrhea (BAD)

The Canadian Association of Gastroenterology (CAG) has issued guidelines on the diagnosis and treatment of bile
acid diarrhea (BAD).[37]

Diagnosis of bile acid diarrhea

In patients with chronic nonbloody diarrhea, the initial assessment for suspected bile acid diarrhea (BAD) should
be based on risk factors (history of cholecystectomy, terminal ileal resection, radiotherapy) rather than symptoms.

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 In patients with chronic diarrhea, including diarrhea-predominant irritable bowel syndrome (IBS-D) and functional
diarrhea, 75selenium homocholic acid taurine (SeHCAT) testing or 7α-hydroxy-4-cholesten-3-one (C4) assay is
recommended to evaluate for BAD. SeHCAT testing is also recommended in patients with persistent diarrhea who
have Crohn disease of the small intestine without objective evidence of inflammation. The guidelines do not take a
position for or against the use of fibroblast growth factor 19 (FGF19) assay for BAD diagnosis.

In patients with suspected BAD, SeHCAT testing is preferred over initiation of empiric bile acid sequestrant therapy
(BAST) to establish diagnosis.

Induction therapy for bile acid diarrhea

In patients with type 1 or type 3 BAD, any remediable causes (eg, Crohn disease, microscopic colitis, small
intestinal bacterial overgrowth [SIBO]) should be treated along with BAD to induce a clinical response.

In patients with BAD, cholestyramine treatment is preferred over no treatment to induce a clinical response.
Cholestyramine is preferred over other BASTs as initial therapy except in patients who cannot tolerate
cholestyramine.

In patients who are receiving empiric BAST, the daily dose should be gradually titrated to minimize adverse effects.

BAST is discouraged in patients with Crohn disease with extensive ileal involvement or resection.

Patients with BAD who have recurrent or worsening symptoms despite stable BAST therapy should be re-
evaluated diagnostically.

Concurrent medications should be reviewed in patients being considered for BAST therapy to minimize the
possibility of drug interactions.

Maintenance treatment for bile acid diarrhea

In patients with BAD in whom BAST elicits a response, a trial of intermittent on-demand dosing is recommended.

Patients who are unable to tolerate BAST should receive alternative antidiarrheal agents instead of no treatment to
alleviate long-term symptoms.

Empiric BAST being given as maintenance therapy should be administered at the lowest dose necessary to
minimize symptoms. The guidelines do not take a position on whether to recommend for or against measuring fat-
soluble vitamin levels at baseline and annually thereafter.

Medication

Medication Summary
Diarrheal diseases have been the object of numerous forms of treatment, both dietetic and pharmacologic, for
centuries. However, the evidence is now clear that, in most cases, the best option for treatment of acute-onset
diarrhea is the early use of oral rehydration therapy (ORT).[1] Pharmacological treatment is rarely of any use, and
antidiarrheal drugs are often harmful.

In terms of recommended antimicrobial treatment in the immunocompetent host, enteric bacterial and protozoan
pathogens can be grouped as follows:

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 Agents for whom antimicrobial therapy is always indicated: The consensus includes only V cholerae, Shigella
species, and G lamblia.

Agents for whom antimicrobial therapy is indicated only in selected circumstances, include the following:

Infections by enteropathogenic E coli, when running a prolonged course

Enteroinvasive E coli, based on the serologic, genetic, and pathogenic similarities with Shigella

Yersinia infections in subjects with sickle cell disease

Salmonella infections in very young infants, if febrile or with positive blood culture findings

Probiotics

Recently, some strains of probiotics (defined as live microorganisms that when ingested in adequate doses,
provide a benefit to the host) have been found to be effective as an adjunct when treating children with acute
diarrhea. Data from well-conducted randomized controlled trials on efficacy of probiotics in children with diarrhea
are definitely positive. They consistently show a statistically significant benefit and moderate clinical benefit of a
few, now well-identified probiotic strains (mostly Lactobacillus GG and Saccharomyces boulardii but also
Lactobacillus reuteri) in the treatment of acute watery diarrhea (primarily rotaviral) in infants and young children in
developed countries.

