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Diarrhea
Updated: Oct 31, 2018
Author: Stefano Guandalini, MD; 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.
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:
Use of child daycare (common pathogens: rotavirus, astrovirus, calicivirus; Campylobacter, Shigella, Giardia, and
Cryptosporidium species [spp])
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)
Dehydration: Lethargy, depressed consciousness, sunken anterior fontanel, dry mucous membranes, sunken eyes, lack
of tears, poor skin turgor, delayed capillary refill
Abdominal pain/cramping
Borborygmi
Perianal erythema
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See Clinical Presentation for more detail.
Diagnosis
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
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
Serum albumin levels: Low in protein-losing enteropathies from enteroinvasive intestinal infections (eg, Salmonella spp,
enteroinvasive E coli)
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)
Management
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
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Vancomycin
Tetracycline
Nitazoxanide
Rifaximin
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.
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.
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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 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).
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
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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).
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)
Stool
Small Bowel Large Bowel
Characteristics
Reducing
Possibly positive Negative
substances
Invasive bacteria
Plesiomonas species
Organisms
Enterotoxigenic bacteria
E coli
Cholera species
Vibrio species
Parasites
Parasites
Giardia species
Entamoeba organisms
Cryptosporidium species
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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.
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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.
Guidelines on fruit juice intake for children by the American Academy of Pediatrics recommend that 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]
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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.
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
Travel to South America and Central America -Entamoeba species, V cholerae, enterotoxigenic E coli
Salmonella species - Intestinal dysmotility, malnutrition, achlorhydria, hemolytic anemia (especially sickle cell
disease), immunosuppression, malaria
Rotavirus - Hospitalization
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Physical
The following may be observed:
Dehydration
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)
Skin Pinch retracts immediately Pinch retracts slowly Pinch stays folded
Reduced muscle and fat mass or peripheral edema may be clues to the presence of carbohydrate, fat, and/or
protein malabsorption.
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Abdominal pain
Nonspecific nonfocal abdominal pain and cramping are common with some organisms.
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 bile acid malabsorption can result in a severe diaper dermatitis that is often characterized as a "burn."
Causes
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.
Infections
Extraintestinal infections
Drug-induced
Antibiotic-associated
Laxatives
Opiate withdrawal
Other drugs
Olestra
Glucose-galactose malabsorption
Sucrase-isomaltase deficiency
Acute appendicitis
Intussusception
Vitamin deficiencies
Niacin deficiency
Folate deficiency
Vitamin toxicity
Vitamin C
Niacin, vitamin B3
Ingestion of plants (eg, hyacinths, daffodils, azalea, mistletoe, Amanita species mushrooms
Viruses
Bacteria
V cholerae - Unknown
Parasites
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]
DDx
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Differential Diagnoses
Appendicitis
Carcinoid Tumor
Giardiasis
Glucose-galactose malabsorption
Intussusception
Pediatric Hyperthyroidism
Protein Intolerance
Shigella Infection
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.
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.
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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)
Plesiomonas
Blood agar Oxidase-positive GNR
species
Blood agar - All aerobic bacteria and yeast; detects cytochrome oxidase production
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 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:
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Younger than 3 months
Fever of 38ºC or higher in infants younger than 3 months or 39ºC or higher in children aged 3-36 months
High-output diarrhea
Persistent emesis
Signs of dehydration as reported by caregiver, including sunken eyes, decreased tears, dry mucous membranes, and
decreased urine output
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.
Minimal or no dehydration
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
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 physiologic, and most effective
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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.
Aeromonas species: Use cefixime and most third-generation and fourth-generation cephalosporins.
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.
Cryptosporidium parvum: Administer paromomycin; however, effectiveness is not proven. Nitazoxanide, a newer
anthelmintic, is effective against C parvum.
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.
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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
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.
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 withdrawal of breastfeeding during diarrhea has
been shown to have a deleterious effect on the development of dehydration in infants with acute watery diarrhea.
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.
Guidelines
Guidelines Summary
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British Society of Gastroenterology guidelines for the investigation of chronic diarrhoea in adults[35]
Clinical assessment
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.
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.
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.
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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:
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:
Enteroinvasive E coli, based on the serologic, genetic, and pathogenic similarities with Shigella
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.
Evidence of
Patients and Efficacy
Condition Most-Studied Probiotics
Controls
(- to +++)
Bifidobacterium lactis
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Lactobacillus reuteri
Lactobacillus casei
Lactobacillus GG
Infectious Diarrhea 3500 +++
Saccharomyces boulardii
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 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.
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.
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.
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.
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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.
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]).
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
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
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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 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:
Campylobacter species -Bacteremia, meningitis, cholecystitis, urinary tract infection, pancreatitis, Reiter syndrome (RS)
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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.
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.
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.
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What is diarrhea?
What causes acute diarrhea in children and what is the most common complication of acute diarrhea?
Presentation
What can be helpful in determining whether the source of diarrhea is from the small or large bowel?
How can food history be helpful in the diagnosis of diarrhea and which organisms cause food poisoning?
What is the presentation of failure to thrive and malnutrition in children with diarrhea?
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What is the most common cause for sporadic or endemic episodes of acute diarrhea?
DDX
Workup
What should be examined in the workup of diarrhea and what finding suggests colitis?
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?
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?
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Medications
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?
Author
Stefano Guandalini, MD Founder and Medical Director, Celiac Disease Center, Chief, Section of Pediatric Gastroenterology,
Hepatology and Nutrition, Department of Pediatrics, University of Chicago Medical Center; Professor, Department of Pediatrics,
Section of Gastroenterology, Hepatology and Nutrition, University of Chicago Division of the Biological Sciences, The Pritzker
School of Medicine
Stefano Guandalini, MD is a member of the following medical societies: American Gastroenterological Association, European
Society for Paediatric Gastroenterology, Hepatology & Nutrition, North American Society for Pediatric Gastroenterology,
Hepatology and Nutrition, North American Society for the Study of Celiac Disease
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, 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
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
Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-
Chief, Medscape Drug Reference
Chief Editor
Carmen Cuffari, MD Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins
University School of Medicine
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
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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
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