Such a beneficial effect seems to result in a reduction of the duration of diarrhea of about one day and seems to be
exerted mostly on rotaviral diarrhea, with much less evidence of efficacy in invasive bacterial diarrhea. The effect is
not only strain-dependent but also dose-dependent, with doses of at least 5 billion/d being required for effect.[14]
Shortening the duration of diarrhea by one day may not appear to be hugely beneficial. However, in consideration
of the high morbidity of the infection, even a reduction of this order is indeed desirable because it affords
considerable savings in terms of loss of working days and direct health costs.

Furthermore, probiotics may reduce the risk of spreading rotavirus infection by shortening diarrhea duration and
volume of watery stool output and by reducing the fecal shedding of rotavirus, and they have been found useful in
preventing the dissemination of hospital-acquired diarrheas.

A recent position paper jointly published by the ESPGHAN and the European Society for Pediatric Infectious
Disease (ESPID) stated, ‘‘Probiotics may be an effective adjunct to the management of diarrhea. However,
because there is no evidence of efficacy for many preparations, we suggest the use of probiotic strains with proven
efficacy and in appropriate doses for the management of children with acute gastroenteritis as an adjunct to
rehydration therapy (II, B). The following probiotics showed benefit in meta-analyses of randomized controlled
trials: Lactobacillus GG (I, A) and S boulardii (II, B).’’

Table 5 illustrates current assessment of the efficacy of probiotics in conditions characterized by diarrhea.

Table 5. Probiotic Efficacy in Diarrhea (Open Table in a new window)

Evidence of
Patients and Efficacy
Condition Most-Studied Probiotics
Controls
(- to +++)

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 Lactobacillus GG

Bifidobacterium lactis

Prevention of Daycare Lactobacillus reuteri

2000 +
Diarrhea
Lactobacillus casei

Bifidobacterium bifidum +
Streptococcus thermophilus

Prevention of Nosocomial
1000 Lactobacillus GG ++
Diarrhea

Lactobacillus GG
Prevention of Antibiotic-
2000 +++
Associated Diarrhea Saccharomyces boulardii

Lactobacillus GG
Infectious Diarrhea 3500 +++
Saccharomyces boulardii

Persistent Diarrhea 460 Lactobacillus GG +

Antibiotic and antiparasitics agents

Class Summary
Antimicrobial agents, in addition to the immune system, help destroy offending organisms. Their use is confined to
specific etiologies and/or clinical circumstances.

Cefixime (Suprax)
Potent long-acting oral cephalosporin with increased gram-negative coverage. Inhibits bacterial cell wall synthesis

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 by binding to 1 or more PBPs. Bacteria eventually lyse because of ongoing activity of cell wall autolytic enzymes
while cell wall assembly is arrested.

Ceftriaxone (Rocephin)
A third-generation cephalosporin antibiotic with activity against gram-positive and some gram-negative bacteria.
Binds to PBPs, inhibiting bacterial cell wall growth.

Cefotaxime (Claforan)
Third-generation cephalosporin antibiotic with activity against gram-positive and some gram-negative bacteria.
Binds to PBPs, inhibiting bacterial cell wall growth.

Erythromycin (E.E.S., E-Mycin, Eryc, Ery-Tab, Erythrocin)

Bacteriostatic macrolide with activity against most gram-positive organisms and atypical respiratory organisms.
Useful for Campylobacter species and vibrio enteritis.

Furazolidone (Furoxone)
Antiparasitic agent with wide coverage. Nitrofuran with antiprotozoal activity. Alternative drug for children because
availability in liquid suspension. Most common adverse effects are GI upset and brown discoloration of urine.

Iodoquinol (Vytone, Yodoxin)

Antiparasitic agents with wide coverage.

Metronidazole (Flagyl)
Very active against Giardia species, gram-negative anaerobes, and Entamoeba species. Imidazole ring-based
antibiotic active against various anaerobic bacteria and protozoa. Often used in combination with other
antimicrobial agents except for C difficile enterocolitis).

Paromomycin (Humatin)
Amebicidal and antibacterial aminoglycoside obtained from a strain of Streptomyces rimosus, active in intestinal
amebiasis. Recommended for treatment of Diphyllobothrium latum, Taenia saginata, T solium, Dipylidium caninum,
and Hymenolepis nana.

Quinacrine (Atabrine)
Very effective antiparasitic against Giardia species.

Sulfamethoxazole and trimethoprim (Bactrim, Septra, Cotrim)

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 Folate-synthesis blocker with wide antibiotic coverage. Inhibits bacterial growth by inhibiting synthesis of
dihydrofolic acid. Effective in E coli infections. Dosage form contains 5:1 ratio of sulfamethoxazole to trimethoprim.

Vancomycin (Vancocin)
Effective treatment (when PO) for antibiotic-associated colitis due to C difficile. However, reserve for individuals
whose symptoms are not responding to less expensive and almost equally effective metronidazole.

Tetracycline (Sumycin)
Treats gram-positive and gram-negative organisms as well as mycoplasmal, chlamydial, and rickettsial infections.
Good agent in older children who present with severe Yersinia species infection.

Nitazoxanide (Alinia)
Inhibits growth of C parvum sporozoites and oocysts and G lamblia trophozoites. Elicits antiprotozoal activity by
interfering with pyruvate-ferredoxin oxidoreductase (PFOR) enzyme-dependent electron transfer reaction, which is
essential to anaerobic energy metabolism. Available as a 20-mg/mL oral susp.

Rifaximin (Xifaxan, RedActiv, Flonorm)

Nonabsorbed (< 0.4%), broad-spectrum antibiotic specific for enteric pathogens of the gastrointestinal tract (ie,
Gram-positive, Gram-negative, aerobic and anaerobic). Rifampin structural analog. Binds to beta-subunit of
bacterial DNA-dependent RNA polymerase, thereby inhibiting RNA synthesis. Indicated for E coli (enterotoxigenic
and enteroaggregative strains) associated with travelers' diarrhea.

Vaccines

Class Summary
These agents elicit active immunization to increase resistance to infection. Vaccines consist of microorganisms or
cellular components, which act as antigens. Administration of the vaccine stimulates the production of antibodies
with specific protective properties.

Rotavirus vaccine (RotaTeq, Rotarix)

Currently, 2 PO administered live-virus vaccines are marketed in the United States. Both are indicated to prevent
rotavirus gastroenteritis, a major cause of severe diarrhea in infants.

RotaTeq is a pentavalent vaccine that contains 5 live reassortant rotaviruses and is administered as a 3-dose
regimen against G1, G2, G3, and G4 serotypes, the 4 most common rotavirus group A serotypes. It also contains
attachment protein P1A (genotype P[8]).

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 Rotarix protects against rotavirus gastroenteritis caused by G1, G3, G4, and G9 strains and is administered as a 2-
dose series in infants aged 6-24 wk.

Clinical trials found that the vaccines prevented 74-78% of all rotavirus gastroenteritis cases, nearly all severe
rotavirus gastroenteritis cases, and nearly all hospitalizations.

Follow-up

Further Outpatient Care

Follow-up care depends on the severity of diarrhea and the child's age. Uncomplicated diarrhea in a school-aged
child may not require follow-up care if the caregiver is reliable and has quick access to a physician. Closely monitor
young children to ensure that complications do not occur. Closely monitor children who require labor-intensive
ORT. Neonates require strict follow-up care within a few days of illness to ensure that malabsorption and
dehydration do not occur.

Further Inpatient Care

Admit neonates or young infants with moderate dehydration, suspected infection with enterohemorrhagic E coli, or
bloody diarrhea.

Oral rehydration therapy (ORT) is the universally recommended form of treatment, proven to be successful even in
children who vomit or have mild-to-moderate dehydration. Admit a child with severe dehydration. Also, ORT
requires vigilance. If the caregiver cannot comply with protocol, consider admission.

Deterrence/Prevention
Vaccines are indicated for persons with high risk of exposure to some pathogens.

In February 2006, the United States Food and Drug Administration (FDA) approved an oral vaccine for
rotavirus (RotaTeq). Soon thereafter, the AAP and the Advisory Committee on Immunization Practices
(ACIP) recommended RotaTeq to be part of regularly scheduled childhood immunizations. RotaTeq is
administered in a 3-dose series starting between age 6-12 weeks and completing before 32 weeks. An
older rotavirus vaccine (RotaShield) was associated with an increased incidence of intussusception and is
no longer on the market, but RotaTeq did not show an increased risk compared with placebo in clinical
trials.

In April 2008, the FDA approved Rotarix, another oral vaccine, for prevention of rotavirus gastroenteritis.
The current recommendation is to administer 2 separate doses of Rotarix to patients aged 6-24 weeks.
Rotarix was efficacious in a large study, which reported that Rotarix protected patients with severe rotavirus
gastroenteritis and decreased the rate of severe diarrhea or gastroenteritis of any cause.[15]

A study that involved over 63,000 patients who received Rotarix or placebo at age 2 months and at age 4

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 months reported a decreased risk of intussusception in patients who received Rotarix.[15] The
intussusception data was determined over a 31-day observation period (inpatient or outpatient) after each
dose of the Rotarix vaccine; this also included a 100-day surveillance period for all serious adverse events.
Although more patients who received Rotarix were observed to have seizures or pneumonia-related deaths,
this link has not been directly established to Rotarix. However, on March 22, 2010, the FDA recommended
the temporary discontinuation of its use, pending further studies on the reported presence of an apparently
benign pig virus in the Rotarix vaccine.

A Cochrane Database review evaluated the results of 43 trials with 190,551 participants comparing
rotavirus vaccines, both the monovalent and pentavalent types (RV1 and RV5), with placebo. Both vaccines
were found to be effective in preventing rotavirus diarrhea.[16]

The Salmonella typhi vaccine is recommended for travelers to countries with a high risk of this infection,
persons with intimate exposure to a documented typhoid fever carrier, and workers with frequent exposure
to this bacteria. Live-attenuated, killed whole-cell, and capsular polysaccharide vaccines are available.

The Vibrio species vaccine is available but only protects 50% of immunized persons for 3-6 months. It is not
indicated for use.

A study documented a diverse range of pathogens associated with community diarrhea in children in low-
income and middle-income countries to make an estimate of pathogen-specific diarrhea burdens in the
community. The study concluded that there was substantial heterogeneity in pathogen-specific burdens of
diarrhea, with important determinants including age, geography, season, rotavirus vaccine usage, and
symptoms. The authors also added that these findings suggest that although single-pathogen strategies
have an important role in the reduction of the burden of severe diarrheal disease, the effect of such
interventions on total diarrheal incidence at the community level might be limited.[17]

Complications
Common complications include the following:

Aeromonas caviae - Intussusception, gram-negative sepsis, hemolytic-uremic syndrome (HUS)

Campylobacter species -Bacteremia, meningitis, cholecystitis, urinary tract infection, pancreatitis, Reiter
syndrome (RS)

C difficile - Chronic diarrhea

C perfringens serotype C - Enteritis necroticans

Enterohemorrhagic E coli - Hemorrhagic colitis

Enterohemorrhagic E coli O157:H7 - HUS

Plesiomonas species - Septicemia

Salmonella species - Seizures, HUS, perforation, RS

Vibrio species - Rapid dehydration

Y enterocolitica - Appendicitis, perforation, intussusception, peritonitis, toxic megacolon, cholangitis,

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 bacteremia, RS

Rotavirus - Isotonic dehydration, carbohydrate intolerance

Giardia species - Chronic fat malabsorption

Cryptosporidium species - Chronic diarrhea

Entamoeba species - Colonic perforation, liver abscess

Enteric fever is caused by S typhi. This syndrome has an insidious onset of malaise, fever, abdominal pain, and
bradycardia. Diarrhea and rash (rose spots) appear after 1 week of symptoms. Bacteria may have disseminated at
that time, and treatment is required to prevent systemic complications such as hepatitis, myocarditis, cholecystitis,
or GI bleeding.

HUS is caused by damage to vascular endothelial cells by verotoxin (released by enterohemorrhagic E coli and by
Shigella organisms). Thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure characterize
HUS. Symptoms usually develop one week after onset of diarrhea, when the organism may be absent.

RS can complicate acute infections and is characterized by arthritis, urethritis, conjunctivitis, and mucocutaneous
lesions. Individuals with RS usually do not demonstrate all features.

Carrier states are observed after some bacterial infections.

After diarrhea caused by Salmonella organisms, 1-4% of individuals with nontyphoid and enteric fever
infections become carriers. The carrier stage for Salmonella organisms is more likely for females, infants,
and individuals with biliary tract disease.

Asymptomatic C difficile carriage may be observed in as many as 20% of hospitalized patients receiving
antibiotics and in 50% of infants.

Rotavirus is excreted asymptomatically in feces of children who were previously infected, typically for as
long as 1-2 weeks.

Prognosis
In developed countries, with proper management, prognosis is very good. However, data show an increase in
diarrhea-associated deaths among US children from the mid-1980s through 2006. During 2005-2007, 1087
diarrhea-associated infant deaths were reported with 86% of deaths occurring among low birthweight (< 2500g)
infants. Risk factors for these infants included male sex, black race, and low 5-minute Apgar score (< 7).[7]

Death is caused predominantly by dehydration and secondary malnutrition from a protracted course. Severe
dehydration must be managed with parenteral fluids. Once malnutrition from secondary malabsorption begins,
prognosis turns grim unless the patient is hospitalized and supplemental parenteral nutrition is started. Neonates
and young infants are at particular risk of dehydration, malnutrition, and malabsorption syndromes.

Even though the mortality rate is low in developed countries, children can die from complications; however,
prognosis for children in countries without modern medical care and children with comorbid conditions is more
guarded.

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 Patient Education
Education is most important for prevention and treatment. Proper ORT prevents dehydration, and early refeeding
speeds recovery of intestinal mucosa. With caregiver, emphasize proper hygiene and food preparation practices to
prevent future infections and spread.

For patient education resources, see the Esophagus, Stomach, and Intestine Center, as well as Irritable Bowel
Syndrome, Inflammatory Bowel Disease, and Diarrhea.

Questions & Answers

Overview

What is diarrhea?

How are acute and chronic diarrhea defined?

What should be considered to determine the cause of diarrhea?

What are the signs and symptoms of diarrhea?

Which fecal lab studies are performed in the workup of diarrhea?

What lab studies are performed in the workup of diarrhea?

How is diarrhea treated?

Which drugs are used to treat diarrhea?

How is acute diarrhea defined?

What causes acute diarrhea in children and what is the most common complication of acute diarrhea?

Is acute gastroenteritis synonymous with acute diarrhea?

How are diarrheal episodes characterized?

What is the pathogenesis of diarrhea?

What is the pathophysiology of osmotic diarrhea?

What is the pathophysiology of secretory diarrhea?

What is the incidence of diarrhea in the US?

What is the global incidence of diarrhea?

What is the mortality and morbidity from diarrhea?

Does the incidence of diarrhea vary among males and females?

Does the incidence of diarrhea vary among age groups?

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 Presentation

What is the clinical presentation and disease course of acute diarrhea?

What is the incidence of acute diarrhea?

How is diarrhea defined in children?

What does flatulence associated with foul-smelling stools suggest?

What can be helpful in determining whether the source of diarrhea is from the small or large bowel?

What are the systemic symptoms of diarrhea?

Which organisms may increase the risk of diarrhea in daycare settings?

How can food history be helpful in the diagnosis of diarrhea and which organisms cause food poisoning?

How does water exposure increase the risk of diarrhea?

Why is travel history important in suspected diarrhea?

How does animal exposure increase the risk for diarrhea?

Which factors predispose patients to infectious causes of diarrhea?

Which physical findings suggest dehydration in patients with diarrhea?

What is the presentation of failure to thrive and malnutrition in children with diarrhea?

How is abdominal pain characterized in patients with diarrhea?

What is the presentation of borborygmi in patients with diarrhea?

What is the presentation of perianal erythema in patients with diarrhea?

What is the most common cause for sporadic or endemic episodes of acute diarrhea?

What are possible causes of acute onset diarrhea?

What are infectious causes of acute diarrhea in developed countries?

Which pathogens cause pediatric nosocomial diarrhea?

DDX

What are the differential diagnoses for Diarrhea?

Workup

Which findings suggest carbohydrate intolerance in patients with diarrhea?

Which findings suggest an enteroinvasive infectious cause of diarrhea?

What should be examined in the workup of diarrhea and what finding suggests colitis?

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 What is the role of culture in the workup of diarrhea?

What should prompt additional screening for Clostridium difficile (C diff) infection in the workup of diarrhea?

What should prompt additional screening for E coli in the workup of diarrhea?

What should prompt additional screening for Vibrio and Plesiomonas infections in the workup of diarrhea?

Which culture mediums are used to isolate bacteria in the workup of diarrhea?

Which test is performed to identify rotavirus infection in the workup of diarrhea?

Which test is performed to identify adenovirus in the workup of diarrhea?

How are parasitic causes of diarrhea identified?

When is leukocytosis present in diarrhea?

What does a finding of protein-losing enteropathy suggest in the workup of diarrhea?

What is the role of an anion gap test in the workup of diarrhea?

When are procedures performed in the workup of diarrhea?

Treatment

What are the CDC recommendations for the evaluation of acute pediatric diarrhea?

What are the CDC recommendations in the treatment of dehydration due to diarrhea?

What is oral rehydration therapy (ORT) for diarrhea and how is it administered?

What has been added to oral rehydration therapy (ORT) to improve effectiveness in treating diarrhea in developing
countries?

Which beverages may be effective in the treatment of diarrhea?

When can feeding be resumed in children with diarrhea?

What is the role of antimotility and antimicrobial therapy for diarrhea?

What are the treatment options for nonviral diarrhea?

When should consultations be considered for patients with diarrhea?

How should infants with acute diarrhea be fed?

What diet is suggested in the treatment of diarrhea?

Medications

What is the best option for treatment of acute-onset diarrhea?

Which antimicrobial agents are used in the treatment of diarrhea?

What is the efficacy of probiotics in the treatment of diarrhea?

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 Which medications in the drug class Vaccines are used in the treatment of Diarrhea?

Which medications in the drug class Antibiotic and antiparasitics agents are used in the treatment of Diarrhea?

Contributor Information and Disclosures

Author

Stefano Guandalini, MD, AGAF Founder and Director Emeritus, Celiac Disease Center, University of Chicago;
Former Chief, Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics,
University of Chicago Medicine; Professor Emeritus, The University of Chicago Pritzker School of Medicine

Stefano Guandalini, MD, AGAF is a member of the following medical societies: American Gastroenterological
Association, European Society for Paediatric Gastroenterology, Hepatology and Nutrition, North American Society
for Pediatric Gastroenterology, Hepatology and Nutrition, North American Society for the Study of Celiac Disease

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Imaware.health.

Coauthor(s)

Richard E Frye, MD, PhD Professor of Child Health, University of Arizona College of Medicine at Phoenix; Chief
of Neurodevelopmental Disorders, Director of Autism and Down Syndrome and Fragile X Programs, Division of
Neurodevelopmental Disorders, Department of Neurology, Barrow Neurological Institute at Phoenix Children's
Hospital

Richard E Frye, MD, PhD is a member of the following medical societies: American Academy of Neurology,
American Academy of Pediatrics, Child Neurology Society

Disclosure: Nothing to disclose.

M Akram Tamer, MD Professor, Program Director, Department of Pediatrics, University of Miami, Leonard M Miller
School of Medicine

M Akram Tamer, MD is a member of the following medical societies: American Medical Association, Florida
Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of
Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Carmen Cuffari, MD Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns

Hopkins University School of Medicine

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 Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology,
American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and
Nutrition, Royal College of Physicians and Surgeons of Canada

Disclosure: Received honoraria from Prometheus Laboratories for speaking and teaching; Received honoraria
from Abbott Nutritionals for speaking and teaching. for: Abbott Nutritional, Abbvie, speakers' bureau.

Additional Contributors

Chris A Liacouras, MD Director of Pediatric Endoscopy, Division of Gastroenterology and Nutrition, Children's
Hospital of Philadelphia; Associate Professor of Pediatrics, University of Pennsylvania School of Medicine

Chris A Liacouras, MD is a member of the following medical societies: American Gastroenterological Association

Disclosure: Nothing to disclose.

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